A cdK kinase inhibitor and its pharmaceutical use

Abstract

The present invention relates to a CDK kinase inhibitor and its pharmaceutical use. In particular, the present invention relates to a CDK inhibitor having the structure of formula (I) and its pharmaceutical composition, and its use as a CDK inhibitor and its use in the manufacture of a medicament for treating a cancer or a tumor at least partially associated with CDK. Wherein each substituent of formula (I) is the same as defined in the specification.

Description

A CDK kinase inhibitor and its pharmaceutical application Technical Field

[0001] The present invention belongs to the field of drug synthesis, and in particular relates to a CDK kinase inhibitor and its pharmaceutical application. Background Art

[0002] Cyclin-dependent kinases (CDKs) are an important class of cellular serine / threonine kinases that are crucial for regulating the cell cycle and transcription. The human genome encodes over 20 CDKs, which are functionally divided into two subfamilies: cell cycle-related CDKs (CDKs 1-7 and 14-18) and transcription-related CDKs (CDKs 7-13, 19, and 20). Different CDKs interact with different cyclins to regulate various phases of the cell cycle or perform other functions.

[0003] The disorder of CDK activity is closely related to the occurrence and development of tumors. Among them, CDK4 and CDK6 are important regulators of the G1 / S node in the cell cycle. They are regulated by D-type cyclins (Cyclin D) and INK4 endogenous CDK inhibitors (such as p16 INK4a ) is regulated by multiple mitotic signaling pathways, including PI3K-AKT, RAS-MEK, and estrogen receptor pathways. Increased Cyclin D expression activates the activities of CDK4 and CDK6, phosphorylating the negative cell cycle regulator RB1, dissociating it from the transcription factors E2F1 / 2 / 3. This activates the transcriptional activity of E2F1 / 2 / 3, promoting the transcription of genes required for cell entry into the S phase and ultimately prompting cells to complete the G1-S transition. Reports indicate that dysregulation of the cyclin D-CDK4 / 6-INK4-retinoblastoma protein (Rb) signaling pathway is associated with resistance to endocrine therapy.

[0004] Breast cancer is the most common malignant tumor in women. Data from the International Agency for Research on Cancer indicate that in recent years, nearly two-thirds of new cancer cases and deaths worldwide have been concentrated in ten cancer types. Breast cancer ranks second in terms of incidence, with over 2.3 million new cases annually, accounting for 11.6% of the total. In terms of mortality, breast cancer accounts for 6.9%. Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer accounts for 60-70% of all breast cancer cases. Endocrine therapy is one of the mainstays of treatment, but resistance can also develop. With the continued pursuit of reversing endocrine therapy resistance, CDK4 / 6 inhibitors have garnered significant attention since their discovery. CDK4 / 6 inhibitors selectively inhibit CDK4 / 6 kinase activity, arresting the G1 / S phase transition and thereby inhibiting the proliferation of tumor cells. Furthermore, CDK4 / 6 inhibitors can inhibit the expression of the estrogen receptor signaling pathway, creating a synergistic effect with endocrine therapy, delaying and reversing endocrine therapy resistance. The development of CDK4 / 6 inhibitors has changed the traditional model of endocrine therapy. CDK4 / 6 inhibitors combined with endocrine therapy have shown significant efficacy in patients with HR-positive HER2-negative breast cancer and have become the new standard for first-line and second-line treatment of patients with HR-positive HER2-negative breast cancer.

[0005] However, clinical studies have shown that treatment with CDK4 / 6 inhibitors can cause adverse reactions, such as gastrointestinal and / or hematologic toxicities, and acquired resistance may develop with prolonged treatment. Accumulating data indicate that the hematologic toxicities observed clinically are associated with CDK6 / cyclin D3. Furthermore, numerous preclinical studies have demonstrated that breast cancer development and progression are primarily dependent on CDK4, and knocking out CDK4 in mouse breast cancer models completely eliminates breast cancer. Furthermore, when mouse breast tumors were removed and cultured in vitro, and CDK4 and CDK6 knocked down separately before being inoculated back into the mouse mammary glands, breast cancer cells lacking CDK4 were unable to regenerate tumors, while tumors in breast cancer cells with low CDK6 expression grew normally. Furthermore, CRISPR knockout screening data in numerous cell lines also demonstrate that human breast cancer cell lines are more sensitive to CDK4 depletion, while hematologic cell lines are more sensitive to CDK6 depletion. In summary, CDK4-selective inhibitors may offer improved safety and efficacy compared to CDK4 / 6 inhibitors. Therefore, the development of CDK4-selective inhibitors holds great clinical value. Summary of the Invention

[0006] The present invention provides a CDK kinase inhibitor and its pharmaceutical application. The compounds of this invention exhibit potent inhibitory effects on CDK kinases, particularly selective inhibition of CDK4 kinase, and are widely used in the preparation of medicaments for treating cancers or tumors at least partially associated with CDKs.

[0007] The first aspect of the present invention provides a compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0008] wherein X1 is CR5 or N; X2 is selected from CR6 or N;

[0009] Ring A is C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0010] Ring B is C 6-10 Aryl or 6-10 membered heteroaryl;

[0011] m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12)2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0012] R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-8 Alkyl, halogen substituted C 1-8 Alkyl, deuterium substituted C 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C0-8 Alkyl-N(R 13 )-C(O)R 12 , provided that, when ring B is phenyl, R2 is not hydrogen, C 1-8 Alkyl, C 6-10 Aryl, -C 0-8 Alkyl-OR 11 and -C 0-8 Alkyl-C(O)R 12 ;

[0013] R3 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 ;

[0014] n is 0, 1, 2, 3 or 4; each R4 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-O-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 , or, when n≥2, two adjacent R4 together with their directly connected parts form a C 4-10 Cycloalkyl, 4-10 membered heterocyclyl, 5-10 membered heteroaryl or C 6-10 Aryl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-O-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-O-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0015] R5 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13)-C(O)R 12 ;

[0016] R6 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 , or, R6 and R3 together with the part to which they are directly connected form a 4-10 membered heterocyclic group, a 5-10 membered heteroaryl group or a C6-10 Aryl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0017] Each R7 is independently selected from hydrogen, deuterium, C1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)R 12 and -C 0-8 Alkyl-C(O)NR 13 R 14 The above groups are optionally further substituted by one or more groups selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0018] Each R8 and each R9 are independently selected from hydrogen, deuterium, hydroxyl, C1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl, or, R8 and R9 together with the sulfur atom to which they are directly connected form a 3-10 membered heterocyclic group, the above groups are optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0019] Each R 10 independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl and -NR 13 R 14The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, hydroxyl, =O, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent;

[0020] Each R 11 independently selected from hydrogen, deuterium, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent;

[0021] Each R 12 independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent;

[0022] Each R 13 and each R 14 are independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-10 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono C 1-10 Alkylamino, di-C 1-10 Alkylamino and C 1-10 substituted with an alkanoyl substituent;

[0023] Or, R 13 and R 14 Together with the nitrogen atom directly connected thereto, a 4-10 membered heterocyclic group or a 5-10 membered heteroaryl group is formed, wherein the 4-10 membered heterocyclic group or the 5-10 membered heteroaryl group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, ═O, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono C 1-10Alkylamino, di-C 1-10 Alkylamino and C 1-10 substituted with an alkanoyl substituent;

[0024] Each r is independently 0, 1 or 2.

[0025] As a preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0026] R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C3-6 Cycloalkyl, 3-6 membered heterocyclic group, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , provided that, when ring B is phenyl, R2 is not hydrogen, C 1-4 Alkyl, -C 0-4 Alkyl-OR 11 and -C 0-4 Alkyl-C(O)R 12 ;

[0027] R3 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 ;

[0028] n is 0, 1, 2, 3 or 4; each R4 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , or, when n≥2, two adjacent R4 together with their directly connected parts form a C 4-6 Cycloalkyl, 4-8 membered heterocyclyl, 5-8 membered heteroaryl or phenyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0029] R5 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 ;

[0030] R6 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , or, R6 and R3 together with the part directly connected thereto form a 5-8 membered heterocyclic group, a 5-8 membered heteroaryl group or a phenyl group, the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0031] Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 and r are as defined for the compound of formula (I).

[0032] As a preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R7 is independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 10 、-C 0-4Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)R 12 and -C 0-4 Alkyl-C(O)NR 13 R 14 The above groups are optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0033] Each R8 and each R9 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl or 5-8 membered heteroaryl, or, R8 and R9 together with the sulfur atom to which they are directly connected form a 3-8 membered heterocyclic group, the above groups are optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0034] Each R 10 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl and -NR 13 R 14 The above groups are independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, hydroxyl, =O, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent;

[0035] Each R 11 independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl and 5-8 membered heteroaryl, the above groups are independently optionally further substituted by one or more selected from deuterium, halogen, hydroxyl, =O, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent;

[0036] Each R 12 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 13 R 14 The above groups are optionally further substituted by one or more groups selected from deuterium, halogen, hydroxyl, =O, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent;

[0037] Each R 13 and each R 14 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8Aryl, 5-8 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-4 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 substituted with an alkanoyl substituent;

[0038] Or, R 13 and R 14 Together with the nitrogen atom directly connected thereto, a 4-6 membered heterocyclic group or a 5-8 membered heteroaryl group is formed, wherein the 4-6 membered heterocyclic group or the 5-8 membered heteroaryl group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, ═O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 The alkanoyl group is substituted with an alkanoyl substituent.

[0039] As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, for

[0040] Among them, R 4a and R 4b are each independently selected from hydrogen, deuterium, cyano, C 1-4 Alkyl, C2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-C(O)R 12 and -C 0-4 Alkyl-C(O)NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13)R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0041] Y1, Y2, Y3, Y4 and Y5 are each independently selected from N or CR 4c ; Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13)-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , or, where two adjacent R 4c Together with its directly connected parts, it forms a C 4-6 Cycloalkyl, 5-6 membered heterocyclyl, 5-6 membered heteroaryl or phenyl, the above groups are independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13)-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0042] Y6, Y7, Y9 and Y 10 Each independently selected from N or CR 4d ; Each R 4d are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , or, where two adjacent R 4d Together with the part directly connected thereto, a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group is formed, wherein the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0043] Y8 and Y 11 Each independently selected from N or CR 4e ; Each R 4e are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent;

[0044] Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 and r are as defined for the compound of formula (I).

[0045] As a further preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IIa):

[0046] Wherein, X1 is CR5 or N;

[0047] Y1, Y2, Y3, Y4 and Y5 are each independently selected from N or CR 4c ; Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 , or, where two adjacent R 4c Together with its directly connected parts, it forms a C 4-6 Cycloalkyl, 5-6 membered heterocyclyl, 5-6 membered heteroaryl or phenyl, the above groups are independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0048] Ring A is C 5-8 Cycloalkyl, 5-8 membered heterocyclyl, phenyl or 5-6 membered heteroaryl;

[0049] Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0050] R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 , the condition is that when Y1, Y2, Y3, Y4 and Y5 are all CR 4c When R2 is not hydrogen, C 1-4 Alkyl, -OR 11 and -C(O)R 12 ;

[0051] R3 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 ;

[0052] R5 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 ;

[0053] R6 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 , or, R6 and R3 together with the part directly connected thereto form a 5-8 membered heterocyclic group, a 5-8 membered heteroaryl group or a phenyl group, the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0054] Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 , m and r are as defined for the compound of formula (I).

[0055] As a further preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IIIa1):

[0056] Wherein, Y1, Y2, Y3 and Y5 are each independently selected from N or CR 4c; Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12)2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0057] Ring A is C 5-8 Cycloalkyl, 5-8 membered heterocyclyl, phenyl or 5-6 membered heteroaryl;

[0058] m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0059] R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 ;

[0060] R is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF, hydroxyl, amino, methylamino and dimethylamino;

[0061] R6 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino; or,

[0062] R6 and R3 together with the part to which they are directly connected form a 5-8 membered heteroaryl or phenyl group, wherein the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0063] Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 and r are as defined for the compound of formula (I).

[0064] As a further preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IVa11), formula (IVa12) or formula (IVa13):

[0065] Among them, each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0066] Each R3 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino;

[0067] Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino, and the above groups are independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0068] Among them, ring A, R1, R2, R 11 、R 12 、R 13 、R 14 and m are as defined for the compound of formula (IIIa1).

[0069] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 , substituted by a substituent, the above groups are independently further optionally substituted by one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclyl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0070] Each R3 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, isopropyl, methoxy, trifluoromethyl, trideuteriomethyl, cyclopropyl, hydroxy, amino, methylamino and dimethylamino;

[0071] Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, methoxy, trifluoromethyl, trideuteriomethyl, trideuteriomethoxy, cyclopropyl, hydroxyl, amino, methylamino and dimethylamino;

[0072] Among them, R 11 、R 12 、R 13 and R 14 As defined in the compound of formula (IVa11), formula (IVa12) or formula (IVa13).

[0073] As a further preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IVa14):

[0074] wherein Ring C is a 5-6 membered nitrogen-containing heteroaryl group, wherein the 5-6 membered nitrogen-containing heteroaryl group optionally contains one or more oxygen or sulfur heteroatoms; R 6a Selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino;

[0075] Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0076] Among them, ring A, R1, R2, R 11 、R 12 、R 13 、R 14 and m are as defined for the compound of formula (IIIa1).

[0077] As a further preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is a compound of formula (IIIa2) or a compound of formula (IIIa3):

[0078] wherein each Y4 is independently selected from N or CR 4c ;

[0079] Ring D and Ring E are each independently C 5-6Cycloalkyl, 5-6 membered heterocyclyl, 5-6 membered heteroaryl or phenyl, wherein the 5-6 membered heterocyclyl or 5-6 membered heteroaryl contains one or more heteroatoms selected from nitrogen, oxygen or sulfur;

[0080] Each p is independently 0, 1 or 2; each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0081] Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino;

[0082] Among them, ring A, R1, R2, R 11 、R 12 、R 13 、R 14 and m are as defined for the compound of formula (IIa).

[0083] As a further preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is a compound of formula (IIb) or formula (IIc):

[0084] wherein each X1 is independently CR5 or N;

[0085] R 4a and R 4b are each independently selected from hydrogen, deuterium, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-C(O)R 12 and -C(O)NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0086] Y6, Y7, Y9 and Y 10 Each independently selected from N or CR 4d ; Each R 4d are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 , or, where two adjacent R 4d Together with the part directly connected thereto, a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group is formed, wherein the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0087] Y8 and Y 11 Each independently selected from N or CR 4e ; Each R 4e are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0088] Each ring A is independently C 5-8 Cycloalkyl, 5-8 membered heterocyclyl, phenyl or 5-6 membered heteroaryl;

[0089] m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0090] Each R2 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14)R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 ;

[0091] Each R3 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 ;

[0092] Each R5 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 ;

[0093] Each R6 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 , or, R6 and R3 together with the part directly connected thereto form a 5-8 membered heterocyclic group or a 5-8 membered heteroaryl group, the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0094] Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 and r are as defined for the compound of formula (I).

[0095] As a further preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is a compound of formula (IIIb) or formula (IIIc):

[0096] Among them, R 4a and R 4b are independently selected from hydrogen, deuterium, cyano, hydroxyl, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O)2R 10 and acetyl, the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0097] Each R 4d are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0098] Each R6 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0099] Among them, ring A, R1, R2, R 11 、R 12 、R 13 、R14 and m are as defined for the compound of formula (IIb) or (IIc).

[0100] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 4a and R 4b are each independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, methylsulfinyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, aminosulfonyl and C 1-4 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, halogen substituted C 1-4 Alkyl, halogen substituted C 1-4 Alkoxy, deuterium substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyloxy, =O, -NR 13 R 14 and -C(O)NR 13 R 14 substituted by a substituent;

[0101] Each R 4d are independently selected from hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 1-4 Alkoxy, methylsulfinyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, aminosulfonyl and C 1-4 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, halogen substituted C 1-4 Alkyl, halogen substituted C 1-4 Alkoxy, deuterium substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyloxy, =O, -NR 13 R 14 and -C(O)NR 13 R 14 substituted by a substituent;

[0102] Among them, R13 and R 14 As defined for compounds of formula (IIIb) or (IIIc).

[0103] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts, ring A is selected from phenyl, 5-6 membered heteroaryl, C 5-8 Cycloalkyl or 5-8 membered heterocyclic group, wherein the 5-6 membered heteroaryl or 5-8 membered heterocyclic group contains one or more heteroatoms selected from nitrogen, oxygen or sulfur; preferably, ring A is selected from phenyl, pyridyl, pyrimidinyl, pyridazinyl, triazinyl, furyl, thienyl, imidazolyl, triazolyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, C 5-8 Cycloalkyl or 5-8 membered heterocyclic group, wherein the 5-8 membered heterocyclic group contains one or more heteroatoms selected from nitrogen, oxygen or sulfur;

[0104] m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0105] R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 ;

[0106] Among them, R 10 、R 11 、R 12 、R 13 、R 14 and r are as defined for the compound of formula (I).

[0107] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the Selected from the following structures:

[0108] Among them, each R 1a , each R 1b , each R 1d , each R 1e , each R1f , each R 1g , each R 1h , each R 1i and each R 1k are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0109] Each R 1c and R 1jare each independently selected from hydrogen, deuterium, cyano, nitro, C 1-4 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, -S(O)2R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 and -C(O)NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent;

[0110] Each R2 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 ;

[0111] Among them, R 10 、R 11 、R 12 、R 13 、R 14 and r are as defined for the compound of formula (I).

[0112] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R 10independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -NR 13 R 14 The above groups are independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, hydroxyl, =O, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyl and -NR 13 R 14 substituted by a substituent;

[0113] Each R 11 independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, the above groups are independently optionally further substituted by one or more selected from deuterium, halogen, hydroxyl, =O, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyl and -NR 13 R 14 substituted by a substituent;

[0114] Each R 12 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 Alkenyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyl and -NR 13 R 14 The above groups are optionally further substituted by one or more groups selected from deuterium, halogen, hydroxyl, =O, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyl and -NR 13 R 14 substituted by a substituent;

[0115] Among them, R 13 and R 14 As defined for the compounds of formula (I).

[0116] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R 13 and each R 14 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-4 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 substituted with an alkanoyl substituent;

[0117] Or, R 13 and R 14 Together with the nitrogen atom directly connected thereto, a 4-6 membered heterocyclic group is formed, wherein the 4-6 membered heterocyclic group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 The cycloalkyl group and the 3- to 6-membered heterocyclic group are substituted.

[0118] As the most preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof include but are not limited to the following compounds:

[0119] In a second aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0120] The present invention also relates to the use of the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof in the preparation of drugs for treating at least some tumors associated with CDK.

[0121] As a preferred embodiment, the tumor is cancer.

[0122] As a preferred embodiment, the tumor is breast cancer, malignant brain tumor, colon cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, secondary pancreatic cancer or secondary brain metastasis.

[0123] The present invention also relates to the use of the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof for treating at least some tumors associated with CDK.

[0124] As a preferred embodiment, the tumor is breast cancer, malignant brain tumor, colon cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, secondary pancreatic cancer or secondary brain metastasis.

[0125] The present invention also relates to a method for treating tumors at least partially associated with CDK, comprising administering the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof to a patient in need thereof.

[0126] As a preferred embodiment, the tumor is breast cancer, malignant brain tumor, colon cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, secondary pancreatic cancer or secondary brain metastasis. DETAILED DESCRIPTION

[0127] After extensive and in-depth research, the inventors of this application have developed, for the first time, a CDK inhibitor having the structure of Formula (I) below. This series of compounds can be widely used in the preparation of drugs for treating at least some CDK-related cancers and tumors, and is expected to be developed into a new generation of CDK inhibitors. This has led to the completion of the present invention.

[0128] Detailed Description: Unless otherwise stated or specifically indicated, the following terms used in the specification and claims have the following meanings.

[0129] "Alkyl" refers to a straight-chain or branched saturated aliphatic hydrocarbon group, preferably a straight-chain alkyl group and a branched alkyl group having 1 to 10, 1 to 6, or 1 to 4 carbon atoms, including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl , 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl or its various branched chain isomers, etc. “C 1-10 "Alkyl" refers to a straight chain alkyl group or a branched chain alkyl group containing 1 to 10 carbon atoms. 1-4 "Alkyl" refers to straight chain alkyl and branched chain alkyl groups containing 1 to 4 carbon atoms, "C 0-8 "Alkyl" refers to straight chain alkyl and branched chain alkyl groups including 0 to 8 carbon atoms, "C 0-4 The term "alkyl" refers to straight-chain and branched-chain alkyl groups having 0 to 4 carbon atoms.

[0130] Alkyl groups may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0131] "Cycloalkyl" or "carbocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic aliphatic hydrocarbon substituent. The partially unsaturated cyclic hydrocarbon refers to a cyclic hydrocarbon that may contain one or more (preferably 1, 2 or 3) double bonds, but no ring has a completely conjugated π electron system. Cycloalkyl is divided into monocyclic cycloalkyl and polycyclic cycloalkyl, preferably including 3 to 12 or 3 to 8 or 3 to 6 carbon atoms. For example, "C 3-12 "Cycloalkyl" refers to a cycloalkyl group comprising 3 to 12 carbon atoms, "C 4-8 "Cycloalkyl" refers to a cycloalkyl group comprising 4 to 8 carbon atoms, "C 3-8 "Cycloalkyl" refers to a cycloalkyl group comprising 3 to 8 carbon atoms, "C 3-6 "Cycloalkyl" refers to a cycloalkyl group comprising 3 to 6 carbon atoms, wherein:

[0132] Monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, and the like.

[0133] Polycyclic cycloalkyl groups include spiro, fused, and bridged cycloalkyl groups. "Spiroalkyl" refers to a polycyclic group in which the rings share a carbon atom (called a spiro atom). These may contain one or more (preferably 1, 2, or 3) double bonds, but no ring has a completely conjugated π electron system. Spiroalkyl groups are classified as monospiroalkyl, bispiroalkyl, or polyspiroalkyl groups based on the number of spiro atoms shared between the rings. Spiroalkyl groups include, but are not limited to:

[0134] "Fused cycloalkyl" refers to an all-carbon polycyclic group in which each ring shares a pair of adjacent carbon atoms with other rings in the system, wherein one or more rings may contain one or more (preferably 1, 2, or 3) double bonds, but no ring has a completely conjugated π electron system. Depending on the number of constituent rings, fused cycloalkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Fused cycloalkyl groups include, but are not limited to:

[0135] "Bridged cycloalkyl" refers to an all-carbon polycyclic group in which any two rings share two carbon atoms that are not directly connected. These may contain one or more (preferably 1, 2, or 3) double bonds, but no ring has a completely conjugated π electron system. Depending on the number of constituent rings, bridged cycloalkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Bridged cycloalkyl groups include, but are not limited to:

[0136] The cycloalkyl ring may be fused to an aryl, heteroaryl or heterocycloalkyl ring, wherein the ring connected to the parent structure is a cycloalkyl, including but not limited to indanyl, tetrahydronaphthyl, benzocycloheptanyl and the like.

[0137] Cycloalkyl may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0138] "Heterocyclyl" or "heterocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic aliphatic hydrocarbon substituent, wherein the partially unsaturated cyclic hydrocarbon refers to a cyclic hydrocarbon that may contain one or more (preferably 1, 2 or 3) double bonds, but no ring has a completely conjugated π electron system, and one or more (preferably 1, 2, 3 or 4) ring atoms in the heterocyclyl are selected from N, O, N·O or S(O) r (wherein r is an integer of 0, 1, or 2), but excluding the ring portion of -OO-, -OS-, or -SS-, the remaining ring atoms are carbon. Preferably, the heterocyclyl group comprises 3 to 12, 3 to 8, or 3 to 6 ring atoms, for example, "3-6 membered heterocyclyl" refers to a heterocyclyl group comprising 3 to 6 ring atoms, "3-8 membered heterocyclyl" refers to a heterocyclyl group comprising 3 to 8 ring atoms, "4-8 membered heterocyclyl" refers to a heterocyclyl group comprising 4 to 8 ring atoms, "4-10 membered heterocyclyl" refers to a heterocyclyl group comprising 4 to 10 ring atoms, "5-8 membered heterocyclyl" refers to a heterocyclyl group comprising 5 to 8 ring atoms, and "3-12 membered heterocyclyl" refers to a heterocyclyl group comprising 3 to 12 ring atoms.

[0139] Monocyclic heterocyclyl groups include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, oxetanyl, tetrahydrofuranyl, and the like.

[0140] Polycyclic heterocyclic groups include spiro, fused and bridged heterocyclic groups. "Spiro heterocyclic group" refers to a polycyclic heterocyclic group in which the single rings share an atom (called a spiro atom), wherein one or more (preferably 1, 2, 3 or 4) ring atoms are selected from N, O, N·O or S(O). r (where r is an integer 0, 1, or 2) with the remaining ring atoms being carbon. These may contain one or more double bonds (preferably 1, 2, or 3), but no ring has a completely conjugated π electron system. Spiro heterocyclic groups are classified as monospiro heterocyclic groups, dispiro heterocyclic groups, or polyspiro heterocyclic groups based on the number of spiro atoms shared between the rings. Spiro heterocyclic groups include, but are not limited to:

[0141] "Fused heterocyclyl" refers to a polycyclic heterocyclic group in which each ring in the system shares a pair of adjacent atoms with the other rings in the system, one or more (preferably 1, 2, 3 or 4) rings may contain one or more (preferably 1, 2 or 3) double bonds, but no ring has a completely conjugated π electron system, wherein one or more (preferably 1, 2, 3 or 4) ring atoms are selected from N, O, N·O or S(O) r (where r is an integer of 0, 1, or 2) and the remaining ring atoms are carbon. Depending on the number of rings, fused heterocyclic alkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Fused heterocyclic groups include, but are not limited to:

[0142] "Bridged heterocyclic group" refers to a polycyclic heterocyclic group in which any two rings share two atoms that are not directly connected, these may contain one or more (preferably 1, 2 or 3) double bonds, but no ring has a completely conjugated π electron system, wherein one or more (preferably 1, 2, 3 or 4) ring atoms are selected from N, O, N·O or S(O) r (where r is an integer of 0, 1, or 2) and the remaining ring atoms are carbon. Depending on the number of rings, bridged heterocyclic groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Bridged heterocyclic groups include, but are not limited to:

[0143] The heterocyclyl ring may be fused to an aryl, heteroaryl or cycloalkyl ring, wherein the ring connected to the parent structure is a heterocyclyl, including but not limited to:

[0144] The heterocyclic group may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0145] "Aryl" or "aromatic ring" refers to an all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of carbon atoms) group, a polycyclic (i.e., rings with adjacent pairs of carbon atoms) group having a conjugated π electron system, preferably an all-carbon aromatic group containing 6-10 or 6-8 carbon atoms, for example, "C 6-10 "Aryl" refers to an all-carbon aromatic group containing 6-10 carbon atoms, including but not limited to phenyl and naphthyl. 6-8 "Aryl" refers to an all-carbon aromatic group containing 6-8 carbon atoms. The aromatic ring may be fused to a heteroaryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is an aromatic ring, including but not limited to:

[0146] "Aryl" may be substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0147] "Heteroaryl" refers to a heteroaromatic system containing one or more (preferably 1, 2, 3 or 4) heteroatoms, including N, O, N·O and S(O)r (wherein r is an integer of 0, 1 or 2), preferably a heteroaromatic system containing 5-10, 5-8 or 5-6 ring atoms, for example, "5-8 membered heteroaryl" refers to a heteroaromatic system containing 5-8 ring atoms, and "5-10 membered heteroaryl" refers to a heteroaromatic system containing 5-10 ring atoms, including but not limited to furanyl, thienyl, pyridyl, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, imidazolyl, tetrazolyl, etc. The heteroaryl ring can be fused to an aryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is a heteroaryl ring, including but not limited to:

[0148] "Heteroaryl" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0149] "Alkenyl" refers to an alkyl group as defined above consisting of at least two carbon atoms and at least one carbon-carbon double bond, preferably a straight or branched alkenyl group containing 2-10 or 2-4 carbon atoms, for example, "C 2-10 "Alkenyl" refers to a straight or branched chain alkenyl containing 2 to 10 carbon atoms. 2-4"Alkenyl" refers to a straight or branched chain alkenyl group containing 2 to 4 carbon atoms, including but not limited to ethenyl, 1-propenyl, 2-propenyl, 1-, 2- or 3-butenyl, etc.

[0150] "Alkenyl" may be substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0151] "Alkynyl" refers to an alkyl group as defined above consisting of at least two carbon atoms and at least one carbon-carbon triple bond, preferably a straight or branched chain alkynyl group containing 2-10 or 2-4 carbon atoms, for example, "C 2-10 "Alkynyl" refers to a straight or branched chain alkynyl containing 2 to 10 carbon atoms. 2-4 "Alkynyl" refers to a straight or branched chain alkynyl containing 2-4 carbon atoms, including but not limited to ethynyl, 1-propynyl, 2-propynyl, 1-, 2- or 3-butynyl, etc.

[0152] "Alkynyl" may be substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0153] "Alkoxy" refers to an -O-alkyl group, wherein alkyl is as defined above, for example, "C 1-10 "Alkoxy" refers to an alkyloxy group containing 1 to 10 carbon atoms. 1-4 "Alkoxy" refers to an alkyloxy group containing 1 to 4 carbon atoms. 1-2 The term "alkoxy" refers to an alkyloxy group containing 1 to 2 carbon atoms, including but not limited to methoxy, ethoxy, propoxy, butoxy, etc.

[0154] "Alkoxy" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0155] "Cycloalkoxy" or "cycloalkyloxy" refers to an -O-cycloalkyl group, wherein cycloalkyl is as defined above, for example, "C 3-12 "Cycloalkyloxy" refers to a cycloalkyloxy group containing 3 to 12 carbon atoms. 3-6 The term "cycloalkyloxy" refers to cycloalkyloxy groups containing 3 to 6 carbon atoms, including but not limited to cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and the like.

[0156] "Cycloalkoxy" or "cycloalkyloxy" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0157] "Heterocyclyloxy" or "heterocyclyloxy" refers to an -O-heterocyclyl group wherein heterocyclyl is as defined above and includes, but is not limited to, azetidinyloxy, oxetanyloxy, azopentyloxy, nitrogen, oxhexyloxy, and the like.

[0158] "Heterocyclyloxy" or "heterocyclyloxy" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent.

[0159] “C 1-10 "Alkanoyl" refers to C 1-10 The monovalent atomic group remaining after removing the hydroxyl group from the alkyl acid is usually expressed as "C 0-9 "C1 alkyl-C(O)-" refers to acetyl; "C2 alkyl-C(O)-" refers to propionyl; "C3 alkyl-C(O)-" refers to butyryl or isobutyryl.

[0160] "-C 0-8 Alkyl-S(O)(=N-R7)R8" refers to the sulfur atom in -S(O)(=N-R7)R8 attached to the C 0-8 On the alkyl group, where C 0-8Alkyl is as defined above.

[0161] "-C 0-8 Alkyl-N=S(O)R8R9" refers to the nitrogen atom in -N=S(O)R8R9 connected to the C 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0162] "-C 0-8 Alkyl-N=SR8R9" refers to the nitrogen atom in -N=SR8R9 connected to the C 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0163] "-C 0-8 Alkyl-OS(O)2R 10 ” refers to -OS(O)2R 10 The oxygen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0164] "-C 0-8 Alkyl-S(O) r R 10 ” refers to -S(O) r R 10 The sulfur atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0165] "-C 0-8 Alkyl-P(O)(R 12 )2” refers to -P(O)(R 12 )2 in which the phosphorus atom is connected to the C 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0166] "-C 0-8 Alkyl-OR 11 " refers to -OR 11 The oxygen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0167] "-C 0-8 Alkyl-C(O)OR 11 " refers to -C(O)OR 11 The carbonyl group is connected to C 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0168] "-C 0-8Alkyl-C(O)SR 11 ” refers to -C(O)SR 11 The carbonyl group is connected to C 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0169] "-C 0-8 Alkyl-SC(O)R 12 ” refers to -SC(O)R 12 The sulfur atom in the 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0170] "-C 0-8 Alkyl-C(O)R 12 ” refers to -C(O)R 12 The carbonyl group is connected to C 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0171] "-C 0-8 Alkyl-OC(O)R 12 ” refers to -OC(O)R 12 The oxygen atom in the 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0172] "-C 0-8 Alkyl-NR 13 R 14 ” refers to -NR 13 R 14 The nitrogen atom in the 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0173] "-C 0-8 Alkyl-C(=NR 13 )R 12 " refers to -C(=NR 13 )R 12 The carbon atoms in the 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0174] "-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 ” refers to -N(R 13 )-C(=NR 14 )R 12 The nitrogen atom in the0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0175] "-C 0-8 Alkyl-C(O)NR 13 R 14 ” refers to -C(O)NR 13 R 14 The carbonyl group is connected to C 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0176] "-C 0-8 Alkyl-N(R 13 )-C(O)R 12 ” refers to -N(R 13 )-C(O)R 12 The nitrogen atom in the 0-8 On the alkyl group, where C 0-8 The alkyl group is as defined above.

[0177] "Halogen-substituted C 1-10 The term "alkyl" refers to an alkyl group of 1 to 10 carbon atoms in which the hydrogen atoms on the alkyl group are optionally replaced by fluorine, chlorine, bromine or iodine atoms, including but not limited to difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl and tribromomethyl.

[0178] "Halogen-substituted C 1-10 "Alkoxy" refers to an alkoxy group of 1-10 carbon atoms in which the hydrogen atoms on the alkyl group are optionally replaced by fluorine, chlorine, bromine or iodine atoms. It includes but is not limited to difluoromethoxy, dichloromethoxy, dibromomethoxy, trifluoromethoxy, trichloromethoxy, tribromomethoxy and the like.

[0179] "Deuterium replaces C 1-10 "Alkyl" refers to an alkyl group of 1 to 10 carbon atoms in which the hydrogen atoms on the alkyl group are optionally replaced by deuterium atoms, including but not limited to monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, etc.

[0180] "Halogen" refers to fluorine, chlorine, bromine or iodine.

[0181] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs or does not occur, i.e., includes both substituted and unsubstituted instances. For example, "a heterocyclic group optionally substituted with an alkyl group" means that an alkyl group may but need not be present, and the description includes both instances where the heterocyclic group is substituted with an alkyl group and where the heterocyclic group is not substituted with an alkyl group.

[0182] "Substituted" means that one or more "hydrogen atoms" in a group are independently replaced by a corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, consistent with chemical valence theory, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without undue effort. For example, amino or hydroxy groups with free hydrogens may be unstable when combined with carbon atoms with unsaturated bonds (such as olefins).

[0183] "Stereoisomers," whose English name is stereoisomer, refer to isomers resulting from the different spatial arrangements of atoms in a molecule. They can be divided into two types: cis-trans isomers and enantiomers, or into two major categories: enantiomers and diastereomers. Stereoisomers caused by rotation about single bonds are called conformational stereoisomers, sometimes also called rotamers. Stereoisomers caused by bond length, bond angle, the presence of double bonds or rings in the molecule are called configuration stereoisomers, which are further divided into two categories. Among them, isomers caused by the inability to rotate freely around double bonds or single bonds of ring carbon atoms are called geometric isomers, also called cis-trans isomers, and are divided into two configurations: Z and E. For example, cis-2-butene and trans-2-butene are a pair of geometric isomers. Stereoisomers with different optical rotation properties due to the lack of anti-axial symmetry in the molecule are called optical isomers and are divided into R and S configurations. In this invention, "stereoisomers," unless otherwise specified, are understood to include one or more of the aforementioned enantiomers, configurational isomers, and conformational isomers.

[0184] "Pharmaceutically acceptable salt" in the present invention refers to pharmaceutically acceptable acid addition salts, including inorganic acid salts and organic acid salts, which can be prepared by methods known in the art.

[0185] A "pharmaceutical composition" refers to a mixture containing one or more compounds described herein, or their physiologically / pharmaceutically acceptable salts or prodrugs, together with other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitating absorption of the active ingredient and thereby exerting its biological activity.

[0186] The present invention will be further described in detail and completely below with reference to the embodiments, but the present invention is by no means limited thereto, and the present invention is not limited to the contents of the embodiments.

[0187] The structures of the compounds of the present invention are determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 / 500 NMR spectrometer, using deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), and deuterated chloroform (CDCl3) as the solvents, with tetramethylsilane (TMS) as the internal standard.

[0188] Liquid chromatography-mass spectrometry (LC-MS) was performed using an Agilent 6120 mass spectrometer. HPLC was performed using an Agilent 1200DAD high-pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high-pressure liquid chromatograph (Gimini C18 150×4.6 mm column).

[0189] Thin layer chromatography silica gel plates use Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The specifications used for TLC are 0.15mm-0.20mm, and the specifications used for thin layer chromatography separation and purification products are 0.4mm-0.5mm. Column chromatography generally uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier.

[0190] The starting materials in the examples of the present invention are known and can be purchased commercially, or can be synthesized using or according to methods known in the art.

[0191] Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in a dry nitrogen or argon atmosphere, with dry solvents and reaction temperatures expressed in degrees Celsius (°C).

[0192] Preparation of Examples

[0193] Example A1: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((isopropylamino)methyl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0194] Step 1: Synthesis of 5-bromo-4-isopropylnicotinate

[0195] Under nitrogen, to a solution of methyl 5-bromonicotinate (3.0 g, 13.887 mmol) in tetrahydrofuran (20 mL) was added boron trifluoride etherate (2.17 g, 15.289 mmol). The reaction mixture was allowed to react at -78°C under nitrogen for 30 minutes. Isopropylmagnesium chloride lithium chloride complex (12.819 mL, 1.3 M, 16.664 mmol) was added to the reaction mixture, and the reaction mixture was allowed to react at -78°C under nitrogen for two hours. DDQ (6.30 g, 27.774 mmol) was added to the reaction mixture, and the mixture was allowed to return to room temperature and react for two hours. After dilution with dichloromethane (50 mL), saturated aqueous sodium chloride solution (150 mL) was added, and the mixture was extracted three times with dichloromethane (40 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The organic phase was separated by column chromatography (EA / PA = 0-35%) to obtain methyl 5-bromo-4-isopropylnicotinate (2.7 g, yield: 76.22%). MS (ESI): m / z 258.0 [M+H] + .

[0196] Step 2: Synthesis of (5-bromo-4-isopropylpyridin-3-yl)methanol

[0197] Under nitrogen, lithium aluminum tetrahydride (20 mL, 2.5 M, 50.000 mmol) was added dropwise to a solution of methyl 5-bromo-4-isopropylnicotinate (5.0 g, 19.371 mmol) in tetrahydrofuran (50 mL). The reaction mixture was allowed to react at -78°C under nitrogen for 4 hours. Sodium sulfate decahydrate (10 g) was added to quench the mixture, and the mixture was filtered. The organic phase was concentrated and separated by column chromatography (MeOH / DCM = 0-5%) to afford (5-bromo-4-isopropylpyridin-3-yl)methanol (4.0 g, yield: 67.31%). MS (ESI): m / z 230.1 [M+H] + .

[0198] Step 3: Synthesis of 5-bromo-4-isopropylnicotinaldehyde

[0199] To a solution of (5-bromo-4-isopropylpyridin-3-yl)methanol (4.0 g, 17.384 mmol) in dichloromethane (40 mL) was added manganese dioxide (9.07 g, 104.302 mmol). The reaction mixture was stirred at room temperature for 16 hours. The mixture was filtered through celite, and the organic phase was concentrated and separated by column chromatography (EA / PE = 0-45%) to afford 5-bromo-4-isopropylnicotinaldehyde (3.25 g, yield: 81.97%). MS (ESI): m / z 228.1 [M+H] + .

[0200] Step 4: Synthesis of 4-isopropyl-5-((trimethylsilyl)ethynyl)nicotinaldehyde

[0201] To a solution of 5-bromo-4-isopropylnicotinaldehyde (560 mg, 2.455 mmol) and trimethylsilyl acetylene (723.44 mg, 7.366 mmol) in tetrahydrofuran (10 mL) were added tetrakis(triphenylphosphine)palladium (283.72 mg, 0.246 mmol), triethylamine (2732.83 mg, 27.007 mmol), and cuprous iodide (77.91 mg, 0.246 mmol). The reaction mixture was allowed to react at 100°C under a nitrogen atmosphere for 16 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane (20 mL), and filtered through celite. The organic phase was concentrated and separated by column chromatography (EA / PA = 0-35%) to afford 4-isopropyl-5-((trimethylsilyl)ethynyl)nicotinaldehyde (435.67 mg, yield: 72.31%). MS (ESI): m / z 246.3 [M+H] + .

[0202] Step 5: Synthesis of 5-ethynyl-4-isopropylnicotinaldehyde

[0203] Potassium carbonate (726.38 mg, 5.256 mmol) was added to a solution of 4-isopropyl-5-((trimethylsilyl)ethynyl)nicotinaldehyde (430 mg, 1.752 mmol) in methanol (5 mL). The reaction mixture was stirred at room temperature for 4 hours. The mixture was filtered, the organic phase was concentrated, and column chromatography (MeOH / CH2Cl2 = 0-5%) was used to obtain 5-ethynyl-4-isopropylnicotinaldehyde (160 mg, yield: 52.71%). MS (ESI): m / z 174.2 [M+H] + .

[0204] Step 6: Synthesis of 5-((2,5-dichloropyrimidin-4-yl)ethynyl)-4-isopropylnicotinaldehyde

[0205] To a solution of 5-ethynyl-4-isopropylnicotinaldehyde (160 mg, 0.924 mmol) and 2,4,5-trichloropyrimidine (508.26 mg, 2.771 mmol) in tetrahydrofuran (5 mL) were added tetrakis(triphenylphosphine)palladium (106.74 mg, 0.092 mmol), triethylamine (1028.14 mg, 10.160 mmol), and cuprous iodide (29.31 mg, 0.092 mmol). The reaction mixture was allowed to react at 100°C under a nitrogen atmosphere for 16 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane (20 mL), and filtered through celite. The organic phase was concentrated and separated by column chromatography (EA / PA = 0-35%) to afford 5-((2,5-dichloropyrimidin-4-yl)ethynyl)-4-isopropylnicotinaldehyde (165 mg, yield: 55.79%). MS (ESI): m / z 320.0 [M+H] + .

[0206] Step 7: Synthesis of 5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylnicotinaldehyde

[0207] Potassium carbonate (32.34 mg, 0.234 mmol) was added to a solution of 5-((2,5-dichloropyrimidin-4-yl)ethynyl)-4-isopropylnicotinaldehyde (25 mg, 0.078 mmol) and (3S,4R)-4-aminotetrahydro-2H-pyran-3-ol (18.28 mg, 0.156 mmol) in NMP (3 mL). The reaction mixture was stirred at 100°C for 16 hours. The reaction mixture was cooled to room temperature, added with water, and extracted with dichloromethane. The organic phase was concentrated and separated by column chromatography (MeOH / CH2Cl2 = 0-15%) to obtain 5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylnicotinaldehyde (23.79 mg, yield: 76%). MS (ESI): m / z 401.1 [M+H] + .

[0208] Step 8: Synthesis of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((isopropylamino)methyl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0209] To a solution of 5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylnicotinaldehyde (40 mg, 0.100 mmol) and isopropylamine (11.82 mg, 0.200 mmol) in dichloromethane (3 mL) was added acetic acid (0.6 mg, 0.010 mmol). The reaction mixture was stirred at 0°C for 30 minutes, and then sodium cyanoborohydride (12.57 mg, 0.200 mmol) was added. The mixture was allowed to react at room temperature for 3 hours. Water was then added and the mixture was extracted three times with dichloromethane (20 mL*3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography (MeOH / CH2Cl2 = 0-5%) to give (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((isopropylamino)methyl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (1.35 mg, yield: 3.05%). MS (ESI): m / z 444.2 [M+H] + .

[0210] 1 H NMR (400MHz, DMSO-d6) δ8.59(s,1H),8.50(s,1H),8.46(s,1H),7.61(s,1H),4.94(d,J=5.2Hz,1H),3.87-3.68(m,6H),3.64- 3.55(m,1H),3.52-3.42(m,2H),3.07-2.97(m,1H),2.89-2.64(m,1H),1.89(s,1H),1.53-1.38(m,7H),1.02(d,J=6.2Hz,6H).

[0211] Example A6: Preparation of (3S,4R)-4-((5-chloro-4-((5-((cyclopropylamino)methyl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0212] Step 1: Synthesis of 5-bromo-4-isopropylnicotinate

[0213] Under nitrogen, to a solution of methyl 5-bromonicotinate (3 g, 13.887 mmol) in tetrahydrofuran (20 mL) was added boron trifluoride etherate (2.17 g, 15.289 mmol). The reaction mixture was allowed to react at -78°C under nitrogen for 30 minutes. Isopropylmagnesium chloride lithium chloride complex (12.819 mL, 1.3 M, 16.664 mmol) was added to the reaction mixture, and the reaction mixture was allowed to react at -78°C under nitrogen for two hours. DDQ (6.30 g, 27.774 mmol) was added to the reaction mixture, and the mixture was allowed to return to room temperature and react for two hours. After dilution with dichloromethane (50 mL), saturated aqueous sodium chloride solution (150 mL) was added, and the mixture was extracted three times with dichloromethane (40 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The organic phase was separated by column chromatography (EA / PA = 0-35%) to obtain methyl 5-bromo-4-isopropylnicotinate (2.7 g, yield: 76.22%). MS (ESI): m / z 258.0 [M+H] + .

[0214] Step 2: Synthesis of (5-bromo-4-isopropylpyridin-3-yl)methanol

[0215] Under nitrogen, lithium aluminum tetrahydride (20 mL, 2.5 M, 50.000 mmol) was added dropwise to a solution of methyl 5-bromo-4-isopropylnicotinate (5 g, 19.371 mmol) in tetrahydrofuran (50 mL). The reaction mixture was allowed to react at -78°C under nitrogen for 4 hours. Sodium sulfate decahydrate (10 g) was added to quench the mixture, and the mixture was filtered. The organic phase was concentrated and separated by column chromatography (MeOH / DCM = 0-5%) to afford (5-bromo-4-isopropylpyridin-3-yl)methanol (4.0 g, yield: 67.31%). MS (ESI): m / z 230.1 [M+H] + .

[0216] Step 3: Synthesis of (5-bromo-4-isopropylpyridin-3-yl)methyl ethanesulfonate

[0217] Dissolve (5-bromo-4-isopropylpyridin-3-yl)methanol (450 mg, 1.956 mmol) and triethylamine (816 μL, 5.868 mmol) in DCM (5 mL), and add ethanesulfonyl chloride (377 mg, 2.934 mmol) dropwise. Incubate the reaction at room temperature for 1 hour. After the reaction is complete, use the product directly in the next step. MS (ESI): m / z 322.0 [M+H] + .

[0218] Step 4: Synthesis of N-((5-bromo-4-isopropylpyridin-3-yl)methyl)cyclopropylamine

[0219] Cyclopropylamine (1.355 mL, 19.552 mmol) was added to the reaction mixture and heated to 50°C with stirring for 3 hours. After the reaction was complete, the organic phase was concentrated and separated by column chromatography (MeOH / DCM = 0-5%) to afford N-((5-bromo-4-isopropylpyridin-3-yl)methyl)cyclopropylamine (270 mg, yield: 87%). MS (ESI): m / z 269.2 [M+H] + .

[0220] Step 5: Synthesis of (3S,4R)-4-((5-chloro-4-((5-((cyclopropylamino)methyl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0221] N-((5-bromo-4-isopropylpyridin-3-yl)methyl)cyclopropylamine (270 mg, 1.003 mmol) and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (330 mg, 1.304 mmol) were dissolved in THF (5 mL), and di(tri-tert-butylphosphine)palladium (51.2 mg, 0.100 mmol), cuprous iodide (19.1 mg, 0.100 mmol) and DIPEA (388 mg, 3.009 mmol) were added sequentially. The mixture was heated to 50 ° C and stirred under nitrogen for 3 hours. After the reaction was completed, the mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated. The mixture was separated by reverse phase column chromatography (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to give (3S,4R)-4-((5-chloro-4-((5-((cyclopropylamino)methyl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (36 mg, yield: 8%). MS (ESI): m / z 442.2 [M+H] + .

[0222] 1 H NMR (400MHz, CD3OD) δ8.60(s,1H),8.47(s,1H),8.34(s,1H),3.99-3.86(m,5H),3.68-3.55(m,2H),3.53-3.42(m,1H),3. 25-3.13(m,1H),2.20-2.03(m,2H),1.66-1.56(m,1H),1.55(dd,J=7.0,1.7Hz,6H),0.50-0.42(m,2H),0.38-0.31(m,2H).

[0223] Example A7: Preparation of (3S,4R)-4-((5-chloro-4-((5-(2-hydroxypropan-2-yl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0224] Step 1: Synthesis of 5-chloro-2-(methylthio)-4-((triisopropylsilyl)ethynyl)pyrimidine

[0225] 4,5-Dichloro-2-(methylthio)pyrimidine (3.5 g, 17.943 mmol) was dissolved in DMF (35 mL). Triisopropylsilyl acetylene (9.82 g, 53.829 mmol), Pd(PPh3)2Cl2 (1.26 g, 1.794 mmol), CuI (0.34 g, 1.794 mmol), and DIPEA (6.96 g, 53.830 mmol) were added sequentially. The mixture was sealed under nitrogen and heated to 80°C with stirring overnight. After the reaction, most of the DMF was removed, saturated ammonium chloride was added, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The product was separated by silica gel column chromatography (10% ethyl acetate-petroleum ether) and concentrated to afford 5-chloro-2-(methylthio)-4-((triisopropylsilyl)ethynyl)pyrimidine (5.4 g, yield: 88%) as a yellow oil. MS (ESI): m / z 341.2 [M+H] + .

[0226] Step 2: Synthesis of 5-chloro-2-(methylsulfinyl)-4-((triisopropylsilyl)ethynyl)pyrimidine

[0227] 5-Chloro-2-(methylthio)-4-((triisopropylsilyl)ethynyl)pyrimidine (5.4 g, 15.836 mmol) was dissolved in DCM (100 mL), and mCPBA (5.14 g, 25.338 mmol) was added and stirred overnight. After completion of the reaction, the mixture was cooled to 0°C and quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted three times with dichloromethane. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (50% ethyl acetate-petroleum ether) to afford 5-chloro-2-(methylsulfinyl)-4-((triisopropylsilyl)ethynyl)pyrimidine (4.71 g, yield: 83%). MS (ESI): m / z 357.2 [M+H] + .

[0228] Step 3: Synthesis of (3S,4R)-4-((5-chloro-4-((triisopropylsilyl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0229] 5-Chloro-2-(methylsulfinyl)-4-((triisopropylsilyl)ethynyl)pyrimidine (2.5 g, 7.003 mmol), (3S,4R)-4-aminotetrahydropyran-3-ol hydrochloride (1.61 g, 10.505 mmol), and DIPEA (3.62 g, 28.013 mmol) were dissolved in DMA (25 mL), heated to 90°C, and stirred overnight. After completion of the reaction, the mixture was cooled to room temperature, quenched with water, and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (40% ethyl acetate-petroleum ether) to afford (3S,4R)-4-((5-chloro-4-((triisopropylsilyl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (2.08 g, yield: 72%). MS (ESI): m / z 410.2 [M+H] + .

[0230] Step 4: Synthesis of (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0231] (3S,4R)-4-((5-chloro-4-((triisopropylsilyl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (2.08 g, 5.073 mmol) was dissolved in THF (10 mL). A solution of TBAF in THF (6.087 mL, 6.087 mmol, 1.0 mol / L) was added under ice-cooling. The mixture was stirred under ice-cooling for 1 hour. The reaction was quenched by addition of saturated ammonium chloride and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (50% ethyl acetate-petroleum ether) to give (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (1.2 g, yield: 93%). MS (ESI): m / z 254.1 [M+H] + .

[0232] Step 5: Synthesis of 2-(5-bromo-4-isopropylpyridin-3-yl)propan-2-ol

[0233] Methyl 5-bromo-4-isopropyl nicotinate (700 mg, 3.1 mmol) was dissolved in tetrahydrofuran (5 mL). Methylmagnesium chloride (5.2 mL, 15.6 mmol, 3 M in THF) was added dropwise to the solution under ice-cooling and stirred at room temperature for 2 hours. After completion of the reaction, saturated aqueous ammonium chloride was added and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The mixture was separated by silica gel column chromatography (30% ethyl acetate-petroleum ether) and concentrated to yield 2-(5-bromo-4-isopropylpyridin-3-yl)propan-2-ol (570 mg, yield: 81%). MS (ESI): m / z 258.1 [M+H] + .

[0234] Step 6: Synthesis of (3S,4R)-4-((5-chloro-4-((5-(2-hydroxypropan-2-yl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0235] 2-(5-Bromo-4-isopropylpyridin-3-yl)propan-2-ol (300 mg, 1.16 mmol) and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (245 mg, 0.97 mmol) were dissolved in DMF (1.5 mL), and Pd(PhCN)2Cl2 (37.2 mg, 0.097 mmol), cuprous iodide (18.5 mg, 0.097 mmol), 10% tri-tert-butylphosphine solution (393 mg, 0.194 mmol) and DIPEA (376 mg, 2.91 mmol) were added in sequence. The mixture was heated to 50°C and stirred for 3 hours under nitrogen protection. After the reaction was completed, the mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated. The mixture was separated by reverse phase column chromatography (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to give (3S,4R)-4-((5-chloro-4-((5-(2-hydroxypropan-2-yl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (18 mg, 4% yield). MS (ESI): m / z 431.2 [M+H] + .

[0236] 1H NMR (400MHz, DMSO-d6) δ8.66(s,1H),8.58(s,1H),8.46(s,1H),7.60(s,1H),5.39(s,1H),4.95(d,J=5.3Hz,1H),4.29-4.19(m,1H),3.80(dt,J=1 1.5Hz,5.7Hz,3H),3.47(s,1H),3.29(s,1H),3.03(t,J=10.4Hz,1H),1.8 9(s,1H),1.59(s,6H),1.50(dd,J=7.2Hz,2.8Hz,6H),1.48-1.43(m,1H).

[0237] Examples A8-1 and A8-2: Preparation of (3S,4R)-4-((5-chloro-4-((5-((R)-1-hydroxyethyl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (A8-1) and (3S,4R)-4-((5-chloro-4-((5-((S)-1-hydroxyethyl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (A8-2)

[0238] The racemic compound of Example A8 (300 mg, 0.719 mmol) was separated by chiral SFC (column type: Chiralpak AD-3 50×4.6 mm ID, 3 um; mobile phase A: CO2, mobile phase B: methanol (0.2% MNH3); flow rate: 4.0 mL / min; column temperature: 35°C; detection wavelength: 254 nm) to obtain two optically pure chiral monomer compounds (Examples A8-1 and A8-2) with retention times of 0.758 min (peak 1: 111.4 mg) and 1.186 min (peak 2: 112.9 mg), respectively.

[0239] Peak 1 compound: 1 H NMR (400MHz, DMSO-d6) δ8.68(s,1H),8.58(s,1H),8.46(s,1H),7.60(s,1H),5.45(d,J=4.0Hz,1H),5.16–5.07(m,1H),4.93(d,J=5. 2Hz,1H),3.86–3.73(m,3H),3.64–3.36(m,3H),3.03(t,J=10.4Hz,1H),1.95–1.82(m,1H),1.51–1.43(m,7H),1.38(d,J=6.4Hz,3H).

[0240] Peak 2 compounds: 1 H NMR (400MHz, DMSO-d6) δ8.67(s,1H),8.58(s,1H),8.45(s,1H),7.60(s,1H),5.49–5.40(m,1H),5.19–5.04(m,1H),4.93(d,J=5.2H z,1H),3.85–3.72(m,3H),3.63–3.34(m,3H),3.03(t,J=10.4Hz,1H),1.95–1.81(m,1H),1.49–1.42(m,7H),1.38(d,J=6.0Hz,3H).

[0241] Examples A12-1 and A12-2: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((S)-pyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (A12-1) and (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((R)-pyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (A12-2)

[0242] Step 1: Synthesis of 3-bromo-5-(3,4-dihydro-2H-pyrrol-5-yl)-4-isopropylpyridine

[0243] LiHMDS (19.4 mL, 19.4 mmol) was placed in tetrahydrofuran (25 mL). Under nitrogen, the mixture was cooled to -40°C, followed by the addition of 1-vinylpyrrolidin-2-one (1.55 mL, 14.5 mmol). The mixture was stirred at -40°C for 30 minutes. Methyl 5-bromo-4-isopropyl nicotinate (2.50 g, 9.69 mmol) was then added, and the mixture was stirred at room temperature overnight. Concentrated hydrochloric acid (5 mL) and water (7.5 mL) were added to the reaction solution, and the resulting solution was concentrated. The residue was then placed in concentrated hydrochloric acid (20 mL) and water (20 mL), and the mixture was stirred at 115°C overnight. The reaction solution was diluted with aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the mixture was separated by column chromatography (DCM / MeOH = 100:0-95:5) to obtain 3-bromo-5-(3,4-dihydro-2H-pyrrol-5-yl)-4-isopropylpyridine (1.695 g, yield: 65.5%). MS (ESI): m / z: 267.0 [M+H] + .

[0244] Step 2: Synthesis of 3-bromo-4-isopropyl-5-(pyrrolidin-2-yl)pyridine

[0245] 3-Bromo-5-(3,4-dihydro-2H-pyrrol-5-yl)-4-isopropylpyridine (3.39 g, 12.7 mmol) was placed in methanol (24 mL) and acetic acid (6 mL). Under nitrogen, the mixture was cooled to -50°C, and sodium borohydride (960 mg, 25.4 mmol) was added portionwise. The mixture was stirred at -50°C to room temperature for 2 hours. The reaction solution was diluted with aqueous sodium hydroxide and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the organic phase was separated by column chromatography (DCM / MeOH = 100:0-93:7) to obtain 3-bromo-4-isopropyl-5-(pyrrolidin-2-yl)pyridine (1.82 g, yield: 53.3%). MS (ESI): m / z 269.0 [M+H] + .

[0246] Step 3: Synthesis of tert-butyl 2-(5-bromo-4-isopropylpyridin-3-yl)pyrrolidine-1-carboxylate

[0247] 3-Bromo-4-isopropyl-5-(pyrrolidin-2-yl)pyridine (1.82 g, 6.76 mmol) was placed in dichloromethane (30 mL). The mixture was cooled to 0°C, and then 4-dimethylaminopyridine (83 mg, 0.68 mmol), triethylamine (1.37 g, 13.5 mmol), and di-tert-butyl dicarbonate (2.21 g, 10.1 mmol) were added sequentially. The mixture was stirred at room temperature overnight. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the organic phase was separated by column chromatography (PE / EA = 100:0–85:15) to obtain tert-butyl 2-(5-bromo-4-isopropylpyridin-3-yl)pyrrolidine-1-carboxylate (1.86 g, yield: 74.5%). MS (ESI): m / z 369.1 [M+H] + .

[0248] Step 4: Synthesis of tert-butyl 2-(5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)pyrrolidine-1-carboxylate

[0249] Tert-butyl 2-(5-bromo-4-isopropylpyridin-3-yl)pyrrolidine-1-carboxylate (2.55 g, 6.91 mmol) and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (2.63 g, 10.4 mmol) were placed in N,N-dimethylformamide (30 mL). Cuprous iodide (65.8 mg, 0.35 mmol), bis(tri-tert-butylphosphine)palladium (353 mg, 0.69 mmol), and N,N-diisopropylethylamine (2.68 g, 20.7 mmol) were then added sequentially. The mixture was heated to 50°C and stirred under nitrogen for 3 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the residue was separated by column chromatography (DCM / MeOH = 100:0-95:5) to give tert-butyl 2-(5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)pyrrolidine-1-carboxylate (1.62 g, yield: 43.3%). MS (ESI): m / z 542.3 [M+H] + .

[0250] Step 5: Synthesis of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(pyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0251] Tert-butyl 2-(5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)pyrrolidine-1-carboxylate (1.62 g, 2.99 mmol) was placed in dichloromethane (30 mL), followed by the addition of trifluoroacetic acid (10 mL). The mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated, diluted with sodium bicarbonate, and separated by reverse-phase column chromatography (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to afford (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(pyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (1.17 g, yield: 88.6%). MS (ESI): m / z 442.2 [M+H] + .

[0252] 1H NMR (400MHz, CD3OD) δ8.68(s,1H),8.59(s,1H),8.34(s,1H),4.56-4.52(m,1H),3.97-3.88(m,3H),3.63-3.55(m,2H),3.51-3 .45(m,1H),3.23-3.16(m,2H),3.06-3.00(m,1H),2.35-2.28(m,1H),2.11-2.06(m,1H),1.99-1.89(m,2H),1.67-1.53(m,8H).

[0253] Step 6: Synthesis of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((S)-pyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol and (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((R)-pyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0254] The racemic compound of Example A12 (103 mg, 0.233 mmol) was prepared and separated by chiral SFC (column type: Chiralcel OD-100×4.6 mm ID, 5 um; mobile phase A: CO2, mobile phase B: ethanol (0.02% methylamine); flow rate: 2.0 mL / min; column temperature: 35°C; detection wavelength: 254 nm) to obtain two optically pure chiral monomer compounds (Examples A12-1 and A12-2) with retention times of 1.501 min (peak 1: 41 mg) and 2.942 min (peak 2: 28 mg), respectively.

[0255] Peak 1 compound: 1 H NMR (400MHz, CD3OD) δ8.68(s,1H),8.58(s,1H),8.34(s,1H),4.54-4.50(m,1H),3.97-3.88(m,3H),3.63-3.55(m,2H),3.51-3 .45(m,1H),3.23-3.16(m,2H),3.06-3.00(m,1H),2.35-2.28(m,1H),2.11-2.06(m,1H),1.99-1.89(m,2H),1.67-1.53(m,8H).

[0256] Peak 2 compounds: 1H NMR (400MHz, CD3OD) δ8.68(s,1H),8.58(s,1H),8.34(s,1H),4.58-4.54(m,1H),3.97-3.88(m,3H),3.64-3.55(m,2H),3.51-3 .45(m,1H),3.23-3.16(m,2H),3.06-3.00(m,1H),2.38-2.28(m,1H),2.11-2.06(m,1H),1.99-1.89(m,2H),1.67-1.53(m,8H).

[0257] Example A13: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(tetrahydrofuran-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0258] Step 1: Synthesis of (5-bromo-4-isopropylpyridin-3-yl)(cyclopropyl)methanone

[0259] Methyl 5-bromo-4-isopropyl nicotinate (2.0 g, 7.75 mmol) was placed in tetrahydrofuran (20 mL), and cyclopropylmagnesium bromide (11.6 mL, 11.6 mmol) was added dropwise under ice-cooling. The mixture was stirred at 0°C for 1 hour. The reaction solution was diluted with aqueous ammonium chloride and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, it was separated by column chromatography (PE / EA = 100:0-90:10) to obtain (5-bromo-4-isopropylpyridin-3-yl)(cyclopropyl)methanone (400 mg, yield: 19.3%). MS (ESI): m / z 268.0 [M+H] + .

[0260] Step 2: Synthesis of 1-(5-bromo-4-isopropylpyridin-3-yl)-4-chlorobutan-1-one

[0261] (5-Bromo-4-isopropylpyridin-3-yl)(cyclopropyl)methanone (200 mg, 0.75 mmol) was placed in concentrated hydrochloric acid (4 mL). The mixture was stirred at 100°C overnight. The reaction solution was diluted with sodium hydroxide solution and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the organic phase was separated by column chromatography (PE / EA = 100:0-90:10) to obtain 1-(5-bromo-4-isopropylpyridin-3-yl)-4-chlorobutan-1-one (205 mg, yield: 90.2%). MS (ESI): m / z 306.0 [M+H] + .

[0262] Step 3: Synthesis of 1-(5-bromo-4-isopropylpyridin-3-yl)-4-chlorobutan-1-ol

[0263] 1-(5-Bromo-4-isopropylpyridin-3-yl)-4-chlorobutan-1-one (226 mg, 0.74 mmol) was placed in methanol (10 mL) and sodium borohydride (42.1 mg, 1.11 mmol) was added under ice-cooling. The mixture was stirred at 0°C for 20 minutes. The reaction solution was diluted with aqueous ammonium chloride and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, it was separated by column chromatography (PE / EA = 100:0-70:30) to obtain 1-(5-Bromo-4-isopropylpyridin-3-yl)-4-chlorobutan-1-ol (213 mg, yield: 93.6%). MS (ESI): m / z 308.0 [M+H] + .

[0264] Step 4: Synthesis of 3-bromo-4-isopropyl-5-(tetrahydrofuran-2-yl)pyridine

[0265] 1-(5-Bromo-4-isopropylpyridin-3-yl)-4-chlorobutan-1-ol (213 mg, 0.695 mmol) was placed in DMF (6 mL) and sodium hydride (42 mg, 1.04 mmol) was added under ice-cooling. The mixture was stirred at 0°C for 1 hour. The reaction solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, it was separated by column chromatography (PE / EA = 100:0-90:10) to obtain 3-bromo-4-isopropyl-5-(tetrahydrofuran-2-yl)pyridine (162 mg, yield: 86.3%). MS (ESI): m / z 270.0 [M+H] + .

[0266] Step 5: Synthesis of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(tetrahydrofuran-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0267] 3-Bromo-4-isopropyl-5-(tetrahydrofuran-2-yl)pyridine (162 mg, 0.60 mmol) and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (182.5 mg, 0.72 mmol) were placed in N,N-dimethylformamide (7 mL), followed by the addition of cuprous iodide (11.4 mg, 0.06 mmol), bis(tri-tert-butylphosphine)palladium (31 mg, 0.06 mmol), and N,N-diisopropylethylamine (232.5 mg, 1.80 mmol). The mixture was heated to 50°C and stirred under nitrogen for 3 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the product was separated by column chromatography (DCM / MeOH = 100:0-95:5) and reverse phase column chromatography (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to give (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(tetrahydrofuran-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (143.5 mg, yield: 54.0%). MS (ESI): m / z 443.2 [M+H] + .

[0268] 1 H NMR (400MHz, CD3OD) δ8.61(s,1H),8.60(s,1H),8.34(s,1H),5.24-5.21(m,1H),4.20-4.14(m,1H),3.97-3.88(m,4H),3.61-3.55(m,1H) ),3.51-3.45(m,2H),3.23-3.17(m,1H),2.53-2.45(m,1H),2.13-2.03(m,3H),1.75-1.68(m,1H),1.65-1.59(m,1H),1.56-1.54(m,6H).

[0269] Example A49: Preparation of (S)-1-((5-((5-chloro-2-((5-(6-ethyl-2,6-diazaspiro[3.3]heptane-2-yl)pyridin-2-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol

[0270] Step 1: Synthesis of tert-butyl 6-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate

[0271] 5-Fluoropyridine (644.98 mg, 4.539 mmol) was dissolved in DMF (10 mL). To the solution was added tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate (900 mg, 4.539 mmol) and DIEA (1760.10 mg, 13.618 mmol). The reaction mixture was stirred at 80°C for 18 hours. The reaction mixture was diluted with ethyl acetate and water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and concentrated under reduced pressure. The resulting residue was separated by silica gel column chromatography (ethyl acetate / petroleum ether = 0%-30%) to give tert-butyl 6-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (900 mg, yield: 61.89%). MS (ESI): m / z 321.1 [M+H]. + .

[0272] Step 2: Synthesis of 2-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane trifluoroacetate

[0273] Tert-butyl 6-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (250 mg, 0.780 mmol) was dissolved in dichloromethane (2 mL), and trifluoroacetic acid (1 mL) was added. The reaction solution was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the crude product of 2-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane trifluoroacetate (137 mg, yield: 39%). MS (ESI): m / z: 221.0 [M+H] + .

[0274] Step 3: Synthesis of 2-ethyl-6-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane

[0275] 2-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane trifluoroacetate (137 mg, 0.622 mmol) was dissolved in methanol (2 mL). Triethylamine (0.173 mL, 1.244 mmol), acetaldehyde (0.175 mL, 3.110 mmol), sodium cyanoborohydride (195.46 mg, 3.110 mmol), and 1 drop of acetic acid were added sequentially. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and separated by silica gel column chromatography (ethyl acetate / petroleum ether = 0%-30%) to obtain 2-ethyl-6-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane (150 mg, yield: 97.12%). MS (ESI): m / z 249.2 [M+H]+ .

[0276] Step 4: Synthesis of 5-(6-ethyl-2,6-diazaspiro[3.3]heptane-2-yl)pyridin-2-amine

[0277] 2-Ethyl-6-(6-nitropyridin-3-yl)-2,6-diazaspiro[3.3]heptane (150 mg, 0.604 mmol) was dissolved in methanol (5 mL), and 10% Pd / C (64.29 mg) was added. The mixture was stirred at room temperature overnight under a hydrogen atmosphere. The reaction solution was diluted with dichloromethane, filtered, and washed with 10 mL of ethyl acetate. The filtrates were combined, concentrated, and separated by reverse phase chromatography (0.1% ammonium bicarbonate water: acetonitrile = 0-100%) to obtain 5-(6-ethyl-2,6-diazaspiro[3.3]heptane-2-yl)pyridin-2-amine (130 mg, yield: 98.57%). MS (ESI): m / z 219.2 [M+H] + .

[0278] Step 5: Synthesis of (S)-1-((5-bromo-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol

[0279] 5-Bromo-4-isopropylnicotinaldehyde (980 mg, 4.297 mmol) was dissolved in dichloromethane (5 mL). (S)-piperidin-3-ol (869.19 mg, 8.593 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. Sodium triacetylborohydride (2732.61 mg, 12.890 mmol) was then added and the reaction mixture was stirred at room temperature overnight. After completion of the reaction, the mixture was quenched with water and extracted three times with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was separated by silica gel column chromatography (20% ethyl acetate-petroleum ether) to afford (S)-1-((5-bromo-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol (930 mg, yield: 69.1%). MS (ESI): m / z 313.2 [M+H] + .

[0280] Step 6: Synthesis of (S)-1-((4-isopropyl-5-((trimethylsilyl)ethynyl)pyridin-3-yl)methyl)piperidin-3-ol

[0281] (S)-1-((5-bromo-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol (300 mg, 0.958 mmol) was dissolved in acetonitrile (4 mL). Trimethylsilylacetylene (0.215 mL, 0.958 mmol), bis(acetonitrile)palladium(II) chloride (24.85 mg, 0.096 mmol), Xphos (45.66 mg, 0.096 mmol), and triethylamine (0.399 mL, 2.873 mmol) were added sequentially. The reaction mixture was allowed to react at 90°C under a nitrogen atmosphere overnight. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the crude product (S)-1-((4-isopropyl-5-((trimethylsilyl)ethynyl)pyridin-3-yl)methyl)piperidin-3-ol, which was used in the next reaction (316 mg, yield: 100%). MS (ESI): m / z 331.3 [M+H] + .

[0282] Step 7: Synthesis of (S)-1-((5-ethynyl-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol

[0283] (S)-1-((4-isopropyl-5-((trimethylsilyl)ethynyl)pyridin-3-yl)methyl)piperidin-3-ol (300 mg, 0.908 mmol) was dissolved in methanol (10 mL) and potassium carbonate (1254.27 mg, 9.076 mmol) was added. The reaction mixture was allowed to react at room temperature for 1 hour. The reaction was completed. The reaction mixture was concentrated under reduced pressure and separated by column chromatography (0%-60% ethyl acetate in petroleum ether as eluent) to obtain (S)-1-((5-ethynyl-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol (170 mg, yield: 72.50%). MS (ESI): m / z 259.3 [M+H]+.

[0284] Step 8: Synthesis of (S)-1-((5-((2,5-dichloropyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol

[0285] (S)-1-((5-ethynyl-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol (130 mg, 0.503 mmol) was dissolved in tetrahydrofuran (2 mL), and 2,4,5-trichloropyrimidine (184.58 mg, 1.006 mmol), tetrakis(triphenylphosphine)palladium (4.47 mg, 0.004 mmol), cuprous iodide (9.58 mg, 0.050 mmol) and triethylamine (0.210 mL, 1.509 mmol) were added in sequence. The reaction solution was reacted at 80 ° C under nitrogen protection for 12 hours. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The organic phase was filtered, concentrated, and separated by column chromatography (0%-30% ethyl acetate in petroleum ether as eluent) to obtain (S)-1-((5-((2,5-dichloropyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol (186 mg, yield: 54.72%). MS (ESI): m / z 405.1 [M+H] + .

[0286] Step 9: Synthesis of (S)-1-((5-((5-chloro-2-((5-(6-ethyl-2,6-diazaspiro[3.3]heptane-2-yl)pyridin-2-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol

[0287] 5-(6-Ethyl-2,6-diazaspiro[3.3]heptan-2-yl)pyridin-2-amine (32.32 mg, 0.148 mmol) was dissolved in toluene (2 mL) and tert-butanol (0.5 mL). (S)-1-((5-((2,5-dichloropyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol (60 mg, 0.148 mmol), cesium carbonate (80.39 mg, 0.247 mmol), Pd2(dba)3 (11.30 mg, 0.012 mmol), and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (5.88 mg, 0.012 mmol) were added. The reaction mixture was stirred at 100°C overnight under a nitrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated and separated by preparative liquid chromatography to obtain (S)-1-((5-((5-chloro-2-((5-(6-ethyl-2,6-diazaspiro[3.3]heptane-2-yl)pyridin-2-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)methyl)piperidin-3-ol (7.4 mg, yield: 8.51%). MS (ESI): m / z 587.4 [M+H] + .

[0288] 1 H NMR (400MHz, DMSO-d6) δ9.93(s,1H),8.65(d,J=6.0Hz,2H),8.43(s,1H),7.87(d,J=8.8Hz,1H),7.57(d,J=3.0 Hz,1H),6.92(dd,J=8.8,3.0Hz,1H),4.62(d,J=4.7Hz,1H),3.88(s,4H),3.66-3.55(m,2H),3.52-3.45(m,2H) ,3.21(s,4H),2.75-2.70(m,1H),2.64-2.58(m,1H),2.32(t,J=7.1Hz,2H),1.94-1.86(m,1H),1.76(q,J=12.2 Hz,2H),1.66-1.58(m,1H),1.48(d,J=7.1Hz,6H),1.38-1.30(m,1H),1.12-1.02(m,1H),0.85(t,J=7.1Hz,3H).

[0289] Examples A53-1 and A53-2: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((R)-1-(methylamino)ethyl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (A53-1) and (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((S)-1-(methylamino)ethyl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (A53-2)

[0290] The racemic compound of Example A53 (110 mg, 0.2558 mmol) was prepared and separated by chiral SFC (column type: Column: ChiralCel OJ-H 150×4.6 mm ID, 5 um; mobile phase A: CO2, mobile phase B: methanol (0.05% diethanolamine); flow rate: 2.5 mL / min; column temperature: 40°C; detection wavelength: 220 nm) to obtain two optically pure chiral monomer compounds (Examples A53-1 and A53-2) with retention times of 2.743 min (peak 1: 33.4 mg) and 3.138 min (peak 2: 35.3 mg), respectively.

[0291] Peak 1 compound: 1H NMR (400MHz, DMSO-d6) δ8.69(s,1H),8.56(s,1H),8.46(s,1H),7.61(s,1H),4.93(d,J=5.3Hz,1H),4.12-3.97(m,1H),3.87-3.60(m,5H) ,3.54-3.42(m,1H),3.29-3.25(m,1H),3.03(t,J=10.4Hz,1H),2.15(s,3H),1.92-1.86(m,1H),1.49-1.43(m,7H),1.28(d,J=6.5Hz,3H).

[0292] Peak 2 compounds: 1 H NMR (400MHz, DMSO-d6) δ8.69(s,1H),8.57(s,1H),8.46(s,1H),7.61(s,1H),4.93(d,J=5.3Hz,1H),4.13-4.00(m,1H),3.89-3.58(m,5H),3.54 -3.41(m,1H),3.30-3.25(m,1H),3.03(t,J=10.4Hz,1H),2.16(s,3H),1.93-1.86(m,1H),1.46(dd,J=12.1,7.1Hz,7H),1.28(d,J=6.5Hz,3H).

[0293] Examples A56-1 and A56-2: Preparation of (3S,4R)-4-((4-((5-((R)-1-aminoethyl)-4-isopropylpyridin-3-yl)ethynyl)-5-chloropyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (A56-1) and (3S,4R)-4-((4-((5-((S)-1-aminoethyl)-4-isopropylpyridin-3-yl)ethynyl)-5-chloropyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (A56-2)

[0294] The racemic compound of Example A56 (88 mg, 0.2116 mmol) was separated by chiral SFC (column type: Chiralpak AD-3 50×4.6 mm ID, 3 um; mobile phase A: CO2, mobile phase B: isopropanol (0.2% MNH3); flow rate: 4 mL / min; column temperature: 35°C; detection wavelength: 220 nm) to obtain two optically pure chiral monomer compounds (Examples A56-1 and A56-2) with retention times of 0.621 min (peak 1: 25.3 mg) and 0.926 min (peak 2: 21.1 mg), respectively.

[0295] Peak 1 compound: 1 H NMR (400MHz, CD3OD) δ8.71(s,1H),8.60(s,1H),8.35(s,1H),4.57(q,J=6.7Hz,1H),3.98-3.88(m,3H),3.71-3 .55(m,2H),3.52-3.45(m,1H),3.23-3.17(m,1H),2.13-2.07(m,1H),1.62-1.53(m,7H),1.45(d,J=6.7Hz,3H).

[0296] Peak 2 compounds: 1 H NMR (400MHz, CD3OD) δ8.70(s,1H),8.60(s,1H),8.35(s,1H),4.59(q,J=6.6Hz,1H),3.98-3.88(m,3H),3.69-3 .55(m,2H),3.51-3.45(m,1H),3.22-3.17(m,1H),2.13-2.06(m,1H),1.61-1.52(m,7H),1.45(d,J=6.7Hz,3H).

[0297] Examples A92-1 and A92-2: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((R)-1-(methylamino)ethyl-2,2,2-d3)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol and (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((S)-1-(methylamino)ethyl-2,2,2-d3)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0298] The racemic compound (70 mg, 0.1617 mmol) was prepared and separated by chiral SFC (column type: ChiralCel OJ-H150×4.6 mm ID, 5 um; mobile phase A: CO2, mobile phase B: methanol (0.05% diethanolamine); flow rate: 2.5 mL / min; column temperature: 40°C; detection wavelength: 220 nm) to obtain two optically pure chiral monomer compounds (Examples A92-1 and A92-2) with retention times of 2.739 min (peak 1: 15.2 mg) and 3.129 min (peak 2: 16.5 mg), respectively.

[0299] Peak 1 compound: 1H NMR (400MHz, DMSO-d6) δ8.69(s,1H),8.56(s,1H),8.46(s,1H),7.61(s,1H),4.93(d,J=5.3Hz,1H),4.09-3.96(m,1H),3.88-3 .62(m,5H),3.54-3.40(m,1H),3.30-3.24(m,1H),3.03(t,J=10.4Hz,1H),2.15(s,3H),1.94-1.85(m,1H),1.49-1.43(m,7H).

[0300] Peak 2 compounds: 1 H NMR (400MHz, DMSO-d6) δ8.69(s,1H),8.57(s,1H),8.46(s,1H),7.61(s,1H),4.94(d,J=5.3Hz,1H),4.10-3.97(m,1H),3.92-3 .57(m,5H),3.54-3.42(m,1H),3.30-3.24(m,1H),3.03(t,J=10.4Hz,1H),2.16(s,3H),1.94-1.85(m,1H),1.50-1.42(m,7H).

[0301] Examples A99-1 and A99-2: Preparation of (3S,4R)-4-((5-chloro-4-((5-((S)-1-(ethylamino)ethyl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol and (3S,4R)-4-((5-chloro-4-((5-((R)-1-(ethylamino)ethyl)-4-isopropylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0302] The racemic compound (400 mg, 0.9029 mmol) was separated by chiral SFC (column type: ChiralCel OJ-H150×4.6 mm ID, 5 um; mobile phase A: CO2; mobile phase B: methanol (0.05% diethanolamine); flow rate: 2.5 mL / min; column temperature: 40°C; detection wavelength: 220 nm) to obtain two optically pure chiral monomer compounds A99-1 and A99-2 with retention times of 2.502 min (peak 1: 121.3 mg) and 2.900 min (peak 2: 132.0 mg), respectively.

[0303] Peak 1 compound: (400MHz, DMSO-d6) δ8.71(s,1H),8.56(s,1H),8.45(s,1H),7.60(s,1H),4.93(d,J=5.3Hz,1H),4.14(t,J=6.7Hz,1H),3.80(dt,J=11.7,5.5Hz,3H),3.72(d,J=7.1Hz,1H),3.51–3.42(m,1H),3.35(d,J=2.3Hz, 1H),3.29(d,J=2.6Hz,1H),3.03(t,J=10.4Hz,1H),2.44(dd,J=10.9,6.7Hz,1H),2.34–2.25(m,1H),1.90(d ,J=13.1Hz,1H),1.50(d,J=7.5Hz,1H),1.46(t,J=7.1Hz,6H),1.28(d,J=6.6Hz,3H),0.99(t,J=7.0Hz,3H).

[0304] Peak 2 compound: (400MHz, DMSO-d6) δ8.71(s,1H),8.56(s,1H),8.46(s,1H),7.61(s,1H),4.94(d,J=5.3Hz,1H),4.15(t,J=6.8Hz,1H),3.80(dt,J=10.5,5.2Hz,3H),3.74–3.67(m,1H),3.47(dt,J=10.4,5.1Hz,1H),3.35(d,J=2 .1Hz,1H),3.29(d,J=2.1Hz,1H),3.03(t,J=10.4Hz,1H),2.46–2.39(m,1H),2.34–2.26(m,1H),1.90(d,J=12 .9Hz,1H),1.50(d,J=7.0Hz,1H),1.46(dd,J=10.8,7.1Hz,6H),1.29(d,J=6.5Hz,3H),0.99(t,J=7.0Hz,3H).

[0305] Example A114: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(1-methylpyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0306] Step 1: Synthesis of 3-bromo-4-isopropyl-5-(1-methylpyrrolidin-2-yl)pyridine

[0307] 3-Bromo-4-isopropyl-5-(pyrrolidin-2-yl)pyridine (200 mg, 0.74 mmol) was placed in formic acid (0.8 mL) and 37% formaldehyde (0.8 mL). The mixture was stirred at 80°C for 3 hours. The reaction solution was diluted with sodium hydroxide solution and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, it was separated by column chromatography (PE / EA = 100:0-85:15) to obtain 3-bromo-4-isopropyl-5-(1-methylpyrrolidin-2-yl)pyridine (152 mg, yield: 72.3%). MS (ESI): m / z 283.0 [M+H] + .

[0308] Step 2: Synthesis of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(1-methylpyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0309] 3-Bromo-4-isopropyl-5-(1-methylpyrrolidin-2-yl)pyridine (112 mg, 0.40 mmol) and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (131 mg, 0.51 mmol) were placed in N,N-dimethylformamide (3 mL). Cuprous iodide (7.5 mg, 0.04 mmol), bis(tri-tert-butylphosphine)palladium (20.2 mg, 0.04 mmol), and N,N-diisopropylethylamine (153.3 mg, 1.19 mmol) were then added sequentially. The mixture was heated to 50°C and stirred under nitrogen for 3 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the mixture was separated by column chromatography (DCM / MeOH = 100:0-95:5) and reverse-phase column chromatography (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to give (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(1-methylpyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (92.5 mg, yield: 51.3%). MS (ESI): m / z 456.2 [M+H] + .

[0310] 1H NMR: (400MHz, CD3OD) δ8.71(s,1H),8.58(s,1H),8.34(s,1H),3.98-3.88(m,3H),3.72-3.68(m,1H),3.62-3.56(m,2H),3.52-3.45(m ,1H),3.28-3.18(m,2H),2.41-2.31(m,2H),2.22(s,3H),2.12-2.08(m,1H),1.99-1.86(m,2H),1.67-1.58(m,2H),1.56-1.52(m,6H).

[0311] Example A139: Preparation of (3S,4R)-4-((5-chloro-4-((2-fluoro-4-isopropyl-5-((isopropylamino)methyl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0312] Step 1: Synthesis of methyl 5-bromo-6-fluoro-4-isopropyl nicotinate

[0313] Under nitrogen, boron trifluoride etherate (13.191 mL, 104.094 mmol) was added to a solution of methyl 5-bromo-6-fluoronicotinate (20.3 g, 86.745 mmol) in tetrahydrofuran (200 mL). The reaction mixture was allowed to react at 0°C under nitrogen for 30 minutes. After cooling the reaction mixture to -78°C, isopropylmagnesium chloride lithium chloride complex (86.745 mL, 112.768 mmol, 1.3 M) was added and the reaction mixture was allowed to react at this temperature for two hours. DDQ (23.63 g, 104.094 mmol) was added to the reaction mixture, and the mixture was allowed to return to room temperature and react for 12 hours. After dilution with water, extraction with ethyl acetate was performed. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The organic phase was filtered, concentrated, and separated by column chromatography (EA / PA = 0-10%) to obtain methyl 5-bromo-6-fluoro-4-isopropyl nicotinate (8.34 g, yield: 34.82%). MS (ESI): m / z 276.0 [M+H] + .

[0314] Step 2: Synthesis of (5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methanol

[0315] Under nitrogen, diisobutylaluminum hydride (75.513 mL, 75.513 mmol, 1.0 M) was added dropwise to a solution of 5-bromo-6-fluoro-4-isopropyl nicotinate (8.34 g, 30.205 mmol) in tetrahydrofuran (80 mL). The reaction mixture was allowed to react at 0°C for 2 hours. Methanol was slowly added dropwise until no bubbles formed. Saturated sodium potassium tartrate solution (100 mL) was added and stirred for 30 minutes. Ethyl acetate was then added for extraction. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The organic phase was separated by column chromatography (EA / PA = 0-15%) to afford (5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methanol (4.5 g, yield: 60.08%). MS (ESI): m / z 248.1 [M+H] + .

[0316] Step 3: Synthesis of N-((5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methyl)propane-2-amine

[0317] To a solution of (5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methanol (780 mg, 3.144 mmol) and N-ethyldiisopropylamine (2.738 mL, 15.719 mmol) in acetonitrile (10 mL) was added ethylsulfonyl chloride (0.599 mL, 6.288 mmol). The reaction mixture was stirred at room temperature for 2 hours, followed by the addition of isopropylamine (1.347 mL, 15.719 mmol). The reaction mixture was allowed to react at 50°C for 12 hours. The reaction mixture was concentrated and separated by column chromatography (MeOH / DCM = 0-8%) to afford N-((5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methyl)propan-2-amine (806 mg, yield: 88.65%). MS (ESI): m / z 289.0 [M+H] + .

[0318] Step 4: Synthesis of tert-butyl ((5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methyl) (isopropyl) carbamate

[0319] To a solution of N-((5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methyl)propan-2-amine (806 mg, 2.787 mmol) and N-ethyldiisopropylamine (0.971 mL, 5.574 mmol) in dichloromethane (10 mL) was added di-tert-butyl dicarbonate (0.960 mL, 4.181 mmol). The reaction mixture was allowed to react at 25°C for 12 hours. The reaction mixture was diluted with 10% citric acid solution (50 mL) and extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The organic phase was separated by column chromatography (EA / PA = 0-15%) to afford tert-butyl ((5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate (877 mg, yield: 80.83%). MS (ESI): m / z 389.0 [M+H] + .

[0320] Step 5: Synthesis of tert-butyl ((6-fluoro-4-isopropyl-5-((triisopropylsilyl)ethynyl)pyridin-3-yl)methyl) (isopropyl)carbamate

[0321] Under nitrogen protection, to a solution of tert-butyl ((5-bromo-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate (877 mg, 2.253 mmol), triisopropylsilyl acetylene (2.527 mL, 11.264 mmol), and N-ethyldiisopropylamine (1.177 mL, 6.758 mmol) in N,N-dimethylformamide (10 mL) were added cuprous iodide (42.90 mg, 0.225 mmol) and bis(tri-tert-butylphosphine)palladium(0) (115.13 mg, 0.225 mmol). The reaction mixture was reacted at 100°C under nitrogen protection for 12 hours. The reaction mixture was cooled and diluted with water (100 mL), extracted with ethyl acetate, and the combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The organic phase was filtered, concentrated, and separated by column chromatography (EtOAc / PE = 0-5%) to give tert-butyl ((6-fluoro-4-isopropyl-5-((triisopropylsilyl)ethynyl)pyridin-3-yl)methyl)(isopropyl)carbamate (1.1 g, yield: 99.50%). MS (ESI): m / z 491.3 [M+H] + .

[0322] Step 6: Synthesis of tert-butyl ((5-ethynyl-6-fluoro-4-isopropylpyridin-3-yl)methyl) (isopropyl) carbamate

[0323] To a solution of tert-butyl ((6-fluoro-4-isopropyl-5-((triisopropylsilyl)ethynyl)pyridin-3-yl)methyl)(isopropyl)carbamate (1.1 g, 2.241 mmol) in tetrahydrofuran (10 mL) was added tetrabutylammonium fluoride (2.465 mL, 2.465 mmol, 1.0 M). The reaction mixture was allowed to react at room temperature for 1 hour. The reaction mixture was diluted with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The organic phase was filtered, concentrated, and separated by column chromatography (EA / PA = 0-6%) to afford tert-butyl ((5-ethynyl-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate (604 mg, yield: 80.58%). MS (ESI): m / z 335.2 [M+H] + .

[0324] Step 7: Synthesis of tert-butyl ((5-((2,5-dichloropyrimidin-4-yl)ethynyl)-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate

[0325] To a solution of tert-butyl ((5-ethynyl-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate (564 mg, 1.69 mmol), 2,4,5-trichloropyrimidine (386.66 μL, 3.373 mmol), and N-ethyldiisopropylamine (881.28 μL, 5.06 mmol) in N,N-dimethylformamide (10 mL) was added cuprous iodide (32.12 mg, 0.169 mmol) and tetrakis(triphenylphosphine)palladium (194.88 mg, 0.169 mmol) under nitrogen. The reaction mixture was reacted at 80°C under nitrogen for 12 hours. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated, and separated by column chromatography (EtOAc / PE = 0-10%) to give tert-butyl ((5-((2,5-dichloropyrimidin-4-yl)ethynyl)-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate (500 mg, yield: 61.59%). MS (ESI): m / z 481.1 [M+H] + .

[0326] Step 8: Synthesis of tert-butyl ((5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate

[0327] To a solution of tert-butyl ((5-((2,5-dichloropyrimidin-4-yl)ethynyl)-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate (500 mg, 1.04 mmol) and N-ethyldiisopropylamine (542.77 μL, 3.14 mmol) in NMP (10 mL) was added (3S,4R)-4-aminotetrahydropyran-3-ol hydrochloride (239.31 mg, 1.56 mmol). The reaction mixture was reacted at 80°C for 12 hours. The reaction mixture was cooled and diluted with water, extracted with ethyl acetate, and the combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated, and separated by column chromatography (EtOAc / PE = 0-60%) to give tert-butyl ((5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate (550 mg, 65% purity, yield: 61.24%). MS (ESI): m / z 562.3 [M+H] + .

[0328] Step 9: Synthesis of (3S,4R)-4-((5-chloro-4-((2-fluoro-4-isopropyl-5-((isopropylamino)methyl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0329] To a solution of tert-butyl ((5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-6-fluoro-4-isopropylpyridin-3-yl)methyl)(isopropyl)carbamate (550 mg, 0.636 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (1 mL). The reaction mixture was allowed to react at room temperature for 2 hours. The reaction mixture was diluted with saturated sodium bicarbonate solution and extracted with dichloromethane. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The product was filtered and concentrated. Preparative HPLC (acetonitrile-ammonium bicarbonate aqueous solution) yielded (3S,4R)-4-((5-chloro-4-((2-fluoro-4-isopropyl-5-((isopropylamino)methyl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (61.8 mg, yield: 20.82%). MS (ESI): m / z 462.1 [M+H]. + .

[0330] 1H NMR (400MHz, DMSO-d6) δ8.47(s,1H),8.18(s,1H),7.65(s,1H),4.93(d,J=5.2Hz,1H),3.87-3.76(m,3H),3.74(s,2H),3.68-3.56(m,1H),3. 53-3.42(m,1H),3.30-3.24(m,1H),3.02(t,J=10.4Hz,1H),2.80-2.67(m,1H),1.98-1.75(m,2H),1.53-1.39(m,7H),1.02(d,J=6.0Hz,6H).

[0331] Example A223: Preparation of (3S,4R)-4-((5-chloro-4-((6-fluoro-4-isopropyl-5-((isopropylamino)methyl)-2-methylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0332] Step 1: Synthesis of methyl 2-amino-6-chloro-4-(prop-1-en-2-yl) nicotinate

[0333] Methyl 2-amino-4,6-dichloronicotinate (10 g, 45.241 mmol) was dissolved in toluene (200 mL) and water (50 mL), and 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (8.36 g, 49.765 mmol), palladium acetate (0.51 g, 30.03 mmol), tricyclohexylphosphine (1.27 g, 4.524 mmol), and K2CO3 (12.50 g, 90.483 mmol) were added in sequence. The mixture was heated to 100°C under nitrogen protection and stirred overnight. After the reaction, an appropriate amount of water was added, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10% ethyl acetate-petroleum ether) to obtain methyl 2-amino-6-chloro-4-(prop-1-en-2-yl) nicotinate (5.1 g, yield: 29%, the more polar isomer being the product). MS (ESI): m / z 227.0 [M+H] + .

[0334] Step 2: Synthesis of methyl 2-amino-6-methyl-4-(prop-1-en-2-yl) nicotinate

[0335] Methyl 2-amino-6-chloro-4-(prop-1-en-2-yl) nicotinate (5.1 g, 13.500 mmol) was dissolved in toluene (100 mL) and water (20 mL). 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborin (3.39 g, 27.00 mmol), palladium acetate (0.30 g, 1.35 mmol), tricyclohexylphosphine (0.38 g, 1.350 mmol), and K2CO3 (3.73 g, 27.00 mmol) were added in sequence. The mixture was heated to 100°C under nitrogen protection and stirred overnight. After the reaction was complete, an appropriate amount of water was added and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10% ethyl acetate-petroleum ether) to afford methyl 2-amino-6-methyl-4-(prop-1-en-2-yl) nicotinate (1.2 g, yield: 43%). MS (ESI): m / z 207.0 [M+H] + .

[0336] Step 3: Synthesis of methyl 2-amino-4-isopropyl-6-methyl nicotinate

[0337] Methyl 2-amino-6-methyl-4-(prop-1-en-2-yl) nicotinate (1.2 g, 5.82 mmol) was dissolved in methanol (20 mL). Pd(OH)2 / C (600 mg, 20%) was added. The mixture was heated to 45°C under a hydrogen atmosphere and stirred overnight. After the reaction was complete, the mixture was cooled to room temperature, filtered, and concentrated to afford methyl 2-amino-4-isopropyl-6-methylnicotinate (1.2 g, yield: 100%). MS (ESI): m / z 209.2 [M+H] + .

[0338] Step 4: Synthesis of methyl 2-amino-5-bromo-4-isopropyl-6-methyl nicotinate

[0339] Methyl 2-amino-4-isopropyl-6-methylnicotinate (1.47 g, 7.06 mmol) was dissolved in dichloromethane (25 mL), and NBS (1.38 g, 7.76 mmol) was added. The mixture was stirred at room temperature overnight, and the reaction was quenched by adding saturated aqueous sodium bicarbonate. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Methyl 2-amino-5-bromo-4-isopropyl-6-methylnicotinate (1.67 g, yield: 82%) was obtained by silica gel column chromatography (10% ethyl acetate-petroleum ether). MS (ESI): m / z 287.0 [M+H] + .

[0340] Step 5: Synthesis of methyl 5-bromo-2-fluoro-4-isopropyl-6-methylnicotinate

[0341] Methyl 2-amino-5-bromo-4-isopropyl-6-methylnicotinate (1.67 g, 5.816 mmol) was dissolved in tetrahydrofuran (20 mL) and placed in an ice-water bath. Hydrogen fluoride pyridine solution (3.32 g, 116.313 mmol, 70%) and sodium nitrite (0.60 g, 8.723 mmol) were added sequentially. The mixture was heated to 35°C under nitrogen and stirred overnight. After completion of the reaction, the mixture was placed in an ice-water bath and quenched with saturated sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10-20% ethyl acetate in petroleum ether) to afford methyl 5-bromo-2-fluoro-4-isopropyl-6-methylnicotinate (1.12 g, yield: 66%). MS (ESI): m / z 287.0 [M+H] + .

[0342] Step 6: Synthesis of (5-bromo-2-fluoro-4-isopropyl-6-methylpyridin-3-yl)methanol

[0343] Methyl 5-bromo-2-fluoro-4-isopropyl-6-methylnicotinate (1.1 g, 3.79 mmol) was dissolved in THF (10 mL) and placed in an ice-water bath. DIBAL-H (11.37 mL, 11.374 mmol, 1 M THF solution) was added dropwise and stirred at room temperature for 1 to 2 hours. After completion of the reaction, the mixture was placed in an ice-water bath and quenched with methanol dropwise until bubbling ceased. An appropriate amount of aqueous potassium sodium tartrate was added and stirred for at least 30 minutes. The mixture was filtered and the filtrate was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to yield (5-bromo-2-fluoro-4-isopropyl-6-methylpyridin-3-yl)methanol (730 mg, yield: 73%). MS (ESI): m / z 262.0 [M+H] + .

[0344] Step 7: Synthesis of (5-bromo-2-fluoro-4-isopropyl-6-methylpyridin-3-yl)methyl ethanesulfonate

[0345] Dissolve (5-bromo-2-fluoro-4-isopropyl-6-methylpyridin-3-yl)methanol (730 mg, 2.785 mmol) in dichloromethane (10 mL) and place in an ice-water bath. Add DIPEA (719.91 mg, 5.570 mmol) and ethylsulfonyl chloride (429.67 mg, 3.34 mmol) sequentially. Return to room temperature and stir for 2 hours. Once the reaction is complete, concentrate the resulting solution and use it directly in the next step (986 mg, yield: 100%). MS (ESI): m / z 354.0 [M+H] + .

[0346] Step 8: Synthesis of N-((5-bromo-2-fluoro-4-isopropyl-6-methylpyridin-3-yl)methyl)propane-2-amine

[0347] Dissolve (5-bromo-2-fluoro-4-isopropyl-6-methylpyridin-3-yl)methylethanesulfonate (986 mg, 2.783 mmol) in acetonitrile (10 mL), add DIPEA (1.08 g, 8.35 mmol) and isopropylamine (658 mg, 11.13 mmol), and stir at room temperature overnight. After completion of the reaction, place in an ice-water bath, quench with saturated sodium bicarbonate solution, and extract three times with ethyl acetate. The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Separate by silica gel column chromatography (20% ethyl acetate-petroleum ether) to afford N-((5-bromo-2-fluoro-4-isopropyl-6-methylpyridin-3-yl)methyl)propan-2-amine (760 mg, yield: 90%). MS (ESI): m / z 303.0 [M+H] + .

[0348] Step 9: Synthesis of (3S,4R)-4-((5-chloro-4-((6-fluoro-4-isopropyl-5-((isopropylamino)methyl)-2-methylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0349] N-((5-bromo-2-fluoro-4-isopropyl-6-methylpyridin-3-yl)methyl)propan-2-amine (300 mg, 0.989 mmol) and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (326 mg, 1.29 mmol) were dissolved in DMF (3 mL). Di(tri-tert-butylphosphine)palladium (101 mg, 0.198 mmol), CuI (18.84 mg, 0.099 mmol), and DIPEA (383.63 mg, 2.968 mmol) were added sequentially. The atmosphere was replaced with nitrogen three times, and the reaction solution was placed in an oil bath preheated to 60°C and stirred for 3 hours. After the reaction was completed, the mixture was cooled to room temperature and quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was separated by silica gel column chromatography (10% methanol-dichloromethane system). The crude product was then separated by reverse phase separation (0.1% aqueous ammonium bicarbonate: acetonitrile = 0-100%) to give (3S,4R)-4-((5-chloro-4-((6-fluoro-4-isopropyl-5-((isopropylamino)methyl)-2-methylpyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (38 mg, yield: 8%). MS (ESI): m / z 476.4 [M+H] + .

[0350] 1 H NMR (400MHz, CD3OD) δ8.34 (s, 1H), 4.00-3.83 (m, 5H), 3.70-3.55 (m, 2H), 3.46 (td, J = 11.7, 2.3Hz, 1H), 3.23-3.13 (m, 1H), 2. 99-2.88(m,1H),2.69(s,3H),2.11(d,J=13.2Hz,1H),1.67-1.60(m,1H),1.58(dd,J=7.1,3.0Hz,6H),1.15(d,J=6.3Hz,6H).

[0351] Example A281: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(5-methylpyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0352] Step 1: Synthesis of tert-butyl 2-methyl-5-oxopyrrolidine-1-carboxylate

[0353] 5-Methylpyrrolidin-2-one (3.0 g, 30.3 mmol) was placed in dichloromethane (60 mL). The mixture was cooled to 0°C, and then 4-dimethylaminopyridine (369.7 mg, 3.03 mmol), triethylamine (6.12 g, 60.5 mmol), and di-tert-butyl dicarbonate (9.91 g, 45.4 mmol) were added in sequence. The mixture was stirred at room temperature overnight. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, it was separated by column chromatography (PE / EA = 100:0-85:15) to obtain tert-butyl 2-methyl-5-oxopyrrolidine-1-carboxylate (5.71 g, yield: 94.7%). MS (ESI): m / z 200.1 [M+H] + .

[0354] Step 2: Synthesis of tert-butyl (5-(5-bromo-4-isopropylpyridin-3-yl)-5-oxopentan-2-yl)carbamate

[0355] 3,5-Dibromo-4-isopropylpyridine (4.5 g, 16.1 mmol) was placed in tetrahydrofuran (60 mL). The mixture was cooled to 0°C, and then isopropylmagnesium chloride (8.79 mL, 17.7 mmol) was added dropwise. The mixture was stirred at 0°C for 1 hour. Tert-butyl-2-methyl-5-carbonylpyrrolidine-1-carboxylate (3.75 g, 17.7 mmol) was then added. The mixture was stirred at room temperature overnight. The reaction solution was diluted with aqueous ammonium chloride and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (PE / EA = 100:0-80:20) to provide tert-butyl (5-(5-bromo-4-isopropylpyridin-3-yl)-5-oxopentan-2-yl)carbamate (800 mg, yield: 12.4%). MS (ESI): m / z 399.1 [M+H] + .

[0356] Step 3: Synthesis of 3-bromo-4-isopropyl-5-(2-methyl-3,4-dihydro-2H-pyrrol-5-yl)pyridine

[0357] Tert-butyl (5-(5-bromo-4-isopropylpyridin-3-yl)-5-oxopentan-2-yl)carbamate (800 mg, 2.0 mmol) was dissolved in methanol (5 mL). The mixture was cooled to 0°C, and then 1,4-dioxane hydrochloride (7.5 mL, 30.0 mmol) was added. The mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with sodium hydroxide solution and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The resulting mixture was separated by column chromatography (PE / EA = 100:0-70:30) to afford 3-bromo-4-isopropyl-5-(2-methyl-3,4-dihydro-2H-pyrrol-5-yl)pyridine (414 mg, yield: 73.5%). MS (ESI): m / z 281.1 [M+H] + .

[0358] Step 4: Synthesis of 3-bromo-4-isopropyl-5-(5-methylpyrrolidin-2-yl)pyridine

[0359] 3-Bromo-4-isopropyl-5-(2-methyl-3,4-dihydro-2H-pyrrol-5-yl)pyridine (414 mg, 1.47 mmol) was placed in methanol (6 mL) and acetic acid (1.5 mL). Under nitrogen, the mixture was cooled to -50°C. Sodium borohydride (122.5 mg, 3.24 mmol) was then added portionwise. The mixture was stirred at -50°C to room temperature for 1 hour. The reaction solution was diluted with aqueous sodium hydroxide and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the precipitate was separated by column chromatography (DCM / MeOH = 100:0 to 93:7) to afford 3-bromo-4-isopropyl-5-(5-methylpyrrolidin-2-yl)pyridine (347 mg, yield: 83.2%). MS (ESI): m / z 283.1 [M+H] + .

[0360] Step 5: Synthesis of tert-butyl 2-(5-bromo-4-isopropylpyridin-3-yl)-5-methylpyrrolidine-1-carboxylate

[0361] 3-Bromo-4-isopropyl-5-(5-methylpyrrolidin-2-yl)pyridine (347 mg, 1.23 mmol) was placed in dichloromethane (10 mL). The mixture was cooled to 0°C, and then 4-dimethylaminopyridine (15 mg, 0.12 mmol), triethylamine (248 mg, 2.45 mmol), and di-tert-butyl dicarbonate (401 mg, 1.84 mmol) were added in sequence. The mixture was stirred at room temperature overnight. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, it was separated by column chromatography (PE / EA = 100:0-90:10) to obtain tert-butyl 2-(5-bromo-4-isopropylpyridin-3-yl)-5-methylpyrrolidine-1-carboxylate (225 mg, yield: 47.9%). MS (ESI): m / z 383.1 [M+H] + .

[0362] Step 6: Synthesis of tert-butyl 2-(5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)-5-methylpyrrolidine-1-carboxylate

[0363] Tert-butyl 2-(5-bromo-4-isopropylpyridin-3-yl)-5-methylpyrrolidine-1-carboxylate (225 mg, 0.59 mmol) and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (178.7 mg, 0.70 mmol) were placed in N,N-dimethylformamide (5 mL), followed by the addition of cuprous iodide (11.2 mg, 0.06 mmol), bis(tri-tert-butylphosphine)palladium (30 mg, 0.06 mmol), and N,N-diisopropylethylamine (227.6 mg, 1.76 mmol). The mixture was heated to 50°C and stirred under nitrogen for 3 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the residue was separated by column chromatography (DCM / MeOH = 100:0-95:5) to give tert-butyl 2-(5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)-5-methylpyrrolidine-1-carboxylate (214 mg, yield: 65.6%). MS (ESI): m / z 556.3 [M+H]. + .

[0364] Step 7: Synthesis of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(5-methylpyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0365] Tert-butyl 2-(5-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-4-isopropylpyridin-3-yl)-5-methylpyrrolidine-1-carboxylate (214 mg, 0.39 mmol) was placed in dichloromethane (4 mL), and trifluoroacetic acid (4 mL) was added. The mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated, diluted with sodium bicarbonate, and separated by reverse phase column chromatography (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to give (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-(5-methylpyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (136.5 mg, yield: 77.8%). MS (ESI): m / z 456.2 [M+H] + .

[0366] 1 H NMR(400MHz,CD3OD)δ8.83(s,1H),8.57(s,1H),8.34(s,1H),4.55-4.52(m,1H),3.97-3.88(m,3H),3.61-3.55(m,2H),3.51-3.45(m,1H), 3.28-3.17(m,1H),2.31-2.28(m,1H),2.13-2.00(m,2H),1.68-1.58(m,3H),1.54-1.52(m,6H),1.49-1.44(m,1H),1.29(d,J=8.0Hz,3H).

[0367] Examples A281-1 and A281-2: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((2R,5R)-5-methylpyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol and (3S,4R)-4-((5-chloro-4-((4-isopropyl-5-((2S,5S)-5-methylpyrrolidin-2-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0368] The racemic compound of Example A281 (112 mg, 0.246 mmol) was prepared and separated by chiral SFC (column type: Chiralpak AD-3.50×4.6 mm ID, 3 um; mobile phase A: CO2, mobile phase B: isopropanol (0.02% methylamine); flow rate: 4.0 mL / min; column temperature: 35°C; detection wavelength: 254 nm) to obtain two optically pure chiral monomer compounds (Examples A281-1 and A281-2) with retention times of 0.798 min (peak 1: 50.1 mg) and 1.473 min (peak 2: 47.8 mg), respectively.

[0369] Peak 1 compound: 1 H NMR(400MHz,CD3OD)δ8.83(s,1H),8.57(s,1H),8.34(s,1H),4.55-4.52(m,1H),3.97-3.88(m,3H),3.61-3.55(m,2H),3.51-3.45(m,1H), 3.28-3.17(m,1H),2.31-2.28(m,1H),2.13-2.00(m,2H),1.68-1.58(m,3H),1.54-1.52(m,6H),1.49-1.44(m,1H),1.29(d,J=8.0Hz,3H).

[0370] Peak 2 compounds: 1 H NMR(400MHz,CD3OD)δ8.83(s,1H),8.57(s,1H),8.34(s,1H),4.55-4.52(m,1H),3.97-3.88(m,3H),3.61-3.55(m,2H),3.51-3.45(m,1H), 3.28-3.17(m,1H),2.31-2.28(m,1H),2.13-2.00(m,2H),1.68-1.58(m,3H),1.54-1.52(m,6H),1.49-1.44(m,1H),1.29(d,J=8.0Hz,3H).

[0371] Example A305: Preparation of (3S,4R)-4-((5-chloro-4-((3-isopropyl-2-((isopropylamino)methyl)pyridin-4-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0372] Step 1: Synthesis of 3-bromo-2-methylpyridin-4-amine

[0373] Dissolve 2-methylpyridin-4-amine (18.7 g, 172.92 mmol) in DCM (400 mL) and place in an ice-water bath. Add NBS (33.86 g, 190.21 mmol) in portions and stir at room temperature overnight under nitrogen. After the reaction is complete, add saturated sodium bicarbonate solution to quench the reaction. Extract three times with ethyl acetate. The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (5% methanol-dichloromethane) to afford 3-bromo-2-methylpyridin-4-amine (19.0 g, yield: 58%). MS (ESI): m / z 187.0 [M+H] + .

[0374] Step 2: Synthesis of 2-methyl-3-(prop-1-en-2-yl)pyridin-4-amine

[0375] Dissolve 3-bromo-2-methylpyridin-4-amine (5.0 g, 26.732 mmol) in dioxane (50 mL) and water (20 mL), add 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (8.98 g, 53.46 mmol), Pd(dppf)Cl2 (0.98 g, 1.34 mmol), and cesium carbonate (21.77 g, 66.83 mmol), heat to 100 ° C under nitrogen protection, and stir overnight. After the reaction was completed, the mixture was cooled to room temperature and quenched with water. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated. The mixture was separated by silica gel column chromatography (10% methanol-dichloromethane system) to give 2-methyl-3-(prop-1-en-2-yl)pyridin-4-amine (4.0 g, yield: 96%). MS (ESI): m / z 149.0 [M+H] + .

[0376] Step 3: Synthesis of 3-isopropyl-2-methylpyridin-4-amine

[0377] Dissolve 2-methyl-3-(prop-1-en-2-yl)pyridin-4-amine (3.3 g, 22.266 mmol) in methanol (50 mL), add palladium hydroxide on carbon (2.0 g, 14.242 mmol), and stir at 65°C under a hydrogen atmosphere for 48 hours. Filter and concentrate to obtain 3-isopropyl-2-methylpyridin-4-amine (1.55 g, yield: 40%). MS (ESI): m / z 151.0 [M+H] + .

[0378] Step 4: Synthesis of 4-bromo-3-isopropyl-2-methylpyridine

[0379] 3-Isopropyl-2-methylpyridin-4-amine (3.3 g, 22.27 mmol) was dissolved in acetonitrile (20 mL). tert-Butyl nitrite (4.26 g, 41.27 mmol) and cuprous bromide (5.92 g, 41.27 mmol) were added sequentially. The mixture was stirred at 50°C overnight. After completion of the reaction, brine was added to quench the reaction. The mixture was filtered and concentrated to remove the acetonitrile. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (20% ethyl acetate-petroleum ether) to afford 4-bromo-3-isopropyl-2-methylpyridine (2.48 g, yield: 56%). MS (ESI): m / z 214.0 [M+H] + .

[0380] Step 5: Synthesis of 4-bromo-2-(bromomethyl)-3-isopropylpyridine

[0381] Dissolve 4-bromo-3-isopropyl-2-methylpyridine (2.48 g, 11.58 mmol) in carbon tetrachloride (20 mL), then add NBS (2.27 g, 12.74 mmol) and dibenzoyl peroxide (0.37 g, 1.16 mmol) sequentially. Heat to 80°C under nitrogen and stir overnight. After completion of the reaction, quench with saturated sodium bicarbonate solution and extract three times with ethyl acetate. The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10-20% ethyl acetate in petroleum ether) to afford 4-bromo-2-(bromomethyl)-3-isopropylpyridine (1.05 g, yield: 41%). MS (ESI): m / z 292.0 [M+H] + .

[0382] Step 6: Synthesis of N-((4-bromo-3-isopropylpyridin-2-yl)methyl)propane-2-amine

[0383] 4-Bromo-2-(bromomethyl)-3-isopropylpyridine (1.05 g, 3.58 mmol) was dissolved in acetonitrile (10 mL). DIPEA (0.69 g, 5.38 mmol) and isopropylamine (0.28 g, 4.66 mmol) were added sequentially. The mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was concentrated and separated by silica gel column chromatography (10% methanol-dichloromethane) to obtain N-((4-bromo-3-isopropylpyridin-2-yl)methyl)propan-2-amine (0.5 g, yield: 51%). MS (ESI): m / z 271.0 [M+H] + .

[0384] Step 7: Synthesis of tert-butyl ((4-bromo-3-isopropylpyridin-2-yl)methyl) (isopropyl) carbamate

[0385] Dissolve N-((4-bromo-3-isopropylpyridin-2-yl)methyl)propan-2-amine (400 mg, 1.48 mmol) in dichloromethane (10 mL) and place in an ice-water bath. Add triethylamine (224.0 mg, 2.21 mmol) and di-tert-butyl dicarbonate (418.47 mg, 1.92 mmol) sequentially. Return to room temperature and stir overnight. After the reaction is complete, concentrate the reaction solution and separate it by silica gel column chromatography (10% ethyl acetate-petroleum ether) to obtain tert-butyl ((4-bromo-3-isopropylpyridin-2-yl)methyl)(isopropyl)carbamate (387 mg, yield: 70%). MS (ESI): m / z 371.2 [M+H] + .

[0386] Step 8: Synthesis of tert-butyl ((4-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-3-isopropylpyridin-2-yl)methyl)(isopropyl)carbamate

[0387] Tert-butyl((4-bromo-3-isopropylpyridin-2-yl)methyl)(isopropyl)carbamate (95 mg, 0.256 mmol) was dissolved in DMF (3 mL), and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (97 mg, 0.384 mmol), di(tri-tert-butylphosphine)palladium (26 mg, 0.051 mmol), CuI (4.8 mg, 0.026 mmol), and DIPEA (99.2 mg, 0.768 mmol) were added sequentially. The atmosphere was replaced with nitrogen three times, and the reaction solution was placed in an oil bath preheated to 55°C and stirred for 3 hours. After the reaction was completed, the mixture was cooled to room temperature and quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was separated by silica gel column chromatography (10% methanol-dichloromethane system). The crude product was then separated by reverse phase separation (0.1% aqueous ammonium bicarbonate: acetonitrile = 0-100%) to give tert-butyl ((4-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-3-isopropylpyridin-2-yl)methyl)(isopropyl)carbamate (50 mg, yield: 36%). MS (ESI): m / z 544.3 [M+H] + .

[0388] Step 9: Synthesis of (3S,4R)-4-((5-chloro-4-((3-isopropyl-2-((isopropylamino)methyl)pyridin-4-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0389] Tert-butyl ((4-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-3-isopropylpyridin-2-yl)methyl)(isopropyl)carbamate (50 mg, 0.092 mmol) was dissolved in DCM (3 mL), TFA (1 mL) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was completed, the product was quenched with saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate, filtered, concentrated, and subjected to reverse phase separation (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to afford (3S,4R)-4-((5-chloro-4-((3-isopropyl-2-((isopropylamino)methyl)pyridin-4-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (35 mg, yield: 85%). MS (ESI): m / z 444.2 [M+H] + .

[0390] 1 H NMR (400MHz, CD3OD) δ8.47(d,J=5.0Hz,1H),8.36(s,1H),7.50(d,J=5.0Hz,1H),4.21(s,2H),4.02-3.85(m,3H),3.62-3 .44(m,3H),3.22-3.12(m,2H),2.14-2.04(m,1H),1.67-1.56(m,1H),1.54(dd,J=7.0,1.6Hz,6H),1.27(d,J=6.4Hz,6H).

[0391] Example A172: Preparation of (3S,4R)-4-((5-chloro-4-((3-isopropyl-4-((isopropylamino)methyl)pyridin-2-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0392] Step 1: Synthesis of 2-(benzyloxy)-3-bromo-5-chloropyridine

[0393] Dissolve 3-bromo-5-chloropyridin-2-ol (5 g, 23.99 mmol) in toluene (100 mL), add benzyl bromide (4.51 g, 26.39 mmol) and silver carbonate (7.28 g, 26.39 mmol) sequentially, heat to 70°C under nitrogen, and stir overnight. After the reaction is complete, filter and concentrate the product. The crude product is slurried with n-heptane to yield 2-(benzyloxy)-3-bromo-5-chloropyridine (6 g, yield: 83%). MS (ESI): m / z 298.0 [M+H] + .

[0394] Step 2: Synthesis of methyl 2-(benzyloxy)-3-bromo-5-chloroisonicotinate

[0395] 2-(Benzyloxy)-3-bromo-5-chloropyridine (9.5 g, 31.82 mmol) was dissolved in THF (200 mL), cooled to -78°C, and LDA (17.5 mL, 35.00 mmol, 2.0 M) was added dropwise. The mixture was stirred for 1 hour, followed by the addition of methyl chloroformate (4.51 g, 47.73 mmol) and stirring for 3 hours. After the reaction was complete, an appropriate amount of saturated aqueous ammonium chloride was added to quench the reaction. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10% ethyl acetate in petroleum ether) to afford methyl 2-(benzyloxy)-3-bromo-5-chloroisonicotinate (10.2 g, yield: 81%). MS (ESI): m / z 356.0 [M+H] + .

[0396] Step 3: Synthesis of methyl 2-(benzyloxy)-5-chloro-3-(prop-1-en-2-yl) isonicotinate

[0397] Methyl 2-(benzyloxy)-3-bromo-5-chloroisonicotinate (7.5 g, 21.03 mmol) was dissolved in dioxane (80 mL) and water (20 mL). 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (5.30 g, 31.55 mmol), Pd(dppf)Cl2 (1.54 g, 2.10 mmol), and potassium carbonate (7.27 g, 52.58 mmol) were added. The mixture was heated to 105°C under nitrogen protection and stirred overnight. After the reaction was completed, the mixture was cooled to room temperature and quenched with water. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10% ethyl acetate-petroleum ether) to afford methyl 2-(benzyloxy)-5-chloro-3-(prop-1-en-2-yl) isonicotinate (6.2 g, yield: 75%). MS (ESI): m / z 318.1 [M+H] + .

[0398] Step 4: Synthesis of methyl 2-hydroxy-3-isopropyl isonicotinate

[0399] Methyl 2-(benzyloxy)-5-chloro-3-(prop-1-en-2-yl) isonicotinate (6.2 g, 19.51 mmol) was dissolved in methanol (100 mL), and palladium hydroxide on carbon (2.74 g, 19.51 mmol) was added. The mixture was stirred at 55°C overnight under a hydrogen atmosphere. After the reaction was complete, the mixture was filtered and concentrated, and then separated by silica gel column chromatography (50-70% ethyl acetate-petroleum ether) to afford methyl 2-hydroxy-3-isopropyl isonicotinate (1.55 g, yield: 40%). MS (ESI): m / z 196.0 [M+H] + .

[0400] Step 5: Synthesis of 2-chloro-3-isopropylmethyl isonicotinate

[0401] Methyl 2-hydroxy-3-isopropyl isonicotinoate (0.8 g, 4.10 mmol) was dissolved in phosphorus oxychloride (20 mL) and placed in an ice-water bath. Phosphorus pentachloride (853.27 mg, 4.10 mmol) was added, and the mixture was heated to 110°C under nitrogen and stirred for 48 hours. After the reaction, the phosphorus oxychloride was removed, and the mixture was placed in an ice-water bath. The mixture was quenched with saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10-20% ethyl acetate in petroleum ether) to afford methyl 2-chloro-3-isopropyl isonicotinoate (780 mg, yield: 89%). MS (ESI): m / z 214.0 [M+H] +.

[0402] Step 6: Synthesis of (2-chloro-3-isopropylpyridin-4-yl)methanol

[0403] Dissolve methyl 2-chloro-3-isopropyl isonicotinate (780 mg, 3.65 mmol) in THF (10 mL) and place in an ice-water bath. Add DIBAL-H (9.74 mL, 14.60 mmol, 1.0 mol / L THF solution) dropwise and stir in an ice-water bath for 1 to 2 hours. After completion, place in an ice-water bath and quench the reaction with methanol dropwise until bubbling ceases. Add an appropriate amount of aqueous potassium sodium tartrate and stir for at least 30 minutes. Filter and extract the filtrate three times with ethyl acetate. The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to yield (2-chloro-3-isopropylpyridin-4-yl)methanol (680 mg, yield: 95%). MS (ESI): m / z 186.0 [M+H] + .

[0404] Step 7: Synthesis of (2-chloro-3-isopropylpyridin-4-yl)methyl ethanesulfonate

[0405] Dissolve (2-chloro-3-isopropylpyridin-4-yl)methanol (980 mg, 5.28 mmol) in dichloromethane (10 mL) and place in an ice-water bath. Add DIPEA (2.05 g, 15.84 mmol) and ethylsulfonyl chloride (882.29 mg, 6.86 mmol) sequentially. Return to room temperature and stir for 2 hours. Once the reaction is complete, concentrate the resulting solution and use it directly in the next step (1.4 g, yield: 100%). MS (ESI): m / z 278.0 [M+H] + .

[0406] Step 8: Synthesis of N-((2-chloro-3-isopropylpyridin-4-yl)methyl)propane-2-amine

[0407] Dissolve (2-chloro-3-isopropylpyridin-4-yl)methyl ethanesulfonate (1.4 g, 5.04 mmol) in acetonitrile (10 mL), add DIPEA (1.95 g, 15.121 mmol) and isopropylamine (1.49 g, 25.20 mmol), and stir at 45°C overnight. After completion of the reaction, place in an ice-water bath and quench with saturated sodium bicarbonate solution. Extract three times with ethyl acetate. The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (6% methanol-methylene chloride system) to afford N-((2-chloro-3-isopropylpyridin-4-yl)methyl)propan-2-amine (1.0 g, yield: 87%). MS (ESI): m / z 227.1 [M+H] + .

[0408] Step 9: Synthesis of tert-butyl ((2-chloro-3-isopropylpyridin-4-yl)methyl) (isopropyl) carbamate

[0409] N-((2-chloro-3-isopropylpyridin-4-yl)methyl)propan-2-amine (1.0 g, 4.41 mmol) was dissolved in DCM (10 mL), and DIPEA (1.14 g, 8.82 mmol) and Boc2O (1.44 g, 6.62 mmol) were added. The mixture was stirred at room temperature overnight. After completion of the reaction, the mixture was placed in an ice-water bath and quenched with saturated aqueous sodium bicarbonate. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10-20% ethyl acetate in petroleum ether) to afford tert-butyl ((2-chloro-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate (1.17 g, yield: 81%). MS (ESI): m / z 327.1 [M+H] + .

[0410] Step 10: Synthesis of tert-butyl isopropyl ((3-isopropyl-2-((triisopropylsilyl)ethynyl)pyridin-4-yl)methyl)carbamate

[0411] Dissolve tert-butyl((2-chloro-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate (1.07 g, 3.274 mmol) in DMF (8 mL), and add triisopropylsilyl acetylene (1.19 g, 6.54 mmol), di(tri-tert-butylphosphine)palladium (170 mg, 0.327 mmol), CuI (30.0 mg, 0.164 mmol), and DIPEA (1.27 g, 9.82 mmol) in sequence. Replace the mixture with nitrogen three times, heat to 100°C, and stir overnight. After the reaction was completed, the mixture was cooled to room temperature and quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated. The mixture was separated by silica gel column chromatography (10-20% ethyl acetate-petroleum ether) to give tert-butyl isopropyl ((3-isopropyl-2-((triisopropylsilyl)ethynyl)pyridin-4-yl)methyl)carbamate (1.1 g, yield: 35%). MS (ESI): m / z 473.4 [M+H] + .

[0412] Step 11: Synthesis of tert-butyl ((2-ethynyl-3-isopropylpyridin-4-yl)methyl) (isopropyl) carbamate

[0413] Tert-butyl isopropyl ((3-isopropyl-2-((triisopropylsilyl)ethynyl)pyridin-4-yl)methyl)carbamate (1.1 g, 2.33 mmol) was dissolved in THF (10 mL) and placed in an ice bath. A solution of TBAF in THF (2.33 mL, 2.33 mmol, 1.0 M) was added, and the mixture was stirred overnight in an ice bath. After completion of the reaction, the mixture was quenched with saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10-20% ethyl acetate in petroleum ether) to afford tert-butyl ((2-ethynyl-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate (168 mg, yield: 23%). MS (ESI): m / z 317.2 [M+H] + .

[0414] Step 12: Synthesis of tert-butyl ((2-((2,5-dichloropyrimidin-4-yl)ethynyl)-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate

[0415] Tert-butyl ((2-ethynyl-3-isopropylpyridin-4-yl)methyl) (isopropyl) carbamate (168 mg, 0.531 mmol) was dissolved in DMF (3 mL), and 2,4,5-trichloropyrimidine (389.5 mg, 2.12 mmol), di(tri-tert-butylphosphine)palladium (54 mg, 0.106 mmol), CuI (10 mg, 0.053 mmol), and DIPEA (206 mg, 1.59 mmol) were added in sequence. The atmosphere was replaced with nitrogen three times, and the reaction solution was placed in an oil bath preheated to 50°C and stirred for 3 hours. After the reaction was completed, the mixture was cooled to room temperature and quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated. The crude product was separated by silica gel column chromatography (10% methanol-dichloromethane system). The crude product was then separated by reverse phase chromatography (50% acetonitrile-ammonium bicarbonate system) to give tert-butyl ((2-((2,5-dichloropyrimidin-4-yl)ethynyl)-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate (140 mg, yield: 57%). MS (ESI): m / z 463.2 [M+H] + .

[0416] Step 13: Synthesis of tert-butyl ((2-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate

[0417] Dissolve tert-butyl ((2-((2,5-dichloropyrimidin-4-yl)ethynyl)-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate (140 mg, 0.302 mmol) in DMF (3 mL), add (3S,4R)-4-aminotetrahydro-2H-pyran-3-ol hydrochloride (46.4 mg, 0.302 mmol) and potassium carbonate (125 mg, 0.906 mmol). Heat to 90°C and stir overnight. After the reaction was completed, the product was quenched with saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (10-20% ethyl acetate-petroleum ether system) to give tert-butyl ((2-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate (18 mg, yield: 11%). MS (ESI): m / z 544.4 [M+H] + .

[0418] Step 14: Synthesis of (3S,4R)-4-((5-chloro-4-((3-isopropyl-4-((isopropylamino)methyl)pyridin-2-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0419] Tert-butyl ((2-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-3-isopropylpyridin-4-yl)methyl)(isopropyl)carbamate (18 mg, 0.033 mmol) was dissolved in DCM (3 mL), TFA (1 mL) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was completed, the product was quenched with saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate, filtered, concentrated, and subjected to reverse phase separation (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to give (3S,4R)-4-((5-chloro-4-((3-isopropyl-4-((isopropylamino)methyl)pyridin-2-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (9 mg, yield: 61%). MS (ESI): m / z 444.2 [M+H] + .

[0420] 1 H NMR (400MHz, CD3OD) δ8.38(d,J=5.1Hz,1H),8.35(s,1H),7.54(d,J=5.1Hz,1H),3.98-3.87(m,5H),3.77-3.54(m,2H),3.47(td,J=11.7,2 .4Hz,1H),3.25-3.19(m,1H),2.95-2.86(m,1H),2.14-2.06(m,1H),1.66-1.58(m,1H),1.55(dd,J=7.2,2.2Hz,6H),1.15(d,J=6.3Hz,6H).

[0421] Example B1: Preparation of (3S,4R)-4-((5-chloro-4-((8-((dimethylamino)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0422] Step 1: Synthesis of 4-bromo-2,3-dihydroxybenzaldehyde

[0423] 3-Bromobenzene-1,2-diol (20 g, 189.01 mmol) was dissolved in acetonitrile (300 mL). Magnesium chloride (60.44 g, 95.20 mmol), paraformaldehyde (25.42 g, 30.03 mmol), and triethylamine (74.95 g, 101.19 mmol) were added sequentially. The mixture was heated to 65°C under nitrogen and stirred overnight. After the reaction, most of the acetonitrile was removed and the pH was adjusted to 2-3 with 1N aqueous hydrochloric acid. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The mixture was then slurried with ethyl acetate and petroleum ether and filtered to yield 4-bromo-2,3-dihydroxybenzaldehyde (13 g, yield: 56.6%). MS (ESI): m / z 215.2 [M+H] + .

[0424] Step 2: Synthesis of 8-bromo-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde

[0425] 4-Bromo-2,3-dihydroxybenzaldehyde (5 g, 23.04 mmol) was dissolved in DMF (70 mL), and cesium carbonate (22.52 g, 69.12 mmol) was added. After stirring at room temperature for half an hour, 1,2-dibromoethane (8.66 g, 46.08 mmol) was added, and the mixture was heated to 70°C and stirred overnight. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (15% ethyl acetate-petroleum ether system) to obtain 8-bromo-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (3.4 g, yield: 60%). MS (ESI): m / z 243.0 [M+H] + .

[0426] Step 3: Synthesis of 8-((trimethylsilyl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde

[0427] Place 8-bromo-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (3.9 g, 16.04 mmol), Pd(PPh3)2Cl2 (1.13 g, 1.61 mmol), cuprous iodide (0.31 g, 1.61 mmol), ethynyltrimethylsilane (2.36 g, 24.07 mmol), and triethylamine (4.87 g, 48.14 mmol) in a glass tube, add THF (80 mL) under a nitrogen atmosphere, seal the tube, heat to 80°C, and stir overnight. After the reaction was complete, the mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated. The mixture was separated by silica gel column chromatography (20% ethyl acetate-petroleum ether) to afford 8-((trimethylsilyl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (4.2 g, yield: 95%). MS (ESI): m / z 261.2 [M+H] + .

[0428] Step 4: Synthesis of 8-ethynyl-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde

[0429] 8-((Trimethylsilyl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (2.2 g, 8.45 mmol) was dissolved in methanol (10 mL) and tetrahydrofuran (10 mL). Potassium carbonate (0.23 g, 1.69 mmol) was added and stirred at room temperature for 3 hours. After removing the methanol, the reaction was quenched by adding 1N aqueous hydrochloric acid. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (20% ethyl acetate-petroleum ether) to afford 8-ethynyl-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (1.1 g, yield: 55%). MS (ESI): m / z 189.0 [M+H] + .

[0430] Step 5: Synthesis of 8-((2,5-dichloropyrimidin-4-yl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde

[0431] 8-Ethynyl-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (650 mg, 3.45 mmol) and 2,4,5-trichloropyrimidine (823.63 mg, 4.49 mmol) were dissolved in tetrahydrofuran (15 mL), and Pd(PPh3)4 (399 mg, 0.34 mmol), cuprous iodide (66 mg, 0.34 mmol), and triethylamine (1.05 g, 10.36 mmol) were added in sequence. The mixture was heated to 65°C under nitrogen protection and stirred overnight. After the reaction was completed, the mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated. The mixture was separated by silica gel column chromatography (50% ethyl acetate-petroleum ether) to give 8-((2,5-dichloropyrimidin-4-yl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (440 mg, yield: 32%). MS (ESI): m / z 335.0 [M+H] + .

[0432] Step 6: Synthesis of 8-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde

[0433] 8-((2,5-Dichloropyrimidin-4-yl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (53 mg, 0.16 mmol) and (3S,4R)-4-aminooxan-3-ol hydrochloride (56 mg, 0.36 mmol) were dissolved in NMP (2 mL). Potassium carbonate (87 mg, 0.63 mmol) was added, and the mixture was heated to 100°C under nitrogen and stirred overnight. The reaction was quenched by the addition of 1N aqueous hydrochloric acid, and the resulting mixture was directly separated by reverse phase separation (50% acetonitrile-aqueous TFA system) to afford 8-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (7 mg, yield: 8%). MS (ESI): m / z 416.2 [M+H] + .

[0434] Step 7: Synthesis of (3S,4R)-4-((5-chloro-4-((8-((dimethylamino)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0435] 8-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (7 mg, 0.017 mmol) was dissolved in dichloromethane (3 mL), and dimethylamine (0.013 mL, 0.025 mmol, 2 mol / L) was added successively. The mixture was stirred at room temperature for 3 hours, and an appropriate amount of methanol was added to quench the reaction. The resulting reaction solution was concentrated and directly subjected to preparative HPLC (acetonitrile-ammonium bicarbonate aqueous solution) to give (3S,4R)-4-((5-chloro-4-((8-((dimethylamino)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (1 mg, yield: 14%). MS (ESI): m / z 445.2 [M+H] + .

[0436] 1 H NMR (400MHz, DMSO-d6) δ8.41(s,1H),7.52(s,1H),7.08(d,J=7.9Hz,1H),6.93(d,J=7.9Hz,1H),4.93(d,J=5.3Hz,1H),4.46–4 .23(m,4H),3.84-3.74(m,3H),3.49–3.34(m,4H),3.04(t,J=10.4Hz,1H),2.16(s,6H),1.96–1.81(m,1H),1.54-1.39(m,1H).

[0437] Example B2: Preparation of (3S,4R)-4-((5-chloro-4-((5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-8-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0438] Step 1: Synthesis of 5-bromo-3-methoxy-2-methylpyridin-4(1H)-one

[0439] Dissolve 3-methoxy-2-methylpyridin-4(1H)-one (7 g, 50.31 mmol) in DCM (150 mL), add NBS (9.85 g, 55.34 mmol), and stir at room temperature for 2 hours. Filter, concentrate the filtrate, and separate by silica gel column chromatography (10% methanol-dichloromethane system) to obtain 5-bromo-3-methoxy-2-methylpyridin-4(1H)-one (9.2 g, yield: 83%). MS (ESI): m / z 218.0 [M+H] + .

[0440] Step 2: Synthesis of 5-bromo-2-methylpyridine-3,4-diol

[0441] Dissolve 5-bromo-3-methoxy-2-methylpyridin-4(1H)-one (6.2 g, 28.4 mmol) in aqueous hydrogen bromide (60 mL), heat to 130°C, and stir overnight. The reaction solution is directly concentrated and dried to obtain 5-bromo-2-methylpyridine-3,4-diol (8.1 g), which is used directly in the next step. MS (ESI): m / z 201.8 [MH] + .

[0442] Step 3: Synthesis of 8-bromo-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine

[0443] The crude product 5-bromo-2-methylpyridine-3,4-diol (8.1 g, 28.43 mmol) was dissolved in DMF (80 mL) and potassium carbonate (19.64 g, 142.13 mmol) was added. After stirring at room temperature for half an hour, 1,2-dibromoethane (10.68 g, 56.86 mmol) was added, and the mixture was heated to 70°C and stirred overnight. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (30% ethyl acetate-petroleum ether) to obtain 8-bromo-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine (1.0 g, yield: 16%). MS (ESI): m / z 230.0 [M+H] + .

[0444] Step 4: Synthesis of 5-methyl-8-((trimethylsilyl)ethynyl)-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine

[0445] 8-Bromo-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine (200 mg, 0.87 mmol), Pd(PPh3)4 (100.46 mg, 0.087 mmol), cuprous iodide (0.31 g, 1.61 mmol), ethynyltrimethylsilane (170.77 mg, 1.74 mmol), and triethylamine (16.56 mg, 0.087 mmol) were placed in a glass tube, and THF (5 mL) was added under a nitrogen atmosphere. After sealing, the tube was heated to 80°C and stirred overnight. After the reaction was complete, the mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated, and separated by silica gel column chromatography (20% ethyl acetate-petroleum ether) to afford 5-methyl-8-((trimethylsilyl)ethynyl)-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine (180 mg, yield: 59%). MS (ESI): m / z 248.0 [M+H] + .

[0446] Step 5: Synthesis of 8-ethynyl-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine

[0447] 5-Methyl-8-((trimethylsilyl)ethynyl)-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine (180 mg, 0.73 mmol) was dissolved in methanol (5 mL) and tetrahydrofuran (1 mL). Potassium carbonate (100.6 mg, 0.73 mmol) was added and stirred at room temperature for 3 hours. After removing the methanol, the reaction was quenched by adding 1N aqueous hydrochloric acid. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (25% ethyl acetate-petroleum ether) to afford 8-ethynyl-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine (100 mg, yield: 78%). MS (ESI): m / z 176.0 [M+H] + .

[0448] Step 6: Synthesis of 8-((2,5-dichloropyrimidin-4-yl)ethynyl)-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine

[0449] 8-Ethynyl-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine (100 mg, 0.57 mmol) and 2,4,5-trichloropyrimidine (314.09 mg, 1.71 mmol) were dissolved in tetrahydrofuran (5 mL), and Pd(PPh3)4 (66 mg, 0.057 mmol), cuprous iodide (10.87 mg, 0.057 mmol), and triethylamine (288.80 mg, 2.85 mmol) were added in sequence. The mixture was heated to 65°C under nitrogen protection and stirred overnight. After the reaction was completed, the mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated. The mixture was separated by silica gel column chromatography (25% ethyl acetate-petroleum ether) to give 8-((2,5-dichloropyrimidin-4-yl)ethynyl)-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine (100 mg, yield: 54%). MS (ESI): m / z 322.0 [M+H] + .

[0450] Step 7: Synthesis of (3S,4R)-4-((5-chloro-4-((5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-8-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0451] 8-((2,5-Dichloropyrimidin-4-yl)ethynyl)-5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridine (70 mg, 0.22 mmol) and (3S,4R)-4-aminooxan-3-ol hydrochloride (100.46 mg, 0.65 mmol) were dissolved in NMP (2 mL), and cesium carbonate (156 mg, 0.48 mmol) was added. The mixture was heated to 100° C. under nitrogen protection and stirred overnight. The reaction was quenched by adding 1N aqueous hydrochloric acid, and the resulting mixture was directly separated by preparative HPLC (acetonitrile-ammonium bicarbonate aqueous solution) to afford (3S,4R)-4-((5-chloro-4-((5-methyl-2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-8-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (2 mg, yield: 2%). MS (ESI): m / z 403.2 [M+H] + .

[0452] 1H NMR (400MHz, DMSO-d6) δ8.43(s,1H),8.12(s,1H),7.57(s,1H),4.93(d,J=5.4Hz,1H),4.51-4.44(m,2H),4.42-4.35(m,2H),3.8 6-3.70(m,3H),3.48-3.39(m,1H),3.04(t,J=10.4Hz,1H),2.36(s,3H),2.36-2.31(m,1H),1.92-1.82(m,1H),1.53-1.39(m,1H).

[0453] Example B37: Preparation of (3S,4R)-4-((5-chloro-4-((4-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0454] Step 1: Synthesis of 6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine

[0455] 6,7-Dihydro-5H-pyrrolo[3,4-b]pyridine dihydrochloride (4.5 g, 23.3 mmol) was placed in dichloromethane (60 mL). The mixture was cooled to 0°C, and then N,N-diisopropylethylamine (15.1 g, 116.5 mmol) and methylsulfonyl chloride (3.21 g, 28.0 mmol) were added sequentially. The mixture was stirred at room temperature overnight. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the organic phase was separated by column chromatography (DCM / MeOH = 100:0-95:5) to obtain 6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (3.21 g, yield: 69.3%). MS (ESI): m / z 199.1 [M+H] + .

[0456] Step 2: Synthesis of 6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-1-oxide

[0457] 6-(Methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (3.5 g, 17.7 mmol) was placed in dichloromethane (60 mL). The mixture was cooled to 0°C, and then m-chloroperbenzoic acid (7.53 g, 37.1 mmol) was added. The mixture was stirred at room temperature overnight. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate, then with methanol / ethyl acetate (1 / 1). The filtrate was concentrated to give 6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-1-oxide (3.0 g, yield: 79.3%). MS (ESI): m / z 215.0 [M+H] + .

[0458] Step 3: Synthesis of 4-chloro-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine

[0459] 6-(Methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-1-oxide (3.0 g, 14.0 mmol) was placed in DMF (30 mL). The mixture was cooled to 0°C, and then oxalyl chloride (3.56 g, 28.0 mmol) was added. The mixture was stirred at room temperature overnight. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, it was separated by column chromatography (PE / EA = 100:0-50:50) to obtain 4-chloro-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (750 mg, yield: 23%). MS (ESI): m / z 233.0 [M+H] + .

[0460] Step 4: Synthesis of 6-(methylsulfonyl)-4-(prop-1-en-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine

[0461] 4-Chloro-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (850 mg, 3.65 mmol) was placed in 1.4-dioxane (10 mL) and water (2 mL), followed by the addition of potassium carbonate (1.51 g, 11.0 mmol), Pd(dppf)Cl2 (267.3 mg, 0.37 mmol), and isopropenylboronic acid pinacol ester (1.23 g, 7.3 mmol). The mixture was stirred at 95°C overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the residue was separated by column chromatography (PE / EA = 100:0-50:50) to give 6-(methylsulfonyl)-4-(prop-1-en-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (721 mg, yield: 82.8%). MS (ESI): m / z 239.1 [M+H] + .

[0462] Step 5: Synthesis of 4-isopropyl-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine

[0463] 6-(Methylsulfonyl)-4-(prop-1-en-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (721 mg, 3.03 mmol) was placed in methanol (10 mL), and then 10% palladium on carbon (30 mg) was added. The mixture was stirred at room temperature overnight under a hydrogen atmosphere. The reaction mixture was filtered, concentrated, and separated by column chromatography (PE / EA = 100:0-50:50) to give 4-isopropyl-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (655 mg, yield: 90%). MS (ESI): m / z 241.1 [M+H] + .

[0464] Step 6: Synthesis of 3-bromo-4-isopropyl-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine

[0465] 4-Isopropyl-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (655 mg, 2.73 mmol) was placed in acetonitrile (10 mL), followed by the addition of acetic acid (491 mg, 8.18 mmol) and NBS (728 mg, 4.09 mmol). The mixture was stirred at 60°C overnight. The reaction solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the organic phase was separated by column chromatography (PE / EA = 100:0-40:60) to give 3-bromo-4-isopropyl-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (132 mg, yield: 15.2%). MS (ESI): m / z 319.0 [M+H] + .

[0466] Step 7: Synthesis of 3-bromo-4-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine

[0467] 3-Bromo-4-isopropyl-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (132 mg, 0.41 mmol) was placed in acetic acid (5 mL), and then hydrobromic acid (5 mL) was added. The mixture was stirred at 110°C overnight. The reaction solution was diluted with sodium carbonate solution and extracted with dichloromethane. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, it was separated by column chromatography (DCM / MeOH = 100:0-90:10) to obtain 3-bromo-4-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (30.2 mg, yield: 30.3%). MS (ESI): m / z 241.0 [M+H] + .

[0468] Step 8: Synthesis of (3S,4R)-4-((5-chloro-4-((4-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0469] 3-Bromo-4-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (30.2 mg, 0.13 mmol) and (3S,4R)-4-((5-chloro-4-ethynylpyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (38.0 mg, 0.15 mmol) were placed in N,N-dimethylformamide (1.5 mL). Cuprous iodide (2.4 mg, 0.013 mmol), bis(tri-tert-butylphosphine)palladium (6.5 mg, 0.013 mmol), and N,N-diisopropylethylamine (48.1 mg, 0.39 mmol) were then added sequentially. The mixture was heated to 50°C and stirred under nitrogen for 3 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration, the product was separated by column chromatography (DCM / MeOH = 100:0-90:10) and reverse phase column chromatography (0.1% aqueous ammonium bicarbonate:acetonitrile = 0-100%) to give (3S,4R)-4-((5-chloro-4-((4-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-3-yl)ethynyl)pyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (10.2 mg, yield: 23.8%). MS (ESI): m / z 414.2 [M+H]. + .

[0470] 1 H NMR(400MHz,DMSO-d6)δ8.61(s,1H),8.49(s,1H),7.62(s,1H),4.98(s,1H),3.87-3.78(m,7H),3.58-3.4 9(m,1H),3.31-3.25(m,1H),3.08-3.05(m,1H),2.83-2.75(m,1H),2.12-2.07(m,1H),1.66-1.55(m,7H).

[0471] Example C1: Preparation of 4-((5-chloro-2-((5-(1-methylpiperidin-4-yl)pyridin-2-yl)amino)pyrimidin-4-yl)ethynyl)-5-isopropyl-1-methylpyridin-2(1H)-one

[0472] Step 1: Synthesis of 4-bromo-5-iodopyridin-2(1H)-one

[0473] Concentrated sulfuric acid (20 mL) was added to a round-bottom flask containing 4-bromo-5-iodopyridin-2-amine (5 g, 16.727 mmol) and sodium nitrite (1.38 g, 20.073 mmol). The reaction mixture was allowed to react at 100°C for 16 hours. The reaction mixture was cooled to room temperature, poured into 200 g of ice, and stirred for 10 minutes. A 2M aqueous sodium hydroxide solution was added to adjust the pH to 6, filtered, washed three times with water, and dried at 60°C to obtain 4-bromo-5-iodopyridin-2(1H)-one (4.9 g, yield: 97.68%). MS (ESI): m / z 299.8 [M+H] + .

[0474] Step 2: Synthesis of 4-bromo-5-iodo-1-methylpyridin-2(1H)-one

[0475] To a solution of 4-bromo-5-iodopyridin-2(1H)-one (2 g, 6.669 mmol) in THF (20 mL) was added sodium hydride (0.48 g, 20.007 mmol). The reaction mixture was stirred at 0°C for 30 minutes, followed by the addition of iodomethane (2.84 g, 20.007 mmol). The mixture was allowed to react at room temperature for 3 hours. Water (100 mL) was then added and the mixture was extracted three times with dichloromethane (20 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography (MeOH / CH2Cl2 = 0-5%) to afford 4-bromo-5-iodo-1-methylpyridin-2(1H)-one (2.07 g, yield: 98.87%). MS (ESI): m / z 313.9 [M+H] + .

[0476] Step 3: Synthesis of 4-bromo-1-methyl-5-(prop-1-en-2-yl)pyridin-2(1H)-one

[0477] To a solution of 4-bromo-5-iodo-1-methylpyridin-2(1H)-one (2.09 g, 6.658 mmol) and 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (1.23 g, 7.324 mmol) in dioxane (20 mL) were added Pd(dppf)2Cl2 (0.54 mg, 0.666 mmol), potassium carbonate (2.76 g, 19.973 mmol), and water (2 mL). The reaction mixture was reacted at 60°C under a nitrogen atmosphere for 16 hours. The reaction mixture was cooled to room temperature, diluted with 40 mL of dichloromethane, dried over anhydrous sodium sulfate, filtered through celite, and the organic phase concentrated. The mixture was separated by column chromatography (EA / PA = 0-35%) to afford 4-bromo-1-methyl-5-(prop-1-en-2-yl)pyridin-2(1H)-one (1 g, yield: 65.85%). MS (ESI): m / z 228.1 [M+H]+ .

[0478] Step 4: Synthesis of 4-bromo-5-isopropyl-1-methylpyridin-2(1H)-one

[0479] Rhodium on carbon (0.05 g, 0.438 mmol) was added to a solution of 4-bromo-1-methyl-5-(prop-1-en-2-yl)pyridin-2(1H)-one (1 g, 4.384 mmol) in EA (15 mL). The reaction mixture was allowed to react at room temperature under a hydrogen atmosphere for 16 hours. Filtered through celite, the organic phase was concentrated to afford 4-bromo-5-isopropyl-1-methylpyridin-2(1H)-one (1 g, yield: 99.13%). MS (ESI): m / z 230.1 [M+H] + .

[0480] Step 5: Synthesis of 5-isopropyl-1-methyl-4-((trimethylsilyl)ethynyl)pyridin-2(1H)-one

[0481] To a solution of 4-bromo-5-isopropyl-1-methylpyridin-2(1H)-one (1 g, 4.346 mmol) and trimethylsilyl acetylene (1.28 g, 13.038 mmol) in tetrahydrofuran (10 mL) were added tetrakis(triphenylphosphine)palladium (0.50 g, 0.435 mmol), triethylamine (4.40 g, 43.459 mmol), and cuprous iodide (0.14 g, 0.435 mmol). The reaction mixture was allowed to react at 100°C under a nitrogen atmosphere for 16 hours. The reaction mixture was cooled to room temperature, diluted with 20 mL of dichloromethane, and filtered through Celite. The organic phase was concentrated and separated by column chromatography (EA / PA = 0-35%) to afford 5-isopropyl-1-methyl-4-((trimethylsilyl)ethynyl)pyridin-2(1H)-one (1.02 g, yield: 94.86%). MS (ESI): m / z 248.2 [M+H] + .

[0482] Step 6: Synthesis of 4-ethynyl-5-isopropyl-1-methylpyridin-2(1H)-one

[0483] Potassium carbonate (1.71 g, 12.369 mmol) was added to a solution of 5-isopropyl-1-methyl-4-((trimethylsilyl)ethynyl)pyridin-2(1H)-one (1.02 g, 4.123 mmol) in methanol (10 mL). The reaction mixture was stirred at room temperature for 4 hours. The mixture was filtered, the organic phase was concentrated, and column chromatography (MeOH / CH2Cl2 = 0-5%) was used to obtain 4-ethynyl-5-isopropyl-1-methylpyridin-2(1H)-one (650 mg, yield: 89.98%). MS m / z (ESI): 176.2 [M+H] + .

[0484] Step 7: Synthesis of 4-((2,5-dichloropyrimidin-4-yl)ethynyl)-5-isopropyl-1-methylpyridin-2(1H)-one

[0485] To a solution of 4-ethynyl-5-isopropyl-1-methylpyridin-2(1H)-one (650 mg, 3.709 mmol) and 2,4,5-trichloropyrimidine (2041.14 mg, 11.128 mmol) in tetrahydrofuran (10 mL) were added tetrakis(triphenylphosphine)palladium (428.66 mg, 0.371 mmol), triethylamine (4128.91 mg, 40.804 mmol), and cuprous iodide (117.72 mg, 0.371 mmol). The reaction mixture was allowed to react at room temperature under a nitrogen atmosphere for 16 hours. The mixture was diluted with 20 mL of dichloromethane and filtered through celite. The organic phase was concentrated and separated by column chromatography (EA / PA = 0-35%) to give 4-((2,5-dichloropyrimidin-4-yl)ethynyl)-5-isopropyl-1-methylpyridin-2(1H)-one (900 mg, yield: 75.31%). MS (ESI): m / z 322.1 [M+H] + .

[0486] Step 8: Synthesis of 4-((5-chloro-2-((5-(1-methylpiperidin-4-yl)pyridin-2-yl)amino)pyrimidin-4-yl)ethynyl)-5-isopropyl-1-methylpyridin-2(1H)-one

[0487] To a mixed solution of 4-((2,5-dichloropyrimidin-4-yl)ethynyl)-5-isopropyl-1-methylpyridin-2(1H)-one (70 mg, 0.217 mmol) and 5-(1-methylpiperidin-4-yl)pyridin-2-amine (45.71 mg, 0.239 mmol) in toluene (2 mL) and tert-butanol (0.5 mL) were added Pd2(dba)3 (19.90 mg, 0.022 mmol), X-Phos (10.36 mg, 0.022 mmol), and cesium carbonate (212.37 mg, 0.652 mmol). The reaction mixture was reacted at 100°C under nitrogen for 16 hours. Water (100 mL) was added, and the mixture was extracted three times with dichloromethane (20 mL*3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography (MeOH / CH2Cl2 = 0-5%) to give 4-((5-chloro-2-((5-(1-methylpiperidin-4-yl)pyridin-2-yl)amino)pyrimidin-4-yl)ethynyl)-5-isopropyl-1-methylpyridin-2(1H)-one (5.85 mg, yield: 5.64%). MS (ESI): m / z 477.3 [M+H] + .

[0488] 1 H NMR (400MHz, DMSO-d6) δ10.22(s,1H),8.68(s,1H),8.13(d,J=2.5Hz,1H),7.96(d,J=8.6Hz,1H),7.69-7.57(m,2H),6.63(s,1H ),3.40(s,3H),3.08-3.00(m,1H),2.94-2.84(m,2H),2.30-2.18(m,4H),2.09(s,2H),1.76-1.55(m,4H),1.18(d,J=6.9Hz,6H).

[0489] Example D1: Preparation of 2-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-1-isopropyl-6-((methylamino)methyl)pyridin-4(1H)-one

[0490] Step 1: Synthesis of 2,6-dichloro-1-isopropylpyridin-4(1H)-one

[0491] Cesium carbonate (8.94 g, 27.44 mmol) was added to a solution of 2,6-dichloropyridin-4-ol (3.0 g, 18.29 mmol) and 2-bromopropane (3.37 g, 27.44 mmol) in DMF (50 mL). The reaction mixture was allowed to react at 70°C for 18 hours. The reaction mixture was cooled to room temperature, diluted with water, extracted with MTBE, washed with saturated brine, and dried over anhydrous sodium sulfate. After concentration, the residue was separated by column chromatography to obtain 2,6-dichloro-1-isopropylpyridin-4(1H)-one (3.68 g, yield: 97.5%). MS m / z (ESI): 206.1 [M+H] + .

[0492] Step 2: Synthesis of 2-chloro-1-isopropyl-6-vinylpyridin-4(1H)-one

[0493] 2,6-Dichloro-1-isopropylpyridin-4(1H)-one (8.16 g, 39.64 mmol), potassium trifluoro(vinyl)borate (5.42 g, 40.43 mmol), triethylamine (6.02 g, 59.46 mmol), and Pd(dppf)Cl2 (1.45 g, 1.982 mmol) were placed in isopropanol (150 mL) and stirred at 80°C under nitrogen for 3 hours. The reaction mixture was concentrated and separated by column chromatography to obtain 2-chloro-1-isopropyl-6-vinylpyridin-4(1H)-one (6.83 g, yield: 60.5%). MS m / z (ESI): 198.1 [M+H] + .

[0494] Step 3: Synthesis of 6-chloro-1-isopropyl-4-oxo-1,4-dihydropyridine-2-carbaldehyde

[0495] 2-Chloro-1-isopropyl-6-vinylpyridin-4(1H)-one (6.33 g, 32.03 mmol) was dissolved in THF (100 mL), and water (100 mL) was added. Then sodium periodate (10.27 g, 48.04 mmol) and dihydroxydicarbonyl-λ were added. 6 -Osmium(VI) dipotassium dihydrate (0.35 g, 0.961 mmol) was stirred at room temperature for 30 minutes, and sodium periodate (10.27 g, 48.04 mmol) was added. The reaction solution was stirred for an additional hour. After the reaction was completed, saturated aqueous sodium sulfite solution was added to quench the reaction, and a large amount of water was added. The mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography to obtain 6-chloro-1-isopropyl-4-oxo-1,4-dihydropyridine-2-carbaldehyde (3.98 g, yield: 60.7%). MS (ESI): m / z 200.1 [M+H]+ .

[0496] Step 4: Synthesis of 2-chloro-1-isopropyl-6-((methylamino)methyl)pyridin-4(1H)-one

[0497] 6-Chloro-1-isopropyl-4-oxo-1,4-dihydropyridine-2-carbaldehyde (3.0 g, 15.03 mmol) was placed in anhydrous ethanol (100 mL). Methylamine hydrochloride (10.15 g, 150.3 mmol) and DIPEA (34.8 mL, 195.4 mmol) were added sequentially. The mixture was stirred at 80°C for 2 hours. After cooling to room temperature, sodium borohydride (1.016 g, 30.06 mmol) was added. The mixture was stirred at room temperature for 10 minutes and used directly in the next step. MS m / z (ESI): 215.2 [M+H] + .

[0498] Step 5: Synthesis of tert-butyl ((6-chloro-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl) (methyl) carbamate

[0499] Di-tert-butyl dicarbonate (6.56 g, 30.06 mmol) was added to the reaction mixture. After addition, the mixture was stirred at 50°C for 1 hour. The reaction mixture was concentrated and separated using a reverse phase column to obtain tert-butyl ((6-chloro-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate (1.28 g, yield: 20.5%). MS m / z (ESI): 315.2 [M+H] + .

[0500] Step 6: Synthesis of tert-butyl ((1-isopropyl-4-oxo-6-((trimethylsilyl)ethynyl)-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate

[0501] Tert-butyl ((6-chloro-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate (2.0 g, 6.353 mmol) and ethynyltrimethylsilane (6.24 g, 63.53 mmol) were dissolved in acetonitrile (50 mL), and bis(acetonitrile)palladium chloride (131.9 mg, 0.508 mmol), X-Phos (302.9 mg, 1.794 mmol), and triethylamine (1.93 g, 19.06 mmol) were added in sequence. The tube was sealed under nitrogen protection and heated to 90°C and stirred overnight. After the reaction was complete, most of the acetonitrile was removed, saturated ammonium chloride was added, and the mixture was extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Tert-butyl ((1-isopropyl-4-oxo-6-((trimethylsilyl)ethynyl)-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate (1.66 g, yield: 54.7%) was isolated by silica gel column chromatography. MS (ESI): m / z 377.4 [M+H] + .

[0502] Step 7: Synthesis of tert-butyl ((6-ethynyl-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl) (methyl) carbamate

[0503] Tert-butyl ((1-isopropyl-4-oxo-6-((trimethylsilyl)ethynyl)-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate (1.66 g, 4.419 mmol) was dissolved in methanol (15 mL), potassium carbonate (1.83 g, 13.26 mmol) was added, and the mixture was stirred at room temperature for 15 minutes. The reaction solution was filtered and dried, and then separated by silica gel column chromatography to obtain tert-butyl ((6-ethynyl-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate (796 mg, yield: 59%). MS m / z (ESI): 305.2 [M+H] + .

[0504] Step 8: Synthesis of 4,5-dichloro-2-(methylsulfinyl)pyrimidine

[0505] Dissolve 4,5-dichloro-2-(methylthio)pyrimidine (1.0 g, 5.13 mmol) in DCM (20 mL), add m-CPBA (2.21 g, 12.82 mmol), and stir for 15 minutes. Quench with saturated sodium bicarbonate solution, extract three times with dichloromethane, and combine the organic phases, wash with saturated sodium bicarbonate solution and saturated brine, then dry over anhydrous sodium sulfate, filter, and concentrate. 4,5-dichloro-2-(methylsulfinyl)pyrimidine (629 mg, yield: 58%) was obtained by silica gel column chromatography. MS (ESI): m / z 211.1 [M+H] + .

[0506] Step 9: Synthesis of (3S,4R)-4-((4,5-dichloropyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol

[0507] 4,5-Dichloro-2-(methylsulfinyl)pyrimidine (595 mg, 2.82 mmol), (3S,4R)-4-aminotetrahydropyran-3-ol hydrochloride (866 mg, 5.64 mmol), and DIPEA (1.46 g, 11.28 mmol) were dissolved in DMSO (10 mL), heated to 100°C, and stirred for 45 minutes. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography to afford (3S,4R)-4-((4,5-dichloropyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (177 mg, yield: 23%). MS (ESI): m / z 264.1 [M+H] + .

[0508] Step 10: Synthesis of tert-butyl ((6-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate

[0509] (3S,4R)-4-((4,5-dichloropyrimidin-2-yl)amino)tetrahydro-2H-pyran-3-ol (88 mg, 0.33 mmol), tert-butyl ((6-ethynyl-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate (304 mg, 1.00 mmol), bis(acetonitrile)palladium chloride (6.9 mg, 0.027 mmol), X-Phos (15.9 mg, 0.033 mmol) and DIPEA (129 mg, 1.00 mmol) were placed in acetonitrile (5 mL) and the mixture was stirred at 50 ° C overnight under nitrogen protection. The reaction mixture was concentrated and separated by column chromatography to give tert-butyl ((6-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate (40 mg, yield: 22%). MS m / z (ESI): 532.3 [M+H] + .

[0510] Step 11: Synthesis of 2-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-1-isopropyl-6-((methylamino)methyl)pyridin-4(1H)-one

[0511] Tert-butyl ((6-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-1-isopropyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamate (40 mg, 0.075 mmol) was placed in dichloromethane (1.5 mL), and trifluoroacetic acid (0.5 mL) was added. The mixture was concentrated and analyzed by HPLC (water (TFA) / acetonitrile system) to give 2-((5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)ethynyl)-1-isopropyl-6-((methylamino)methyl)pyridin-4(1H)-one (2.0 mg, yield: 4.7%). MS m / z(ESI):432.2[M+H] + .

[0512] 1H NMR (400MHz, CD3OD) δ8.35(s,1H),7.26(d,J=2.3Hz,1H),7.07(d,J=2.3Hz,1H),4.31(s,2H),4.00-3.86(m,3H),3.62-3.54(m,1H),3. 53-3.43(m,1H),3.19(t,J=10.4Hz,1H),2.79(s,3H),2.10-2.02(m,1H),1.67-1.54(m,1H),1.38(d,J=6.0Hz,6H),1.34-1.27(m,1H).

[0513] The following example compounds can be prepared by selecting corresponding raw materials with reference to or in accordance with all or part of the synthesis methods of Examples A1, A6, A7, A13, A49, A114, A139, A172, A223, A281, A305, B1, B2, B37, C1 or D1:

[0514] The NMR data of the compound prepared in the above example are as follows:

[0515] Biological test evaluation

[0516] 1. In vitro biochemical kinase activity analysis of CDK2 / cyclin E1

[0517] The present invention uses the TR-FRET (time-resolved fluorescence resonance energy transfer) method to determine the inhibitory properties of the compound on CDK2 / cyclin E1 kinase activity. The specific experimental process is as follows:

[0518] 1. The kinase reaction performed in the present invention was performed in a 384-well plate, using 1 nM CDK2 / cyclin E1 kinase (Carna), 1 mM ATP, and 50 nM labeled substrate protein ULight-4E-BP1 (Thr37 / 46) (Revvity) in a reaction system of 10 mM MgCl2, 2 mM DTT, 0.01% Triton X-100, 0.01% BSA, and 50 mM pH 7.5 HEPES buffer, and incubated at room temperature for 30 minutes.

[0519] 2. Add detection solution (Revvity) to stop the reaction.

[0520] 3. Transfer the plate to Envision to read the data to measure the energy transfer (FRET) signal (read the emission light at 665nM and 615nM wavelengths respectively to calculate the 665 / 615 ratio).

[0521] 4. Use XLfit statistical software to analyze the inhibition rate at different compound concentrations to determine IC50 The enzymatic activities of the compounds in the specific examples are shown in Table 1.

[0522] II. In vitro biochemical kinase activity analysis of CDK4 / cyclin D1

[0523] The present invention uses the TR-FRET (time-resolved fluorescence resonance energy transfer) method to determine the inhibitory properties of the compound on CDK4 / cyclin D1 kinase activity. The specific experimental process is as follows:

[0524] 1. The kinase reaction performed in the present invention was performed in a 384-well plate using 1 nM CDK4 / cyclin D1 kinase (Invitrogen), 3 mM ATP, and 50 nM labeled substrate protein ULight-4E-BP1 (Thr37 / 46) (Revvity) in a reaction system of 10 mM MgCl2, 2 mM DTT, 0.01% Triton X-100, 0.01% BSA, and 50 mM pH 7.5 HEPES buffer, and incubated at room temperature for 30 minutes.

[0525] 2. Add detection solution (Revvity) to stop the reaction.

[0526] 3. Transfer the plate to Envision to read the data to measure the energy transfer (FRET) signal (read the emission light at 665nM and 615nM wavelengths respectively to calculate the 665 / 615 ratio).

[0527] 4. Use XLfit statistical software to analyze the inhibition rate at different compound concentrations to determine IC 50 The enzymatic activities of the compounds in the specific examples are shown in Table 1.

[0528] III. In vitro biochemical kinase activity analysis of CDK6 / cyclin D3

[0529] The present invention uses the TR-FRET (time-resolved fluorescence resonance energy transfer) method to determine the inhibitory properties of the compound on CDK6 / cyclin D3 kinase activity. The specific experimental process is as follows:

[0530] 1. The kinase reaction performed in the present invention was performed in a 384-well plate, using 1 nM CDK6 / cyclin D3 kinase (Carna), 3 mM ATP, and 50 nM labeled substrate protein ULight-4E-BP1 (Thr37 / 46) (Revvity) in a reaction system of 10 mM MgCl2, 2 mM DTT, 0.01% Triton X-100, 0.01% BSA, and 50 mM pH 7.5 HEPES buffer, and incubated at room temperature for 30 minutes.

[0531] 2. Add detection solution (Revvity) to stop the reaction.

[0532] 3. Transfer the plate to Envision to read the data to measure the energy transfer (FRET) signal (read the emission light at 665nM and 615nM wavelengths respectively to calculate the 665 / 615 ratio).

[0533] 4. Use XLfit statistical software to analyze the inhibition rate at different compound concentrations to determine IC 50 The enzymatic activities of the compounds in the specific examples are shown in Table 1.

[0534] Table 1 Enzyme activity test results of compounds

[0535] IV. Determination of the antiproliferative effects of compounds on MCF7 and MV4-11 cells

[0536] Antiproliferative activity of compounds was evaluated using MCF7 and MV4-11 cell lines. MCF7 cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum and penicillin-streptomycin. MV4-11 cells were cultured in IMDM medium supplemented with 20% fetal bovine serum and penicillin-streptomycin.

[0537] 1. MCF7 and MV4-1 cells in the logarithmic growth phase were plated in 96-well flat-bottom plates (Greiner) and cultured overnight at 37°C and 5% CO2.

[0538] 2. On the second day, dissolve the compound in DMSO, dilute it with DMSO and culture medium in turn and transfer it to the cell plate. The final concentration of the compound is 10uM, diluted 4-fold, and 9 concentration gradients are added with DMSO control.

[0539] 3. Remove cells that have not been treated with compound and assay cell viability using the CellTiter-Glo Luminescent Cell Viability Assay (Promega) according to the kit instructions. Luminescent signals were then detected in the EnVision Multilabel Reader. Simultaneously, the cell plate treated with compound was incubated at 37°C, 5% CO₂ for 6 consecutive days, and cell viability was then assayed using the CellTiter-Glo assay.

[0540] 4. Finally, the dose-response curve was drawn using the four-parameter dose-response curve module of GraphPad Prism v 10.1.2 software and the IC of proliferation inhibition was calculated. 50 (nM), the cell activities of the specific examples of compounds are shown in Table 2.

[0541] Table 2 Cytological activity test results of compounds

[0542] From the biological activity data of the specific example compounds in Tables 1 and 2, it can be seen that the series of compounds of the present invention have high inhibitory activity against CDK4 and / or CDK2 kinases, and some compounds have high selectivity for CDK6 kinase. At the same time, the series of compounds of the present invention have strong inhibitory activity against the proliferation of MCF7 and / or MV4-1 cells.

[0543] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above disclosure, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof: in, X1 is CR5 or N; X2 is selected from CR6 or N; Ring A is C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; Ring B is C 6-10 Aryl or 6-10 membered heteroaryl; m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-8 Alkyl, halogen substituted C 1-8 Alkyl, deuterium substituted C 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 , provided that, when ring B is phenyl, R2 is not hydrogen, C 1-8 Alkyl, C 6-10 Aryl, -C 0-8 Alkyl-OR 11 and -C 0-8 Alkyl-C(O)R 12 ; R3 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 ; n is 0, 1, 2, 3 or 4; each R4 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-O-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 , or, when n≥2, two adjacent R4 together with their directly connected parts form a C 4-10 Cycloalkyl, 4-10 membered heterocyclyl, 5-10 membered heteroaryl or C 6-10 Aryl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-O-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-O-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; R5 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 ; R6 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 , or, R6 and R3 together with the part to which they are directly connected form a 4-10 membered heterocyclic group, a 5-10 membered heteroaryl group or a C 6-10 Aryl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=N-R7)R8, -C 0-8 Alkyl-N=S(O)R8R9, -C 0-8 Alkyl-N=SR8R9, -C 0-8 Alkyl-OS(O)2R 10 、-C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)SR 11 、-C 0-8 Alkyl-SC(O)R 12 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-P(O)(R 12 )2. -C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Each R7 is independently selected from hydrogen, deuterium, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)R 12 and -C 0-8 Alkyl-C(O)NR 13 R 14 The above groups are optionally further substituted by one or more groups selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Each R8 and each R9 are independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl, or, R8 and R9 together with the sulfur atom to which they are directly connected form a 3-10 membered heterocyclic group, the above groups are optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 10 、-C 0-8 Alkyl-OR 11 、-C 0-8 Alkyl-C(O)OR 11 、-C 0-8 Alkyl-C(O)R 12 、-C 0-8 Alkyl-OC(O)R 12 、-C 0-8 Alkyl-NR 13 R 14 、-C 0-8 Alkyl-C(=NR 13 )R 12 、-C 0-8 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-8 Alkyl-C(O)NR 13 R 14 and -C 0-8 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Each R 10 independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl and -NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, hydroxyl, =O, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent; Each R 11 independently selected from hydrogen, deuterium, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent; Each R 12 independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent; Each R 13 and each R 14 are independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-10 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono C 1-10 Alkylamino, di-C 1-10 Alkylamino and C 1-10 substituted with an alkanoyl substituent; Or, R 13 and R 14 Together with the nitrogen atom directly connected thereto, a 4-10 membered heterocyclic group or a 5-10 membered heteroaryl group is formed, wherein the 4-10 membered heterocyclic group or the 5-10 membered heteroaryl group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, ═O, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono C 1-10 Alkylamino, di-C 1-10 Alkylamino and C 1-10 substituted with an alkanoyl substituent; Each r is independently 0, 1 or 2.

2. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , provided that, when ring B is phenyl, R2 is not hydrogen, C 1-4 Alkyl, -C 0-4 Alkyl-OR 11 and -C 0-4 Alkyl-C(O)R 12 ; R3 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 ; n is 0, 1, 2, 3 or 4; each R4 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , or, when n≥2, two adjacent R4 together with their directly connected parts form a C 4-6 Cycloalkyl, 4-8 membered heterocyclyl, 5-8 membered heteroaryl or phenyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; R5 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 ; R6 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , or, R6 and R3 together with the part directly connected thereto form a 5-8 membered heterocyclic group, a 5-8 membered heteroaryl group or a phenyl group, the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 and r as claimed in claim 1.

3. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each R7 is independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)R 12 and -C 0-4 Alkyl-C(O)NR 13 R 14 The above groups are optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Each R8 and each R9 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl or 5-8 membered heteroaryl, or, R8 and R9 together with the sulfur atom to which they are directly connected form a 3-8 membered heterocyclic group, the above groups are optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Each R 10 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl and -NR 13 R 14 The above groups are independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, hydroxyl, =O, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent; Each R 11 independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl and 5-8 membered heteroaryl, the above groups are independently optionally further substituted by one or more selected from deuterium, halogen, hydroxyl, =O, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent; Each R 12 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 13 R 14 The above groups are optionally further substituted by one or more groups selected from deuterium, halogen, hydroxyl, =O, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 13 R 14 substituted by a substituent; Each R 13 and each R 14 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-4 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 substituted with an alkanoyl substituent; Or, R 13 and R 14 Together with the nitrogen atom directly connected thereto, a 4-6 membered heterocyclic group or a 5-8 membered heteroaryl group is formed, wherein the 4-6 membered heterocyclic group or the 5-8 membered heteroaryl group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, ═O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 The alkanoyl group is substituted with an alkanoyl substituent.

4. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: for Among them, R 4a and R 4b are each independently selected from hydrogen, deuterium, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-C(O)R 12 and -C 0-4 Alkyl-C(O)NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Y1, Y2, Y3, Y4 and Y5 are each independently selected from N or CR 4c ; Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , or, where two adjacent R 4c Together with its directly connected parts, it forms a C 4-6 Cycloalkyl, 5-6 membered heterocyclyl, 5-6 membered heteroaryl or phenyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-O-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Y6, Y7, Y9 and Y 10 Each independently selected from N or CR 4d ; Each R 4d are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 , or, where two adjacent R 4d Together with the part directly connected thereto, a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group is formed, wherein the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Y8 and Y 11 Each independently selected from N or CR 4e ; Each R 4e are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=N-R7)R8, -C 0-4 Alkyl-N=S(O)R8R9, -C 0-4 Alkyl-N=SR8R9, -C 0-4 Alkyl-OS(O)2R 10 、-C 0-4 Alkyl-S(O) r R 10 、-C 0-4 Alkyl-OR 11 、-C 0-4 Alkyl-C(O)OR 11 、-C 0-4 Alkyl-C(O)SR 11 、-C 0-4 Alkyl-SC(O)R 12 、-C 0-4 Alkyl-C(O)R 12 、-C 0-4 Alkyl-OC(O)R 12 、-C 0-4 Alkyl-P(O)(R 12 )2. -C 0-4 Alkyl-NR 13 R 14 、-C 0-4 Alkyl-C(=NR 13 )R 12 、-C 0-4 Alkyl-N(R 13 )-C(=NR 14 )R 12 、-C 0-4 Alkyl-C(O)NR 13 R 14 and -C 0-4 Alkyl-N(R 13 )-C(O)R 12 substituted by a substituent; Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 and r as claimed in claim 1.

5. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is the compound of formula (IIa): Wherein, X1 is CR5 or N; Y1, Y2, Y3, Y4 and Y5 are each independently selected from N or CR 4c ; Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 , or, where two adjacent R 4c Together with its directly connected parts, it forms a C 4-6 Cycloalkyl, 5-6 membered heterocyclyl, 5-6 membered heteroaryl or phenyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Ring A is C 5-8 Cycloalkyl, 5-8 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 , the condition is that when Y1, Y2, Y3, Y4 and Y5 are all CR 4c When R2 is not hydrogen, C 1-4 Alkyl, -OR 11 and -C(O)R 12 ; R3 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 ; R5 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 ; R6 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 , or, R6 and R3 together with the part directly connected thereto form a 5-8 membered heterocyclic group, a 5-8 membered heteroaryl group or a phenyl group, the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 , m and r as described in claim 1.

6. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is the compound of formula (IIIa1): Wherein, Y1, Y2, Y3 and Y5 are each independently selected from N or CR 4c ; Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-O-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Ring A is C 5-8 Cycloalkyl, 5-8 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 ; R is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF, hydroxyl, amino, methylamino and dimethylamino; R6 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino; or, R6 and R3 together with the part to which they are directly connected form a 5-8 membered heteroaryl or phenyl group, wherein the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 and r as claimed in claim 1.

7. The compound of formula (I) according to claim 6, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IVa11), formula (IVa12) or formula (IVa13): Among them, each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each R3 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino; Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino, and the above groups are independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Among them, ring A, R1, R2, R 11 、R 12 、R 13 、R 14 and m as described in claim 6.

8. The compound of formula (I) according to claim 7, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclyl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each R3 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, isopropyl, methoxy, trifluoromethyl, trideuteriomethyl, cyclopropyl, hydroxy, amino, methylamino and dimethylamino; Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, methoxy, trifluoromethyl, trideuteriomethyl, trideuteriomethoxy, cyclopropyl, hydroxyl, amino, methylamino and dimethylamino; Among them, R 11 、R 12 、R 13 and R 14 As described in claim 7.

9. The compound of formula (I) according to claim 6, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is the compound of formula (IVa14): wherein Ring C is a 5-6 membered nitrogen-containing heteroaryl group, wherein the 5-6 membered nitrogen-containing heteroaryl group optionally contains one or more oxygen or sulfur heteroatoms; R 6a Selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino; Each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Among them, ring A, R1, R2, R 11 、R 12 、R 13 、R 14 and m as described in claim 6.

10. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIIa2) or a compound of formula (IIIa3): wherein each Y4 is independently selected from N or CR 4c ; Ring D and Ring E are each independently C 5-6 Cycloalkyl, 5-6 membered heterocyclyl, 5-6 membered heteroaryl or phenyl, wherein the 5-6 membered heterocyclyl or 5-6 membered heteroaryl contains one or more heteroatoms selected from nitrogen, oxygen or sulfur; Each p is independently 0, 1 or 2; each R 4c are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-O-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trideuteriomethyl, trifluoromethoxy, trideuteriomethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopropyloxy, cyclobutyloxy, oxetanyl, azetidinyl, -SF5, hydroxyl, amino, methylamino and dimethylamino; Among them, ring A, R1, R2, R 11 、R 12 、R 13 、R 14 and m as described in claim 5.

11. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIb) or formula (IIc): wherein each X1 is independently CR5 or N; R 4a and R 4b are each independently selected from hydrogen, deuterium, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-C(O)R 12 and -C(O)NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Y6, Y7, Y9 and Y 10 Each independently selected from N or CR 4d ; Each R 4d are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 , or, where two adjacent R 4d Together with the part directly connected thereto, a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group is formed, wherein the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Y8 and Y 11 Each independently selected from N or CR 4e ; Each R 4e are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each ring A is independently C 5-8 Cycloalkyl, 5-8 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each R2 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -S(O)(=N-R7)R8, -N=S(O)R8R9, -N=SR8R9, -OS(O)2R 10 、-S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)SR 11 、-SC(O)R 12 、-C(O)R 12 、-OC(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(=NR 13 )R 12 、-N(R 13 )-C(=NR 14 )R 12 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 ; Each R3 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 ; Each R5 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 ; Each R6 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 , or, R6 and R3 together with the part directly connected thereto form a 5-8 membered heterocyclic group or a 5-8 membered heteroaryl group, the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Among them, R7, R8, R9, R 10 、R 11 、R 12 、R 13 、R 14 and r as claimed in claim 1.

12. The compound of formula (I) according to claim 11, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIIb) or formula (IIIc): Among them, R 4a and R 4b are independently selected from hydrogen, deuterium, cyano, hydroxyl, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O)2R 10 and acetyl, the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each R 4d are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each R6 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -SF5, -OR 11 and -NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -OR 11 、-C(O)OR 11 、-C(O)R 12 、-P(O)(R 12 )2、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Among them, ring A, R1, R2, R 11 、R 12 、R 13 、R 14 and m as described in claim 11.

13. The compound of formula (I) according to claim 12, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 4a and R 4b are each independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, methylsulfinyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, aminosulfonyl and C 1-4 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, halogen substituted C 1-4 Alkyl, halogen substituted C 1-4 Alkoxy, deuterium substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyloxy, =O, -NR 13 R 14 and -C(O)NR 13 R 14 substituted by a substituent; Each R 4d are independently selected from hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 1-4 Alkoxy, methylsulfinyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, aminosulfonyl and C 1-4 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, halogen substituted C 1-4 Alkyl, halogen substituted C 1-4 Alkoxy, deuterium substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyloxy, =O, -NR 13 R 14 and -C(O)NR 13 R 14 substituted by a substituent; Among them, R 13 and R 14 As described in claim 12.

14. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Ring A is selected from phenyl, 5-6 membered heteroaryl, C 5-8 Cycloalkyl or 5-8 membered heterocyclic group, wherein the 5-6 membered heteroaryl or 5-8 membered heterocyclic group contains one or more heteroatoms selected from nitrogen, oxygen or sulfur; preferably, ring A is selected from phenyl, pyridyl, pyrimidinyl, pyridazinyl, triazinyl, furyl, thienyl, imidazolyl, triazolyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, C 5-8 Cycloalkyl or 5-8 membered heterocyclic group, wherein the 5-8 membered heterocyclic group contains one or more heteroatoms selected from nitrogen, oxygen or sulfur; m is 0, 1, 2, 3 or 4; each R1 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 ; Among them, R 10 、R 11 、R 12 、R 13 、R 14 and r as claimed in claim 1.

15. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: described Selected from the following structures: Among them, each R 1a , each R 1b , each R 1d , each R 1e , each R 1f , each R 1g , each R 1h , each R 1i and each R 1k are each independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 The above groups are independently optionally further substituted with one or more substituents selected from deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each R 1c and R 1j are each independently selected from hydrogen, deuterium, cyano, nitro, C 1-4 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, -S(O)2R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 and -C(O)NR 13 R 14 The above groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 substituted by a substituent; Each R2 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 10 、-OR 11 、-C(O)OR 11 、-C(O)R 12 、-OC(O)R 12 、-NR 13 R 14 、-C(O)NR 13 R 14 and -N(R 13 )-C(O)R 12 ; Among them, R 10 、R 11 、R 12 、R 13 、R 14 and r as claimed in claim 1.

16. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each R 10 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -NR 13 R 14 The above groups are independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, hydroxyl, =O, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyl and -NR 13 R 14 substituted by a substituent; Each R 11 independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, the above groups are independently optionally further substituted by one or more selected from deuterium, halogen, hydroxyl, =O, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyl and -NR 13 R 14 substituted by a substituent; Each R 12 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 Alkenyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyl and -NR 13 R 14 The above groups are optionally further substituted by one or more groups selected from deuterium, halogen, hydroxyl, =O, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclyl, 3-6 membered heterocyclyl and -NR 13 R 14 substituted by a substituent; Among them, R 13 and R 14 As claimed in claim 1.

17. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each R 13 and each R 14 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-4 Alkanoyl, the above groups are independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 substituted with an alkanoyl substituent; Or, R 13 and R 14 Together with the nitrogen atom directly connected thereto, a 4-6 membered heterocyclic group is formed, wherein the 4-6 membered heterocyclic group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 The cycloalkyl group and the 3- to 6-membered heterocyclic group are substituted.

18. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Selected from the following compounds:

19. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 18, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

20. Use of a compound of formula (I) according to any one of claims 1 to 18, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating at least some CDK-related tumors; preferably, the tumor is breast cancer, malignant brain tumor, colon cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, secondary pancreatic cancer, or secondary brain metastasis.

21. A compound of formula (I) according to any one of claims 1 to 18, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, for treating at least some tumors associated with CDK; preferably, the tumor is breast cancer, malignant brain tumor, colon cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, secondary pancreatic cancer, or secondary brain metastasis.

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