Ring-fused heteroaromatic ring compound as well as intermediate, preparation method and application thereof

Abstract

The invention discloses a ring-fused heteroaromatic ring compound as well as an intermediate, a preparation method and application thereof. The invention provides a compound as shown in a formula I, and pharmaceutically acceptable salts or isotope compounds thereof. Compared with the prior art, the ATPase activity and the protein inhibition effect of the compound are greatly improved. # imgabs0 #

Description

Technical Field

[0001] The invention relates to a cyclic heteroaromatic ring compound, an intermediate thereof, a preparation method and application. Background Art

[0002] DNA damage is an important mechanism by which many chemotherapeutic drugs exert their anti-tumor effects. DNA double-strand breaks (DSBs) are one of the most common types of damage in cells, which can be directly caused by ionizing radiation or induced by ultraviolet rays, reactive oxygen species (ROS) or other mutagens, such as common chemotherapeutic drugs cisplatin, 5-FU, etoposide, etc. Unrepaired DNA damage can lead to functional blockade of cell transcription and replication, induce cell apoptosis or necrosis, and be cleared by immune cells. There are efficient damage repair or alternative repair pathways in tumor cells. Targeting the key proteins of the DNA damage repair pathway, causing the unrepaired DNA damage to continue to accumulate, and ultimately leading to cell death, is one of the important strategies for cancer treatment.

[0003] DNA double-strand breaks are usually repaired by three methods: non-homologous end joining (NHEJ), homologous recombination (HR), and alternative non-homologous end joining (Alt-NHEJ, also known as micro-homologous end joining MMEJ or TMEJ). Among them, the HR repair pathway only occurs in the G2 and S phases, and completes error-free repair in the presence of sister chromatids. In mammals, more than 90% of DSB damage is repaired by the NHEJ pathway. It is an error-prone repair that forms a deletion mutation of <30bp or an insertion mutation of <5bp or a micro-homology sequence of <2bp. The latest studies have shown that when HR and / or NHEJ are defective, cells are highly dependent on the third method, MMEJ, to repair broken DNA. Inhibition of MMEJ can lead to cell apoptosis. MMEJ is also an error-prone repair pathway that relies on DNA polymerase theta to connect micro-homologous end sequences (Theta mediated end joining, TMEJ) to complete the repair of DNA double-strand breaks.

[0004] DNA polymerase theta (Pol theta or Polθ) is a key protein in the MMEJ repair pathway. It is a unique multifunctional polymerase consisting of an N-terminal helicase domain, a central domain, and a C-terminal polymerase domain. Basic research has found that the polymerase domain is necessary for DNA extension at the DSB damage repair site, while the helicase domain and the central domain play a key role in the recognition and binding of Polθ to the substrate. Polθ can release the interaction between DNA and the damage repair complex (such as competitive binding with RAD51 to single-stranded DNA), inhibiting the HR repair pathway. In addition, the helicase domain of Polθ is also involved in DNA replication arrest, and its functional loss will lead to increased replication pressure of tumor cells and apoptosis.

[0005] Polθ is not expressed or expressed at a low level in normal tissue cells, but is highly expressed in a variety of tumors such as lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, and colon cancer, and is associated with a poor prognosis. Among them, Polθ is overexpressed in more than 70% of breast cancers. These phenomena indicate that Polθ may play an important role in these cancers and is a potential tumor-specific target.

[0006] Studies that knock down or knock out Polθ in tumor cells have found that Polθ deficiency can sensitize these cells to radiation, induce the generation of DSBs, enhance replication fork instability, and make tumor cells sensitive to genotoxic agents, which may enhance the effects of radiotherapy and chemotherapy, and is a potential drug target. Studies have also found that Polθ and HR deficiency have a combined lethal effect, and its small molecule inhibitors can kill HR-deficient tumor cells in vivo and in vitro. In particular, in PARP inhibitor-resistant tumors (Olaparib, etc.) with HR defective reversion mutations, Polθ inhibitors can sensitize cells to PARPi again, providing valuable treatment opportunities. In addition, given that Polθ is a key protein in the MMEJ pathway, its functional defects can also lead to enhanced genomic instability in cancer cells, increase somatic mutations, and facilitate the production of tumor neoantigens. In addition, it has been reported that Polθ is involved in cGAS-STING-mediated immune activation, so targeting Polθ also has the potential to enhance immunotherapy.

[0007] In short, Polθ is a highly potential target for cancer treatment. By designing ATPase activity inhibitors targeting Polθ protein and inhibiting intracellular MMEJ, it can be used alone or in combination with other chemotherapy, radiotherapy, antibody therapy, immunotherapy, etc. to kill tumor cells. It has great potential in the treatment of lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, colon cancer, prostate cancer, pancreatic cancer and other tumors. Summary of the invention

[0008] The technical problem to be solved by the present invention is to overcome the relatively simple structure of the polymerase theta inhibitor compounds in the prior art. To this end, the present invention provides a paracyclic heteroaromatic ring compound, its intermediate, preparation method and application. The ATPase activity and protein inhibition effect of the compound are greatly improved compared with the prior art, and the proliferation inhibition effect on DLD1BRCA2- / - cells and DLD1 wild-type cells is highly selective.

[0009] The present invention solves the above technical problems through the following technical solutions.

[0010] The present invention provides a compound as shown in Formula I, a pharmaceutically acceptable salt thereof or an isotope compound thereof,

[0011]

[0012] in:

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

[0014] Ring A is a benzene ring, a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatoms in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0015] R 1 is unsubstituted or substituted with one or more R 1-1 substituted 6-12 membered aryl, unsubstituted or replaced by one or more R 1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 1-3 Substituted 4-12 membered heterocycloalkenyl; the heteroatoms in the 5-12 membered heteroaryl and the 4-12 membered heterocycloalkenyl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0016] Each R 1-1 , R 1-2 and R 1-3 are independently deuterium, halogen, cyano, amino, hydroxyl, oxo, unsubstituted or substituted with one or more R 1-1-1Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 1-1-3 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 1-1-4 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 1-1-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 1-1-6 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 1-1-13 Substituted 4-12 membered heterocycloalkenyl, -COOR 1-1-7 、-C(O)R 1-1-8 、-C(O)N(R 1-1-9 )2. or N(R 1-1-12 )2; the heteroatoms in the 4-12 membered heterocyclic group and the 4-12 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0017] Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 and R 1-1-13 are independently deuterium, hydroxyl, cyano or halogen;

[0018] Each R 1-1-7 , R 1-1-8 , R 1-1-9 and R 1-1-12 are independently hydrogen or C1-C6 alkyl;

[0019] Each R 1-1-10 and R 1-1-11 are independently hydroxyl or C1-C6 alkyl;

[0020] Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-2 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-4 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6Substituted 5-12 membered heteroaryl, -O-5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12-membered heterocyclyl, 4-12-membered heterocycloalkenyl, 5-12-membered heteroaryl and -O-5-12-membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0021] Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-1-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0022] Each R 2-4 , R 2-5 and R 2-9 are independently oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R 2 -5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-5-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5-6 Substituted 4-12 membered heterocyclic group, -N(R 2 -5-3 )2. The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0023] Each R 2-6 are independently oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-5-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-6-2 Substituted 4-12 membered heterocyclic group, -N(R 2-6-3 )2. The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0024] Each R 2-7 are independently hydrogen, unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-8-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0025] Each R 2-8 are independently unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-8-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0026] Each R 2-1-1 and R 2-1-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0027] Each R 2-1-3 are independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0028] Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0029] Each R 2-4-1 , R 2-5-3 and R 2-6-3 are independently hydrogen or C1-C6 alkyl;

[0030] Each R 2-5-1 , R 2-5-2 and R 2-7-1 are independently deuterium, hydroxyl, cyano or halogen;

[0031] Each R 2-5-4 and R 2-7-3 are independently C1-C6 alkyl or 3-6 membered cycloalkyl;

[0032] Each R 2-5-5 , R2-5-6 and R 2-6-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0033] Each R 2-6-1 are independently hydroxy, cyano, halogen or C1-C6 alkoxy;

[0034] Each R 2-7-2 and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0035] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2, 3 or 4;

[0036] Each R b-1 are independently deuterium, oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -N(R b-1-3 )2、-C(O)N(R b-1-4) 2. -COOR b-1-5 ,

[0037] Each R b-1-1 and R b-1-2 are independently deuterium, hydroxyl, halogen or -NR b-1-1-1 R b-1-1-1 ;

[0038] Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or C1-C6 alkyl;

[0039] Each R b-1-6 are independently hydroxyl or C1-C6 alkyl;

[0040] Each R b-1-8 are independently hydroxyl or C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein in the 4-6 membered heterocyclic group, when the number of heteroatom groups is 1, the heteroatom group is P(O); when the number of heteroatoms or heteroatom groups is 2 or 3, one of the heteroatom groups is P(O), and the remaining heteroatoms are independently selected from one or two of N, O and S;

[0041] Each R b-1-1-1 are independently hydrogen, C1-C6 alkyl or -C(O)R b-1-1-1-1 ;

[0042] R b-1-1-1-1 is a C1-C6 alkyl group;

[0043] Each R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-3 substituted 4-12 membered cycloalkenyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 、-NH(CH2) p R 5 、-O(CH2) q R 6 , unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl or unsubstituted or with one or more R 3-8 Substituted-OR 7 The heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0044] p is 0, 1, 2 or 3;

[0045] q is 1, 2, or 3;

[0046] Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl, halogen, cyano, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, oxo, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-N(R 3 -4-2 )2. The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0047] Each R 3-5 and R 3-6 are independently deuterium, hydroxyl, halogen, cyano, amino, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-NR 3-4-2 R 3-4-2 , The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0048] Each R 3-2-1 and R 3-4-2 are independently hydrogen or C1-C6 alkyl;

[0049] Each R 3-2-3 , R 3-5-1 and R 3-5-2 are independently hydroxyl or C1-C6 alkyl;

[0050] Each R 3-2-2 are independently hydroxy or halogen;

[0051] R 3-4-1 is hydroxyl, amino or C1-C6 alkyl;

[0052] R 4 is unsubstituted or substituted with one or more R 4-1 substituted 4-6 membered heterocyclic group or unsubstituted or replaced by one or more R 4-2 Substituted C1-C6 alkyl; the heteroatom in the 4-6 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0053] Each R 4-1 are independently hydroxyl groups;

[0054] Each R 4-2 are independently hydroxy or halogen;

[0055] R 5 is unsubstituted or substituted with one or more R 5-1 Substituted 3-6 membered cycloalkyl;

[0056] R 6 is unsubstituted or substituted with one or more R 6-1 Substituted 3-6 membered cycloalkyl;

[0057] Each R 5-1 and R 6-1 are independently hydroxyl groups;

[0058] R 7 is a 3-6 membered cycloalkyl group;

[0059] And the compound shown in formula I is not

[0060] The present invention provides a compound as shown in Formula I, a pharmaceutically acceptable salt thereof or an isotope compound thereof,

[0061]

[0062] in:

[0063] m is 0, 1, 2 or 3; n is 1, 2 or 3;

[0064] Ring A is a benzene ring, a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatoms in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0065] R 1 is unsubstituted or substituted with one or more R 1-1 substituted 6-12 membered aryl, unsubstituted or replaced by one or more R 1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 1-3 Substituted 4-12 membered heterocycloalkenyl; the heteroatoms in the 5-12 membered heteroaryl and the 4-12 membered heterocycloalkenyl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0066] Each R 1-1 , R 1-2 and R 1-3 are independently deuterium, halogen, cyano, amino, hydroxyl, oxo (=O), unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R1-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 1-1-3 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 1-1-4 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 1-1-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 1-1-6 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 1-1-13 Substituted 4-12 membered heterocycloalkenyl, -COOR 1-1-7 、-C(O)R 1-1-8 、-C(O)N(R 1-1-9 )2. or N(R 1-1-12 )2; the heteroatoms in the 4-12 membered heterocyclic group and the 4-12 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0067] Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 and R 1-1-13 are independently deuterium, hydroxyl, cyano or halogen;

[0068] Each R 1-1-7 , R 1-1-8 , R 1-1-9 and R 1-1-12 are independently hydrogen or C1-C6 alkyl;

[0069] Each R 1-1-10 and R 1-1-11 are independently hydroxyl or C1-C6 alkyl;

[0070] Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-1 Substituted C2-C6 alkyl, unsubstituted or replaced by one or more R 2-2 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-4 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6Substituted 5-12 membered heteroaryl, -O-5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12-membered heterocyclyl, 4-12-membered heterocycloalkenyl, 5-12-membered heteroaryl and -O-5-12-membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0071] Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-1-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0072] Each R 2-4 , R 2-5 and R 2-9 are independently oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R 2 -5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-5-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5-6 Substituted 4-12 membered heterocyclic group, -N(R 2 -5-3 )2. The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0073] Each R 2-6 are independently oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-5-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-6-2 Substituted 4-12 membered heterocyclic group, -N(R 2-6-3 )2. The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0074] Each R 2-7 are independently hydrogen, unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-8-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0075] Each R 2-8 are independently unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-8-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0076] Each R 2-1-1 and R 2-1-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0077] Each R 2-1-3 are independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0078] Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0079] Each R 2-4-1 , R 2-5-3 and R 2-6-3 are independently hydrogen or C1-C6 alkyl;

[0080] Each R 2-5-1 , R 2-5-2 and R 2-7-1 are independently deuterium, hydroxyl, cyano or halogen;

[0081] Each R 2-5-4 and R 2-7-3 are independently C1-C6 alkyl or 3-6 membered cycloalkyl;

[0082] Each R 2-5-5 , R2-5-6 and R 2-6-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0083] Each R 2-6-1 are independently hydroxy, cyano, halogen or C1-C6 alkoxy;

[0084] Each R 2-7-2 and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0085] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2, 3 or 4;

[0086] Each R b-1 are independently deuterium, oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -N(R b-1-3 )2、-C(O)N(R b-1-4) 2. -COOR b-1-5 ,

[0087] Each R b-1-1 and R b-1-2 are independently deuterium, hydroxyl, halogen or -NR b-1-1-1 R b-1-1-1 ;

[0088] Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or C1-C6 alkyl;

[0089] Each R b-1-6 are independently hydroxyl or C1-C6 alkyl;

[0090] Each R b-1-8 are independently hydroxyl or C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein in the 4-6 membered heterocyclic group, when the number of heteroatom groups is 1, the heteroatom group is P(O); when the number of heteroatoms or heteroatom groups is 2 or 3, one of the heteroatom groups is P(O), and the remaining heteroatoms are independently selected from one or two of N, O and S;

[0091] Each R b-1-1-1 are independently hydrogen, C1-C6 alkyl or -C(O)R b-1-1-1-1 ;

[0092] R b-1-1-1-1 is a C1-C6 alkyl group;

[0093] R 3 is hydrogen, unsubstituted or replaced by one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-3 substituted 4-12 membered cycloalkenyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 、-NH(CH2) p R 5 、-O(CH2) q R 6 , unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl or unsubstituted or with one or more R 3-8 Substituted-OR 7 The heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0094] p is 0, 1, 2 or 3;

[0095] q is 1, 2, or 3;

[0096] Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl, halogen, cyano, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, oxo, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-N(R 3 -4-2 )2. The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0097] Each R 3-5 and R 3-6 are independently deuterium, hydroxyl, halogen, cyano, amino, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-NR 3-4-2 R 3-4-2 , The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0098] Each R 3-2-1 and R 3-4-2 are independently hydrogen or C1-C6 alkyl;

[0099] Each R 3-2-3 , R 3-5-1 and R 3-5-2 are independently hydroxyl or C1-C6 alkyl;

[0100] Each R 3-2-2 are independently hydroxy or halogen;

[0101] R 3-4-1 is hydroxyl, amino or C1-C6 alkyl;

[0102] R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group; the heteroatom in the 4-6 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0103] Each R 4-1 are independently hydroxyl groups;

[0104] R 5 is unsubstituted or substituted with one or more R5-1 Substituted 3-6 membered cycloalkyl;

[0105] R 6 is unsubstituted or substituted with one or more R 6-1 Substituted 3-6 membered cycloalkyl;

[0106] Each R 5-1 and R 6-1 are independently hydroxyl groups;

[0107] R 7 is a 3-6 membered cycloalkyl group;

[0108] And the compound shown in formula I is not

[0109] The present invention provides a compound as shown in Formula I, a pharmaceutically acceptable salt thereof or an isotope compound thereof,

[0110]

[0111] in:

[0112] m is 0, 1, 2 or 3; n is 1, 2 or 3;

[0113] Ring A is a benzene ring, a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatoms in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0114] R 1 is unsubstituted or substituted with one or more R 1-1 substituted 6-12 membered aryl, unsubstituted or replaced by one or more R 1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 1-3 Substituted 4-12 membered heterocycloalkenyl; the heteroatoms in the 5-12 membered heteroaryl and the 4-12 membered heterocycloalkenyl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0115] Each R 1-1 , R 1-2 and R 1-3 are independently deuterium, halogen, cyano, amino, hydroxyl, oxo (=O), unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 1-1-3 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 1-1-4Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 1-1-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 1-1-6 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 1-1-13 Substituted 4-12 membered heterocycloalkenyl, -COOR 1-1-7 、-C(O)R 1-1-8 、-C(O)N(R 1-1-9 )2. or N(R 1-1-12 )2; the heteroatoms in the 4-12 membered heterocyclic group and the 4-12 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0116] Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 and R 1-1-13 are independently deuterium, hydroxyl, cyano or halogen;

[0117] Each R 1-1-7 , R 1-1-8 , R 1-1-9 and R 1-1-12 are independently hydrogen or C1-C6 alkyl;

[0118] Each R 1-1-10 and R 1-1-11 are independently hydroxyl or C1-C6 alkyl;

[0119] Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, one or more R 2-2 Substituted C2-C6 alkenyl, substituted by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-4 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -O-5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12-membered heterocyclyl, 4-12-membered heterocycloalkenyl, 5-12-membered heteroaryl and -O-5-12-membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0120] Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-1-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0121] Each R 2-4 Independently

[0122] Each R 2-5 and R 2-9 are independently oxo, halogen, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, 3-6 membered cycloalkyl, 4-12 membered heterocyclic group, -N(R 2 -5-3 )2 or The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0123] Each R 2-6 are independently oxo, cyano, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-6-2 Substituted 4-12 membered heterocyclic group or -N(R 2-6-3 )2; the heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0124] Each R 2-7 are independently hydrogen, unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0125] Each R 2-8 are independently unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0126] Each R 2-1-1 and R 2-1-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0127] Each R 2-1-3 are independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0128] Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0129] Each R 2-4-1 are independently hydrogen or C1-C6 alkyl;

[0130] Each R 2-5-1 and R 2-5-2 are independently deuterium, hydroxyl, cyano or halogen;

[0131] Each R 2-5-3 are independently hydrogen or C1-C6 alkyl;

[0132] Each R 2-5-4 are independently C1-C6 alkyl;

[0133] Each R 2-6-1 are independently cyano, halogen or C1-C6 alkoxy;

[0134] Each R 2-6-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0135] Each R 2-6-3 are independently hydrogen or C1-C6 alkyl;

[0136] Each R 2-7-1 are independently deuterium, hydroxyl, cyano or halogen;

[0137] Each R 2-7-2 are independently C1-C6 alkyl;

[0138] Each R 2-7-3 are independently 3-6 membered cycloalkyl;

[0139] Each R 2-8-1are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0140] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2, 3 or 4;

[0141] Each R b-1 are independently deuterium, oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -N(R b-1-3 )2、-C(O)N(R b-1-4) 2. -COOR b-1-5 ,

[0142] Each R b-1-1 and R b-1-2 are independently deuterium, hydroxyl, halogen or -NR b-1-1-1 R b-1-1-1 ;

[0143] Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or C1-C6 alkyl;

[0144] Each R b-1-6 are independently hydroxyl or C1-C6 alkyl;

[0145] Each R b-1-8 are independently hydroxyl or C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein in the 4-6 membered heterocyclic group, when the number of heteroatom groups is 1, the heteroatom group is P(O); when the number of heteroatoms or heteroatom groups is 2 or 3, one of the heteroatom groups is P(O), and the remaining heteroatoms are independently selected from one or two of N, O and S;

[0146] Each R b-1-1-1 are independently hydrogen, C1-C6 alkyl or -C(O)R b-1-1-1-1 ;

[0147] R b-1-1-1-1 is a C1-C6 alkyl group;

[0148] R 3 is hydrogen, unsubstituted or replaced by one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-3 substituted 4-12 membered cycloalkenyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 、-NH(CH2) p R 5 、-O(CH2) q R 6 , unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl or unsubstituted or with one or more R 3-8 Substituted-OR 7 The heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0149] p is 0, 1, 2 or 3;

[0150] q is 1, 2, or 3;

[0151] Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl, halogen, cyano, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, oxo, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-N(R 3 -4-2 )2. The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0152] Each R 3-5 and R 3-6 are independently deuterium, hydroxyl, halogen, cyano, amino, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-NR 3-4-2 R 3-4-2 , The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0153] Each R 3-2-1 and R 3-4-2 are independently hydrogen or C1-C6 alkyl;

[0154] Each R 3-2-3 , R 3-5-1 and R 3-5-2 are independently hydroxyl or C1-C6 alkyl;

[0155] Each R 3-2-2 are independently hydroxy or halogen;

[0156] R 3-4-1 is hydroxyl, amino or C1-C6 alkyl;

[0157] R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group; the heteroatom in the 4-6 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0158] Each R 4-1 are independently hydroxyl groups;

[0159] R 5 is unsubstituted or substituted with one or more R 5-1 Substituted 3-6 membered cycloalkyl;

[0160] R 6 is unsubstituted or substituted with one or more R 6-1 Substituted 3-6 membered cycloalkyl;

[0161] Each R 5-1 and R 6-1 are independently hydroxyl groups;

[0162] R 7 is a 3-6 membered cycloalkyl group;

[0163] And the compound shown in formula I is not

[0164] In a preferred embodiment, the compound of formula I, its pharmaceutically acceptable salt or isotope compound; the definitions of certain groups may be as described below, and the definitions of other groups may be as described in any of the above embodiments (hereinafter referred to as "in a preferred embodiment"): the compound of formula I is a compound of formula I',

[0165]

[0166] In a preferred embodiment, in ring A, the 5-6 membered heteroaromatic ring may be a 6 membered heteroaromatic ring, the heteroatom in the 6 membered heteroaromatic ring may be N, the number of heteroatoms may be 1, preferably a pyridine ring, for example

[0167] In a preferred embodiment, in ring A, the 5-6 membered heterocycloalkenyl group may be a 6 membered heterocycloalkenyl group, the heteroatom in the 6 membered heterocycloalkenyl group may be N, the number of heteroatoms may be 1, preferably a pyridone group, for example

[0168] In a preferred embodiment, in ring A, the oxo-substituted 5-6-membered heterocycloalkenyl group may be an oxo-substituted 5-6-membered heterocycloalkenyl group containing 1 or 2 carbon-carbon double bonds.

[0169] In a preferred embodiment, R 1 In the above, the 6-12 membered aryl group may be a 6-10 membered aryl group, or may be a phenyl group or a naphthyl group, preferably a phenyl group.

[0170] In a preferred embodiment, R 1 In the above, the 5-12 membered heteroaryl group may be a 5-10 membered heteroaryl group, the heteroatom in the 5-10 membered heteroaryl group may be N, and the number of heteroatoms may be 1 or 2; the 5-12 membered heteroaryl group is preferably a 5-6 membered heteroaryl group; more preferably For example

[0171] In a preferred embodiment, R 1 In the above, the 4-12 membered heterocycloalkenyl group may be a 4-6 membered heterocycloalkenyl group, the heteroatom in the 4-6 membered heterocycloalkenyl group may be N, the number of heteroatoms may be 1, and preferably a dihydropyridyl group, for example

[0172] In a preferred embodiment, R 1 In the above, the 4-12 membered heterocycloalkenyl group may be a 4-12 membered heterocycloalkenyl group containing at least 2 carbon-carbon double bonds.

[0173] In a preferred embodiment, each R 1-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine.

[0174] In a preferred embodiment, each R 1-1 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0175] In a preferred embodiment, each R 1-1 In the above, the C1-C6 alkoxy group may be a C1-C4 alkoxy group, or may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group.

[0176] In a preferred embodiment, each R 1-2 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine.

[0177] In a preferred embodiment, each R 1-2 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0178] In a preferred embodiment, each R 1-2 In the above, the C1-C6 alkoxy group may be a C1-C4 alkoxy group, or may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group.

[0179] In a preferred embodiment, each R 1-2 In the above, the 3-6 membered cycloalkyl group may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopropyl or cyclobutyl.

[0180] In a preferred embodiment, each R 1-2 In the above, the 4-12 membered heterocyclic group may be a 4-12 membered monocyclic heterocyclic group or a 4-12 membered polycyclic heterocyclic group (preferably a spirocyclic group); the 4-12 membered monocyclic heterocyclic group is preferably a 4-7 membered monocyclic heterocyclic group, the heteroatom in the 4-7 membered monocyclic heterocyclic group is preferably N and / or O, the number of heteroatoms is preferably 1, and more preferably The 4-12 membered polycyclic heterocyclic group is preferably a 4-10 membered polycyclic heterocyclic group, the heteroatom in the 4-10 membered polycyclic heterocyclic group is preferably O or N, the number of heteroatoms is preferably 1, and more preferably

[0181] In a preferred embodiment, each R 1-2In the above, the 4-12 membered heterocycloalkenyl group may be a 4-12 membered monocyclic heterocycloalkenyl group or a 4-12 membered polycyclic heterocycloalkenyl group (preferably a spirocyclic group); the 4-12 membered polycyclic heterocycloalkenyl group is preferably a 4-10 membered polycyclic heterocycloalkenyl group, the heteroatom in the 4-10 membered polycyclic heterocycloalkenyl group is preferably O or N, the number of heteroatoms is preferably 1, and more preferably

[0182] In a preferred embodiment, each R 1-2 In the above, the 4-12 membered heterocycloalkenyl group may contain 1 or 2 carbon-carbon double bonds.

[0183] In a preferred embodiment, each R 1-3 In the above, the C1-C6 alkoxy group may be a C1-C4 alkoxy group, or may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group.

[0184] In a preferred embodiment, each R 1-1-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine, for example fluorine.

[0185] In a preferred embodiment, each R 1-1-2 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine.

[0186] In a preferred embodiment, each R 1-1-12 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0187] In a preferred embodiment, each R 2 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0188] In a preferred embodiment, each R 2 In the above, the C2-C6 alkynyl group may be a C2-C4 alkynyl group, or may be Best

[0189] In a preferred embodiment, each R 2 In the above, the 3-6 membered cycloalkyl group may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopropyl.

[0190] In a preferred embodiment, each R 2wherein the ring in the 4-12 membered heterocyclic group may be a monocyclic ring, a spirocyclic ring, a fused ring or a bridged ring, the number of rings in the spirocyclic ring, the fused ring or the bridged ring may be 2, and the spirocyclic ring may be a 3-membered spiro 5-membered heterocyclic group, a 3-membered spiro 6-membered heterocyclic group, a 4-membered spiro 4-membered heterocyclic group, a 4-membered spiro 5-membered heterocyclic group, a 4-membered spiro 6-membered heterocyclic group, a 4-membered spiro 7-membered heterocyclic group, a 5-membered spiro 4-membered heterocyclic group, a 5-membered spiro 5-membered heterocyclic group, a 5-membered spiro 6-membered heterocyclic group, a 5-membered spiro 7-membered heterocyclic group, a 6-membered spiro 4-membered heterocyclic group The cyclic radical may be a 4-membered 5-membered heterocyclic radical, a 4-membered 6-membered heterocyclic radical, a 5-membered 5-membered heterocyclic radical, a 5-membered 6-membered heterocyclic radical or a 6-membered 6-membered heterocyclic radical; the bridging ring may be a 4-membered 5-membered heterocyclic radical, a 4-membered 6-membered heterocyclic radical, a 5-membered 6-membered heterocyclic radical or a 6-membered 6-membered heterocyclic radical; the heteroatoms in the 4-12-membered heterocyclic radical may be N and / or O, and the number of heteroatoms may be 1 or 2; preferably

[0191] In a preferred embodiment, each R 2 In the above, the 4-12 membered heterocyclic group may be a 4-12 membered monocyclic heterocyclic group or a 4-12 membered polycyclic heterocyclic group (e.g., a spirocyclic group, a fused ring or a bridged ring); the 4-12 membered monocyclic heterocyclic group is preferably a 4-7 membered monocyclic heterocyclic group, the heteroatoms in the 4-7 membered monocyclic heterocyclic group are preferably N and / or O, and the number of heteroatoms is preferably 1 or 2; the 4-12 membered polycyclic heterocyclic group is preferably a 4-10 membered polycyclic heterocyclic group, the heteroatoms in the 4-10 membered polycyclic heterocyclic group are preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0192] In a preferred embodiment, each R 2 In the above, the ring in the 4-12 membered heterocycloalkenyl ring may be a monocyclic ring or a cyclic ring, and the cyclic ring may be a 4-membered and 5-membered heterocycloalkenyl, a 4-membered and 6-membered heterocycloalkenyl, a 5-membered and 5-membered heterocycloalkenyl, a 5-membered and 6-membered heterocycloalkenyl or a 6-membered and 6-membered heterocycloalkenyl, and the heteroatom in the 4-12 membered heterocycloalkenyl may be N, and the number of heteroatoms may be 1 or 2; preferably For example Another example

[0193] In a preferred embodiment, each R 2In the above, the 4-12 membered heterocycloalkenyl group may be a 4-12 membered monocyclic heterocycloalkenyl group or a 4-12 membered polycyclic heterocycloalkenyl group (e.g., a cyclic group); the 4-12 membered monocyclic heterocycloalkenyl group is preferably a 4-7 membered monocyclic heterocycloalkenyl group, and the heteroatom in the 4-7 membered monocyclic heterocycloalkenyl group is preferably N, and the number of heteroatoms is preferably 1 or 2; the 4-12 membered polycyclic heterocycloalkenyl group is preferably a 4-10 membered polycyclic heterocycloalkenyl group, and the heteroatom in the 4-10 membered polycyclic heterocycloalkenyl group is preferably N, and the number of heteroatoms is preferably 1 or 2.

[0194] In a preferred embodiment, each R 2 In the above, the 5-12 membered heteroaryl group may be a 5-12 membered monocyclic heteroaryl group or a 5-12 membered polycyclic heteroaryl group (e.g., a ring); the 5-12 membered monocyclic heteroaryl group is preferably a 5-6 membered monocyclic heteroaryl group, the heteroatom in the 5-6 membered monocyclic heteroaryl group is preferably N and / or O, and the number of heteroatoms is preferably 1, 2 or 3, and more preferably

[0195] For example Another example The 5-12 membered polycyclic heteroaryl is preferably a 5-10 membered polycyclic heteroaryl, the heteroatoms in the 5-10 membered polycyclic heteroaryl are preferably N and / or O, and the number of heteroatoms is preferably 1, 2 or 3, and more preferably

[0196] In a preferred embodiment, each R 2 In the -O-5-12-membered heteroaryl group, the -O-5-6-membered heteroaryl group may be a -O-5-6-membered heteroaryl group, the heteroatom in the 5-6-membered heteroaryl group in the -O-5-6-membered heteroaryl group may be N and / or S, and the number of heteroatoms may be 1 or 2, preferably

[0197] In a preferred embodiment, each R 2-1 In the above, the 5-12 membered heteroaryl group may be a 5-6 membered heteroaryl group, the heteroatoms in the 5-6 membered heteroaryl group may be N and / O, and the number of heteroatoms may be 1, 2 or 3, preferably

[0198] In a preferred embodiment, each R 2-3 In the embodiment, the 4-12 membered heterocyclic group may be a 4-6 membered heterocyclic group, the heteroatom in the 4-6 membered heterocyclic group may be O, the number of heteroatoms may be 1, preferably

[0199] In a preferred embodiment, each R 2-3 In the above, the 5-12 membered heteroaryl group may be a 5-6 membered heteroaryl group, the heteroatom in the 5-6 membered heteroaryl group may be N, and the number of heteroatoms may be 1 or 2, preferably

[0200] In a preferred embodiment, each R 2-5 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group or a tert-butyl group.

[0201] In a preferred embodiment, each R 2-6 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0202] In a preferred embodiment, each R 2-6 In the embodiment, the 4-12 membered heterocyclic group may be a 4-6 membered heterocyclic group, the heteroatom in the 4-6 membered heterocyclic group may be N, and the number of heteroatoms may be 1, preferably

[0203] In a preferred embodiment, each R 2-7 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0204] In a preferred embodiment, each R 2-7 In the above, the 5-12 membered heteroaryl group may be a 5-6 membered heteroaryl group, the heteroatom in the 5-6 membered heteroaryl group may be N and / or S, and the number of heteroatoms may be 1, 2 or 3, preferably

[0205] In a preferred embodiment, each R 2-8 In the above, the 4-12 membered heterocyclic group may be a 4-6 membered heterocyclic group, the heteroatom in the 4-6 membered heterocyclic group may be N and / or O, and the number of heteroatoms may be 1 or 2, preferably

[0206] In a preferred embodiment, each R 2-9 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine, for example fluorine.

[0207] In a preferred embodiment, each R 2-9 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0208] In a preferred embodiment, each R 2-9In the above, the C1-C6 alkoxy group may be a C1-C4 alkoxy group, or may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group.

[0209] In a preferred embodiment, each R 2-9 In the above, the 3-6 membered cycloalkyl group may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclobutyl.

[0210] In a preferred embodiment, each R 2-9 In the above, the 4-12 membered heterocyclic group may be a 4-12 membered monocyclic heterocyclic group or a 4-12 membered polycyclic heterocyclic group (e.g., a spirocyclic group); the 4-12 membered monocyclic heterocyclic group is preferably a 4-6 membered monocyclic heterocyclic group, the heteroatom in the 4-6 membered monocyclic heterocyclic group is preferably N, the number of heteroatoms is preferably 1, and more preferably The 4-12 membered polycyclic heterocyclic group is preferably a 4-10 membered polycyclic heterocyclic group, the heteroatoms in the 4-10 membered polycyclic heterocyclic group are preferably N and / or O, the number of heteroatoms is preferably 1 or 2, and more preferably

[0211] In a preferred embodiment, each R 2-1-2 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0212] In a preferred embodiment, each R 2-1-3 In the above, the 4-12 membered heterocyclic group may be a 4-6 membered heterocyclic group, the heteroatom in the 4-6 membered heterocyclic group may be N and / or O, and the number of heteroatoms may be 1 or 2, preferably

[0213] In a preferred embodiment, each R 2-4-1 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0214] In a preferred embodiment, each R 2-5-1 In the above, the halogen may be fluorine, halogen, bromine or iodine, preferably fluorine.

[0215] In a preferred embodiment, each R 2-5-3 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0216] In a preferred embodiment, each R 2-5-4In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0217] In a preferred embodiment, each R 2-6-1 In the above, the halogen may be fluorine, halogen, bromine or iodine, preferably fluorine.

[0218] In a preferred embodiment, each R 2-6-1 In the above, the C1-C6 alkoxy group may be a C1-C4 alkoxy group, or may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group.

[0219] In a preferred embodiment, each R 2-6-2 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0220] In a preferred embodiment, each R 2-6-3 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0221] In a preferred embodiment, each R 2-7-2 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0222] In a preferred embodiment, each R 2-7-3 In the above, the 3-6 membered cycloalkyl group may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclobutyl.

[0223] In a preferred embodiment, each R 2-1-3-1 In the above, the halogen may be fluorine, halogen, bromine or iodine, preferably fluorine.

[0224] In a preferred embodiment, each R 2-1-3-1 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0225] In a preferred embodiment, in ring B, the number of heteroatoms in the 5-20-membered heteroaromatic ring may be 1, 2, 3 or 4, and the number of rings may be 2 or 3; the 5-20-membered heteroaromatic ring is preferably a 5-15-membered heteroaromatic ring, and the 5-15-membered heteroaromatic ring is preferably a five-membered and five-membered heteroaromatic ring, a five-membered and six-membered heteroaromatic ring, a five-membered and seven-membered heteroaromatic ring, a six-membered and six-membered heteroaromatic ring, a five-membered and six-membered heteroaromatic ring, a five-membered and six-membered heteroaromatic ring, a five-membered and six-membered heteroaromatic ring, more preferably a five-membered and five-membered heteroaromatic ring, a five-membered and six-membered heteroaromatic ring, a five-membered and seven-membered heteroaromatic ring, a six-membered and six-membered heteroaromatic ring, a five-membered and five-membered and six-membered heteroaromatic ring, a five-membered and six-membered heteroaromatic ring, or a five-membered and six-membered heteroaromatic ring, and further preferably

[0226]

[0227] For example

[0228] In a preferred embodiment, each R b-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine.

[0229] In a preferred embodiment, each R b-1 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0230] In a preferred embodiment, each R b-1 In the above, the C1-C6 alkoxy group may be a C1-C4 alkoxy group, or may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group.

[0231] In a preferred embodiment, each R b-1 In the -0-3-6-membered cycloalkyl group, the -3-6-membered cycloalkyl group may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopropyl.

[0232] In a preferred embodiment, each R b-1-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine.

[0233] In a preferred embodiment, each R b-1-2 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine.

[0234] In a preferred embodiment, each R b-1-4In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0235] In a preferred embodiment, each R b-1-5 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0236] In a preferred embodiment, each R b-1-6 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0237] In a preferred embodiment, each R b-1-8 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0238] In a preferred embodiment, each R b-1-8 The number of heteroatom groups in the 4-6 membered heterocyclic group may be 1, and the heteroatom group may be P(O), preferably

[0239] In a preferred embodiment, R 3 In the above, the 3-12 membered cycloalkyl group may be a 3-6 membered cycloalkyl group, or may be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, preferably a cyclopropyl group or a cyclohexyl group.

[0240] In a preferred embodiment, R 3 In the above, the 4-12 membered heterocycloalkyl may be a 4-12 membered monocyclic heterocycloalkyl or a 4-12 membered polycyclic heterocycloalkyl (e.g., a spirocyclic, a paracyclic, or a bridged ring); the 4-12 membered monocyclic heterocycloalkyl is preferably a 4-7 membered monocyclic heterocycloalkyl, and the heteroatoms in the 4-7 membered monocyclic heterocycloalkyl are preferably one or more of N, O, and S, and the number of heteroatoms is preferably 1 or 2, and more preferably

[0241] The 4-12 membered polycyclic heterocycloalkyl is preferably a 4-10 membered polycyclic heterocycloalkyl, the heteroatom in the 4-10 membered polycyclic heterocycloalkyl is preferably N or O, the number of heteroatoms is preferably 1, and more preferably

[0242] In a preferred embodiment, R 3In the embodiment, the 4-12 membered cycloalkenyl group may be a 4-12 membered monocyclic cycloalkenyl group or a 4-12 membered polycyclic cycloalkenyl group (e.g., a spirocyclic ring), and the 4-12 membered monocyclic cycloalkenyl group is preferably a 4-6 membered monocyclic cycloalkenyl group, and more preferably The 4-12 membered polycyclic cycloalkenyl is preferably a 4-10 membered polycyclic cycloalkenyl, more preferably

[0243] In a preferred embodiment, R 3 In the above, the 4-12 membered heterocycloalkenyl group may be a 4-12 membered monocyclic heterocycloalkenyl group or a 4-12 membered polycyclic heterocycloalkenyl group (e.g., a spirocycle), the 4-12 membered monocyclic heterocycloalkenyl group is preferably a 4-6 membered monocyclic heterocycloalkenyl group, the heteroatom in the 4-6 membered monocyclic heterocycloalkenyl group is preferably N and / or O, the number of heteroatoms is preferably 1, and more preferably The 4-12 membered polycyclic heterocycloalkenyl is preferably a 4-10 membered polycyclic heterocycloalkenyl, more preferably

[0244] In a preferred embodiment, R 3 In the above, the 6-10 membered aryl group may be phenyl or naphthyl, preferably phenyl.

[0245] In a preferred embodiment, R 3 In the embodiment, the 5-10 membered heteroaryl group may be a 5-10 membered monocyclic heteroaryl group or a 5-10 membered polycyclic heteroaryl group (e.g., a ring-containing group), the 5-10 membered monocyclic heteroaryl group is preferably a 5-6 membered monocyclic heteroaryl group, and the heteroatom in the 5-6 membered monocyclic heteroaryl group is preferably N and / or O, and more preferably For example The heteroatom in the 5-10 membered polycyclic heteroaryl is preferably N, and the number of heteroatoms is preferably 1 or 2.

[0246] In a preferred embodiment, R 3 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group or an isopropyl group, for example, an isopropyl group.

[0247] In a preferred embodiment, each R 3-1 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0248] In a preferred embodiment, each R 3-1 In the above, the C1-C6 alkoxy group may be a C1-C4 alkoxy group, or may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group.

[0249] In a preferred embodiment, each R 3-2 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine.

[0250] In a preferred embodiment, each R 3-2 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0251] In a preferred embodiment, each R 3-4 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0252] In a preferred embodiment, each R 3-6 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably chlorine.

[0253] In a preferred embodiment, each R 3-6 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0254] In a preferred embodiment, each R 3-7 The heteroatom in the 4-6 membered heterocyclic group is preferably 0, and the number of heteroatoms is preferably 1, more preferably

[0255] In a preferred embodiment, each R 3-2-1 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0256] In a preferred embodiment, each R 3-2-2 In the above, the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine.

[0257] In a preferred embodiment, each R 3-4-1 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0258] In a preferred embodiment, each R 3-5-1 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0259] In a preferred embodiment, each R 3-5-2 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group.

[0260] In a preferred embodiment, each R 4 The heteroatoms in the 4-6 membered heterocyclic group are preferably N and / or O, and the number of heteroatoms is preferably 1, more preferably

[0261] In a preferred embodiment, each R 4 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0262] In a preferred embodiment, m is 1.

[0263] In a preferred embodiment, n is 0 or 1.

[0264] In a preferred embodiment, ring A is a benzene ring, a 6-membered heteroaromatic ring or an oxo-substituted 6-membered heterocycloalkenyl group; the heteroatom in the 6-membered heteroaromatic ring and the 6-membered heterocycloalkenyl group is N, and the number of the heteroatom is 1.

[0265] In a preferred embodiment, R 1 is unsubstituted or substituted with one or more R 1-1 Substituted phenyl, unsubstituted or replaced by one or more R 1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 1-3 substituted 4-12 membered heterocycloalkenyl; preferably unsubstituted or substituted by one or more R 1-1 Substituted phenyl or unsubstituted or with one or more R 1-2 Substituted 5-12 membered heteroaryl; for example, unsubstituted or substituted with one or more R 1-2 Substituted 5-12 membered heteroaryl.

[0266] In a preferred embodiment, each R 1-1 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 1-1-2 Substituted C1-C6 alkoxy, preferably halogen or unsubstituted or substituted by one or more R 1-1-2 Substituted C1-C6 alkoxy.

[0267] In a preferred embodiment, each R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 1 -1-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 1-1-6 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 1-1-13 Substituted 4-12 membered heterocycloalkenyl or N(R 1-1-12 )2; preferably halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl; for example, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 1-1-2 Substituted C1-C6 alkoxy.

[0268] In a preferred embodiment, each R 1-3 is independently oxo or unsubstituted or substituted with one or more R 1-1-2 Substituted C1-C6 alkoxy.

[0269] In a preferred embodiment, each R 1-1-1 are independently halogen.

[0270] In a preferred embodiment, each R 1-1-2 is independently deuterium or a halogen.

[0271] In a preferred embodiment, each R 1-1-12 are independently C1-C6 alkyl.

[0272] In a preferred embodiment, each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-1 Substituted C2-C6 alkyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-4 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -O-5-12 membered heteroaryl, -N(R 2-7 )2 or Preferably one or more R 2-1 Substituted C1-C6 alkyl, one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or For example, unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 substituted 5-12 membered heteroaryl; for example, unsubstituted or substituted with one or more R 2-9 Substituted 4-12 membered heterocycloalkenyl.

[0273] In a preferred embodiment, each R 2-1 are independently unsubstituted or substituted with one or more R 2-1-2 Substituted 5-12 membered heteroaryl or Best

[0274] In a preferred embodiment, each R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or unsubstituted or replaced by one or more R 2-1-2 substituted 5-12 membered heteroaryl; preferably unsubstituted or substituted with one or more R 2-1-1 Substituted 4- to 12-membered heterocyclic group.

[0275] In a preferred embodiment, each R 2-5 is independently oxo, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl or

[0276] In a preferred embodiment, each R 2-6 are independently oxo, cyano or unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl; for example, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl.

[0277] In a preferred embodiment, each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl.

[0278] In a preferred embodiment, each R 2-9are independently oxo, halogen, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, 3-6 membered cycloalkyl, 4-12 membered heterocyclic group or -N(R 2-5-3 )2; preferably oxo, halogen, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 2-5-2 Substituted C1-C6 alkoxy; for example, oxo or halogen.

[0279] In a preferred embodiment, each R 2-1-2 are independently C1-C6 alkyl.

[0280] In a preferred embodiment, each R 2-4-1 are independently C1-C6 alkyl.

[0281] In a preferred embodiment, each R 2-5-1 are independently halogen.

[0282] In a preferred embodiment, each R 2-5-2 Independently for deuterium.

[0283] In a preferred embodiment, each R 2-5-3 are independently hydrogen.

[0284] In a preferred embodiment, each R 2-6-1 are independently cyano.

[0285] In a preferred embodiment, ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-15 membered polycyclic heteroaromatic ring; the heteroatoms in the 5-15 membered polycyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, or 4, the single heteroaromatic ring in the 5-15 membered polycyclic heteroaromatic ring is a 5-7 membered heteroaromatic ring, and the number of rings in the 5-15 membered polycyclic heteroaromatic ring is 2 or 3.

[0286] In a preferred embodiment, each R b-1 independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b -1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 , For example, oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy.

[0287] In a preferred embodiment, each R b-1-1 are independently halogen.

[0288] In a preferred embodiment, each R b-1-2 is independently deuterium or a halogen.

[0289] In a preferred embodiment, each R b-1-5 are independently C1-C6 alkyl.

[0290] In a preferred embodiment, each R b-1-6 are independently C1-C6 alkyl.

[0291] In a preferred embodiment, each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, in which the number of heteroatom groups is 1 and the heteroatom group is P(O).

[0292] In a preferred embodiment, R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-3 substituted 4-12 membered cycloalkenyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; preferably hydrogen, unsubstituted or substituted by one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; for example hydrogen, unsubstituted or replaced by one or more R 3-6 substituted 5-10 membered heteroaryl or unsubstituted or with one or more R 3-7 Substituted C1-C6 alkyl; for example hydrogen, unsubstituted or replaced by one or more R 3-6 substituted 5-10 membered heteroaryl, unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl or -C(O)R 4 .

[0293] In a preferred embodiment, each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy.

[0294] In a preferred embodiment, each R 3-2 are independently deuterium, hydroxyl, halogen, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl, oxo, -S(O)2R 3-4-1 or -N(R 3-4-2 )2; preferably hydroxyl or halogen.

[0295] In a preferred embodiment, each R 3-3 are independently hydroxyl, -NHC(O)R 3-2-1 or -N(R 3-4-2 )2.

[0296] In a preferred embodiment, each R 3-4 are independently oxo.

[0297] In a preferred embodiment, each R 3-5 independently -S(O)2R 3-4-1 , or

[0298] In a preferred embodiment, each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl; for example, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl.

[0299] In a preferred embodiment, each R 3-7 are independently 4-6 membered heterocyclic groups.

[0300] In a preferred embodiment, each R 3-2-1 are independently C1-C6 alkyl.

[0301] In a preferred embodiment, each R 3-2-2 are independently hydroxyl.

[0302] In a preferred embodiment, each R 3-4-1 are independently C1-C6 alkyl.

[0303] In a preferred embodiment, each R 3-4-2 are independently hydrogen.

[0304] In a preferred embodiment, each R 3-5-1 and R 3-5-2 are independently C1-C6 alkyl.

[0305] In a preferred embodiment, R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4- to 6-membered heterocyclic group, wherein the heteroatom in the 4- to 6-membered heterocyclic group is N or O, and the number of the heteroatom is 1.

[0306] In a preferred embodiment, R 4 is unsubstituted or substituted with one or more R 4-1 substituted 4-6 membered heterocyclic group or unsubstituted or replaced by one or more R 4-2 Substituted C1-C6 alkyl, the heteroatom in the 4-6 membered heterocyclic group is N or O, and the number of heteroatoms is 1; for example, unsubstituted or substituted with one or more R 4-2 Substituted C1-C6 alkyl.

[0307] In a preferred embodiment, the compound of formula I, its pharmaceutically acceptable salt or its isotope compound is a compound of formula Ia, Ib, Ic, Id, Ie or If,

[0308]

[0309] In a preferred embodiment, the compound of formula I, its pharmaceutically acceptable salt or its isotope compound is a compound of formula Ig,

[0310]

[0311] In a preferred embodiment, m is 1; n is 1;

[0312] Ring A is

[0313] R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1;

[0314] Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy;

[0315] Each R 1-1-1 are independently halogen (e.g. fluorine);

[0316] Each R 2 are independently unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 Substituted 5-6 membered heteroaryl; the heteroatom in the 4-12 membered heterocycloalkenyl and 5-6 membered heteroaryl is independently N, and the number of heteroatoms is 1;

[0317] Each R 2-9 are independently oxo or halogen;

[0318] Each R 2-6 are independently unsubstituted C1-C6 alkyl;

[0319] Ring B is an unsubstituted 5-10-membered heteroaromatic ring; the heteroatoms in the 5-10-membered heteroaromatic ring are selected from N and / or S, and the number of heteroatoms is 2 or 3;

[0320] R 3 is hydrogen, unsubstituted or replaced by one or more R 3-6 A substituted 5-10 membered heteroaryl or an unsubstituted C1-C6 alkyl; the heteroatom in the 5-10 membered heteroaryl is N, and the number of heteroatoms is 1, 2, 3 or 4;

[0321] Each R 3-6 and independently unsubstituted C1-C6 alkyl.

[0322] In a preferred embodiment,

[0323] m is 1; n is 0 or 1;

[0324] Ring A is a benzene ring, a 6-membered heteroaromatic ring or an oxo-substituted 6-membered heterocycloalkenyl group; the heteroatom in the 6-membered heteroaromatic ring and the 6-membered heterocycloalkenyl group is N, and the number of heteroatoms is 1;

[0325] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted phenyl or unsubstituted or with one or more R 1-2 A substituted 5-6 membered heteroaryl group, wherein the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2;

[0326] Each R 1-1are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl;

[0327] Each R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl;

[0328] Each R 1-1-1 , R 1-1-2 and R 1-1-5 are independently deuterium or halogen;

[0329] Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-1 Substituted C2-C6 alkyl, unsubstituted by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12 membered heterocyclyl, 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0330] Each R 2-1 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0331] Each R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0332] Each R 2-5 and R 2-9 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy or

[0333] Each R 2-6 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy;

[0334] Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl; the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0335] R 2-8 is unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3

[0336] Each R 2-1-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0337] R 2-1-3 is independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0338] Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0339] Each R 2-5-1 and R 2-5-2 are independently deuterium or halogen;

[0340] Each R 2-5-4 are independently C1-C6 alkyl;

[0341] Each R 2-6-1 are independently cyano;

[0342] Each R 2-7-2 and R2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0343] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-12-membered cyclic heteroaromatic ring; the heteroatoms in the 5-12-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, or 4, and the number of rings in the 5-12-membered cyclic heteroaromatic ring is 2;

[0344] Each R b-1 independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 ,

[0345] Each R b-1-1 are independently halogen;

[0346] Each R b-1-2 are independently deuterium or halogen;

[0347] Each R b-1-4 are independently hydrogen or C1-C6 alkyl;

[0348] Each R b-1-5 are independently C1-C6 alkyl;

[0349] Each R b-1-6 are independently C1-C6 alkyl;

[0350] Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein the number of heteroatom groups in the 4-6 membered heterocyclic group is 1, and the heteroatom group is P(O);

[0351] R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; the heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0352] Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy;

[0353] Each R 3-2 are independently hydroxy or halogen;

[0354] Each R 3-4 are independently oxo;

[0355] Each R 3-5 independently -S(O)2R 3-4-1 ,

[0356] Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl;

[0357] Each R 3-7 are independently 4-6 membered heterocyclic groups; the heteroatoms in the 4-6 membered heterocyclic groups are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0358] Each R 3-2-2 are independently hydroxyl groups;

[0359] Each R 3-4-1 , R 3-5-1 and R 3-5-2 are independently C1-C6 alkyl;

[0360] R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4- to 6-membered heterocyclic group, wherein the heteroatom in the 4- to 6-membered heterocyclic group is N or O, and the number of the heteroatom is 1.

[0361] In a preferred embodiment,

[0362] m is 1; n is 0 or 1;

[0363] Ring A is a benzene ring, a 6-membered heteroaromatic ring or an oxo-substituted 6-membered heterocycloalkenyl group; the heteroatom in the 6-membered heteroaromatic ring and the 6-membered heterocycloalkenyl group is N, and the number of heteroatoms is 1;

[0364] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted phenyl or unsubstituted or with one or more R 1-2 A substituted 5-6 membered heteroaryl group, wherein the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2;

[0365] Each R 1-1 are independently halogen or unsubstituted or substituted with one or more R 1-1-2 Substituted C1-C6 alkoxy;

[0366] Each R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl;

[0367] Each R 1-1-1 , R 1-1-2 and R 1-1-5 are independently deuterium or halogen;

[0368] Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12 membered heterocyclyl, 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0369] Each R 2-1 Independently

[0370] Each R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0371] Each R 2-5is independently oxo, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl or

[0372] Each R 2-6 are independently oxo, cyano or unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl;

[0373] Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl; the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0374] R 2-8 is unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3

[0375] Each R 2-9 are independently oxo, halogen, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 2-5-2 Substituted C1-C6 alkoxy;

[0376] Each R 2-1-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0377] R 2-1-3 is independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0378] Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0379] Each R 2-5-1 are independently halogen;

[0380] Each R 2-5-2 independently for deuterium;

[0381] Each R 2-5-4 are independently C1-C6 alkyl;

[0382] Each R 2-6-1 are independently cyano;

[0383] Each R 2-7-2 are independently C1-C6 alkyl;

[0384] Each R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0385] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-12-membered cyclic heteroaromatic ring; the heteroatoms in the 5-12-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, or 4, and the number of rings in the 5-12-membered cyclic heteroaromatic ring is 2;

[0386] Each R b-1 independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 ,

[0387] Each R b-1-1 are independently halogen;

[0388] Each R b-1-2 are independently deuterium or halogen;

[0389] Each R b-1-4 are independently hydrogen or C1-C6 alkyl;

[0390] Each R b-1-5 are independently C1-C6 alkyl;

[0391] Each R b-1-6 are independently C1-C6 alkyl;

[0392] Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein the number of heteroatom groups in the 4-6 membered heterocyclic group is 1, and the heteroatom group is P(O);

[0393] R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; the heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0394] Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy;

[0395] Each R 3-2 are independently hydroxy or halogen;

[0396] Each R 3-4 are independently oxo;

[0397] Each R 3-5 independently -S(O)2R 3-4-1 ,

[0398] Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl;

[0399] Each R 3-7 are independently 4-6 membered heterocyclic groups; the heteroatoms in the 4-6 membered heterocyclic groups are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0400] Each R 3-2-2 are independently hydroxyl groups;

[0401] Each R 3-4-1 , R 3-5-1 and R 3-5-2 are independently C1-C6 alkyl;

[0402] R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4- to 6-membered heterocyclic group, wherein the heteroatom in the 4- to 6-membered heterocyclic group is N or O, and the number of the heteroatom is 1.

[0403] In a preferred embodiment,

[0404] m is 1; n is 1;

[0405] Ring A is

[0406] R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1;

[0407] Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy;

[0408] Each R 1-1-1 are independently halogen;

[0409] Each R 2 are independently unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 Substituted 5-6 membered heteroaryl; the heteroatom in the 4-12 membered heterocycloalkenyl and 5-6 membered heteroaryl is independently N, and the number of heteroatoms is 1;

[0410] Each R 2-9 are independently oxo or halogen;

[0411] Each R 2-6 are independently unsubstituted C1-C6 alkyl;

[0412] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-15-membered cyclic heteroaromatic ring; the heteroatoms in the 5-15-membered cyclic heteroaromatic ring are selected from N and / or S, and the number of heteroatoms is 2, 3 or 4;

[0413] Each R b-1 are independently oxo, halogen or C1-C6 alkyl;

[0414] R 3 is hydrogen, unsubstituted or replaced by one or more R 3-6 A substituted 5-10 membered heteroaryl or an unsubstituted C1-C6 alkyl; the heteroatom in the 5-10 membered heteroaryl is N, and the number of heteroatoms is 1, 2, 3 or 4;

[0415] Each R 3-6 and independently unsubstituted C1-C6 alkyl.

[0416] In a preferred embodiment,

[0417] m is 1; n is 1;

[0418] Ring A is a benzene ring, a 5-6-membered heteroaromatic ring or an oxo-substituted 5-6-membered heterocycloalkenyl group; the heteroatom in the 5-6-membered heteroaromatic ring and the 5-6-membered heterocycloalkenyl group is N, and the number of heteroatoms is 1;

[0419] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted 6-12 membered aryl or unsubstituted or replaced by one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2;

[0420] Each R 1-1 and R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl;

[0421] Each R 1-1-1 , R 1-1-2 and R 1-1-5 are independently deuterium or halogen;

[0422] Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-2 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12 membered heterocyclyl, 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0423] Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or The heteroatoms in the 4-12 membered heterocyclic group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0424] Each R 2-5 and R 2-9 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy or

[0425] Each R 2-6 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 2-5-2 Substituted C1-C6 alkoxy;

[0426] Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl; the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0427] Each R 2-8 are independently unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatoms in the 4-12 membered heterocyclic group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0428] Each R 2-1-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0429] Each R 2-1-3 are independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0430] Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0431] Each R 2-5-1 and R 2-5-2 are independently deuterium, hydroxyl, cyano or halogen;

[0432] Each R 2-6-1 are independently cyano;

[0433] Each R 2-7-2 are independently deuterium, hydroxyl, cyano or halogen;

[0434] Each R 2-7-2and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0435] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3 or 4, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2 or 3;

[0436] Each R b-1 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 ,

[0437] Each R b-1-1 and R b-1-2 are independently deuterium or halogen;

[0438] Each R b-1-4 and R b-1-5 are independently hydrogen or C1-C6 alkyl;

[0439] Each R b-1-6 are independently C1-C6 alkyl;

[0440] Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein in the 4-6 membered heterocyclic group, when the number of the heteroatom group is 1, the heteroatom group is P(O);

[0441] R 3 is hydrogen, unsubstituted or replaced by one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; the heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0442] Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy;

[0443] Each R 3-2 are independently hydroxy or halogen;

[0444] Each R 3-4 are independently hydroxy, halogen or cyano;

[0445] Each R 3-5 independently -S(O)2R 3-4-1 ,

[0446] Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl;

[0447] Each R 3-7 are independently 4-6 membered heterocyclic groups; the heteroatoms in the 4-6 membered heterocyclic groups are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0448] Each R 3-2-2 are independently hydroxyl groups;

[0449] Each R 3-4-1 , R 3-5-1 and R 3-5-2 is a C1-C6 alkyl group;

[0450] R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group; the heteroatom in the 4-6 membered heterocyclic group is selected from N and / or O, and the number of heteroatoms is 1 or 2;

[0451] Each R 4-1 are independently hydroxyl.

[0452] In a preferred embodiment,

[0453] m is 1; n is 1;

[0454] Ring A is a benzene ring, a 6-membered heteroaromatic ring or an oxo-substituted 6-membered heterocycloalkenyl group; the heteroatom in the 6-membered heteroaromatic ring and the 6-membered heterocycloalkenyl group is N, and the number of heteroatoms is 1;

[0455] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted phenyl or unsubstituted or with one or more R 1-2 A substituted 5-6 membered heteroaryl group, wherein the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2;

[0456] Each R 1-1 and R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl;

[0457] Each R 1-1-1 , R 1-1-2 and R 1-1-5 are independently deuterium or halogen;

[0458] R 2 For one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-2 Substituted C2-C6 alkenyl, unsubstituted by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12 membered heterocyclyl, 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0459] Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0460] Each R2-5 and R 2-9 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy or

[0461] Each R 2-6 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy;

[0462] Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl; the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0463] Each R 2-8 is unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3

[0464] Each R 2-1-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0465] Each R 2-1-3 is independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0466] Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0467] Each R 2-5-1 and R 2-5-2 are independently deuterium or halogen;

[0468] Each R 2-6-1 are independently cyano;

[0469] Each R 2-7-2 and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl;

[0470] Ring B is unsubstituted or substituted with one or more Rb-1 A substituted 5-15-membered cyclic heteroaromatic ring; the heteroatoms in the 5-15-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, or 4, and the number of rings in the 5-15-membered cyclic heteroaromatic ring is 2 or 3;

[0471] Each R b-1 independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 ,

[0472] Each R b-1-1 and R b-1-2 are independently deuterium or halogen;

[0473] Each R b-1-4 and R b-1-5 are independently hydrogen or C1-C6 alkyl;

[0474] Each R b-1-6 are independently C1-C6 alkyl;

[0475] Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein the number of heteroatom groups in the 4-6 membered heterocyclic group is 1, and the heteroatom group is P(O);

[0476] R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; the heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0477] Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy;

[0478] Each R 3-2 are independently hydroxy or halogen;

[0479] Each R 3-4 are independently oxo;

[0480] Each R 3-5 independently -S(O)2R 3-4-1 ,

[0481] Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl;

[0482] Each R 3-7 are independently 4-6 membered heterocyclic groups; the heteroatoms in the 4-6 membered heterocyclic groups are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2;

[0483] Each R 3-2-2 are independently hydroxyl groups;

[0484] Each R 3-4-1 , R 3-5-1 and R 3-5-2 are independently C1-C6 alkyl;

[0485] R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group or a C1-C6 alkyl group, wherein the heteroatom in the 4-6 membered heterocyclic group is N and / or O, and the number of heteroatoms is 1 or 2;

[0486] Each R 4-1 are independently hydroxyl.

[0487] In a preferred embodiment,

[0488] m is 1; n is 1;

[0489] Ring A is a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatom in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group is N, and the number of heteroatoms is 1;

[0490] R 1 is unsubstituted or substituted with one or more R 1-2A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1;

[0491] Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy;

[0492] Each R 1-1-1 are independently halogen;

[0493] Each R 2 are independently unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 Substituted 5-12 membered heteroaryl; the heteroatoms in the 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from N and / or O, and the number of heteroatoms is 1, 2 or 3;

[0494] Each R 2-9 are independently oxo, halogen or unsubstituted C1-C6 alkyl;

[0495] Each R 2-6 are independently unsubstituted C1-C6 alkyl;

[0496] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3 or 4, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2, 3 or 4;

[0497] Each R b-1 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy;

[0498] Each R b-1-1 and R b-1-2 are independently halogen;

[0499] R 3 is hydrogen, unsubstituted or replaced by one or more R 3-6 A substituted 5-10 membered heteroaryl or an unsubstituted C1-C6 alkyl; the heteroatom in the 5-10 membered heteroaryl is independently N, and the number of heteroatoms is 1, 2, 3 or 4;

[0500] Each R 3-6and independently unsubstituted C1-C6 alkyl.

[0501] In a preferred embodiment,

[0502] m is 1; n is 1;

[0503] Ring A is

[0504] R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1;

[0505] Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy;

[0506] Each R 1-1-1 are independently halogen;

[0507] R 2 is unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 Substituted 5-6 membered heteroaryl; the heteroatoms in the 4-12 membered heterocycloalkenyl and 5-6 membered heteroaryl are independently selected from N and / or O, and the number of heteroatoms is 1, 2 or 3;

[0508] Each R 2-9 are independently oxo, halogen or unsubstituted C1-C6 alkyl;

[0509] Each R 2-6 are independently unsubstituted C1-C6 alkyl;

[0510] Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-15-membered cyclic heteroaromatic ring; the heteroatoms in the 5-15-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, and the number of heteroatoms is 2, 3 or 4;

[0511] Each R b-1 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy;

[0512] Each R b-1-1 and R b-1-2 are independently halogen;

[0513] R 3is hydrogen, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, unsubstituted C1-C6 alkyl or -C(O)R 4 ; The heteroatom in the 5-10 membered heteroaryl is N, and the number of heteroatoms is 1, 2, 3 or 4;

[0514] Each R 3-6 are independently unsubstituted C1-C6 alkyl;

[0515] R 4 It is a C1-C6 alkyl group.

[0516] In a preferred embodiment,

[0517] m is 1; n is 1;

[0518] Ring A is a 6-membered heteroaromatic ring; the heteroatom in the 6-membered heteroaromatic ring is N, and the number of heteroatoms is 1;

[0519] R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-6 membered heteroaryl group; the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1;

[0520] Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy;

[0521] Each R 1-1-1 are independently halogen;

[0522] R 2 is unsubstituted or substituted with one or more R 2-9 Substituted 4-12 membered heterocycloalkenyl; the heteroatom in the 4-12 membered heterocycloalkenyl is independently N, and the number of heteroatoms is 1 or 2;

[0523] Each R 2-9 are independently oxo, halogen or unsubstituted C1-C6 alkyl;

[0524] Ring B is unsubstituted or substituted with one R b-1 A substituted 5-12-membered cyclic heteroaromatic ring; the heteroatoms in the 5-12-membered cyclic heteroaromatic ring are selected from N and / or S, the number of heteroatoms is 1, 2 or 3, and the number of rings in the 5-12-membered cyclic heteroaromatic ring is 2;

[0525] R b-1 is halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2Substituted C1-C6 alkoxy;

[0526] Each R b-1-1 and R b-1-2 are independently halogen;

[0527] R 3 For hydrogen.

[0528] In a preferred embodiment,

[0529] m is 1; n is 1;

[0530] Ring A is

[0531] R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-6 membered heteroaryl group; the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1;

[0532] Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy;

[0533] Each R 1-1-1 are independently halogen (e.g. fluorine);

[0534] R 2 for

[0535] Ring B is unsubstituted or substituted with one R b-1 substituted 5-10 membered heteroaromatic ring; the heteroatoms in the 5-10 membered heteroaromatic ring are selected from N and / or S, and the number of heteroatoms is 1, 2 or 3 (for example

[0536] R b-1 is halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy;

[0537] Each R b-1-1 and R b-1-2 are independently halogen (e.g. fluorine);

[0538] R 3 For hydrogen.

[0539] In a preferred embodiment, R 1 for

[0540]

[0541] In a preferred embodiment, R 2 for

[0542]

[0543] In a preferred embodiment, for

[0544]

[0545] In a preferred embodiment, for

[0546]

[0547] In a preferred embodiment, R 3 For hydrogen,

[0548]

[0549] In one embodiment, the compound represented by formula I is any of the following compounds:

[0550]

[0551]

[0552]

[0553]

[0554]

[0555]

[0556]

[0557]

[0558]

[0559]

[0560] In one embodiment, the pharmaceutically acceptable salt of the compound represented by Formula I is the following compound:

[0561]

[0562] The present invention provides a method for preparing a compound as shown in formula I', which comprises scheme a or scheme b,

[0563] The scheme a comprises the following steps: in a solvent, a compound of formula II and a compound of formula III are subjected to a condensation reaction as shown below to obtain the compound of formula I', that is,

[0564]

[0565] The scheme b comprises the following steps: in a solvent, in the presence of a condensing agent, subjecting the compound of formula IV to a condensation reaction as shown below with the compound of formula V to obtain the compound of formula I', that is,

[0566]

[0567] Y is tributyltin;

[0568] Among them, R 1 , R 2 , Ring A, Ring B and R 3 As mentioned before.

[0569] In scheme a, in the condensation reaction, the molar ratio of the compound of formula II to the compound of formula III can be 1:(0.5-1.5), for example, 1:1, 1:1.1 or 1:1.4.

[0570] In scheme a, in the condensation reaction, the solvent is a conventional organic solvent, preferably an amide solvent and / or a cyanide solvent; the amide solvent is preferably N,N-dimethylformamide; the cyanide solvent is preferably acetonitrile.

[0571] In scheme a, in the condensation reaction, the condensation agent is a conventional condensation agent in the art, such as N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate and N-methylimidazole.

[0572] In scheme a, in the condensation reaction, the molar ratio of the compound of formula II to the condensing agent can be 1:(2-10), for example, 1:4.5, 1:5.5, 1:7, 1:4, 1:4.4 or 1:6.2.

[0573] In scheme a, in the condensation reaction, the reaction temperature of the condensation reaction is a conventional temperature for such reactions in the art, such as 70°C.

[0574] In scheme a, the condensation reaction may further include post-treatment, and the post-treatment step is a conventional post-treatment step of an organic reaction in the art, which may include the following steps: one or more of concentration, water washing, extraction, drying, column chromatography and preparative chromatography.

[0575] In scheme b, in the condensation reaction, the molar ratio of the compound of formula IV to the compound of formula V can be 1:(1-5), for example 1:1.5.

[0576] In scheme b, in the condensation reaction, the solvent is a conventional organic solvent in the art, preferably an aromatic solvent, such as xylene.

[0577] In scheme b, in the condensation reaction, the condensation agent is a conventional condensation agent in the art, such as tetrakistriphenylphosphine palladium.

[0578] In scheme b, in the condensation reaction, the molar ratio of the compound of formula IV to the condensing agent can be (2-5):1, for example 3.3:1.

[0579] In scheme b, in the condensation reaction, the reaction temperature of the condensation reaction is a conventional temperature for such reactions in the art, such as 160°C.

[0580] In scheme b, in the condensation reaction, the condensation reaction may further include post-treatment, and the post-treatment step may be a conventional post-treatment step of an organic reaction in the art, which may include the following steps: one or more of filtration, concentration and preparative chromatography.

[0581] The present invention provides a method for preparing a compound as shown in formula I', which comprises scheme c or scheme d,

[0582] The scheme c comprises the following steps: in a solvent, in the presence of a condensing agent, subjecting the compound of formula IV and the compound of formula VI to a condensation reaction as shown below to obtain the compound of formula I', that is,

[0583]

[0584] The scheme d comprises the following steps: reacting the compound of formula IV in a solvent in the presence of a base to obtain the compound of formula I', that is,

[0585]

[0586] R 3’ C(O)R', R' is C1-C6 alkyl or halogenated C1-C6 alkyl;

[0587] Among them, R 1 , R 2 , Ring A, Ring B and R 3 As mentioned before.

[0588] In scheme c, in the condensation reaction, the molar ratio of the compound of formula IV to the compound of formula VI can be 1:(1-5), for example 1:2.

[0589] In scheme c, in the condensation reaction, the solvent is a conventional organic solvent, preferably an amide solvent, such as N,N-dimethylformamide.

[0590] In scheme c, in the condensation reaction, the condensation agent is a conventional condensation agent in the art, such as 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine.

[0591] In scheme c, in the condensation reaction, the molar ratio of the compound of formula IV to the condensing agent can be 1:(2-10), for example 1:5.

[0592] In scheme c, in the condensation reaction, the reaction temperature of the condensation reaction is a conventional temperature for such reactions in the art, such as room temperature.

[0593] In scheme c, the condensation reaction may further include post-treatment, and the post-treatment step may be a conventional post-treatment step of an organic reaction in the art, which may include the following steps: one or more of extraction, concentration and preparative chromatography.

[0594] In scheme d, the solvent is a conventional organic solvent in the art, preferably an alcohol solvent, such as methanol.

[0595] In scheme d, the base may be an inorganic base, such as potassium carbonate.

[0596] In scheme d, the molar ratio of the compound of formula IV to the base can be 1:(1-5), for example 1:2.

[0597] In scheme d, in the condensation reaction, the reaction temperature of the condensation reaction is a conventional temperature for such reactions in the art, such as room temperature.

[0598] In scheme d, the condensation reaction may further include post-treatment, and the post-treatment step may be a conventional post-treatment step of an organic reaction in the art, which may include the following steps: one or both of filtration and preparative chromatography.

[0599] The present invention provides any of the following compounds or pharmaceutically acceptable salts thereof:

[0600]

[0601] The present invention provides a pharmaceutical composition, comprising:

[0602] (1) (therapeutically effective amount) of substance A, wherein substance A is a compound of formula I as described above, or a pharmaceutically acceptable salt or isotope compound thereof, and

[0603] (2) Pharmaceutically acceptable excipients.

[0604] The present invention provides an application of a substance A in the preparation of a polymerase theta inhibitor, wherein the substance A is a compound represented by formula I as described above, a pharmaceutically acceptable salt thereof, or an isotope compound thereof.

[0605] The present invention provides an application of a substance A in the preparation of a drug, wherein the substance A is a compound represented by formula I as described above, a pharmaceutically acceptable salt thereof or an isotope compound thereof; the drug can be used to treat lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer or colon cancer, or the drug can be used to treat diseases associated with polymerase theta.

[0606] The present invention provides a substance A for use as a medicine, wherein the substance A is a compound represented by formula I as described above, a pharmaceutically acceptable salt thereof or an isotope compound thereof; the medicine can be used to treat lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer or colon cancer, or the medicine can be used to treat diseases associated with polymerase theta.

[0607] The present invention provides a substance A for treating lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer or colon cancer. The substance A is a compound represented by formula I as described above, a pharmaceutically acceptable salt thereof or an isotope compound thereof.

[0608] The present invention provides a substance A used as a polymerase theta inhibitor, wherein the substance A is a compound represented by formula I as described above, a pharmaceutically acceptable salt thereof, or an isotope compound thereof.

[0609] The present invention provides a method for treating a disease, comprising administering (a therapeutically effective amount of) substance A to a subject, wherein substance A is a compound of formula I as described above, a pharmaceutically acceptable salt thereof, or an isotope compound thereof; the disease is lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, or colon cancer, or the disease is a disease associated with polymerase theta.

[0610] Explanation of terms

[0611] The term "a group B which is unsubstituted or substituted by multiple groups A" means that one or more hydrogen atoms in the group B are independently replaced by a group A or B is unsubstituted. When multiple groups A appear at the same time, unless otherwise specified, their definitions are independent of each other and do not affect each other. For example, "a C6-C substituted by 3 halogens" 10 "Aryl" refers to C6~C 10 The aromatic group may be substituted by three halogens, the definitions of which are independent of each other and do not affect each other, including but not limited to: wait.

[0612] The term "plurality" refers to 2 or more, for example, 2, 3, 4, 5.

[0613] The term "pharmaceutically acceptable" means relatively non-toxic, safe, and suitable for use by patients.

[0614] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When the compound contains a relatively acidic functional group, a base addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, sodium salts, potassium salts, calcium salts, aluminum salts, magnesium salts, bismuth salts, ammonium salts, and the like. When the compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochlorides, sulfates, trifluoroacetates, formates, methanesulfonates, and the like. For details, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition).

[0615] "-" in a group means that the group is attached to the rest of the molecule through this site. For example, CH3-C(=O)- means acetyl.

[0616] The term "halogen" refers to fluorine, chlorine, bromine or iodine. The halogen substitution in the present invention includes, but is not limited to, substitution by one halogen, substitution by two halogens, substitution by three halogens, and usually multiple substitutions occur on one carbon atom.

[0617] The term "oxo" refers to =0, an oxygen atom replacing two hydrogens on the same carbon atom, ie, replacing a methylene group with a carbonyl group.

[0618] The term "alkyl" refers to a linear or branched, saturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C1-C6). Alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, etc.

[0619] The term "alkoxy" refers to a group R X -O-, R X The same definition as the term "alkyl". Alkoxy includes, but is not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, and the like.

[0620] The term "alkenyl" refers to a group having the specified number of carbon atoms (e.g., C 2- C6), a linear or branched, unsaturated, monovalent hydrocarbon group having one or more (e.g., 1, 2, or 3) carbon-carbon sp 2 Double bond. Alkenyl groups include but are not limited to: vinyl, wait.

[0621] The term "alkynyl" refers to a radical having the specified number of carbon atoms (e.g., C 2- C6), a linear or branched, unsaturated, monovalent hydrocarbon group having one or more (e.g., 1, 2, or 3) carbon-carbon sp 3 triple bond. Alkynyl groups include but are not limited to: ethynyl, wait.

[0622] The term "cycloalkyl" refers to a cyclic, saturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., 3-6 or 3-12 members) that is a monocyclic ring. Monocyclic rings include, but are not limited to: wait.

[0623] The term "aryl" refers to a cyclic, unsaturated, monovalent hydrocarbon radical having a specified number of carbon atoms (e.g., 6-10 or 6-12 members), which is monocyclic or polycyclic (e.g., 2 or 3), in which case the monocyclic rings share two atoms and a bond, and (at least one ring / each ring) is aromatic. The aryl group is connected to the rest of the molecule through an aromatic ring or a non-aromatic ring. Aryl groups include, but are not limited to, phenyl, naphthyl, wait.

[0624] The term "cycloalkenyl" refers to a cyclic, unsaturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., 4-12 members), which is monocyclic or polycyclic (e.g., 2 or 3, bridged, spiro, and fused). Monocyclic cycloalkenyl groups include, but are not limited to: etc. Bridged ring cycloalkenyl groups include but are not limited to: Spirocyclic cycloalkenyl groups include but are not limited to Etc. Cycloalkenyl includes but is not limited to wait.

[0625] The term "heterocyclyl" (i.e., heterocycloalkyl) refers to a monocyclic, bridged, spirocyclic, or fused ring having a specified number of ring atoms (e.g., 3-10, 4-6, or 4-12), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatoms (one or more of N, O, and S). The monocyclic heterocyclic group is attached to the rest of the molecule through a carbon atom or a heteroatom. Monocyclic heterocyclic groups include, but are not limited to: Spirocyclic heterocyclic groups include, but are not limited to:

[0626] etc. Bridged heterocyclic groups include, but are not limited to: Etc. The heterocyclic group includes but is not limited to wait.

[0627] The term "heterocycloalkenyl" refers to a cyclic, unsaturated, monovalent group having a specified number of ring atoms (e.g., 5-10, 4-6, 5-6 or 4-12), a specified number of heteroatoms (e.g., 1, 2 or 3), a specified type of heteroatoms (one or more of N, O and S), which is monocyclic or polycyclic (e.g., 2 or 3, spirocyclic, fused, bridged). Monocyclic heterocycloalkenyls include, but are not limited to: Spirocyclic heterocycloalkenyl groups include but are not limited to Etc. Cyclic heterocycloalkenyl groups include but are not limited to wait.

[0628] The term "heteroaryl" refers to a cyclic, unsaturated, monovalent group with a specified number of ring atoms (e.g., 5-10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), a specified type of heteroatom (one or more of N, O, and S), which is a single ring or multiple rings, with two atoms and a bond shared between the single rings, and at least one ring is aromatic. The heteroaryl group is connected to the rest of the molecule through a carbon atom or a heteroatom; the heteroaryl group is connected to the rest of the molecule through a ring with heteroatoms or a ring without heteroatoms; the heteroaryl group is connected to the rest of the molecule through a ring with aromatic properties or a ring without aromatic properties. Heteroaryl groups include, but are not limited to:

[0629] wait.

[0630] The term "parallel heteroaromatic ring" refers to a "heteroaromatic ring" and other rings forming a parallel ring, and the "parallel heteroaromatic ring" contains at least two rings, at least one of which is a heteroaromatic ring. The rest of the definition of "heteroaromatic ring" is the same as that of "heteroaryl".

[0631] The term "isotopic compound" refers to a compound in which one or more atoms have an isotopic abundance that differs from its natural abundance. For example, one or more atoms in a compound has been replaced by an atom of a lower mass number that occurs naturally - a hydrogen atom in a compound has been replaced by deuterium, or a C has been replaced by 13 C replacement.

[0632] The term "pharmaceutically acceptable excipients" refers to excipients and additives used in the production of drugs and the preparation of prescriptions. It is all substances contained in drug preparations except active ingredients. Please refer to the Pharmacopoeia of the People's Republic of China (2020 Edition) Part IV, or Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009 Sixth Edition).

[0633] The term "treat" refers to therapeutic treatment. When referring to a specific condition, treatment means: (1) ameliorating the disease or one or more biological manifestations of the condition, (2) interfering with (a) one or more points in the biological cascade leading to or causing the condition or (b) one or more biological manifestations of the condition, (3) ameliorating one or more symptoms, effects, or side effects associated with the condition or one or more symptoms, effects, or side effects associated with the condition or its treatment, or (4) slowing the progression of the condition or one or more biological manifestations of the condition.

[0634] The term "therapeutically effective amount" refers to an amount administered to a patient that is sufficient to effectively treat a disease. The therapeutically effective amount will vary depending on the type of compound, the type of disease, the severity of the disease, the age of the patient, etc., but can be adjusted by those skilled in the art as appropriate.

[0635] In the present invention, "room temperature" means "20 to 30°C".

[0636] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0637] The reagents and raw materials used in the present invention are commercially available.

[0638] The positive and progressive effects of the present invention are that the ATPase activity and the inhibitory effect on proteins of the compounds of the present invention are greatly improved compared with the prior art, and the proliferation inhibition effect on DLD1 BRCA2- / - cells and DLD1 wild-type cells is highly selective. DETAILED DESCRIPTION

[0639] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0640] All compounds of the present invention can be synthesized by different methods by those skilled in the art of organic chemistry. The following describes a general synthetic scheme for preparing the compounds of the present invention. These schemes are general, but are not meant to limit the possible techniques that a person skilled in the art can use to prepare the compounds disclosed herein. The different methods for preparing the compounds of the present invention will be apparent to those skilled in the art. In addition, the various steps in the synthesis can be performed in an alternating order to obtain the desired one or more compounds. The preparation and examples described below give examples of the preparation of the compounds of the present invention by the methods described in the general scheme. The preparation of compounds containing chiral center embodiments can be performed by techniques mastered by those skilled in the art. For example, chiral compounds can be prepared by chiral separation of racemic products by HPLC; alternatively, the example compounds can be prepared by known methods to obtain chiral compounds.

[0641] The chemical reactions and synthesis techniques described herein are carried out in the reagents and corresponding solvents described herein, and the corresponding reaction yields are also affected by the reagents and solvents used. In addition, it should be understood that in the synthetic method described below, all the reaction conditions mentioned, including the choice of solvent, reaction atmosphere, reaction temperature, experimental duration and reaction feeding order, should be regarded as the operating condition standard of the reaction, which should be easily recognized by those skilled in the art. At the same time, it is also understandable to those skilled in the art in the field of organic synthesis. The functional groups present on each part of the molecule must be compatible with the reagents used and the reaction itself. For such restrictions that some functional groups present on each part of the molecule are incompatible with the reaction conditions, alternative methods must be used, which will be obvious to those skilled in the art. It is obvious that it is necessary to judge to adjust the order of the synthetic steps, or to select a specific synthetic process scheme to obtain the desired compound of the present invention. This is understandable and easily recognized by those skilled in the art in the field of organic synthesis. It should also be recognized that another major consideration for any synthetic route designed in this field is the reasonable selection of protecting groups for protecting the tolerance of reactive functional groups present in the compounds described in the present invention. For details, please refer to the work of Greene et al., an authority in the field of chemistry (Protective Groups in Organic Synthesis, Third Edition, Wiley and Sons (1999)).

[0642] Example

[0643] The preparation of the compounds and the intermediates used in the preparation of the compounds can be prepared using the procedures shown in the following examples and related procedures. The methods and conditions used in these examples and the actual compounds prepared in these examples are not meant to be limiting, but are meant to illustrate how to prepare the related compounds. The starting materials and reagents used in these examples, when not prepared by the procedures described herein, are generally available on the market, or reported in the relevant chemical literature, or can be prepared by using the procedures described in the chemical literature.

[0644] In the examples given herein, the term "drying and concentrating" generally refers to adding anhydrous sodium sulfate or magnesium sulfate drying solution to an organic solvent, followed by filtering and removing the solvent from the filtrate (generally under reduced pressure and at a temperature suitable for the stability of the prepared compound). Column chromatography generally uses conventional column chromatography or flash column chromatography for column separation and purification, or uses a medium pressure chromatograph (Biotage Isola One) pre-packed with silica gel columns and eluted in a specified solvent or solvent mixture. In some cases, the final product is quickly purified by preparative thin layer chromatography using 20cm x 20cm x 0.5mm or 20cm x 20cm x1mm silica gel plates in an appropriate solvent system. Preparative high performance liquid chromatography (HPLC) is performed using a reverse phase column (Waters Sunfire C18, Waters Xbridge C18 or similar reverse phase column) of a size appropriate to the amount of compound to be separated, typically using a gradient of methanol or acetonitrile concentration added to the aqueous phase, with the eluent containing 0.05% or 0.1% formic acid, trifluoroacetic acid or 10 mM ammonium acetate, with an elution rate matched to the size of the reverse phase column used and the resolution of the preparation.

[0645] List of abbreviations

[0646]

[0647]

[0648] Example 1: 2'-(difluoromethyl)-N-(6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazole[4,5-c] Pyridin-2-yl)-5'-methoxy-6-(5-methyl-1,3,4-oxadiazol-2-yl)-[4,4'-bipyridine]-3-carboxamide

[0649]

[0650] Step 1: tert-Butyl 6-chloro-4-iodonicotinate

[0651] 6-Chloro-4-iodonicotinic acid (3.00 g, 10.58 mmol), di-tert-butyl dicarbonate (4.62 g, 21.17 mmol) and 4-dimethylaminopyridine (0.13 g, 1.06 mmol) were dissolved in tetrahydrofuran (60 mL), and the reaction mixture was heated to reflux and stirred for 16 hours. After the reaction was complete, water was added to the reaction mixture, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to obtain the title compound (yellow solid, 3.00 g, yield: 83.6%). LC / MS (ESI) m / z: 399.9 [M+H] + .

[0652] Step 2: tert-Butyl 6-chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylate

[0653] To a solution of tert-butyl 6-chloro-4-iodonicotinate (1.00 g, 2.95 mmol) and 2-(difluoromethyl)-5-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.26 g, 4.42 mmol) in 1,4-dioxane / water (20 mL / 4 mL), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.22 g, 0.29 mmol) and potassium carbonate (1.02 g, 7.36 mmol) were added. The reaction mixture was stirred at 100 ° C for 2 hours under nitrogen protection. After the reaction was complete, it was cooled to room temperature, water was added, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to give the title compound (yellow solid, 0.55 g, yield: 50.6%). LC / MS (ESI) m / z: 371.1 [M+H] + .

[0654] Step 3: 2-(Ethylformyl)-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridyl]-5-carboxylic acid tert-butyl ester

[0655] To a solution of 6-chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid tert-butyl ester (500 mg, 1.36 mmol) in ethanol (20 mL) was added [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (198 mg, 0.27 mmol), palladium acetate (61 mg, 0.27 mmol) and triethylamine (412 mg, 4.07 mmol). The reaction mixture was stirred at 75 ° C for 12 hours under a carbon monoxide atmosphere. After the reaction was complete, the mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to give the title compound (white solid, 420 mg, yield: 76.2%). LC / MS (ESI) m / z: 409.2 [M+H] + .

[0656] Step 4: tert-Butyl 2'-(difluoromethyl)-6-(hydrazinecarbonyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylate

[0657] Hydrazine hydrate (2 mL) was added to a solution of 2-(ethyl formate)-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-5-carboxylic acid tert-butyl ester (400 mg, 0.98 mmol) in ethanol (10 mL), and the reaction mixture was stirred at 80°C for 4 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure to obtain the title compound (yellow solid, 380 mg, yield: 98.4%). The crude product was directly used in the next step. LC / MS (ESI) m / z: 395.2 [M+H] + .

[0658] Step 5: 2'-(Difluoromethyl)-5'-methoxy-6-(5-methyl-1,3,4-oxadiazol-2-yl)-[4,4'-bipyridine [[pi]-3-carboxylic acid tert-butyl ester]

[0659] To tert-butyl 2'-(difluoromethyl)-6-(hydrazinecarbonyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylate (380 mg, 0.97 mmol) was added p-toluenesulfonic acid (16.7 mg, 0.097 mmol) and triethyl orthoacetate (5 mL), and the reaction mixture was stirred at 120°C for 16 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 30-70% ethyl acetate) to obtain the title compound (yellow solid, 130 mg, yield: 32.2%). LC / MS (ESI) m / z: 419.2 [M+H] + .

[0660] Step 6: 2'-(Difluoromethyl)-5'-methoxy-6-(5-methyl-1,3,4-oxadiazol-2-yl)-[4,4'-bipyridine [pyridine]-3-carboxylic acid

[0661] 2'-(Difluoromethyl)-5'-methoxy-6-(5-methyl-1,3,4-oxadiazol-2-yl)-[4,4'-bipyridine]-3-carboxylic acid tert-butyl ester (100 mg, 0.24 mmol) and sodium hydroxide (48 mg, 1.20 mmol) were dissolved in tetrahydrofuran (5 mL) and methanol (5 mL), and the reaction mixture was stirred at room temperature for 24 hours. After the reaction was complete, the reaction solution was adjusted to pH = 4 with 1N dilute hydrochloric acid. The reaction solution was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (yellow solid, 60 mg, yield: 69.0%). LC / MS (ESI) m / z: 363.1 [M+H] + .

[0662] Step 7: 2'-(Difluoromethyl)-N-(6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazo[4,5-c]pyrrolidone pyridin-2-yl)-5'-methoxy-6-(5-methyl-1,3,4-oxadiazol-2-yl)-[4,4'-bipyridine]-3-carboxamide

[0663] 6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazo[4,5-c]pyridin-2-amine (40.0 mg, 0.16 mmol), 2'-(difluoromethyl)-5'-methoxy-6-(5-methyl-1,3,4-oxadiazol-2-yl)-[4,4'-bipyridine]-3-carboxylic acid (58.8 mg, 0.16 mmol), N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (68.4 mg, 0.24 mmol) and N-methylimidazole (40.0 mg, 0.48 mmol) were dissolved in acetonitrile (10 mL), and the reaction mixture was stirred at 70°C for 12 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the residue was purified by preparative HPLC to obtain the title compound (white solid, 5.0 mg, yield: 5.2%). 1H NMR(400MHz,DMSO-d6)δ13.59(s,1H),9.21(s,1H),9.20(s,1H),8.52(s,1H),8.41(s,1H),8.27(s,1H),7.90(s ,1H),7.02(t,J=55.0Hz,1H),4.15(s,3H),3.72(s,3H),2.67(s,3H),2.40(s,3H).LC / MS(ESI)m / z:591.2[M+H] + .

[0664] Example 2: 2"-(difluoromethyl)-3-fluoro-N-(6-isopropylthiazolo[4,5-c]pyridin-2-yl)-5'-methoxy 2-oxo-2H-[1,2'-:4'-,4'-bipyridine]-5'-carboxamide

[0665]

[0666] Step 1: 2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-isopropylthiazolo[4,5-c]pyridine

[0667] [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.28 g, 0.379 mmol) was added to a solution of 6-chloro-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-c]pyridine (1 g, 3.79 mmol) in tetrahydrofuran (15 mL). Then, isopropylmagnesium chloride lithium chloride (8.8 mL, 11.4 mmol, 1.3 M) was added dropwise to the reaction mixture at 0°C. The reaction mixture was stirred at room temperature under nitrogen protection for 2 hours. After the reaction was complete, saturated ammonium chloride solution was added, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-10% ethyl acetate) to give the title compound (yellow oil, 520 mg, yield 50.5%). LC / MS (ESI) m / z: 272.2 [M+H] + .

[0668] Step 2: 6-isopropylthiazo[4,5-c]pyridin-2-amine

[0669] 2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-isopropylthiazole [4,5-c] pyridine (520 mg, 1.92 mmol) was dissolved in 5 mL of 2M hydrochloric acid solution, and the mixture was stirred at 80°C for 2 hours. After the reaction was complete, the title compound (brown solid, 350 mg, yield 94.5%) was obtained by concentration under reduced pressure. The crude product was directly used for the next step without purification. LC / MS (ESI) m / z: 194.2 [M+H] + .

[0670] Step 3: 2"-(difluoromethyl)-3-fluoro-5'-methoxy-2-oxo-2H-[1,2'-:4'-,4'-bipyridine]- 5'-Benzyl carboxylate

[0671] 3-Fluoropyridine-2(1H)-one (101 mg, 0.893 mmol), potassium carbonate (205 mg, 1.48 mmol), 8-hydroxyquinoline (54 mg, 0.372 mmol) and cuprous iodide (71 mg, 0.373 mmol) were added to a solution of 6-chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid benzyl ester (300 mg, 0.741 mmol) in dimethyl sulfoxide (5 mL) in sequence. The reaction mixture was stirred at 100°C for 1 hour under nitrogen protection. After the reaction was complete, water was added, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to give the title compound (white solid, 200 mg, yield 56.1%). LC / MS(ESI)m / z:482.2[M+H] + .

[0672] Step 4: 2"-(difluoromethyl)-3-fluoro-5'-methoxy-2-oxo-2H-[1,2'-:4'-,4'-bipyridine]- 5'-Carboxylic acid

[0673] To a solution of 2"-(difluoromethyl)-3-fluoro-5'-methoxy-2-oxo-2H-[1,2'-:4'-,4'-bipyridine]-5'-carboxylic acid benzyl ester (100 mg, 0.208 mmol) in methanol (10 mL) was added 10% wet palladium carbon (30 mg, 0.282 mmol). The reaction mixture was stirred at room temperature in a hydrogen atmosphere for half an hour. After the reaction was complete, the title compound (white solid, 80 mg, yield 98.4%) was obtained by filtration and concentration under reduced pressure, which was directly carried out to the next step without purification. LC / MS (ESI) m / z: 392.1 [M+H] + .

[0674] Step 5: 2"-(Difluoromethyl)-3-fluoro-N-(6-isopropylthiazolo[4,5-c]pyridin-2-yl)-5'-methoxy 2-oxo-2H-[1,2'-:4'-,4'-bipyridine]-5'-carboxamide

[0675] To a mixed solution of 2″-(difluoromethyl)-3-fluoro-5′-methoxy-2-oxo-2H-[1,2′-:4′-,4′-bipyridine]-5′-carboxylic acid (80 mg, 0.204 mmol) in N,N-dimethylformamide (3 mL) and acetonitrile (5 mL) were added 6-isopropylthiazolyl[4,5-c]pyridin-2-amine (40 mg, 0.207 mmol) and N-methylimidazole (84 mg, 1.02 mmol) in sequence. The mixture was heated to 70°C. , then add N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (115 mg, 0.410 mmol) to the mixture. Keep stirring at 70°C for 2 hours. After the reaction is complete, add water, extract with ethyl acetate, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, and concentrate under reduced pressure. The residue is purified by preparative HPLC (mobile phase: CH3CN, H2O (containing 0.1% HCOOH)) to obtain the title compound (near white solid, 34.5 mg, yield 29.8%). 1 H NMR (400MHz, DMSO-d6) δ13.30(s,1H),9.04(s,1H),8.96(s,1H),8.50(s,1H),8.09(s,1H),7.93(s,1H),7.87(d,J=7.2Hz,1H),7.77(s,1H),7. 60-7.54(m,1H),7.01(t,J=55.2Hz,1H),6.48-6.38(m,1H),3.70(s,3H),3.18-3.08(m,1H),1.29(d,J=7.2Hz,6H).LC / MS(ESI)m / z:567.3[M+H] + .

[0676] The compounds of the examples in Table 1 were synthesized using commercially available raw materials and referring to the synthesis steps of Example 2.

[0677] Table 1:

[0678]

[0679]

[0680]

[0681]

[0682]

[0683]

[0684]

[0685]

[0686] Example 39: 2'-(Difluoromethyl)-6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-N-(6-isopropyl Thiazolo[4,5-c]pyridin-2-yl)-5'-methoxy-[4,4'-bipyridine]-3-carboxamide

[0687]

[0688] Step 1: 6-Chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid

[0689] A solution of 6-chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid tert-butyl ester (200 mg, 0.539 mmol) in dioxane hydrochloride (10 mL) was stirred at room temperature for 32 hours. After the reaction was complete, the title compound (white solid, 160 mg, yield 94.3%) was obtained by concentration under reduced pressure, and the next step was carried out directly without purification. LC / MS (ESI) m / z: 315.1 [M+H] + .

[0690] Step 2: 6-chloro-2'-(difluoromethyl)-N-(6-isopropylthiazolo[4,5-c]pyridin-2-yl)-5'-methoxy 4,4'-Bipyridine-3-carboxamide

[0691] To a mixed solution of 6-chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid (160 mg, 0.508 mmol) in N,N-dimethylformamide (3 mL) and acetonitrile (5 mL) were added 6-isopropylthiazole [4,5-c] pyridine-2-amine (108 mg, 0.559 mmol) and N-methylimidazole (209 mg, 2.55 mmol) in sequence. The mixed solution was then heated to 70°C, and N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (285 mg, 1.02 mmol) was added to the mixture. The mixture was stirred at 70°C for 2 hours. After the reaction was complete, water was added, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0-3% methanol) to give the title compound (brown solid, 170 mg, yield 68.2%). LC / MS (ESI) m / z: 490.2 [M+H] + .

[0692] Step 3: 2'-(Difluoromethyl)-6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-N-(6-isopropylthiazole 2-(4,5-c)pyridin-2-yl)-5'-methoxy-[4,4'-bipyridine]-3-carboxamide

[0693] 1,4-dimethyl-5-(tributyltinyl)-1H-1,2,3-triazole (83 mg, 0.215 mmol) and tetrakistriphenylphosphine palladium (50 mg, 0.043 mmol) were added to a solution of 6-chloro-2'-(difluoromethyl)-N-(6-isopropylthiazolo[4,5-c]pyridin-2-yl)-5'-methoxy-[4,4'-bipyridine]-3-carboxamide (70 mg, 0.143 mmol) in xylene (3 mL). The mixture was stirred in a microwave at 160 ° C for 1 hour under nitrogen protection. After the reaction was complete, it was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0-10% methanol) and preparative HPLC to give the title compound (light yellow solid, 6.6 mg, yield 8.38%). 1 H NMR(400MHz,DMSO-d6)δ13.26(s,1H),9.17(s,1H),8.95(s,1H),8.50(s,1H),7.90(s,1H),7.86(s,1H),7.81(s,1H),6.99(t, J=54.8Hz,1H),4.21(s,3H),3.71(s,3H),3.16-3.08(m,1H),2.44(s,3H),1.29(d,J=6.8Hz,6H).LC / MS(ESI)m / z:551.3[M+H] + .

[0694] The compounds of the examples in Table 2 were synthesized using commercially available raw materials and referring to the synthesis steps of Example 39.

[0695] Table 2:

[0696]

[0697] Example 41: 2'-(Difluoromethyl)-N-(6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazole[4,5- c]pyridin-2-yl)-5'-methoxy-1-(5-methyl-1,3,4-oxadiazol-2-yl)-6-oxo-1,6-dihydro-[3,4'- Pyridine]-4-carboxamide

[0698]

[0699] Step 1: 5-bromo-1-(5-methyl-1,3,4-oxadiazol-2-yl)-2-oxo-1,2-dihydropyridine-4-carboxylic acid ester

[0700] Dissolve 5-bromo-2-oxo-1,2-dihydropyridine-4-carboxylic acid methyl ester (700 mg, 3.02 mmol) and 2-bromo-5-methyl-1,3,4-oxadiazole (541 mg, 3.32 mmol) in N,N-dimethylformamide (10 mL) solvent, and add potassium carbonate (834 mg, 6.04 mmol). React at 85°C for 2 hours. After the reaction is complete, add ethyl acetate and water to the reaction solution, separate the layers, wash the organic phase with saturated sodium chloride solution, dry the organic phase with anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure. The residue is purified by column chromatography (eluent: dichloromethane, methanol, gradient: 0%-5% methanol) to obtain the title compound (brown solid, 338 mg, yield 35.7%). LC / MS (ESI) m / z: 313.9 [M+H] + .

[0701] Step 2: 2'-(difluoromethyl)-5'-methoxy-1-(5-methyl-1,3,4-oxadiazol-2-yl)-6-oxo-1, 6-Dihydro-[3,4'-bipyridine]-4-carboxylic acid methyl ester

[0702] Under nitrogen protection, 5-bromo-1-(5-methyl-1,3,4-oxadiazol-2-yl)-2-oxo-1,2-dihydropyridine-4-carboxylic acid methyl ester (338 mg, 1.08 mmol), 2-(difluoromethyl)-5-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (339 mg, 1.19 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (87.8 mg, 0.12 mmol), cesium carbonate (1.16 g, 3.57 mmol) were dissolved in a mixed solvent of dioxane (10 mL) and water (2 mL). The reaction was carried out at 95°C for 1 hour. After the reaction is complete, the residue obtained by concentration under reduced pressure is purified by column chromatography (eluent: petroleum ether, ethyl acetate, gradient: 30%-70% ethyl acetate) to obtain the title compound (yellow solid, 188 mg, yield 44.4%). LC / MS (ESI) m / z: 393.1 [M+H] + .

[0703] Step 3: 2'-(difluoromethyl)-5'-methoxy-1-(5-methyl-1,3,4-oxadiazol-2-yl)-6-oxo-1, 6-Dihydro-[3,4'-bipyridine]-4-carboxylic acid

[0704] Dissolve 2'-(difluoromethyl)-5'-methoxy-1-(5-methyl-1,3,4-oxadiazol-2-yl)-6-oxo-1,6-dihydro-[3,4'-bipyridine]-4-carboxylic acid methyl ester (188 mg, 0.48 mmol) in 10 mL of 1,2-dichloroethane solvent, add trimethyltin hydroxide (868 mg, 4.8 mmol), and react at 80 degrees Celsius for 5 hours. After the reaction is complete, concentrate under reduced pressure, and the residue is purified by column chromatography (eluent: dichloromethane, methanol, gradient: 0%-30% methanol) to obtain the title compound (yellow solid, 150 mg, yield 82.8%). LC / MS (ESI) m / z: 379.1 [M+H] + .

[0705] Step 4: 2'-(Difluoromethyl)-N-(6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazo[4,5-c]pyrrolidone pyridine-2-yl)-5'-methoxy-1-(5-methyl-1,3,4-oxadiazol-2-yl)-6-oxo-1,6-dihydro-[3,4'-bipyridine [pyridine]-4-carboxamide

[0706] 6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazo[4,5-c]pyridin-2-amine (39 mg, 0.16 mmol) and 2'-(difluoromethyl)-5'-methoxy-1-(5-methyl-1,3,4-oxadiazol-2-yl)-6-oxo-1,6-dihydro-[3,4'-bipyridine]-4-carboxylic acid (60 mg, 0.16 mmol) were dissolved in 5 mL of acetonitrile and 1 mL of N,N-dimethylformamide, and N-methylimidazole (53 mg, 0.64 mmol) was added. After stirring at 70°C for 10 minutes, N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (67 mg, 0.24 mmol) was added and reacted at 70°C for 1 hour. Ethyl acetate and water were added to the reaction solution, the layers were separated, the organic phase was washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (white solid, 30 mg, yield 31%). 1 H NMR(400MHz,DMSO-d6)δ13.58(s,1H),9.24(s,1H),8.41(s,1H),8.39(s,1H),8.13(s,1H),7.73(s,1H),7.14(s ,1H),6.96(t,J=55.1Hz,1H),4.15(s,3H),3.66(s,3H),2.64(s,3H),2.39(s,3H).LC / MS(ESI)m / z:607.2[M+H] + .

[0707] Example 42: 2'-(Difluoromethyl)-N-(6-isopropylthiazolo[4,5-c]pyridin-2-yl)-5'-methoxy- 6-(6-Oxopyridazin-1(6H)-yl)-[4,4'-bipyridine]-3-carboxamide

[0708]

[0709] Step 1: 2'-(Difluoromethyl)-5'-methoxy-6-(6-oxopyridazin-1(6H)-yl)-[4,4'-bipyridine]- Benzyl 3-carboxylate

[0710] To a solution of 6-chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid benzyl ester (270 mg, 0.667 mmol) in dimethyl sulfoxide (5 mL) were added pyridazine-3(2H)-one (128 mg, 1.33 mmol), potassium carbonate (184 mg, 1.33 mmol), 8-hydroxyquinoline (19 mg, 0.131 mmol) and cuprous iodide (64 mg, 0.336 mmol) in sequence. The reaction mixture was stirred at 100°C for 16 hours under nitrogen protection. After the reaction was complete, water was added, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-100% ethyl acetate) to give the title compound (brown solid, 130 mg, yield 42.0%). LC / MS(ESI)m / z:465.2[M+H] + .

[0711] Step 2: 2'-(Difluoromethyl)-5'-methoxy-6-(6-oxopyridazin-1(6H)-yl)-[4,4'-bipyridine]- 3-Carboxylic acid

[0712] To a mixed solution of 2'-(difluoromethyl)-5'-methoxy-6-(6-oxopyridazine-1(6H)-yl)-[4,4'-bipyridine]-3-carboxylic acid benzyl ester (100 mg, 0.215 mmol) in tetrahydrofuran (3 mL) and water (1 mL) was added lithium hydroxide (8 mg, 0.334 mmol). The reaction mixture was stirred at 40°C for 1 hour. After the reaction was complete, 1N hydrochloric acid was added to adjust the pH to neutral and the mixture was concentrated under reduced pressure. The residue was purified by reverse phase (eluent: water / acetonitrile, gradient: 0-50% acetonitrile) to give the title compound (yellow solid, 65 mg, yield 80.7%). LC / MS (ESI) m / z: 375.1 [M+H] + .

[0713] Step 3: 2'-(Difluoromethyl)-N-(6-isopropylthiazolo[4,5-c]pyridin-2-yl)-5'-methoxy-6- (6-Oxopyridazin-1(6H)-yl)-[4,4'-bipyridine]-3-carboxamide

[0714] 6-isopropylthiazole [4,5-c] pyridine-2-amine (37 mg, 0.191 mmol) and N-methylimidazole (71 mg, 0.865 mmol) were added to a mixed solution of 2'-(difluoromethyl)-5'-methoxy-6-(6-oxopyridazine-1(6H)-yl)-[4,4'-bipyridine]-3-carboxylic acid (65 mg, 0.174 mmol) in N,N-dimethylformamide (3 mL) and acetonitrile (5 mL) in sequence. Then, N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (97 mg, 0.346 mmol) was added to the mixture at 70°C. The mixture was stirred at 70°C for 2 hours. After the reaction was complete, water was added, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (white solid, 26.1 mg, yield 27.4%). 1 H NMR(400MHz,DMSO-d6)δ13.33(s,1H),9.04(s,1H),9.00(s,1H),8.50(s,1H), 8.13(dd,J=3.6,1.6Hz,1H),7.98(s,1H),7.93(s,1H),7.76(s,1H),7.58(dd, J=9.6,4.0Hz,1H),7.16(dd,J=9.6,1.2Hz,1H),6.93(t,J=55.6Hz,1H),3.70( s,3H),3.18-3.11(m,1H),1.30(d,J=6.8Hz,6H).LC / MS(ESI)m / z:550.3[M+H] + .

[0715] Example 43: N-([1,3]dioxacyclo[4',5':4,5]benzo[1,2-d]thiazol-6-yl)-2"-(difluoromethane 1-(2 ...

[0716]

[0717] At room temperature, [1,3]dioxo[4',5':4,5]benzo[1,2-d]thiazol-6-amine (12 mg, 0.062 mmol), 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxylic acid (20 mg, 0.051 mmol) and N-methylimidazole (17 mg, 0.21 mmol) were dissolved in acetonitrile (2 mL) and N,N-dimethylformamide (0.5 mL). After stirring at 70°C for one minute, a solution of N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (22 mg, 0.078 mmol) in acetonitrile (0.3 mL) was added to the reaction solution, and then the reaction solution was stirred at 70°C for 3 hours. After the reaction was complete, the reaction solution was filtered and purified by preparative HPLC (YMC-Actus Triart C18 250*20mm*5um, 30-95% methanol in H2O solution containing 0.1% FA) was purified to give the title compound (yellow solid, 13 mg, yield 45.6%). 1 HNMR(400MHz,DMSO-d6)δ13.03(s,1H),9.00(s,1H),8.51(s,1H),8.08(s,1H),7.87(d,J=7.1Hz,1H),7.75(s,1H),7.60-7.54(m, 1H),7.53(s,1H),7.34(s,1H),7.01(t,J=55.0Hz,1H),6.47-6.39(m,1H),6.09(s,2H),3.71(s,3H).LC / MS(ESI)(m / z):568[M+H] + .

[0718] The compounds of the examples in Table 3 were synthesized using commercially available raw materials and referring to the synthesis steps of Example 43.

[0719] Table 3:

[0720]

[0721]

[0722] Example 49: 2"-(Difluoromethyl)-3-fluoro-N-(8H-indeno[1,2-d]thiazol-2-yl)-5"-methoxy-2- Oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0723]

[0724] Step 1: 8H-indeno[1,2-d]thiazol-2-amine

[0725] At room temperature, 2,3-dihydro-1H-indene-1-one (100 mg, 0.76 mmol) and thiourea (173 mg, 2.3 mmol) were dissolved in anhydrous ethanol (5 mL), and the reaction solution was reacted at 100 ° C overnight. Water was added to the reaction solution, and a white solid precipitated. It was filtered, and the filter cake was slurried with ether and dried under reduced pressure to obtain the title compound (white solid, 140 mg, yield 78.6%). LC / MS (ESI) m / z: 189.1 [M+H] + . Step 2: 2"-(Difluoromethyl)-3-fluoro-N-(8H-indeno[1,2-d]thiazol-2-yl)-5"-methoxy- 2-Oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0726] At room temperature, 8H-indeno[1,2-d]thiazol-2-amine (10 mg, 0.051 mmol), 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxylic acid (20 mg, 0.051 mmol) and N-methylimidazole (17 mg, 0.21 mmol) were dissolved in acetonitrile (2 mL). After stirring at 70°C for one minute, a solution of N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (22 mg, 0.078 mmol) in acetonitrile (0.3 mL) was added to the reaction solution, and then the reaction solution was stirred at 70°C for 3 hours. After the reaction was complete, the residue was filtered and purified by preparative HPLC (YMC-Actus Triart C18 250*20mm*5um, 25-90% acetonitrile in H2O solution containing 0.1% FA) to obtain the title compound (white solid, 7.1 mg, yield 25%). NMR (400MHz, DMSO-d6) δ13.13(s,1H),9.01(s,1H),8.51(s,1H),8.07(s,1H),7.88(d,J=7.1Hz,1H),7.75(s,1H),7.61-7.53(m,3H),7. 38(t,J=7.5Hz,1H),7.26(t,J=7.6Hz,1H),7.17-6.83(m,1H),6.46-6.37(m,1H),3.90(s,2H),3.72(s,3H).LC / MS(ESI)(m / z):562[M+H] + .

[0727] Example 50: N-(6-chlorothiazolo[5,4]pyridin-2-yl)-2"-(difluoromethyl)-3-fluoro-5"-methoxy-2- Oxo-2H-[1,2':4',4"-bipyridine]-5'-carboxamide

[0728]

[0729] Step 1: N-((5-bromo-2-chloropyridin-4-yl)aminomethylthio)benzamide

[0730] At room temperature, benzoyl isothiocyanate (3.4 g, 0.021 mol) was added in batches to a solution of 5-bromo-2-chloropyridin-4-amine (4 g, 0.019 mol) in acetone (70 mL), and the reaction solution was stirred at 50 ° C for 3 hours. The reaction solution was cooled to room temperature and filtered. The filter cake was washed with acetone and dried under reduced pressure to obtain the title compound (6 g, yellow solid, yield 84.5%). LC / MS (ESI) m / z: 370 [M+H] + . Step 2: 1-(5-bromo-2-chloropyridin-4-yl)thiourea

[0731] At room temperature, N-((5-bromo-2-chloropyridin-4-yl)aminomethylthio)benzamide (6 g, 0.016 mmol) and methanol (50 mL) were added to a reaction flask, followed by sodium hydroxide (50 mL, 6 M) aqueous solution, and the reaction mixture was stirred at 80 ° C for 2 hours. The reaction solution was cooled to room temperature, filtered, and the filter cake was washed with a small amount of ice methanol and dried under reduced pressure to obtain the title compound (4.1 g, light yellow solid, yield 95%). LC / MS (ESI) m / z: 266 [M+H] + .

[0732] Step 3: 6-Chlorothiazolo[5,4-c]pyridin-2-amine

[0733] Under nitrogen protection, 1-(5-bromo-2-chloropyridin-4-yl)thiourea (1g, 3.77mmol) and cesium carbonate (2.46g, 7.54mmol) were dissolved in dimethyl sulfoxide (10mL), followed by the addition of cuprous iodide (14mg, 0.075mmol) and L-proline (5mg, 0.037mmol). The reaction solution was stirred at 70°C under nitrogen protection overnight. The reaction solution was diluted with ethyl acetate, washed with water and saturated brine in turn, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10-70% ethyl acetate) to give the title compound (yellow solid, 550mg, yield 78.5%). LC / MS (ESI) m / z: 186 [M+H] + .

[0734] Step 4: N-(6-chlorothiazolo[5,4]pyridin-2-yl)-2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxothiazolo[5,4]pyridin-2-yl]- Substituted-2H-[1,2':4',4"-bipyridine]-5'-carboxamide

[0735] At room temperature, 6-chlorothiazo[5,4-c]pyridin-2-amine (80 mg, 0.43 mmol), 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo

[0736] -2H-[1,2':4',4"-terpyridine]-5'-carboxylic acid (169 mg, 0.43 mmol) and N-methylimidazole (105 mg, 1.29 mmol) were dissolved in acetonitrile (2 mL) and stirred at 70°C for one minute. Then, a solution of N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (180 mg, 0.65 mmol) in acetonitrile (2 mL) was added to the reaction solution, and then the reaction solution was stirred at 70°C for 3 hours. After the reaction was complete, the reaction solution was filtered and purified by preparative HPLC (Welch-UItimate AQ-C18, 20-95% acetonitrile in H2O solution containing 0.1% FA) to obtain the title compound (yellow solid, 55 mg, yield 23%). 1 H NMR (400MHz, DMSO-d6) δ9.11(s,1H),8.76(s,1H),8.47(s,1H),7.95(s,1H),7.88(d,J=6.8Hz,1H),7.67(s,1H),7 .63-7.47(m,2H),6.99(t,J=55.3Hz,1H),6.41(dd,J=11.9,7.2Hz,1H),3.69(s,3H).LC / MS(ESI)(m / z):559[M+H] + .

[0737] Example 51: N-(5-acetyl-4,5,6,7-tetrahydrothiazol[5,4]pyridin-2-yl)-2"-(difluoromethyl)-3- Fluoro-5"-methoxy-2-oxo-2H-[1,2':4',4"-tripyridine]-5'-carboxamide

[0738]

[0739] Step 1: 2-(2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-2H-[1,2':4',4"-terpyrrolidone tert-Butyl 6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate

[0740] At room temperature, tert-butyl 2-amino-6,7-dihydrothiazolidine [5,4] pyridine-5 (4H) -carboxylate (50 mg, 0.2 mmol), 2 "- (difluoromethyl) -3-fluoro-5 "-methoxy-2-oxo-2H- [1,2': 4', 4" -terpyridine] -5'-carboxylic acid (77 mg, 0.2 mmol) and N-methylimidazole (50 mg, 0.6 mmol) were dissolved in acetonitrile (3 mL) and stirred at 70 ° C for one minute. After that, N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (84 mg, 0.3 mmol) was added to the reaction solution, and then the reaction solution was stirred at 70°C for 3 hours. After the reaction was complete, it was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 20-80% ethyl acetate) to obtain the title compound (yellow solid, 80 mg, yield 99%). LC / MS (ESI) m / z: 629 [M+H] + .

[0741] Step 2: 2"-(Difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-N-(4,5,6,7-tetrahydrothiazolo[5,4- c]pyridin-2-yl)-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0742] At room temperature, 2-(2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxamide)-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester (80 mg, 0.13 mmol) and methanol (2 mL) were added to a reaction bottle, and 4N hydrochloric acid dioxane (2 mL) solution was added to the mixture. The reaction solution gradually became clear, and the reaction solution was stirred at room temperature for 1 hour, and solid precipitated. The reaction solution was concentrated under reduced pressure and slurried with ethyl acetate to obtain the title compound (65 mg, yellow solid, yield 91.5%). LC / MS (ESI) m / z: 529 [M+H] + .

[0743] Step 3: N-(5-acetyl-4,5,6,7-tetrahydrothiazolidine[5,4]pyridin-2-yl)-2"-(difluoromethyl)-3-fluoro- 5"-Methoxy-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0744] Acetic acid (9 mg, 0.14 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (53 mg, 0.14 mmol) and N,N-diisopropylethylamine (0.03 mL, 0.21 mmol) were dissolved in N,N-dimethylformamide (2 mL) at room temperature, and 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-N-(4,5,6,7- Tetrahydrothiazolo[5,4-c]pyridin-2-yl)-2H-[1,2':4',4"-terpyridine]-5'-carboxamide (40 mg, 0.07 mmol) was added and stirred at room temperature for 2 hours. The reaction solution was diluted with ethyl acetate and water, separated and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC (Welch-UItimate AQ-C18, 20-95% acetonitrile in H2O and 0.1% FA) to give the title compound (yellow solid, 18 mg, yield 45%). 1H NMR (400MHz, DMSO-d6) δ12.93-12.74(m,1H),8.95(s,1H),8.54-8.49(m,1H),8. 06(s,1H),7.86(d,J=7.1Hz,1H),7.73(s,1H),7.61-7.53(m,1H),7.01(t,J=55. 1Hz,1H),6.47-6.39(m,1H),4.69-4.58(m,2H),3.81-3.73(m,2H),3.71(s,3H), 2.79-2.76(m,1H),2.70-2.59(m,1H),2.14(s,3H).LC / MS(ESI)(m / z):571[M+H] + .

[0745] Example 52: 2"-(Difluoromethyl)-N-(6,7-dihydro-5H-thiazolo[4,5-f]indol-2-yl)-3-fluoro- 5"-Methoxy-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0746]

[0747] Step 1: 2,2,2-Trifluoro-1-(5-nitroindolin-1-yl)ethan-1-one

[0748] At room temperature, trifluoroacetic anhydride (1.41 g, 6.70 mmol) and triethylamine (0.9 mL, 6.70 mmol) were added to a solution of 5-nitroindole (1 g, 6.09 mmol) in dichloromethane (10 mL). The reaction solution was stirred at room temperature for 1 hour. The reaction solution was poured into water and then extracted with dichloromethane. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to give the title compound (yellow solid, 1 g, yield 63.1%). LC / MS (ESI) (m / z): 261.1 [M+H] + .

[0749] Step 2: 1-(5-aminoindolin-1-yl)-2,2,2-trifluoroethane-1-one

[0750] Under nitrogen protection, palladium carbon (100 mg, 10% wt.) was added to a solution of 2,2,2-trifluoro-1-(5-nitroindolin-1-yl)ethane-1-one (500 mg, 1.92 mmol) in methanol (5 mL). The reaction solution was stirred under hydrogen atmosphere at room temperature for 2 hours. After the reaction was complete, the reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure to obtain the title compound (yellow oil, 427 mg, yield 96.5%), and the crude product was directly used for the next step. LC / MS (ESI) (m / z): 231.2 [M+H] + .

[0751] Step 3: 1-(2-amino-6,7-dihydro-5H-thiazolo[4,5-f]indol-5-yl)-2,2,2-trifluoroethane-1- ketone

[0752] Under nitrogen protection, potassium thiocyanate (721 mg, 7.42 mmol) was added to a solution of 1-(5-aminoindoline-1-yl)-2,2,2-trifluoroethane-1-one (427 mg, 1.85 mmol) in glacial acetic acid (4 mL). The resulting mixture was stirred at room temperature for 10 minutes. Subsequently, liquid bromine (296 mg, 1.85 mmol) was slowly added to the reaction solution, and the mixed solution was stirred at room temperature for 16 hours. The reaction mixture was poured into ice water and adjusted to alkalinity with ammonia water, and extracted with dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to obtain the title compound (yellow solid, 110 mg, yield 20.6%). LC / MS(ESI): m / z 288.1[M+H] + .

[0753] Step 4: 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-carbonyl-N-(5-(2,2,2-trifluoroacetyl)-6, 7-Dihydro-5H-thiazolo[4,5-f]indol-2-yl)-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0754] To a solution of 2″-(difluoromethyl)-3-fluoro-5″-methoxy-2-carbonyl-2H-[1,2′:4′,4″-tripyridine]-5′-carboxylic acid (30 mg, 0.077 mmol) in DMF (2 mL) was added 1-(2-amino-6,7-dihydro-5H-thiazolo[4,5-f]indol-5-yl)-2,2,2-trifluoroethane-1-one (26.4 mg, 0.092 mmol), HATU (43.7 mg, 0.115 mmol) and 4% paraformaldehyde (5% paraformaldehyde) at room temperature. ol) and DIEA (19.8 mg, 0.15 mmol). The resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / ethyl acetate, gradient: 0-10% dichloromethane) to give the title compound (yellow solid, 25 mg, yield 49.4%). LC / MS (ESI) (m / z): 661.3 [M+H] + .

[0755] Step 5: 2"-(Difluoromethyl)-N-(6,7-dihydro-5H-thiazolo[4,5-f]indol-2-yl)-3-fluoro-5"-methyl Oxy-2-carbonyl-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0756] Potassium carbonate (10.5 mg, 0.076 mmol) was added to a solution of 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-carbonyl-N-(5-(2,2,2-trifluoroacetyl)-6,7-dihydro-5H-thiazolo[4,5-f]indol-2-yl)-2H-[1,2':4',4"-tripyridine]-5'-carboxamide (25 mg, 0.038 mmol) in methanol (1 mL) at room temperature, and the reaction solution was stirred at room temperature for 1 hour. The reaction mixture was filtered and the filtrate was purified by preparative HPLC (YMC-Actus Triart C18 250*21 mm, 20-90% methanol in H2O solution containing 0.1% FA) to give the title compound (white solid, 1.30 mg, yield 6.1%). 1 HNMR(400MHz,DMSO-d6)δ8.99(s,1H),8.50(s,1H),8.04(s,1H),7.86(d,J=6.9Hz,1H),7.73(s,1H),7.59-7.53(m,1H),7.42(s,1H),7.15- 6.85(m,2H),6.42(dd,J=11.9,7.3Hz,1H),5.69(s,1H),3.71(s,3H),3.49-3.44(m,2H),3.00(t,J=8.1Hz,2H).LC / MS(ESI)(m / z):565[M+H] + .

[0757] Example 53: 2"-(Difluoromethyl)-3-fluoro-N-(7-fluorothiazolo[5,4]pyridin-2-yl)-5"-methoxy-2- Oxo-2H-[1,2':4',4"-bipyridine]-5'-carboxamide

[0758]

[0759] Step 1: N-((3,5-difluoropyridin-4-yl)aminomethylthio)benzamide

[0760] At room temperature, benzoyl isothiocyanate (451 mg, 2.76 mmol) was added in batches to a solution of 3,5-difluoropyridin-4-amine (300 mg, 2.3 mmol) in acetone (10 mL), and the reaction solution was stirred at 50 ° C for 3 hours. The reaction solution was cooled to room temperature and filtered. The filter cake was washed with acetone and dried under reduced pressure to obtain the title compound (285 mg, yellow solid, yield 42%). LC / MS (ESI) m / z: 294 [M+H] + .

[0761] Step 2: N-(7-fluorothiazo[5,4]pyridin-2-yl)benzamide

[0762] At room temperature, cesium carbonate (613 mg, 1.88 mmol) was added to a DMF (5 mL) solution of N-((3,5-difluoropyridin-4-yl)aminomethylthio)benzamide (275 mg, 0.94 mmol). The reaction solution was stirred at 100°C overnight. After the reaction was complete, the reaction solution was diluted with ethyl acetate and water, separated, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to give the title compound (white solid, 55 mg, yield 21%). LC / MS(ESI)(m / z):274[M+H] + .

[0763] Step 3: 7-Fluorothiazolo[5,4-c]pyridin-2-amine

[0764] At room temperature, N-(7-fluorothiazolyl[5,4]pyridin-2-yl)benzamide (55 mg, 0.2 mmol) was added to 70% sulfuric acid (2 mL). The reaction solution was stirred at 110°C for 1 hour. The reaction solution first gradually dissolved and then slowly precipitated solids. The reaction solution was cooled to 0°C and adjusted to neutral with 6M sodium hydroxide aqueous solution. The mixed solution was filtered, and the filter cake was washed twice with water and methanol, respectively, and dried under reduced pressure to obtain the title compound (21 mg, yellow solid, yield 61.7%). LC / MS(ESI)m / z:170[M+H] + .

[0765] Step 4: 2"-(Difluoromethyl)-3-fluoro-N-(7-fluorothiazolo[5,4]pyridin-2-yl)-5"-methoxy-2-yl Substituted-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0766] At room temperature, 7-fluorothiazolyl[5,4-c]pyridin-2-amine (21 mg, 0.12 mmol), 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxylic acid (48 mg, 0.12 mmol) and N-methylimidazole (29 mg, 0.36 mmol) were dissolved in acetonitrile (2 mL). After stirring at 70°C for one minute, N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (50 mg, 0.18 mmol) was added to the reaction solution, and then the reaction solution was stirred at 70°C for 3 hours. After the reaction was complete, the residue was filtered and purified by preparative HPLC (YMC-Actus Triart C18250*21 mm, 20-90% methanol in H2O solution containing 0.1% The title compound (yellow solid, 1 mg, yield 1.4%) was obtained by purification by FA. 1H NMR (400MHz, DMSO-d6) δ13.81(s,1H),9.26-8.90(m,2H),8.50(s,2H),8.06(s,1H),7.88(d,J=7.0Hz,1H),7.75(s ,1H),7.55(d,J=8.8Hz,1H),7.01(t,J=55.1Hz,1H),6.46-6.39(m,1H),3.70(s,3H).LC / MS(ESI)(m / z):543[M+H] + .

[0767] Example 54: 2"-(difluoromethyl)-5"-methoxy-N-(thiazolo[4,5-b]pyridin-2-yl)-[2,2':4', 4 ” -terpyridine]-5'-carboxamide

[0768]

[0769] Step 1: Benzyl 2"-(difluoromethyl)-5"-methoxy-[2,2':4',4"-terpyridine]-5'-carboxylate

[0770] Under nitrogen protection at room temperature, [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (10 mg, 0.012 mmol) was added to a solution of 6-chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid benzyl ester (100 mg, 0.25 mol) and 2-(tri-n-butyltinyl)pyridine (137 mg, 0.37 mol) in 1,4-dioxane (3 mL), and the mixed solution was replaced with nitrogen three times, and stirred at 100°C under nitrogen protection overnight. The reaction solution was cooled to room temperature, diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 1-20% ethyl acetate) to obtain the title compound (yellow solid, 90 mg, yield 81%). LC / MS(ESI)m / z:448[M+H] + .

[0771] Step 2: 2"-(Difluoromethyl)-5"-methoxy-[2,2':4',4"-terpyridine]-5'-carboxylic acid

[0772] At room temperature, 2"-(difluoromethyl)-5"-methoxy-[2,2':4',4"-terpyridine]-5'-carboxylic acid benzyl ester (90 mg, 0.2 mmol) and tetrahydrofuran (3 mL) were added to a reaction flask, followed by a solution of lithium hydroxide hydrate (25 mg, 0.6 mmol) in water (1 mL). The reaction mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to remove tetrahydrofuran, and the aqueous phase was washed twice with dichloromethane. The aqueous phase was cooled to 0°C, and the pH value was adjusted to ~3 with 1N hydrochloric acid. A white solid precipitated, which was filtered and the filter cake was dried under reduced pressure to obtain the title compound (50 mg, white solid, yield 69%). LC / MS (ESI) m / z: 358 [M+H] + .

[0773] Step 3: 2"-(Difluoromethyl)-5"-methoxy-N-(thiazolo[4,5-b]pyridin-2-yl)-[2,2':4',4"- terpyridine]-5'-carboxamide

[0774] At room temperature, thiazolo[4,5-b]pyridin-2-amine (9 mg, 0.056 mmol), 2"-(difluoromethyl)-5"-methoxy-[2,2':4',4"-terpyridine]-5'-carboxylic acid (20 mg, 0.056 mmol) and N-methylimidazole (13 mg, 0.16 mmol) were dissolved in acetonitrile (2 mL). After stirring at 70°C for one minute, N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (24 mg, 0.084 mmol) was added to the reaction solution, and then the reaction solution was stirred at 70°C for 3 hours. After the reaction was complete, the residue was filtered and purified by preparative HPLC (YMC-Actus Triart C18 250*21 mm, 30-95% methanol in H2O solution containing 0.1% FA) to give the title compound (yellow solid, 15 mg, yield 55.5%). 1 HNMR(400MHz,DMSO-d6)δ13.40(s,1H),9.13(s,1H),8.77-8.74(m,1H),8.60-8.57(m,1H),8.54-8.50(m,2H),8.47-8.43(m,2H),8 .08-8.03(m,1H),7.86(s,1H),7.59-7.55(m,1H),7.36-7.32(m,1H),7.18-6.89(m,1H),3.72(s,3H).LC / MS(ESI)(m / z):491[M+H] + .

[0775] Example 55: 2'-(Difluoromethyl)-6-(4,5-dimethyl-6-oxopyrimidin-1(6H)-yl)-5'-methoxy-N- (Thiazolo[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-carboxamide

[0776]

[0777] Step 1: 2'-(Difluoromethyl)-6-(4,5-dimethyl-6-oxopyrimidin-1(6H)-yl)-5'-methoxy-[4,4'- [Bipyridine]-3-carboxylic acid benzyl ester

[0778] Under nitrogen protection, 6-chloro-2'-(difluoromethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid benzyl ester (300 mg, 0.74 mmol), 5,6-dimethylpyrimidin-4(3H)-one (110 mg, 0.89 mmol), cuprous iodide (71 mg, 0.37 mmol), 8-hydroxyquinoline (30 mg, 0.22 mmol) and potassium carbonate (204 mg, 1.48 mmol) were dissolved in dimethyl sulfoxide (6 mL) and stirred at 100 ° C for 2 hours under nitrogen protection. After the reaction was complete, the reaction solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 30%-70% ethyl acetate) to obtain the title compound (200 mg, white solid, yield: 54.7%). LC / MS(ESI)m / z:493[M+H] + .

[0779] Step 2: 2'-(Difluoromethyl)-6-(4,5-dimethyl-6-oxopyrimidin-1(6H)-yl)-5'-methoxy-[4,4'- [Bipyridine]-3-carboxylic acid

[0780] At room temperature, 2'-(difluoromethyl)-6-(4,5-dimethyl-6-oxopyrimidine-1(6H)-yl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid benzyl ester (200 mg, 0.4 mmol) and tetrahydrofuran (3 mL) were added to a reaction flask, followed by a solution of lithium hydroxide hydrate (50 mg, 1.2 mmol) in water (1 mL), and the reaction mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to remove tetrahydrofuran, and the aqueous phase was washed twice with dichloromethane. The aqueous phase was cooled to 0°C, and the pH value was adjusted to ~3 with 1N hydrochloric acid. A white solid precipitated, which was filtered and the filter cake was dried under reduced pressure to obtain the title compound (70 mg, white solid, yield 43%). LC / MS (ESI) m / z: 403 [M+H] + .

[0781] Step 3: 2'-(Difluoromethyl)-6-(4,5-dimethyl-6-oxopyrimidin-1(6H)-yl)-5'-methoxy-N-(thiazole)- oxazolo[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-carboxamide

[0782] At room temperature, thiazolo[4,5-b]pyridin-2-amine (18 mg, 0.12 mmol), 2"-(difluoromethyl)-5"-methoxy-[2,2':4',4"-bipyridine]-5'-carboxylic acid (50 mg, 0.12 mmol) and N-methylimidazole (26 mg, 0.32 mmol) were dissolved in acetonitrile (2 mL). After stirring at 70°C for one minute, N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (48 mg, 0.16 mmol) was added to the reaction solution, and then the reaction solution was stirred at 70°C for 3 hours. After the reaction was complete, the residue was filtered and purified by preparative HPLC (YMC-Actus Triart C18 250*21 mm, 20-95% methanol in H2O and 0.1% FA) to give the title compound (yellow solid, 10 mg, yield 15%). 1 H NMR (400MHz, DMSO-d6) δ13.48(s,1H),9.06(s,1H),8.60(d,J=3.9Hz,1H),8.55(s,1H),8.51(s,1H),8.49-8.45(m,1H),8.02(s, 1H),7.77(s,1H),7.36-7.34(m,1H),7.02(t,J=55.1Hz,1H),3.71(s,3H),2.33(s,3H),2.04(s,3H).LC / MS(ESI)(m / z):536[M+H] + .

[0783] The compounds of the examples in Table 4 were synthesized using commercially available raw materials and referring to the synthesis steps of Example 55.

[0784] Table 4:

[0785]

[0786]

[0787] Example 61: 2"-(difluoromethyl)-3-fluoro-5"-methoxy-N-(6-methylthiazolo[5,4]pyridin-2-yl)- 2-Oxo-2H-[1,2':4',4"-bipyridine]-5'-carboxamide

[0788]

[0789] Step 1: tert-Butyl (6-chlorothiazolo[5,4]pyridin-2-yl)carbamate

[0790] Under an ice-water bath, 6-chlorothiazolyl[5,4-c]pyridin-2-amine (500 mg, 2.70 mmol) was dissolved in tetrahydrofuran (10 mL), 4-dimethylaminopyridine (90 mg, 0.27 mmol) and di-tert-butyl dicarbonate (706 mg, 3.24 mmol) were added in sequence, and the reaction solution was stirred at 50 ° C for 3 hours. The reaction solution was diluted with ethyl acetate, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-20% ethyl acetate) to obtain the title compound (white solid, 400 mg, yield 52%). LC / MS (ESI) m / z: 286.0 [M+H] + .

[0791] Step 2: tert-Butyl (6-methylthiazolo[5,4]pyridin-2-yl)carbamate

[0792] Under nitrogen protection, tert-butyl (6-chlorothiazolo[5,4]pyridin-2-yl)carbamate (100 mg, 0.35 mmol), 2,4,6-trimethyl-1,3,5,2,4,6-trimethoxytriborane (88 mg, 0.70 mmol) and potassium carbonate (145 mg, 1.05 mmol) were dissolved in dioxane (3 mL) and water (0.3 mL). After nitrogen replacement, Pd(dppf)Cl2 (12 mg, 0.02 mmol) was added. The reaction solution was stirred at 90 ° C for 16 hours under nitrogen protection. The reaction solution was diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10-20% ethyl acetate) to obtain the title compound (white solid, 40 mg, yield 43%). LC / MS(ESI)m / z:266[M+H] + .

[0793] Step 3: 6-Methylthiazo[5,4-c]pyridin-2-amine

[0794] At room temperature, tert-butyl (6-methylthiazolo[5,4]pyridin-2-yl)carbamate (40 mg, 0.15 mmol) was dissolved in 4N hydrochloric acid dioxane (3 mL) solution, and the reaction solution was stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure, and the residue was slurried with ethyl acetate to obtain the title compound (20 mg, light yellow solid, yield 80%). LC / MS (ESI) m / z: 166 [M+H] + .

[0795] Step 4: 2"-(Difluoromethyl)-3-fluoro-5"-methoxy-N-(6-methylthiazolo[5,4]pyridin-2-yl)-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0796] At room temperature, 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxylic acid (47 mg, 0.12 mmol), 6-methylthiazo[5,4-c]pyridine-2-amine hydrochloride (20 mg, 0.12 mmol) and N-methylimidazole (26 mg, 0.317 mmol) were dissolved in acetonitrile (2 mL) and N,N-dimethylformamide (0.5 mL). After stirring at 70°C for five minutes, N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (45 mg, 0.16 mmol) was added to the reaction solution. The reaction solution was basically dissolved, and then the reaction solution was stirred at 70°C for 1 hour. The reaction solution was filtered and the filtrate was purified by preparative HPLC (YMC-ActusTriart C18 250*21 mm, 30-100% methanol in H2O containing 0.1% FA) to afford the title compound (3 mg, white solid, 4.7% yield). 1 H NMR (400MHz, DMSO-d6) δ9.33(s,1H),9.09(s,1H),8.52(s,1H),8.13(s,1H),8.03(s,1H),7.88(d,J=7.1Hz,1H),7.80(s, 1H),7.61-7.55(m,1H),7.02(t,J=55.0Hz,1H),6.47-6.41(m,1H),3.70(s,3H),2.71(s,3H).LC / MS(ESI)(m / z):539[M+H] + .

[0797] Example 62: 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-N-(6-(trifluoromethyl)thiazol[5, 4-c]pyridin-2-yl)-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0798]

[0799] Step 1: 5-Bromo-2-(trifluoromethyl)pyridin-4-amine

[0800] 2-(Trifluoromethyl)pyridin-4-amine (3g, 15.7mmol) was dissolved in dichloromethane (30mL), N-bromosuccinimide (2.20g, 12.3mmol) was added, and the reaction solution was stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10-20% ethyl acetate) to obtain the title compound (white solid, 2.62g, yield 88.2%). LC / MS (ESI) m / z: 241.0 [M+H] + .

[0801] Step 2: N-((5-bromo-2-(trifluoromethyl)pyridin-4-yl)aminomethylthio)benzamide

[0802] At room temperature, 5-bromo-2-(trifluoromethyl)pyridin-4-amine (2.62 g, 10.9 mmol) was dissolved in acetone (30 mL), and benzoyl isothiocyanate (3.2 mL, 21.8 mmol) was added. The reaction solution was stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure, and the residue was diluted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 20-40% ethyl acetate) to obtain the title compound (yellow solid, 2.2 g, yield 50.1%). LC / MS (ESI) m / z: 404.0 [M+H] + .

[0803] Step 3: 1-(5-bromo-2-(trifluoromethyl)pyridin-4-yl)thiourea

[0804] At room temperature, N-((5-bromo-2-(trifluoromethyl)pyridin-4-yl)aminomethylthio)benzamide (500 mg, 1.24 mmol) was dissolved in methanol (5 mL), 6N sodium hydroxide aqueous solution (0.5 mL) was added, and the reaction solution was stirred at 80°C for 2 hours. Saturated ammonium chloride solution was added to the reaction solution, and a white solid precipitated. The filter cake was filtered, washed with water, and dried under reduced pressure to obtain the title compound (white solid, 260 mg, yield 70%). LC / MS (ESI) m / z: 300.0 [M+H] + .

[0805] Step 4: 6-(Trifluoromethyl)thiazo[5,4-c]pyridin-2-amine

[0806] Under nitrogen protection, 1-(5-bromo-2-(trifluoromethyl)pyridin-4-yl)thiourea (100 mg, 0.33 mmol) was dissolved in dimethyl sulfoxide (3 mL), and then L-proline (8 mg, 0.069 mmol), cesium carbonate (217 mg, 0.666 mmol) and cuprous iodide (6 mg, 0.032 mmol) were added in sequence. The reaction solution was stirred at 70 ° C for 16 hours under nitrogen protection. The reaction solution was filtered through diatomaceous earth and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (eluent: water / acetonitrile, gradient: 20-50% acetonitrile) to obtain the title compound (white solid, 15 mg, yield 20.5%). LC / MS (ESI) m / z: 220.1 [M+H] + .

[0807] Step 5: 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-N-(6-(trifluoromethyl)thiazolo[5,4- c]pyridin-2-yl)-2H-[1,2':4',4"-terpyridine]-5'-carboxamide

[0808] At room temperature, 2"-(difluoromethyl)-3-fluoro-5"-methoxy-2-oxo-2H-[1,2':4',4"-terpyridine]-5'-carboxylic acid (20 mg, 0.051 mmol), 6-(trifluoromethyl)thiazo[5,4-c]pyridine-2-amine (15 g, 0.07 mmol) and N-methylimidazole (17 mg, 0.207 mmol) were dissolved in acetonitrile (5 mL) and N,N-dimethylformamide (0.5 mL). After stirring at 70°C for five minutes, N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (29 mg, 0.11 mmol) was added to the reaction solution. The reaction solution was basically dissolved, and then the reaction solution was stirred at 70°C for 2 hours. The reaction solution was filtered and purified by preparative HPLC (YMC-Actus TriartC18 250*21 mm, 30-95% methanol in H2O solution containing 0.1% FA) to give the title compound (4.21 mg, white solid, yield 13.9%). 1 H NMR(400MHz,DMSO-d6)δ13.79(s,1H),9.18(s,1H),9.12(s,1H),8.48(s,1H),8.01(s,1H),7.99(s,1H),7.90-7.86(m,1 H),7.71(s,1H),7.60-7.53(m,1H),7.00(t,J=55.1Hz,1H),6.45-6.37(m,1H),3.69(s,3H).LC / MS(ESI)(m / z):593[M+H] + .

[0809] Effect Example

[0810] Experimental methods:

[0811] 1. Polθ inhibitor biochemical activity detection (ADP Glo assay)

[0812] The N-terminus of Polθ protein contains a helicase domain with ATPase activity, which can hydrolyze ATP into ADP. TM Kinase Assay, Promega, V9102) was used to analyze the ATPase activity of Polθ protein and the inhibitory effect of small molecule compounds on the protein. The specific detection method is as follows:

[0813] 1) Purify the helicase domain of Polθ protein using insect system to obtain protein with purity >90%. Order ssDNA (5'-CCAGTGAATTGTTGCTCGGTACCTGCTAAC-3', Hangzhou Youkang Biotechnology Co., Ltd.) as substrate of Polθ protein; prepare reaction buffer containing 10mM DTT (Dithiothreitol), 20mM MgCl2, Tris-HCl pH7.5;

[0814] 2) Prepare 2x ssDNA-Polθ premix and perform the reaction in a 384-well plate. Set up a control group with only buffer and add the premix to the remaining groups. Use an automatic pipette (Thermo, Multidrop 8) to add the compound, starting at 500 nM and diluting at a 1 / 3 dilution ratio. Set up 9 detection points in total, with 2 replicates per group;

[0815] 3) Prepare 2xATP solution, add equal volume of 2xATP solution to all wells, and let stand at room temperature for 60 minutes;

[0816] 4) According to the Promega reagent instructions, ADP-Glo ​​Detection Reagent was added to the reaction system and allowed to stand at room temperature for 60 min;

[0817] 5) According to the Promega reagent instructions, Kinase Detection Reagent was added to the reaction system, and the reaction was allowed to stand at room temperature for 60 min. The chemiluminescent signal was detected using an ELISA reader (Thermo, VarioskanLUX), and the reading interval for each well was set to 1000 ms;

[0818] Data analysis was performed on the measurement results: the CV% of the control group test results should be less than 10%, and the z' value should be greater than 0.5. The data that met the above quality control results were used to calculate the inhibition rate of the compound (inhibition rate (%) = 100*(control group average value - experimental group) / (control group average value - buffer control group average value). GraphPad Prism8 was used to perform nonlinear regression fitting of the inhibition rate curve of the compound and obtain the IC50 value.

[0819] 2. Polθ inhibitor cell viability assay

[0820] CellTiter Glo reagent (CellTiter- Luminescent Cell Viability Assay, Promega, G7573) was used to test the in vitro effectiveness of the inhibitors for cell viability, i.e., the commonly used CTG test. The specific test method is as follows:

[0821] 1) Culture DLD1 wild-type (ATCC, CCL-221) and DLD1-BRCA2- / - cells. Digest the cells with trypsin (0.25% Trypsin-EDTA, Hyclone) one day before the start of the test, centrifuge at 1000 rpm for 3 minutes, and collect the cells. Count the cells using a counter (Shanghai Mengwei Biomedical Technology Co., Ltd., SmartCell600A.SC1006) and inoculate them into 96-well white culture plates according to the appropriate inoculation ratio.

[0822] 2) 24 hours after cell plating, the cells were treated with drugs, which was recorded as Day 0. An automatic pipette (Thermo, Multidrop8) was used to add compounds. The plate was set as a 96-well plate, the starting concentration was set to 30 μM, and the dilution ratio was 1 / 3. A total of 9 detection points were set, with 2 replicates in each group. The cells were cultured in a 37°C, 5% CO2 incubator;

[0823] 3) Change the medium twice on Day 3 and Day 7, and add the compound according to step 2);

[0824] 4) On Day 10, remove the cell culture plate, add an equal volume of CTG reagent (the CTG reagent needs to be restored to temperature in advance and premixed according to the reagent instructions), gently mix on a constant temperature mixer (Hangzhou Aosheng Instrument Co., Ltd., MSC-100) for 10 min (speed 300), and perform chemiluminescence detection using an enzyme reader (Thermo, VarioskanLUX);

[0825] 5) Data analysis of the measurement results: The CV% of the control group test results should be less than 20%, and the z' value should be greater than 0.5. The data that meet the above quality control results are used to calculate cell survival (inhibition rate (%) = 100*(control group average value-experimental group) / (control group average value-culture solution control group average value). GraphPad Prism8 is used to perform nonlinear regression fitting of the inhibition rate curve of the compound and obtain the IC 50 value.

[0826] The test showed that the example compounds of the present application had a strong proliferation inhibitory effect on DLD1 BRCA2- / - cells, and a very weak proliferation inhibitory effect on DLD1 wild-type cells, indicating that the example compounds of the present application had good selectivity for the proliferation inhibitory effect on the two types of cells.

[0827] Data list:

[0828] NT = not tested;

[0829] Specific data of biochemical experiments and cell survival detection experiments:

[0830]

[0831]

Claims

1. A compound as shown in formula I, a pharmaceutically acceptable salt thereof or an isotope compound thereof, characterized in that: in: m is 0, 1, 2 or 3; n is 1, 2 or 3; Ring A is a benzene ring, a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatoms in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 1 is unsubstituted or substituted with one or more R 1-1 substituted 6-12 membered aryl, unsubstituted or replaced by one or more R 1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 1-3 Substituted 4-12 membered heterocycloalkenyl; the heteroatoms in the 5-12 membered heteroaryl and the 4-12 membered heterocycloalkenyl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 , R 1-2 and R 1-3 are independently deuterium, halogen, cyano, amino, hydroxyl, oxo, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 1-1-3 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 1-1-4 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 1-1-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 1-1-6 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 1-1-13 Substituted 4-12 membered heterocycloalkenyl, -COOR 1-1-7 、-C(O)R 1-1-8 、-C(O)N(R 1-1-9 )2. or N(R 1-1-12 )2; the heteroatoms in the 4-12 membered heterocyclic group and the 4-12 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 and R 1-1-13 are independently deuterium, hydroxyl, cyano or halogen; Each R 1-1-7 , R 1-1-8 , R 1-1-9 and R 1-1-12 are independently hydrogen or C1-C6 alkyl; Each R 1-1-10 and R 1-1-11 are independently hydroxyl or C1-C6 alkyl; Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-2 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-4 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -O-5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12-membered heterocyclyl, 4-12-membered heterocycloalkenyl, 5-12-membered heteroaryl and -O-5-12-membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-1-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-4 , R 2-5 and R 2-9 are independently oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2 -5-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5-6 Substituted 4-12 membered heterocyclic group, -N(R 2-5-3 )2. The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-6 are independently oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-5-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-6-2 Substituted 4-12 membered heterocyclic group, -N(R 2-6-3 )2. The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-7 are independently hydrogen, unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-8-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-8 are independently unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-8-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-1 and R 2-1-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-1-3 are independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-4-1 , R 2-5-3 and R 2-6-3 are independently hydrogen or C1-C6 alkyl; Each R 2-5-1 , R 2-5-2 and R 2-7-1 are independently deuterium, hydroxyl, cyano or halogen; Each R 2-5-4 and R 2-7-3 are independently C1-C6 alkyl or 3-6 membered cycloalkyl; Each R 2-5-5 , R 2-5-6 and R 2-6-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-6-1 are independently hydroxy, cyano, halogen or C1-C6 alkoxy; Each R 2-7-2 and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -N(R b-1-3 )2、-C(O)N(R b-1-4) 2. -COOR b-1-5 , Each R b-1-1 and R b-1-2 are independently deuterium, hydroxyl, halogen or -NR b-1-1-1 R b-1-1-1 ; Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or C1-C6 alkyl; Each R b-1-6 are independently hydroxyl or C1-C6 alkyl; Each R b-1-8 are independently hydroxyl or C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein in the 4-6 membered heterocyclic group, when the number of heteroatom groups is 1, the heteroatom group is P(O); when the number of heteroatoms or heteroatom groups is 2 or 3, one of the heteroatom groups is P(O), and the remaining heteroatoms are independently selected from one or two of N, O and S; Each R b-1-1-1 are independently hydrogen, C1-C6 alkyl or -C(O)R b-1-1-1-1 ; R b-1-1-1-1 is a C1-C6 alkyl group; Each R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-3 substituted 4-12 membered cycloalkenyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 、-NH(CH2) p R 5 、-O(CH2) q R 6 , unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl or unsubstituted or with one or more R 3-8 Substituted-OR 7 The heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; p is 0, 1, 2 or 3; q is 1, 2, or 3; Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl, halogen, cyano, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, oxo, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-N(R 3 -4-2 )2. or The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5 and R 3-6 are independently deuterium, hydroxyl, halogen, cyano, amino, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-NR 3-4-2 R 3-4-2 , The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen or C1-C6 alkyl; Each R 3-2-3 , R 3-5-1 and R 3-5-2 are independently hydroxyl or C1-C6 alkyl; Each R 3-2-2 are independently hydroxy or halogen; R 3-4-1 is hydroxyl, amino or C1-C6 alkyl; R 4 is unsubstituted or substituted with one or more R 4-1 substituted 4-6 membered heterocyclic group or unsubstituted or replaced by one or more R 4-2 Substituted C1-C6 alkyl; the heteroatom in the 4-6 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 4-1 are independently hydroxyl groups; Each R 4-2 are independently hydroxy or halogen; R 5 is unsubstituted or substituted with one or more R 5-1 Substituted 3-6 membered cycloalkyl; R 6 is unsubstituted or substituted with one or more R 6-1 Substituted 3-6 membered cycloalkyl; Each R 5-1 and R 6-1 are independently hydroxyl groups; R 7 is a 3-6 membered cycloalkyl group; And the compound shown in formula I is not 2. The compound of formula I according to claim 1, its pharmaceutically acceptable salt or its isotope compound, characterized in that: in: m is 0, 1, 2 or 3; n is 1, 2 or 3; Ring A is a benzene ring, a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatoms in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 1 is unsubstituted or substituted with one or more R 1-1 substituted 6-12 membered aryl, unsubstituted or replaced by one or more R 1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 1-3 Substituted 4-12 membered heterocycloalkenyl; the heteroatoms in the 5-12 membered heteroaryl and the 4-12 membered heterocycloalkenyl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 , R 1-2 and R 1-3 are independently deuterium, halogen, cyano, amino, hydroxyl, oxo, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 1-1-3 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 1-1-4 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 1-1-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 1-1-6 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 1-1-13 Substituted 4-12 membered heterocycloalkenyl, -COOR 1-1-7 、-C(O)R 1-1-8 、-C(O)N(R 1-1-9 )2. or N(R 1-1-12 )2; the heteroatoms in the 4-12 membered heterocyclic group and the 4-12 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 and R 1-1-13 are independently deuterium, hydroxyl, cyano or halogen; Each R 1-1-7 , R 1-1-8 , R 1-1-9 and R 1-1-12 are independently hydrogen or C1-C6 alkyl; Each R 1-1-10 and R 1-1-11 are independently hydroxyl or C1-C6 alkyl; Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-1 Substituted C2-C6 alkyl, unsubstituted or replaced by one or more R 2-2 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-4 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -O-5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12-membered heterocyclyl, 4-12-membered heterocycloalkenyl, 5-12-membered heteroaryl and -O-5-12-membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-1-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-4 , R 2-5 and R 2-9 are independently oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2 -5-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5-6 Substituted 4-12 membered heterocyclic group, -N(R 2-5-3 )2. The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-6 are independently oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-5-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-6-2 Substituted 4-12 membered heterocyclic group, -N(R 2-6-3 )2. The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-7 are independently hydrogen, unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-8-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-8 are independently unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-8-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-1 and R 2-1-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-1-3 are independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-4-1 , R 2-5-3 and R 2-6-3 are independently hydrogen or C1-C6 alkyl; Each R 2-5-1 , R 2-5-2 and R 2-7-1 are independently deuterium, hydroxyl, cyano or halogen; Each R 2-5-4 and R 2-7-3 are independently C1-C6 alkyl or 3-6 membered cycloalkyl; Each R 2-5-5 , R 2-5-6 and R 2-6-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-6-1 are independently hydroxy, cyano, halogen or C1-C6 alkoxy; Each R 2-7-2 and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -N(R b-1-3 )2、-C(O)N(R b-1-4) 2. -COOR b-1-5 , Each R b-1-1 and R b-1-2 are independently deuterium, hydroxyl, halogen or -NR b-1-1-1 R b-1-1-1 ; Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or C1-C6 alkyl; Each R b-1-6 are independently hydroxyl or C1-C6 alkyl; Each R b-1-8 are independently hydroxyl or C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein in the 4-6 membered heterocyclic group, when the number of heteroatom groups is 1, the heteroatom group is P(O); when the number of heteroatoms or heteroatom groups is 2 or 3, one of the heteroatom groups is P(O), and the remaining heteroatoms are independently selected from one or two of N, O and S; Each R b-1-1-1 are independently hydrogen, C1-C6 alkyl or -C(O)R b-1-1-1-1 ; R b-1-1-1-1 is a C1-C6 alkyl group; R 3 is hydrogen, unsubstituted or replaced by one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-3 substituted 4-12 membered cycloalkenyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 、-NH(CH2) p R 5 、-O(CH2) q R 6 , unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl or unsubstituted or with one or more R 3-8 Substituted-OR 7 The heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; p is 0, 1, 2 or 3; q is 1, 2, or 3; Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl, halogen, cyano, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, oxo, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-N(R 3 -4-2 )2. The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5 and R 3-6 are independently deuterium, hydroxyl, halogen, cyano, amino, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-NR 3-4-2 R 3-4-2 , The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen or C1-C6 alkyl; Each R 3-2-3 , R 3-5-1 and R 3-5-2 are independently hydroxyl or C1-C6 alkyl; Each R 3-2-2 are independently hydroxy or halogen; R 3-4-1 is hydroxyl, amino or C1-C6 alkyl; R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group; the heteroatom in the 4-6 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 4-1 are independently hydroxyl groups; R 5 is unsubstituted or substituted with one or more R 5-1 Substituted 3-6 membered cycloalkyl; R 6 is unsubstituted or substituted with one or more R 6-1 Substituted 3-6 membered cycloalkyl; Each R 5-1 and R 6-1 are independently hydroxyl groups; R 7 is a 3-6 membered cycloalkyl group; And the compound shown in formula I is not 3. The compound of formula I according to claim 1, its pharmaceutically acceptable salt or its isotope compound, characterized in that: in: m is 0, 1, 2 or 3; n is 1, 2 or 3; Ring A is a benzene ring, a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatoms in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 1 is unsubstituted or substituted with one or more R 1-1 substituted 6-12 membered aryl, unsubstituted or replaced by one or more R 1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 1-3 Substituted 4-12 membered heterocycloalkenyl; the heteroatoms in the 5-12 membered heteroaryl and the 4-12 membered heterocycloalkenyl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 , R 1-2 and R 1-3 are independently deuterium, halogen, cyano, amino, hydroxyl, oxo, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 1-1-3 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 1-1-4 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 1-1-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 1-1-6 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 1-1-13 Substituted 4-12 membered heterocycloalkenyl, -COOR 1-1-7 、-C(O)R 1-1-8 、-C(O)N(R 1-1-9 )2. N(R 1-1-12 )2; the heteroatoms in the 4-12 membered heterocyclic group and the 4-12 membered heterocycloalkenyl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 and R 1-1-13 are independently deuterium, hydroxyl, cyano or halogen; Each R 1-1-7 , R 1-1-8 , R 1-1-9 and R 1-1-12 are independently hydrogen or C1-C6 alkyl; Each R 1-1-10 and R 1-1-11 are independently hydroxyl or C1-C6 alkyl; Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, one or more R 2-2 Substituted C2-C6 alkenyl, substituted by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-4 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -O-5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12-membered heterocyclyl, 4-12-membered heterocycloalkenyl, 5-12-membered heteroaryl and -O-5-12-membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-1-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 4-12 membered heterocyclic group and the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-4 Independently Each R 2-5 and R 2-9 are independently oxo, halogen, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, 3-6 membered cycloalkyl, 4-12 membered heterocyclic group, -N(R 2-5-3 )2 or The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-6 are independently oxo, cyano, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-6-2 Substituted 4-12 membered heterocyclic group or -N(R 2-6-3 )2; the heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-7 are independently hydrogen, unsubstituted or substituted with one or more R 2-7-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-7-2 Substituted 5-12 membered heteroaryl or The heteroatoms in the 5-12 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-8 are independently unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-1 and R 2-1-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-1-3 are independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-4-1 are independently hydrogen or C1-C6 alkyl; Each R 2-5-1 and R 2-5-2 are independently deuterium, hydroxyl, cyano or halogen; Each R 2-5-3 are independently hydrogen or C1-C6 alkyl; Each R 2-5-4 are independently C1-C6 alkyl; Each R 2-6-1 are independently cyano, halogen or C1-C6 alkoxy; Each R 2-6-2 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-6-3 are independently hydrogen or C1-C6 alkyl; Each R 2-7-1 are independently deuterium, hydroxyl, cyano or halogen; Each R 2-7-2 are independently C1-C6 alkyl; Each R 2-7-3 are independently 3-6 membered cycloalkyl; Each R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo, halogen, cyano, hydroxyl, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -N(R b-1-3 )2、-C(O)N(R b-1-4) 2. -COOR b-1-5 , Each R b-1-1 and R b-1-2 are independently deuterium, hydroxyl, halogen or -NR b-1-1-1 R b-1-1-1 ; Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or C1-C6 alkyl; Each R b-1-6 are independently hydroxyl or C1-C6 alkyl; Each R b-1-8 are independently hydroxyl or C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein in the 4-6 membered heterocyclic group, when the number of heteroatom groups is 1, the heteroatom group is P(O); when the number of heteroatoms or heteroatom groups is 2 or 3, one of the heteroatom groups is P(O), and the remaining heteroatoms are independently selected from one or two of N, O and S; Each R b-1-1-1 are independently hydrogen, C1-C6 alkyl or -C(O)R b-1-1-1-1 ; R b-1-1-1-1 is a C1-C6 alkyl group; R 3 is hydrogen, unsubstituted or replaced by one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-3 substituted 4-12 membered cycloalkenyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 、-NH(CH2) p R 5 、-O(CH2) q R 6 , unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl or unsubstituted or with one or more R 3-8 Substituted-OR 7 The heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; p is 0, 1, 2 or 3; q is 1, 2, or 3; Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl, halogen, cyano, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, oxo, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-N(R 3 -4-2 )2. The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5 and R 3-6 are independently deuterium, hydroxyl, halogen, cyano, amino, -NHC(O)R 3-2-1 , unsubstituted or replaced by one or more R 3-2-2 Substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -C(O)NH2, unsubstituted or replaced by one or more R 3-2-3 Substituted 3-6 membered cycloalkyl, 4-6 membered heterocyclic group, -S(O)2R 3-4-1 、-NR 3-4-2 R 3-4-2 , The heteroatoms in the 4-6 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen or C1-C6 alkyl; Each R 3-2-3 , R 3-5-1 and R 3-5-2 are independently hydroxyl or C1-C6 alkyl; Each R 3-2-2 are independently hydroxy or halogen; R 3-4-1 is hydroxyl, amino or C1-C6 alkyl; R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group; the heteroatom in the 4-6 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 4-1 are independently hydroxyl groups; R 5 is unsubstituted or substituted with one or more R 5-1 Substituted 3-6 membered cycloalkyl; R 6 is unsubstituted or substituted with one or more R 6-1 Substituted 3-6 membered cycloalkyl; Each R 5-1 and R 6-1 are independently hydroxyl groups; R 7 is a 3-6 membered cycloalkyl group; And the compound shown in formula I is not 4. The compound of formula I according to claim 1, its pharmaceutically acceptable salt or its isotope compound, characterized in that: The compound shown in formula I is a compound shown in formula I', 5. The compound of formula I according to claim 1, its pharmaceutically acceptable salt or its isotope compound, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) In ring A, the 5-6 membered heteroaromatic ring is a 6 membered heteroaromatic ring, the heteroatom in the 6 membered heteroaromatic ring is N, the number of heteroatoms is 1, and preferably a pyridine ring, for example (2) In ring A, the 5-6 membered heterocycloalkenyl is a 6 membered heterocycloalkenyl, the heteroatom in the 6 membered heterocycloalkenyl is N, the number of heteroatoms is 1, preferably a pyridone group, for example (3) In ring A, the oxo-substituted 5-6-membered heterocycloalkenyl group is an oxo-substituted 5-6-membered heterocycloalkenyl group containing 1 or 2 carbon-carbon double bonds; (4)R 1 wherein the 6-12 membered aryl group is a 6-10 membered aryl group, preferably a phenyl group or a naphthyl group, more preferably a phenyl group; (5)R 1 In the above, the 5-12 membered heteroaryl group is a 5-10 membered heteroaryl group, the heteroatom in the 5-10 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2; the 5-12 membered heteroaryl group is preferably a 5-6 membered heteroaryl group; more preferably For example (6)R 1 In the above, the 4-12 membered heterocycloalkenyl group is a 4-6 membered heterocycloalkenyl group, the heteroatom in the 4-6 membered heterocycloalkenyl group is N, the number of heteroatoms is 1, and dihydropyridyl is preferred, for example (7)R 1 In the above, the 4-12 membered heterocycloalkenyl group is a 4-12 membered heterocycloalkenyl group containing at least 2 carbon-carbon double bonds; (8) Each R 1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine; (9) Each R 1-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, and more preferably a methyl group; (10) Each R 1-1 wherein the C1-C6 alkoxy group is a C1-C4 alkoxy group, which may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group; (11) Each R 1-2 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine; (12) Each R 1-2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group; (13) Each R 1-2 wherein the C1-C6 alkoxy group is a C1-C4 alkoxy group, which may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group; (14) Each R 1-2 wherein the 3-6 membered cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopropyl or cyclobutyl; (15) Each R 1-2 wherein the 4-12 membered heterocyclic group is a 4-12 membered monocyclic heterocyclic group or a 4-12 membered polycyclic heterocyclic group; the 4-12 membered monocyclic heterocyclic group is preferably a 4-7 membered monocyclic heterocyclic group, the heteroatom in the 4-7 membered monocyclic heterocyclic group is preferably N and / or O, the number of heteroatoms is preferably 1, and more preferably The 4-12 membered polycyclic heterocyclic group is preferably a 4-10 membered polycyclic heterocyclic group, the heteroatom in the 4-10 membered polycyclic heterocyclic group is preferably O or N, the number of heteroatoms is preferably 1, and more preferably (16) Each R 1-2 wherein the 4-12 membered heterocycloalkenyl group is a 4-12 membered monocyclic heterocycloalkenyl group or a 4-12 membered polycyclic heterocycloalkenyl group; the 4-12 membered polycyclic heterocycloalkenyl group is preferably a 4-10 membered polycyclic heterocycloalkenyl group, the heteroatom in the 4-10 membered polycyclic heterocycloalkenyl group is preferably O or N, the number of heteroatoms is preferably 1, and more preferably (17) Each R 1-2 In the above, the 4-12 membered heterocycloalkenyl group contains 1 or 2 carbon-carbon double bonds; (18) Each R 1-3 wherein the C1-C6 alkoxy group is a C1-C4 alkoxy group, which may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group; (19) Each R 1-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example fluorine; (20) Each R 1-1-2 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (21) Each R 1-1-12 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (22) Each R 2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, and may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (23) Each R 2 In the above, the C2-C6 alkynyl group is a C2-C4 alkynyl group, which may be Best (24) Each R 2 wherein the 3-6 membered cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopropyl; (25) Each R 2 wherein the ring in the 4-12 membered heterocyclic group is a monocyclic ring, a spirocyclic ring, a fused ring or a bridged ring, the number of rings in the spirocyclic ring, the fused ring or the bridged ring may be 2, and the spirocyclic ring may be a 3-membered spiro 5-membered heterocyclic group, a 3-membered spiro 6-membered heterocyclic group, a 4-membered spiro 4-membered heterocyclic group, a 4-membered spiro 5-membered heterocyclic group, a 4-membered spiro 6-membered heterocyclic group, a 4-membered spiro 7-membered heterocyclic group, a 5-membered spiro 4-membered heterocyclic group, a 5-membered spiro 5-membered heterocyclic group, a 5-membered spiro 6-membered heterocyclic group, a 5-membered spiro 7-membered heterocyclic group, a 6-membered spiro 4-membered heterocyclic group The cyclic radical may be a 4-membered 5-membered heterocyclic radical, a 4-membered 6-membered heterocyclic radical, a 5-membered 5-membered heterocyclic radical, a 5-membered 6-membered heterocyclic radical or a 6-membered 6-membered heterocyclic radical; the bridging ring may be a 4-membered 5-membered heterocyclic radical, a 4-membered 6-membered heterocyclic radical, a 5-membered 6-membered heterocyclic radical or a 6-membered 6-membered heterocyclic radical; the heteroatoms in the 4-12-membered heterocyclic radical may be N and / or O, and the number of heteroatoms may be 1 or 2; preferably (26) Each R 2 In the above, the 4-12 membered heterocyclic group is a 4-12 membered monocyclic heterocyclic group or a 4-12 membered polycyclic heterocyclic group; the 4-12 membered monocyclic heterocyclic group is preferably a 4-7 membered monocyclic heterocyclic group, the heteroatom in the 4-7 membered monocyclic heterocyclic group is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2; the 4-12 membered polycyclic heterocyclic group is preferably a 4-10 membered polycyclic heterocyclic group, the heteroatom in the 4-10 membered polycyclic heterocyclic group is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2; (27) Each R 2 wherein the ring in the 4-12 membered heterocycloalkenyl ring is a monocyclic ring or a cyclic ring, the cyclic ring may be a 4-membered and 5-membered heterocycloalkenyl, a 4-membered and 6-membered heterocycloalkenyl, a 5-membered and 5-membered heterocycloalkenyl, a 5-membered and 6-membered heterocycloalkenyl or a 6-membered and 6-membered heterocycloalkenyl, the heteroatom in the 4-12 membered heterocycloalkenyl may be N, and the number of heteroatoms may be 1 or 2; preferably For example Another example (28) Each R 2 In the above, the 4-12 membered heterocycloalkenyl is a 4-12 membered monocyclic heterocycloalkenyl or a 4-12 membered polycyclic heterocycloalkenyl; the 4-12 membered monocyclic heterocycloalkenyl is preferably a 4-7 membered monocyclic heterocycloalkenyl, the heteroatom in the 4-7 membered monocyclic heterocycloalkenyl is preferably N, and the number of heteroatoms is preferably 1 or 2; the 4-12 membered polycyclic heterocycloalkenyl is preferably a 4-10 membered polycyclic heterocycloalkenyl, the heteroatom in the 4-10 membered polycyclic heterocycloalkenyl is preferably N, and the number of heteroatoms is preferably 1 or 2; (29) Each R 2 wherein the 5-12 membered heteroaryl group is a 5-12 membered monocyclic heteroaryl group or a 5-12 membered polycyclic heteroaryl group; the 5-12 membered monocyclic heteroaryl group is preferably a 5-6 membered monocyclic heteroaryl group, the heteroatom in the 5-6 membered monocyclic heteroaryl group is preferably N and / or O, and the number of heteroatoms is preferably 1, 2 or 3, and more preferably For example Another example The 5-12 membered polycyclic heteroaryl is preferably a 5-10 membered polycyclic heteroaryl, the heteroatoms in the 5-10 membered polycyclic heteroaryl are preferably N and / or O, and the number of heteroatoms is preferably 1, 2 or 3, and more preferably (30) Each R 2 wherein the -O-5-12-membered heteroaryl is an -O-5-6-membered heteroaryl, wherein the heteroatom in the 5-6-membered heteroaryl in the -O-5-6-membered heteroaryl is N and / or S, and the number of heteroatoms is 1 or 2, preferably (31) Each R 2-1 wherein the 5-12 membered heteroaryl group is a 5-6 membered heteroaryl group, the heteroatoms in the 5-6 membered heteroaryl group are N and / O, and the number of heteroatoms is 1, 2 or 3, preferably (32) Each R 2-3 In the embodiment, the 4-12 membered heterocyclic group is a 4-6 membered heterocyclic group, the heteroatom in the 4-6 membered heterocyclic group is O, the number of heteroatoms is 1, and preferably (33) Each R 2-3 wherein the 5-12 membered heteroaryl group is a 5-6 membered heteroaryl group, the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2, preferably (34) Each R 2-5 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group or a tert-butyl group; (35) Each R 2-6 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group; (36) Each R 2-6 In the embodiment, the 4-12 membered heterocyclic group is a 4-6 membered heterocyclic group, the heteroatom in the 4-6 membered heterocyclic group is N, the number of heteroatoms is 1, and preferably (37) Each R 2-7 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (38) Each R 2-7 wherein the 5-12 membered heteroaryl group is a 5-6 membered heteroaryl group, the heteroatom in the 5-6 membered heteroaryl group is N and / or S, and the number of heteroatoms is 1, 2 or 3, preferably (39) Each R 2-8 In the above, the 4-12 membered heterocyclic group is a 4-6 membered heterocyclic group, the heteroatom in the 4-6 membered heterocyclic group is N and / or O, the number of heteroatoms is 1 or 2, preferably (40) Each R 2-9 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine, for example fluorine; (41) Each R 2-9 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (42) Each R 2-9 wherein the C1-C6 alkoxy group is a C1-C4 alkoxy group, which may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group; (43) Each R 2-9 wherein the 3-6 membered cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclobutyl; (44) Each R 2-9 wherein the 4-12 membered heterocyclic group is a 4-12 membered monocyclic heterocyclic group or a 4-12 membered polycyclic heterocyclic group; the 4-12 membered monocyclic heterocyclic group is preferably a 4-6 membered monocyclic heterocyclic group, the heteroatom in the 4-6 membered monocyclic heterocyclic group is preferably N, the number of heteroatoms is preferably 1, and more preferably The 4-12 membered polycyclic heterocyclic group is preferably a 4-10 membered polycyclic heterocyclic group, the heteroatoms in the 4-10 membered polycyclic heterocyclic group are preferably N and / or O, the number of heteroatoms is preferably 1 or 2, and more preferably (45) Each R 2-1-2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (46) Each R 2-1-3 In the above, the 4-12 membered heterocyclic group is a 4-6 membered heterocyclic group, the heteroatom in the 4-6 membered heterocyclic group is N and / or O, the number of heteroatoms is 1 or 2, preferably (47) Each R 2-4-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (48) Each R 2-5-1 wherein the halogen is fluorine, halogen, bromine or iodine, preferably fluorine; (49) Each R 2-5-3 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (50), each R 2-5-4 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (51) Each R 2-6-1 wherein the halogen is fluorine, halogen, bromine or iodine, preferably fluorine; (52) Each R 2-6-1 wherein the C1-C6 alkoxy group is a C1-C4 alkoxy group, which may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group; (53) Each R 2-6-2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (54) Each R 2-6-3 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (55) Each R 2-7-2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (56) Each R 2-7-3 wherein the 3-6 membered cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclobutyl; (57) Each R 2-1-3-1 wherein the halogen is fluorine, halogen, bromine or iodine, preferably fluorine; (58) Each R 2-1-3-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (59) In ring B, the number of heteroatoms in the 5-20 membered heteroaromatic ring is 1, 2, 3 or 4, and the number of rings is 2 or 3; the 5-20 membered heteroaromatic ring is preferably a 5-15 membered heteroaromatic ring, and the 5-15 membered heteroaromatic ring is preferably a 5-membered 5-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 7-membered heteroaromatic ring, a 6-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring, a 5-membered 6-membered heteroaromatic ring or a 5-membered 6-membered 7-membered heteroaromatic ring; and further preferably For example (60) Each R b-1 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine; (61) Each R b-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (62) Each R b-1 wherein the C1-C6 alkoxy group is a C1-C4 alkoxy group, which may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group; (63) Each R b-1 wherein the -3-6-membered cycloalkyl in the -O-3-6-membered cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopropyl; (64) Each R b-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (65) Each R b-1-2 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (66) Each R b-1-4 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (67) Each R b-1-5 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (68) Each R b-1-6 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (69) Each R b-1-8 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (70) Each R b-1-8 The number of heteroatom groups in the 4-6 membered heterocyclic group is 1, and the heteroatom group is P(O), preferably (71)R 3 In the above, the 3-12-membered cycloalkyl group is a 3-6-membered cycloalkyl group, which may be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, preferably a cyclopropyl group or a cyclohexyl group; (72)R 3 wherein the 4-12 membered heterocycloalkyl is a 4-12 membered monocyclic heterocycloalkyl or a 4-12 membered polycyclic heterocycloalkyl; the 4-12 membered monocyclic heterocycloalkyl is preferably a 4-7 membered monocyclic heterocycloalkyl, the heteroatoms in the 4-7 membered monocyclic heterocycloalkyl are preferably one or more of N, O and S, the number of heteroatoms is preferably 1 or 2, and more preferably The 4-12 membered polycyclic heterocycloalkyl is preferably a 4-10 membered polycyclic heterocycloalkyl, the heteroatom in the 4-10 membered polycyclic heterocycloalkyl is preferably N or O, the number of heteroatoms is preferably 1, and more preferably (73)R 3 In the embodiment, the 4-12 membered cycloalkenyl group is a 4-12 membered monocyclic cycloalkenyl group or a 4-12 membered polycyclic cycloalkenyl group, and the 4-12 membered monocyclic cycloalkenyl group is preferably a 4-6 membered monocyclic cycloalkenyl group, and more preferably The 4-12 membered polycyclic cycloalkenyl is preferably a 4-10 membered polycyclic cycloalkenyl, more preferably (74)R 3 wherein the 4-12 membered heterocycloalkenyl group is a 4-12 membered monocyclic heterocycloalkenyl group or a 4-12 membered polycyclic heterocycloalkenyl group, the 4-12 membered monocyclic heterocycloalkenyl group is preferably a 4-6 membered monocyclic heterocycloalkenyl group, the heteroatom in the 4-6 membered monocyclic heterocycloalkenyl group is preferably N and / or O, the number of heteroatoms is preferably 1, and more preferably The 4-12 membered polycyclic heterocycloalkenyl is preferably a 4-10 membered polycyclic heterocycloalkenyl, more preferably (75)R 3 In the above, the 6-10 membered aryl group is phenyl or naphthyl, preferably phenyl; (76)R 3 wherein the 5-10 membered heteroaryl is a 5-10 membered monocyclic heteroaryl or a 5-10 membered polycyclic heteroaryl, the 5-10 membered monocyclic heteroaryl is preferably a 5-6 membered monocyclic heteroaryl, the heteroatom in the 5-6 membered monocyclic heteroaryl is preferably N and / or O, and more preferably For example The heteroatom in the 5-10 membered polycyclic heteroaryl is preferably N, and the number of heteroatoms is preferably 1 or 2. (77)R 3 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group or an isopropyl group, such as an isopropyl group; (78) Each R 3-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (79) Each R 3-1 wherein the C1-C6 alkoxy group is a C1-C4 alkoxy group, which may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group or a tert-butoxy group, preferably a methoxy group; (80) Each R 3-2 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (81) Each R 3-2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (82) Each R 3-4 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (83) Each R 3-6 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably chlorine; (84) Each R 3-6 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (85) Each R 3-7 In the 4-6 membered heterocyclic group, the heteroatom is O, the number of heteroatoms is 1, preferably (86) Each R 3-2-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (87) Each R 3-2-2 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (88) Each R 3-4-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (89) Each R 3-5-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (90) Each R 3-5-2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (91) Each R 4 The heteroatom in the 4-6 membered heterocyclic group is N or O, and the number of heteroatoms is 1, preferably and (92) each R 4 In the above, the C1-C6 alkyl group may be a C1-C4 alkyl group, or may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

6. The compound of formula I according to claim 1, its pharmaceutically acceptable salt or its isotope compound, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) m is 1; (2) n is 0 or 1; (3) Ring A is a benzene ring, a 6-membered heteroaromatic ring or an oxo-substituted 6-membered heterocycloalkenyl group; the heteroatom in the 6-membered heteroaromatic ring and the 6-membered heterocycloalkenyl group is N, and the number of heteroatoms is 1; (4)R 1 is unsubstituted or substituted with one or more R 1-1 Substituted phenyl, unsubstituted or replaced by one or more R 1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 1-3 substituted 4-12 membered heterocycloalkenyl; preferably unsubstituted or substituted by one or more R 1-1 Substituted phenyl or unsubstituted or with one or more R 1-2 Substituted 5-12 membered heteroaryl; for example, unsubstituted or substituted with one or more R 1-2 substituted 5-12 membered heteroaryl; (5) Each R 1-1 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 1-1-2 Substituted C1-C6 alkoxy, preferably halogen or unsubstituted or substituted by one or more R 1-1-2 Substituted C1-C6 alkoxy; (6) Each R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 1-1-5 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 1-1-6 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 1-1-13 Substituted 4-12 membered heterocycloalkenyl or N(R 1-1-12 )2; preferably halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl; for example, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 1-1-2 Substituted C1-C6 alkoxy; (7) Each R 1-3 is independently oxo or unsubstituted or substituted with one or more R 1-1-2 Substituted C1-C6 alkoxy; (8) Each R 1-1-1 are independently halogen; (9) Each R 1-1-2 are independently deuterium or halogen; (10) Each R 1-1-12 are independently C1-C6 alkyl; (11) Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-1 Substituted C2-C6 alkyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-4 Substituted 3-6 membered cycloalkyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -O-5-12 membered heteroaryl, -N(R 2-7 )2 or Preferably one or more R 2-1 Substituted C1-C6 alkyl, one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or For example, unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 substituted 5-12 membered heteroaryl; for example, unsubstituted or substituted with one or more R 2-9 Substituted 4-12 membered heterocycloalkenyl; (12) Each R 2-1 are independently unsubstituted or substituted with one or more R 2-1-2 Substituted 5-12 membered heteroaryl or Best (13) Each R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or unsubstituted or replaced by one or more R 2-1-2 substituted 5-12 membered heteroaryl; preferably unsubstituted or substituted by one or more R 2-1-1 substituted 4-12 membered heterocyclic group; (14) Each R 2-5 is independently oxo, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl or (15) Each R 2-6 are independently oxo, cyano or unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl; for example, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl; (16) Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 substituted 5-12 membered heteroaryl; (17) Each R 2-9 are independently oxo, halogen, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy, 3-6 membered cycloalkyl, 4-12 membered heterocyclic group or -N(R 2-5-3 )2; preferably oxo, halogen, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 2-5-2 Substituted C1-C6 alkoxy; for example, oxo or halogen; (18) Each R 2-1-2 are independently C1-C6 alkyl; (19) Each R 2-4-1 are independently C1-C6 alkyl; (20) Each R 2-5-1 are independently halogen; (21) Each R 2-5-2 independently for deuterium; (22) Each R 2-5-3 are independently hydrogen; (23) Each R 2-6-1 are independently cyano; (24) Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-15-membered cyclic heteroaromatic ring; the heteroatoms in the 5-15-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, or 4, the single heteroaromatic ring in the 5-15-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-15-membered cyclic heteroaromatic ring is 2 or 3; (25) Each R b-1 independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 , For example, oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy; (26) Each R b-1-1 are independently halogen; (27) Each R b-1-2 are independently deuterium or halogen; (28) Each R b-1-5 are independently C1-C6 alkyl; (29) Each R b-1-6 are independently C1-C6 alkyl; (30) Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein the number of heteroatom groups in the 4-6 membered heterocyclic group is 1, and the heteroatom group is P(O); (31)R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-3 substituted 4-12 membered cycloalkenyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; preferably hydrogen, unsubstituted or substituted by one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; for example hydrogen, unsubstituted or replaced by one or more R 3-6 substituted 5-10 membered heteroaryl or unsubstituted or with one or more R 3-7 Substituted C1-C6 alkyl; for example hydrogen, unsubstituted or replaced by one or more R 3-6 substituted 5-10 membered heteroaryl, unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl or -C(O)R 4 ; (32) Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy; In a preferred embodiment, each R 3-2 are independently deuterium, hydroxyl, halogen, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl, oxo, -S(O)2R 3-4-1 or -N(R 3-4-2 )2; preferably hydroxyl or halogen; (33) Each R 3-3 are independently hydroxyl, -NHC(O)R 3-2-1 or -N(R 3-4-2 )2; (34) Each R 3-4 are independently oxo; (35) Each R 3-5 independently -S(O)2R 3-4-1 , (36) Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl; for example, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl; (37) Each R 3-7 are independently 4-6 membered heterocyclic groups; (38) Each R 3-2-1 are independently C1-C6 alkyl; (39) Each R 3-2-2 are independently hydroxyl groups; (40) Each R 3-4-1 are independently C1-C6 alkyl; (41) Each R 3-4-2 are independently hydrogen; (42) Each R 3-5-1 and R 3-5-2 are independently C1-C6 alkyl; and (43)R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4- to 6-membered heterocyclic group, wherein the heteroatom in the 4- to 6-membered heterocyclic group is N or O, and the number of the heteroatom is 1.

7. The compound of formula I according to claim 1, its pharmaceutically acceptable salt or its isotope compound, characterized in that: R 4 is unsubstituted or substituted with one or more R 4-1 substituted 4-6 membered heterocyclic group or unsubstituted or replaced by one or more R 4-2 Substituted C1-C6 alkyl, the heteroatom in the 4-6 membered heterocyclic group is N or O, and the number of heteroatoms is 1; for example, unsubstituted or substituted with one or more R 4-2 Substituted C1-C6 alkyl.

8. The compound of formula I, a pharmaceutically acceptable salt thereof, or an isotope compound thereof according to any one of claims 1 to 7, characterized in that: The compound shown in formula I is a compound shown in formula Ia, Ib, Ic, Id, Ie, If or Ig 9. The compound of formula I, a pharmaceutically acceptable salt thereof, or an isotope compound thereof according to any one of claims 1 to 3, characterized in that: The compound as shown in Formula I is Scheme 1, Scheme 2, Scheme 3, Scheme 4, Scheme 5, Scheme 6, Scheme 7, Scheme 8, Scheme 9 or Scheme 10, Solution 1: m is 1; n is 1; Ring A is R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1; Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy; Each R 1-1-1 are independently halogen; Each R 2 are independently unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 Substituted 5-6 membered heteroaryl; the heteroatom in the 4-12 membered heterocycloalkenyl and 5-6 membered heteroaryl is independently N, and the number of heteroatoms is 1; Each R 2-9 are independently oxo or halogen; Each R 2-6 are independently unsubstituted C1-C6 alkyl; Ring B is an unsubstituted 5-10-membered heteroaromatic ring; the heteroatoms in the 5-10-membered heteroaromatic ring are selected from N and / or S, and the number of heteroatoms is 2 or 3; R 3 is hydrogen, unsubstituted or replaced by one or more R 3-6 A substituted 5-10 membered heteroaryl or an unsubstituted C1-C6 alkyl; the heteroatom in the 5-10 membered heteroaryl is N, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently unsubstituted C1-C6 alkyl; Solution 2 m is 1; n is 0 or 1; Ring A is a benzene ring, a 6-membered heteroaromatic ring or an oxo-substituted 6-membered heterocycloalkenyl group; the heteroatom in the 6-membered heteroaromatic ring and the 6-membered heterocycloalkenyl group is N, and the number of heteroatoms is 1; R 1 is unsubstituted or substituted with one or more R 1-1 Substituted phenyl or unsubstituted or with one or more R 1-2 A substituted 5-6 membered heteroaryl group, wherein the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2; Each R 1-1 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl; Each R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl; Each R 1-1-1 , R 1-1-2 and R 1-1-5 are independently deuterium or halogen; Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-1 Substituted C2-C6 alkyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12 membered heterocyclyl, 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-1 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-5 and R 2-9 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy or Each R 2-6 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy; Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl; the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 2-8 is unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 2-1-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; R 2-1-3 is independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-5-1 and R 2-5-2 are independently deuterium or halogen; Each R 2-5-4 are independently C1-C6 alkyl; Each R 2-6-1 are independently cyano; Each R 2-7-2 and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-12-membered cyclic heteroaromatic ring; the heteroatoms in the 5-12-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, or 4, and the number of rings in the 5-12-membered cyclic heteroaromatic ring is 2; Each R b-1 independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 , Each R b-1-1 are independently halogen; Each R b-1-2 are independently deuterium or halogen; Each R b-1-4 are independently hydrogen or C1-C6 alkyl; Each R b-1-5 are independently C1-C6 alkyl; Each R b-1-6 are independently C1-C6 alkyl; Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein the number of heteroatom groups in the 4-6 membered heterocyclic group is 1, and the heteroatom group is P(O); R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; the heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy; Each R 3-2 are independently hydroxy or halogen; Each R 3-4 are independently oxo; Each R 3-5 independently -S(O)2R 3-4-1 , Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl; Each R 3-7 are independently 4-6 membered heterocyclic groups; the heteroatoms in the 4-6 membered heterocyclic groups are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-2 are independently hydroxyl groups; Each R 3-4-1 , R 3-5-1 and R 3-5-2 are independently C1-C6 alkyl; R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group, wherein the heteroatom in the 4-6 membered heterocyclic group is N or O, and the number of the heteroatom is 1; Solution 3 m is 1; n is 0 or 1; Ring A is a benzene ring, a 6-membered heteroaromatic ring or an oxo-substituted 6-membered heterocycloalkenyl group; the heteroatom in the 6-membered heteroaromatic ring and the 6-membered heterocycloalkenyl group is N, and the number of heteroatoms is 1; R 1 is unsubstituted or substituted with one or more R 1-1 Substituted phenyl or unsubstituted or with one or more R 1-2 A substituted 5-6 membered heteroaryl group, wherein the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2; Each R 1-1 are independently halogen or unsubstituted or substituted with one or more R 1-1-2 Substituted C1-C6 alkoxy; Each R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl; Each R 1-1-1 , R 1-1-2 and R 1-1-5 are independently deuterium or halogen; Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12 membered heterocyclyl, 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-1 Independently Each R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-5 is independently oxo, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl or Each R 2-6 are independently oxo, cyano or unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl; Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl; the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 2-8 is unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 2-9 are independently oxo, halogen, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 2-5-2 Substituted C1-C6 alkoxy; Each R 2-1-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; R 2-1-3 is independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-5-1 are independently halogen; Each R 2-5-2 independently for deuterium; Each R 2-5-4 are independently C1-C6 alkyl; Each R 2-6-1 are independently cyano; Each R 2-7-2 are independently C1-C6 alkyl; Each R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-12-membered cyclic heteroaromatic ring; the heteroatoms in the 5-12-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, or 4, and the number of rings in the 5-12-membered cyclic heteroaromatic ring is 2; Each R b-1 independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 , Each R b-1-1 are independently halogen; Each R b-1-2 are independently deuterium or halogen; Each R b-1-4 are independently hydrogen or C1-C6 alkyl; Each R b-1-5 are independently C1-C6 alkyl; Each R b-1-6 are independently C1-C6 alkyl; Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein the number of heteroatom groups in the 4-6 membered heterocyclic group is 1, and the heteroatom group is P(O); R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; the heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy; Each R 3-2 are independently hydroxy or halogen; Each R 3-4 are independently oxo; Each R 3-5 independently -S(O)2R 3-4-1 , Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl; Each R 3-7 are independently 4-6 membered heterocyclic groups; the heteroatoms in the 4-6 membered heterocyclic groups are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-2 are independently hydroxyl groups; Each R 3-4-1 , R 3-5-1 and R 3-5-2 are independently C1-C6 alkyl; R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group, wherein the heteroatom in the 4-6 membered heterocyclic group is N or O, and the number of the heteroatom is 1; Solution 4: m is 1; n is 1; Ring A is R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1; Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy; Each R 1-1-1 are independently halogen; Each R 2 are independently unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 Substituted 5-6 membered heteroaryl; the heteroatom in the 4-12 membered heterocycloalkenyl and 5-6 membered heteroaryl is independently N, and the number of heteroatoms is 1; Each R 2-9 are independently oxo or halogen; Each R 2-6 are independently unsubstituted C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-15-membered cyclic heteroaromatic ring; the heteroatoms in the 5-15-membered cyclic heteroaromatic ring are selected from N and / or S, and the number of heteroatoms is 2, 3 or 4; Each R b-1 are independently oxo, halogen or C1-C6 alkyl; R 3 is hydrogen, unsubstituted or replaced by one or more R 3-6 A substituted 5-10 membered heteroaryl or an unsubstituted C1-C6 alkyl; the heteroatom in the 5-10 membered heteroaryl is N, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently unsubstituted C1-C6 alkyl; Solution 5: m is 1; n is 1; Ring A is a benzene ring, a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatom in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group is N, and the number of heteroatoms is 1; R 1 is unsubstituted or substituted with one or more R 1-1 Substituted 6-12 membered aryl or unsubstituted or replaced by one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl; Each R 1-1-1 , R 1-1-2 and R 1-1-5 are independently deuterium or halogen; Each R 2 Independently for one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-2 Substituted C2-C6 alkenyl, unsubstituted or replaced by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12 membered heterocyclyl, 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or The heteroatoms in the 4-12 membered heterocyclic group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-5 and R 2-9 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy or Each R 2-6 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 2-5-2 Substituted C1-C6 alkoxy; Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl; the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-8 are independently unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatoms in the 4-12 membered heterocyclic group are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-1-3 are independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-5-1 and R 2-5-2 are independently deuterium, hydroxyl, cyano or halogen; Each R 2-6-1 are independently cyano; Each R 2-7-2 are independently deuterium, hydroxyl, cyano or halogen; Each R 2-7-2 and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3 or 4, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2 or 3; Each R b-1 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 , Each R b-1-1 and R b-1-2 are independently deuterium or halogen; Each R b-1-4 and R b-1-5 are independently hydrogen or C1-C6 alkyl; Each R b-1-6 are independently C1-C6 alkyl; Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein in the 4-6 membered heterocyclic group, when the number of the heteroatom group is 1, the heteroatom group is P(O); R 3 is hydrogen, unsubstituted or replaced by one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; the heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy; Each R 3-2 are independently hydroxy or halogen; Each R 3-4 are independently hydroxy, halogen or cyano; Each R 3-5 independently -S(O)2R 3-4-1 , Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl; Each R 3-7 are independently 4-6 membered heterocyclic groups; the heteroatoms in the 4-6 membered heterocyclic groups are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-2 are independently hydroxyl groups; Each R 3-4-1 , R 3-5-1 and R 3-5-2 is a C1-C6 alkyl group; R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group; the heteroatom in the 4-6 membered heterocyclic group is selected from N and / or O, and the number of heteroatoms is 1 or 2; Each R 4-1 are independently hydroxyl groups; Solution 6: m is 1; n is 1; Ring A is a benzene ring, a 6-membered heteroaromatic ring or an oxo-substituted 6-membered heterocycloalkenyl group; the heteroatom in the 6-membered heteroaromatic ring and the 6-membered heterocycloalkenyl group is N, and the number of heteroatoms is 1; R 1 is unsubstituted or substituted with one or more R 1-1 Substituted phenyl or unsubstituted or with one or more R 1-2 A substituted 5-6 membered heteroaryl group, wherein the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently halogen, cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 1-1-2 Substituted C1-C6 alkoxy or unsubstituted or with one or more R 1-1-5 Substituted 3-6 membered cycloalkyl; Each R 1-1-1 , R 1-1-2 and R 1-1-5 are independently deuterium or halogen; R 2 For one or more R 2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-2 Substituted C2-C6 alkenyl, unsubstituted by one or more R 2-3 Substituted C2-C6 alkynyl, unsubstituted or replaced by one or more R 2-5 substituted 4-12 membered heterocyclic group, unsubstituted or replaced by one or more R 2-9 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 2-6 Substituted 5-12 membered heteroaryl, -N(R 2-7 )2 or The heteroatoms in the 4-12 membered heterocyclyl, 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 2-1 , R 2-2 and R 2-3 are independently unsubstituted or substituted with one or more R 2-1-1 substituted 4-12 membered heterocyclic group or The heteroatoms in the 4-12 membered heterocyclic group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-5 and R 2-9 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-5-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy or Each R 2-6 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R 2-6-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-5-2 Substituted C1-C6 alkoxy; Each R 2-7 are independently hydrogen or unsubstituted or substituted by one or more R 2-7-2 Substituted 5-12 membered heteroaryl; the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-8 is unsubstituted or substituted with one or more R 2-8-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 2-1-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-1-3 is independently unsubstituted or substituted with one or more R 2-1-3-1 A substituted 4-12 membered heterocyclic group; the heteroatom in the 4-12 membered heterocyclic group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1-3-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Each R 2-5-1 and R 2-5-2 are independently deuterium or halogen; Each R 2-6-1 are independently cyano; Each R 2-7-2 and R 2-8-1 are independently hydroxy, cyano, halogen or C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-15-membered cyclic heteroaromatic ring; the heteroatoms in the 5-15-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3, or 4, and the number of rings in the 5-15-membered cyclic heteroaromatic ring is 2 or 3; Each R b-1 independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R b-1-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R b-1-8 Substituted-O-3-6-membered cycloalkyl, -C(O)N(R b-1-4) 2. -COOR b-1-5 , Each R b-1-1 and R b-1-2 are independently deuterium or halogen; Each R b-1-4 and R b-1-5 are independently hydrogen or C1-C6 alkyl; Each R b-1-6 are independently C1-C6 alkyl; Each R b-1-8 are independently C1-C6 alkyl, or two R b-1-8 Connected to them Together they form a 4-6 membered heterocyclic group, wherein the number of heteroatom groups in the 4-6 membered heterocyclic group is 1, and the heteroatom group is P(O); R 3 are independently hydrogen, unsubstituted or substituted with one or more R 3-1 Substituted 3-12 membered cycloalkyl, unsubstituted or replaced by one or more R 3-2 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-4 substituted 4-12 membered heterocycloalkenyl, unsubstituted or replaced by one or more R 3-5 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, -C(O)R 4 or unsubstituted or replaced by one or more R 3-7 Substituted C1-C6 alkyl; the heteroatoms in the 4-12 membered heterocycloalkyl, 4-12 membered heterocycloalkenyl and 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-1 are independently hydroxyl, unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl or C1-C6 alkoxy; Each R 3-2 are independently hydroxy or halogen; Each R 3-4 are independently oxo; Each R 3-5 independently -S(O)2R 3-4-1 , Each R 3-6 are independently halogen, cyano or unsubstituted or substituted with one or more R 3-2-2 Substituted C1-C6 alkyl; Each R 3-7 are independently 4-6 membered heterocyclic groups; the heteroatoms in the 4-6 membered heterocyclic groups are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-2 are independently hydroxyl groups; Each R 3-4-1 , R 3-5-1 and R 3-5-2 are independently C1-C6 alkyl; R 4 is unsubstituted or substituted with one or more R 4-1 A substituted 4-6 membered heterocyclic group or a C1-C6 alkyl group, wherein the heteroatom in the 4-6 membered heterocyclic group is N and / or O, and the number of heteroatoms is 1 or 2; Each R 4-1 are independently hydroxyl groups; Solution 7: m is 1; n is 1; Ring A is a 5-6 membered heteroaromatic ring or an oxo-substituted 5-6 membered heterocycloalkenyl group; the heteroatom in the 5-6 membered heteroaromatic ring and the 5-6 membered heterocycloalkenyl group is N, and the number of heteroatoms is 1; R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1; Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy; Each R 1-1-1 are independently halogen; Each R 2 are independently unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 Substituted 5-12 membered heteroaryl; the heteroatoms in the 4-12 membered heterocycloalkenyl and 5-12 membered heteroaryl are independently selected from N and / or O, and the number of heteroatoms is 1, 2 or 3; Each R 2-9 are independently oxo, halogen or unsubstituted C1-C6 alkyl; Each R 2-6 are independently unsubstituted C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-20-membered cyclic heteroaromatic ring; the heteroatoms in the 5-20-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, the number of heteroatoms is 1, 2, 3 or 4, the single heteroaromatic ring in the 5-20-membered cyclic heteroaromatic ring is a 5-7-membered heteroaromatic ring, and the number of rings in the 5-20-membered cyclic heteroaromatic ring is 2, 3 or 4; Each R b-1 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy; Each R b-1-1 and R b-1-2 are independently halogen; R 3 is hydrogen, unsubstituted or replaced by one or more R 3-6 A substituted 5-10 membered heteroaryl or an unsubstituted C1-C6 alkyl; the heteroatom in the 5-10 membered heteroaryl is independently N, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently unsubstituted C1-C6 alkyl; Solution 8: m is 1; n is 1; Ring A is R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-12 membered heteroaryl group; the heteroatom in the 5-12 membered heteroaryl group is N, and the number of heteroatoms is 1; Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy; Each R 1-1-1 are independently halogen; R 2 is unsubstituted or substituted with one or more R 2-9 substituted 4-12 membered heterocycloalkenyl or unsubstituted or with one or more R 2-6 Substituted 5-6 membered heteroaryl; the heteroatoms in the 4-12 membered heterocycloalkenyl and 5-6 membered heteroaryl are independently selected from N and / or O, and the number of heteroatoms is 1, 2 or 3; Each R 2-9 are independently oxo, halogen or unsubstituted C1-C6 alkyl; Each R 2-6 are independently unsubstituted C1-C6 alkyl; Ring B is unsubstituted or substituted with one or more R b-1 A substituted 5-15-membered cyclic heteroaromatic ring; the heteroatoms in the 5-15-membered cyclic heteroaromatic ring are selected from one or more of N, O and S, and the number of heteroatoms is 2, 3 or 4; Each R b-1 are independently oxo, halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy; Each R b-1-1 and R b-1-2 are independently halogen; R 3 is hydrogen, unsubstituted or replaced by one or more R 3-6 Substituted 5-10 membered heteroaryl, unsubstituted C1-C6 alkyl or -C(O)R 4 ; The heteroatom in the 5-10 membered heteroaryl is N, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently unsubstituted C1-C6 alkyl; R 4 is a C1-C6 alkyl group; Solution 9: m is 1; n is 1; Ring A is a 6-membered heteroaromatic ring; the heteroatom in the 6-membered heteroaromatic ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-6 membered heteroaryl group; the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1; Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy; Each R 1-1-1 are independently halogen; R 2 is unsubstituted or substituted with one or more R 2-9 Substituted 4-12 membered heterocycloalkenyl; the heteroatom in the 4-12 membered heterocycloalkenyl is independently N, and the number of heteroatoms is 1 or 2; Each R 2-9 are independently oxo, halogen or unsubstituted C1-C6 alkyl; Ring B is unsubstituted or substituted with one R b-1 A substituted 5-12-membered cyclic heteroaromatic ring; the heteroatoms in the 5-12-membered cyclic heteroaromatic ring are selected from N and / or S, the number of heteroatoms is 1, 2 or 3, and the number of rings in the 5-12-membered cyclic heteroaromatic ring is 2; R b-1 is halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy; Each R b-1-1 and R b-1-2 are independently halogen; R 3 is hydrogen; Solution 10: m is 1; n is 1; Ring A is R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 5-6 membered heteroaryl group; the heteroatom in the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1; Each R 1-2 are independently unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl or unsubstituted C1-C6 alkoxy; Each R 1-1-1 are independently halogen (e.g. fluorine); R 2 for Ring B is unsubstituted or substituted with one R b-1 substituted 5-10 membered heteroaromatic ring; the heteroatoms in the 5-10 membered heteroaromatic ring are selected from N and / or S, and the number of heteroatoms is 1, 2 or 3 (for example ); R b-1 is halogen, cyano, unsubstituted or substituted with one or more R b-1-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R b-1-2 Substituted C1-C6 alkoxy; Each R b-1-1 and R b-1-2 are independently halogen (e.g. fluorine); R 3 For hydrogen.

10. The compound of formula I, a pharmaceutically acceptable salt thereof, or an isotope compound thereof according to any one of claims 1 to 3, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1)R 1 for (2)R 2 for (3) for and (4) R 3 For hydrogen, Preferably, for 11. The compound of formula I, a pharmaceutically acceptable salt thereof, or an isotope compound thereof according to any one of claims 1 to 3; characterized in that: The compound as shown in formula I is any of the following compounds:

12. The compound of formula I, a pharmaceutically acceptable salt thereof, or an isotope compound thereof according to any one of claims 1 to 3, characterized in that: The pharmaceutically acceptable salt of the compound shown in Formula I is the following compound:

13. A method for preparing a compound as shown in formula I', characterized in that: It includes plan a, plan b, plan c or plan d, The scheme a comprises the following steps: in a solvent, a compound of formula II and a compound of formula III are subjected to a condensation reaction as shown below to obtain the compound of formula I', that is, The scheme b comprises the following steps: in a solvent, in the presence of a condensing agent, subjecting the compound of formula IV to a condensation reaction as shown below with the compound of formula V to obtain the compound of formula I', that is, Y is tributyltin; The scheme c comprises the following steps: in a solvent, in the presence of a condensing agent, subjecting the compound of formula IV and the compound of formula VI to a condensation reaction as shown below to obtain the compound of formula I', that is, The scheme d comprises the following steps: reacting the compound of formula IV in a solvent in the presence of a base to obtain the compound of formula I', that is, R 3’ C(O)R', R' is C1-C6 alkyl or halogenated C1-C6 alkyl; Among them, R 1 , R 2 , Ring A, Ring B and R 3 As claimed in any one of claims 1 to 10; Preferably, the method for preparing the compound as shown in Formula I satisfies one or more of the following conditions: (1) In scheme a, in the condensation reaction, the molar ratio of the compound of formula II to the compound of formula III is 1:(0.5-1.5), for example, 1:1, 1:1.1 or 1:1.4; (2) In scheme a, in the condensation reaction, the solvent is an amide solvent and / or a cyanide solvent; the amide solvent is preferably N,N-dimethylformamide; the cyanide solvent is preferably acetonitrile; (3) In scheme a, in the condensation reaction, the condensation agent is N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate and N-methylimidazole; (4) In scheme a, in the condensation reaction, the molar ratio of the compound of formula II to the condensing agent is 1:(2-10), for example, 1:4.5, 1:5.5, 1:7, 1:4, 1:4.4 or 1:6.2; (5) In scheme a, in the condensation reaction, the reaction temperature of the condensation reaction is 70°C; (6) In scheme a, the condensation reaction further comprises post-treatment, and the post-treatment step comprises the following steps: one or more of concentration, water washing, extraction, drying, column chromatography and preparative chromatography; (7) In scheme b, in the condensation reaction, the molar ratio of the compound of formula IV to the compound of formula V is 1:(1-5), for example 1:1.5; (8) In scheme b, in the condensation reaction, the solvent is an aromatic solvent, such as xylene; (9) In scheme b, in the condensation reaction, the condensation agent is tetrakistriphenylphosphine palladium; (10) In scheme b, in the condensation reaction, the molar ratio of the compound of formula IV to the condensing agent is (2-5):1, for example 3.3:1; (11) In scheme b, in the condensation reaction, the reaction temperature of the condensation reaction is 160°C; (12) In scheme b, in the condensation reaction, the condensation reaction further comprises a post-treatment, and the post-treatment step comprises the following steps: one or more of filtration, concentration and preparative chromatography; (13) In scheme c, in the condensation reaction, the molar ratio of the compound of formula IV to the compound of formula VI is 1:(1-5), for example 1:2; (14) In scheme c, in the condensation reaction, the solvent is an amide solvent, such as N,N-dimethylformamide; (15) In scheme c, in the condensation reaction, the condensation agent is 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine; (16) In scheme c, in the condensation reaction, the molar ratio of the compound of formula IV to the condensing agent is 1:(2-10), for example 1:5; (17) In scheme c, in the condensation reaction, the reaction temperature of the condensation reaction is room temperature; (18) In scheme c, the condensation reaction further comprises a post-treatment, and the post-treatment step comprises the following steps: one or more of extraction, concentration and preparative chromatography; (19) In scheme d, the solvent is an organic solvent, preferably an alcohol solvent, such as methanol; (20) In scheme d, the base is an inorganic base, such as potassium carbonate; (21) In scheme d, the molar ratio of the compound of formula IV to the base is 1:(1-5), for example 1:2; (22) In scheme d, in the condensation reaction, the reaction temperature of the condensation reaction is room temperature; In scheme d of (23), the condensation reaction further comprises a post-treatment, and the post-treatment step comprises the following steps: one or both of filtration and preparative chromatography.

14. A pharmaceutical composition, comprising: (1) substance A, wherein substance A is a compound represented by formula I as described in any one of claims 1 to 12, a pharmaceutically acceptable salt thereof, or an isotope compound thereof, and (2) Pharmaceutically acceptable excipients.

15. Use of a substance A in the preparation of a polymerase theta inhibitor, wherein the substance A is a compound of formula I as described in any one of claims 1 to 12, a pharmaceutically acceptable salt thereof, or an isotope compound thereof.

16. Use of a substance A in the preparation of a drug, wherein the substance A is a compound of formula I as described in any one of claims 1 to 12, a pharmaceutically acceptable salt thereof, or an isotope compound thereof; the drug is used to treat lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer or colon cancer, or the drug is used to treat diseases related to polymerase theta.

17. A compound as shown below or a pharmaceutically acceptable salt thereof,

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