Fascin inhibitors
Patent Information
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-05-24
- Publication Date
- 2026-04-08
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Figure CN2024095150_28112024_PF_FP_ABST
Abstract
Description
Fascin inhibitorsTechnical FieldThe invention relates to Fascin inhibitors, a composition containing the inhibitor and the use thereof.Background ArtFascin is an actin-bundling protein widely present in various cells, capable of stabilizing and organizing actin bundles through direct interaction with actin filaments (F-actin) . This interaction is crucial for many biological processes such as cell migration, cell polarity, and cell division. Research has shown that Fascin has low or no expression in normal tissues (such as nerves, intestinal epithelium, and muscles) , but when cells (like epithelial cells) turn into cancer cells, Fascin's expression often significantly increases. This increase in Fascin expression can enhance the invasiveness and migratory ability of tumor cells, thereby promoting the spread and metastasis of tumors. It can be seen that the abnormal expression or activity regulation of Fascin is related to the progression of many diseases, especially in many types of cancers, including gastric cancer, lung cancer, breast cancer, colon cancer, and ovarian cancer. Overexpression of Fascin has also been found to be associated with poor prognosis in tumor patients. In some cancers, such as non-small cell lung cancer, the expression level of Fascin can be used as an independent prognostic marker to predict disease progression and survival rate. Therefore, treatment strategies targeting Fascin may not only inhibit tumor growth and spread, but also improve the survival rate and quality of life of patients.The biochemical properties and functions of Fascin pose some challenges for drug design and development. For instance, Fascin's interaction with actin filaments is through a large area of protein-protein contact, making it extremely difficult to find small molecule compounds that can effectively block this interaction. Moreover, Fascin also has important functions in normal tissues, so any treatment strategies targeting Fascin must carefully consider their potential impact on normal physiological processes to avoid adverse reactions or toxicity. In recent years, although some preliminary studies have shown that some small molecule compounds can inhibit its function by directly interacting with Fascin or indirectly affecting its expression or activity. For example, some compounds can block Fascin's function by interfering with its interaction with actin filaments, whereas other compounds can change its activity by affecting Fascin's expression or phosphorylation state. However, these compounds have poor selectivity for Fascin and often cause toxicity to other cells. Therefore, it is essential to develop Fascin-selective inhibitors and validate the efficacy and safety of these compounds.Summary of InventionThe present invention provides a compound for the treatment of cancer related to overexpression of Fascin, and has better physicochemical properties (e.g., solubility, physical and / or chemical stability) , improved pharmacokinetic properties (e.g., improved bioavailability, proper half-life and duration of action) , improved safety (low toxicity and / or less side effects, wide therapeutic window) , and the like.Provided herein are the following disclosures:[1] . A compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof:Wherein,X1 is selected from N or CR3;R1 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR12, -NR13R14, -SR15, -C (=O) R16, -C (=O) OR12, -OC (=O) R16, -C (=O) NR13R14, -NR13C (=O) R16, -S (=O) R17, -S (=O) OR12, -OS (=O) R17, -S (=O) NR13R14, -NR13S (=O) R17, -S (=O) 2R18, -S (=O) 2OR12, -OS (=O) R18, -S (=O) 2NR13R14, -NR13S (=O) 2R18, -P (=O) (R19) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, oxo, -OR1b, -NR1cR1d, -SR1e, -C (=O) R1f, -C (=O) OR1b, -OC (=O) R1f, -OC (=O) OR1b, -C (=O) NR1cR1d, -OC (=O) NR1cR1d, -C (=NR1c) R1a, -C (=NR1c) NR1cR1d, -NR1cC (=NR1c) NR1cR1d, -NR1cC (=O) R1f, -NR1cC (=O) OR1b, -NR1cC (=O) NR1cR1d, -S (=O) R1g, -S (=O) OR1b, -OS (=O) R1g, -OS (=O) OR1b, -S (=O) NR1cR1d, -NR1cS (=O) R1g, -NR1cS (=O) OR1b, -OS (=O) NR1cR1d, -NR1cS (=O) NR1cR1d, -S (=O) 2R1h, -S (=O) 2OR1b, -OS (=O) 2R1h, -OS (=O) 2OR1b, -S (=O) 2NR1cR1d, -NR1cS (=O) 2R1h, -NR1cS (=O) 2OR1b, -OS (=O) 2NR1cR1d, -NR1cS (=O) 2NR1cR1d, -P (=O) (R1i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R2 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR22, -NR23R24, -SR25, -C (=O) R26, -C (=O) OR22, -OC (=O) R26, -C (=O) NR23R24, -NR23C (=O) R26, -S (=O) R27, -S (=O) OR22, -OS (=O) R27, -S (=O) NR23R24, -NR23S (=O) R27, -S (=O) 2R28, -S (=O) 2OR22, -OS (=O) 2R28, -S (=O) 2NR23R24, -NR23S (=O) 2R28, -P (=O) (R29) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, oxo, -OR2b, -NR2cR2d, -SR2e, -C (=O) R2f, -C (=O) OR2b, -OC (=O) R2f, -OC (=O) OR2b, -C (=O) NR2cR2d, -OC (=O) NR2cR2d, -C (=NR2c) R2a, -C (=NR2c) NR2cR2d, -NR2cC (=NR2c) NR2cR2d, -NR2cC (=O) R2f, -NR2cC (=O) OR2b, -NR2cC (=O) NR2cR2d, -S (=O) R2g, -S (=O) OR2b, -OS (=O) R2g, -OS (=O) OR2b, -S (=O) NR2cR2d, -NR2cS (=O) R2g, -NR2cS (=O) OR2b, -OS (=O) NR2cR2d, -NR2cS (=O) NR2cR2d, -S (=O) 2R2h, -S (=O) 2OR2b, -OS (=O) 2R2h, -OS (=O) 2OR2b, -S (=O) 2NR2cR2d, -NR2cS (=O) 2R2h, -NR2cS (=O) 2OR2b, -OS (=O) 2NR2cR2d, -NR2cS (=O) 2NR2cR2d, -P (=O) (R2i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R3 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR32, -NR33R34, -SR35, -C (=O) R36, -C (=O) OR32, -OC (=O) R36, -C (=O) NR33R34, -NR33C (=O) R36, -N (R33) -C (=O) -C2-6alkenyl-R31, -S (=O) R37, -S (=O) OR32, -OS (=O) R37, -S (=O) NR33R34, -NR33S (=O) R37, -S (=O) 2R38, -S (=O) 2OR32, -OS (=O) R38, -S (=O) 2NR33R34, -NR33S (=O) 2R38, -P (=O) (R39) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, oxo, -OR3b, -NR3cR3d, -SR3e, -C (=O) R3f, -C (=O) OR3b, -OC (=O) R3f, -OC (=O) OR3b, -C (=O) NR3cR3d, -OC (=O) NR3cR3d, -C (=NR3c) R3a, -C (=NR3c) NR3cR3d, -NR3cC (=NR3c) NR3cR3d, -NR3cC (=O) R3f, -NR3cC (=O) OR3b, -NR3cC (=O) NR3cR3d, -S (=O) R3g, -S (=O) OR3b, -OS (=O) R3g, -OS (=O) OR3b, -S (=O) NR3cR3d, -NR3cS (=O) R3g, -NR3cS (=O) OR3b, -OS (=O) NR3cR3d, -NR3cS (=O) NR3cR3d, -S (=O) 2R3h, -S (=O) 2OR3b, -OS (=O) 2R3h, -OS (=O) 2OR3b, -S (=O) 2NR3cR3d, -NR3cS (=O) 2R3h, -NR3cS (=O) 2OR3b, -OS (=O) 2NR3cR3d, -NR3cS (=O) 2NR3cR3d, -P (=O) (R3i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R4 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR42, -NR43R44, -SR45, -C (=O) R46, -C (=O) OR42, -OC (=O) R46, -C (=O) NR43R44, -NR43C (=O) R46, -S (=O) R47, -S (=O) OR42, -OS (=O) R47, -S (=O) NR43R44, -NR43S (=O) R47, -S (=O) 2R48, -S (=O) 2OR42, -OS (=O) R48, -S (=O) 2NR43R44, -NR43S (=O) 2R48, -P (=O) (R49) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, oxo, -OR4b, -NR4cR4d, -SR4e, -C (=O) R4f, -C (=O) OR4b, -OC (=O) R4f, -OC (=O) OR4b, -C (=O) NR4cR4d, -OC (=O) NR4cR4d, -C (=NR4c) R4a, -C (=NR4c) NR4cR4d, -NR4cC (=NR4c) NR4cR4d, -NR4cC (=O) R4f, -NR4cC (=O) OR4b, -NR4cC (=O) NR4cR4d, -S (=O) R4g, -S (=O) OR4b, -OS (=O) R4g, -OS (=O) OR4b, -S (=O) NR4cR4d, -NR4cS (=O) R4g, -NR4cS (=O) OR4b, -OS (=O) NR4cR4d, -NR4cS (=O) NR4cR4d, -S (=O) 2R4h, -S (=O) 2OR4b, -OS (=O) 2R4h, -OS (=O) 2OR4b, -S (=O) 2NR4cR4d, -NR4cS (=O) 2R4h, -NR4cS (=O) 2OR4b, -OS (=O) 2NR4cR4d, -NR4cS (=O) 2NR4cR4d, -P (=O) (R4i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R5 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR52, -NR53R54, -SR55, -C (=O) R56, -C (=O) OR52, -OC (=O) R56, -C (=O) NR53R54, -NR53C (=O) R56, -S (=O) R57, -S (=O) OR52, -OS (=O) R57, -S (=O) NR53R54, -NR53S (=O) R57, -S (=O) 2R58, -S (=O) 2OR52, -OS (=O) R58, -S (=O) 2NR53R54, -NR53S (=O) 2R58, -P (=O) (R59) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, oxo, -OR5b, -NR5cR5d, -SR5e, -C (=O) R5f, -C (=O) OR5b, -OC (=O) R5f, -OC (=O) OR5b, -C (=O) NR5cR5d, -OC (=O) NR5cR5d, -C (=NR5c) R5a, -C (=NR5c) NR5cR5d, -NR5cC (=NR5c) NR5cR5d, -NR5cC (=O) R5f, -NR5cC (=O) OR5b, -NR5cC (=O) NR5cR5d, -S (=O) R5g, -S (=O) OR5b, -OS (=O) R5g, -OS (=O) OR5b, -S (=O) NR5cR5d, -NR5cS (=O) R5g, -NR5cS (=O) OR5b, -OS (=O) NR5cR5d, -NR5cS (=O) NR5cR5d, -S (=O) 2R5h, -S (=O) 2OR5b, -OS (=O) 2R5h, -OS (=O) 2OR5b, -S (=O) 2NR5cR5d, -NR5cS (=O) 2R5h, -NR5cS (=O) 2OR5b, -OS (=O) 2NR5cR5d, -NR5cS (=O) 2NR5cR5d, -P (=O) (R5i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;Optionally, R4 and R5 together with the atoms to which they are both attached form a 3-14 membered carbocyclic ring, a 3-14 membered heterocyclic ring, a 6-12 membered aryl ring or a 5-14 membered heteroaryl ring; each said ring is independent optionally substituted with n3 RS3;RS3 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS32, -NRS33RS34, -SRS35, -C (=O) RS36, -C (=O) ORS32, -OC (=O) RS36, -OC (=O) ORS32, -C (=O) NRS33RS34, -OC (=O) NRS33RS34, -C (=NRS33) RS31, -C (=NRS33) NRS33RS34, -NRS33C (=NRS33) NRS33RS34, -NRS33C (=O) RS36, -NRS33C (=O) ORS32, -NRS33C (=O) NRS33RS34, -S (=O) RS37, -S (=O) ORS32, -OS (=O) RS37, -OS (=O) ORS32, -S (=O) NRS33RS34, -NRS33S (=O) RS37, -NRS33S (=O) ORS32, -OS (=O) NRS33RS34, -NRS33S (=O) NRS33RS34, -S (=O) 2RS38, -S (=O) 2ORS32, -OS (=O) 2RS38, -OS (=O) 2ORS32, -S (=O) 2NRS33RS34, -NRS33S (=O) 2RS38, -NRS33S (=O) 2ORS32, -OS (=O) 2NRS33RS34, -NRS33S (=O) 2NRS33RS34, -P (=O) (RS39) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein said -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-10alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS3b, -NRS3cRS3d, -SRS3e, -C (=O) RS3f, -C (=O) ORS3b, -OC (=O) RS3f, -OC (=O) ORS3b, -C (=O) NRS3cRS3d, -OC (=O) NRS3cRS3d, -C (=NRS3c) RS3a, -C (=NRS3c) NRS3cRS3d, -NRS3cC (=NRS3c) NRS3cRS3d, -NRS3cC (=O) RS3f, -NRS3cC (=O) ORS3b, -NRS3cC (=O) NRS3cRS3d, -S (=O) RS3g, -S (=O) ORS3b, -OS (=O) RS3g, -OS (=O) ORS3b, -S (=O) NRS3cRS3d, -NRS3cS (=O) RS3g, -NRS3aS (=O) ORS3b, -OS (=O) NRS3cRS3d, -NRS3cS (=O) NRS3cRS3d, -S (=O) 2RS3h, -S (=O) 2ORS3b, -OS (=O) 2RS3h, -OS (=O) 2ORS3b, -S (=O) 2NRS3cRS3d, -NRS3cS (=O) 2RS3h, -NRS3cS (=O) 2ORS3b, -OS (=O) 2NRS3cRS3d, -NRS3cS (=O) 2NRS3cRS3d, -P (=O) (RS3i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;n3 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;n4 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;Y1 is selected from -C (RY11) 2-, -RY11C=CRY11-, -C≡C-, -C (=O) -, -O-, -NRY13-, -S-, -S (=O) -, -S (=O) 2-, -P (=O) RY19-, *-C (=O) O-, *-OC (=O) -, *-C (=O) NRY13-, *-NRY13C (=O) -, *-S (=O) O-, *-OS (=O) -, *-S (=O) NRY13-, *-NRY13S (=O) -, *-S (=O) 2O-, *-OS (=O) 2-, *-S (=O) 2NRY13-, *-NRY13S (=O) 2-or *-NRY13P (=O) RY19-;*indicates the attached point to the moiety ofRing A is selected from a 3-14 membered carbocyclic ring, 3-14 membered heterocyclic ring, 6-14 membered aryl ring or 5-14 membered heteroaryl ring; said heterocyclic ring at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) , S (=O) 2; said heteroaryl ring at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;RS1 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS12, -NRS13RS14, -SRS15, -C (=O) RS16, -C (=O) ORS12, -OC (=O) RS16, -OC (=O) ORS12, -C (=O) NRS13RS14, -OC (=O) NRS13RS14, -C (=NRS13) RS11, -C (=NRS13) NRS13RS14, -NRS13C (=NRS13) NRS13RS14, -NRS13C (=O) RS16, -NRS13C (=O) ORS12, -NRS13C (=O) NRS13RS14, -S (=O) RS17, -S (=O) ORS12, -OS (=O) RS17, -OS (=O) ORS12, -S (=O) NRS13RS14, -NRS13S (=O) RS17, -NRS13S (=O) ORS12, -OS (=O) NRS13RS14, -NRS13S (=O) NRS13RS14, -S (=O) 2RS18, -S (=O) 2ORS12, -OS (=O) 2RS18, -OS (=O) 2ORS12, -S (=O) 2NRS13RS14, -NRS13S (=O) 2RS18, -NRS13S (=O) 2ORS12, -OS (=O) 2NRS13RS14, -NRS13S (=O) 2NRS13RS14, -P (=O) (RS19) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein said -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-10alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS1b, -NRS1cRS1d, -SRS1e, -C (=O) RS1f, -C (=O) ORS1b, -OC (=O) RS1f, -OC (=O) ORS1b, -C (=O) NRS1cRS1d, -OC (=O) NRS1cRS1d, -C (=NRS1c) RS1a, -C (=NRS1c) NRS1cRS1d, -NRS1cC (=NRS1c) NRS1cRS1d, -NRS1cC (=O) RS1f, -NRS1cC (=O) ORS1b, -NRS1cC (=O) NRS1cRS1d, -S (=O) RS1g, -S (=O) ORS1b, -OS (=O) RS1g, -OS (=O) ORS1b, -S (=O) NRS1cRS1d, -NRS1cS (=O) RS1g, -NRS1aS (=O) ORS1b, -OS (=O) NRS1cRS1d, -NRS1cS (=O) NRS1cRS1d, -S (=O) 2RS1h, -S (=O) 2ORS1b, -OS (=O) 2RS1h, -OS (=O) 2ORS1b, -S (=O) 2NRS1cRS1d, -NRS1cS (=O) 2RS1h, -NRS1cS (=O) 2ORS1b, -OS (=O) 2NRS1cRS1d, -NRS1cS (=O) 2NRS1cRS1d, -P (=O) (RS1i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;n1 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;Ring B is selected from a 3-14 membered carbocyclic ring, 3-14 membered heterocyclic ring, 6-14 membered aryl ring or 5-14 membered heteroaryl ring; said heterocyclic ring at each occurrence independently contains 1, 2, 3 or 4 heteroatoms selected from N, O, S, S (=O) , S (=O) 2; said heteroaryl ring at each occurrence independently contains 1, 2 or 3 heteroatoms selected from N, O or S;RS2 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS22, -NRS23RS24, -SRS25, -C (=O) RS26, -C (=O) ORS22, -OC (=O) RS26, -OC (=O) ORS22, -C (=O) NRS23RS24, -OC (=O) NRS23RS24, -C (=NRS23) RS21, -C (=NRS23) NRS23RS24, -NRS23C (=NRS23) NRS23RS24, -NRS23C (=O) RS26, -NRS23C (=O) ORS22, -NRS23C (=O) NRS23RS24, -S (=O) RS27, -S (=O) ORS22, -OS (=O) RS27, -OS (=O) ORS22, -S (=O) NRS23RS24, -NRS23S (=O) RS27, -NRS23S (=O) ORS22, -OS (=O) NRS23RS24, -NRS23S (=O) NRS23RS24, -S (=O) 2RS28, -S (=O) 2ORS22, -OS (=O) 2RS28, -OS (=O) 2ORS22, -S (=O) 2NRS23RS24, -NRS23S (=O) 2RS28, -NRS23S (=O) 2ORS22, -OS (=O) 2NRS23RS24, -NRS23S (=O) 2NRS23RS24, -P (=O) (RS29) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein said -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-10alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS2b, -NRS2cRS2d, -SRS2e, -C (=O) RS2f, -C (=O) ORS2b, -OC (=O) RS2f, -OC (=O) ORS2b, -C (=O) NRS2cRS2d, -OC (=O) NRS2cRS2d, -C (=NRS2c) RS2a, -C (=NRS2c) NRS2cRS2d, -NRS2cC (=NRS2c) NRS2cRS2d, -NRS2cC (=O) RS2f, -NRS2cC (=O) ORS2b, -NRS2cC (=O) NRS2cRS2d, -S (=O) RS2g, -S (=O) ORS2b, -OS (=O) RS2g, -OS (=O) ORS2b, -S (=O) NRS2cRS2d, -NRS2cS (=O) RS2g, -NRS2aS (=O) ORS2b, -OS (=O) NRS2cRS2d, -NRS2cS (=O) NRS2cRS2d, -S (=O) 2RS2h, -S (=O) 2ORS2b, -OS (=O) 2RS2h, -OS (=O) 2ORS2b, -S (=O) 2NRS2cRS2d, -NRS2cS (=O) 2RS2h, -NRS2cS (=O) 2ORS2b, -OS (=O) 2NRS2cRS2d, -NRS2cS (=O) 2NRS2cRS2d, -P (=O) (RS2i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;n2 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;R31, RS11, RS21 or RY11 at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -OR6b, -NR6cR6d, -SR6e, -C (=O) R6f, -C (=O) OR6b, -OC (=O) R6f, -OC (=O) OR6b, -C (=O) NR6cR6d, -OC (=O) NR6cR6d, -C (=NR6c) R6a, -C (=NR6c) NR6cR6d, -NR6cC (=NR6c) NR6cR6d, -NR6cC (=O) R6f, -NR6cC (=O) OR6b, -NR6cC (=O) NR6cR6d, -S (=O) R6g, -S (=O) OR6b, -OS (=O) R6g, -OS (=O) OR6b, -S (=O) NR6cR6d, -NR6cS (=O) R6g, -NR6cS (=O) OR6b, -OS (=O) NR6cR6d, -NR6cS (=O) NR6cR6d, -S (=O) 2R6h, -S (=O) 2OR6b, -OS (=O) 2R6h, -OS (=O) 2OR6b, -S (=O) 2NR6cR6d, -NR6cS (=O) 2R6h, -NR6cS (=O) 2OR6b, -OS (=O) 2NR6cR6d, -NR6cS (=O) 2NR6cR6d, -P (=O) (R6i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; said 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl optionally substituted with one or more substituents selected from halogen or haloC1-6alkyl;R12, R15, R22, R25, R32, R35, R42, R45, R52, R55, RS12, RS15, RS22, RS25, RS32 or RS35 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R7f, -C (=O) OR7b, -S (=O) R7g, -S (=O) OR7b, -S (=O) 2R7h, -S (=O) 2OR7b, -P (=O) (R7i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;RY13, R13, R14, R23, R24, R33, R34, R43, R44, R53, R54, RS13, RS14, RS23, RS24, RS33 or RS34 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R8f, -C (=O) OR8b, -C (=O) NR8cR8d, -S (=O) R8g, -S (=O) OR8b, -S (=O) NR8cR8d, -S (=O) 2R8h, -S (=O) 2OR8b, -S (=O) 2NR8cR8d, -P (=O) (R8i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; said -C2-6alkynyl, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl optionally substituted with one or more substituents selected from -C1-6alkyl, Si (C1-6alkyl) 3, haloC1-6alkyl or halogen;RY19, R16, R17, R18, R19, R26, R27, R28, R29, R36, R37, R38, R39, R46, R47, R48, R49, R56, R57, R58, R59, RS16, RS17, RS18, RS19, RS26, RS27, RS28, RS29, RS36, RS37, RS38 or RS39 at each occurrence is selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -OR9b, -NR9cR9d, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; said 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl optionally substituted with one or more substituents selected from -C1-6alkyl, haloC1-6alkyl, -CN, halogen or -C (=O) O-C1-6alkyl;Optionally, (R13 and R14) , (R23 and R24) , (R33 and R34) , (R43 and R44) , (R53 and R54) , (RS13 and RS14) , (RS23 and RS24) or (RS33 and RS34) together with the nitrogen atom to which they are both attached form 3-14 membered heterocyclyl ring or 5-14 membered heteroaryl ring; said 3-14 membered heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, SO or SO2; said 3-14 membered heteroaryl ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S; each said ring is independently optionally substituted with n6 RS4;RS4 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS4b, -NRS4cRS4d, -SRS4e, -C (=O) RS4g, -C (=O) ORS4b, -OC (=O) RS4f, -OC (=O) ORS4b, -C (=O) NRS4cRS4d, -OC (=O) NRS4cRS4d, -C (=NRS4c) RS4a, -C (=NRS4c) NRS4cRS4d, -NRS4cC (=NRS4c) NRS4cRS4d, -NRS4cC (=O) RS4f, -NRS4cC (=O) ORS4b, -NRS4cC (=O) NRS4cRS4d, -S (=O) RS4g, -S (=O) ORS4b, -OS (=O) RS4g, -OS (=O) ORS4b, -S (=O) NRS4cRS4d, -NRS4cS (=O) RS4g, -NRS4cS (=O) ORS4b, -OS (=O) NRS4cRS4d, -NRS4cS (=O) NRS4cRS4d, -S (=O) 2RS4h, -S (=O) 2ORS4b, -OS (=O) 2RS4h, -OS (=O) 2ORS4b, -S (=O) 2NRS4cRS4d, -NRS4cS (=O) 2RS4h, -NRS4cS (=O) 2ORS4b, -OS (=O) 2NRS4cRS4d, -NRS4cS (=O) 2NRS4cRS4d, -P (=O) (RS4i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;n6 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;R1a, R2a, R3a, R4a, R5a, R6a, RS1a, RS2a, RS3a or RS4a at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -ORZ1b, -NRZ1cRZ1d, -SRZ1e, -C (=O) RZ1f, -C (=O) ORZ1b, -OC (=O) RZ1f, -OC (=O) ORZ1b, -C (=O) NRZ1cRZ1d, -OC (=O) NRZ1cRZ1d, -C (=NRZ1c) RZ1a, -C (=NRZ1c) NRZ1cRZ1d, -NRZ1cC (=NRZ1c) NRZ1cRZ1d, -NRZ1cC (=O) RZ1f, -NRZ1cC (=O) ORZ1b, -NRZ1cC (=O) NRZ1cRZ1d, -S (=O) RZ1g, -S (=O) ORZ1b, -OS (=O) RZ1g, -OS (=O) ORZ1b, -S (=O) NRZ1cRZ1d, -NRZ1cS (=O) RZ1g, -NRZ1cS (=O) ORZ1b, -OS (=O) NRZ1cRZ1d, -NRZ1cS (=O) NRZ1cRZ1d, -S (=O) 2RZ1h, -S (=O) 2ORZ1b, -OS (=O) 2RZ1h, -OS (=O) 2ORZ1b, -S (=O) 2NRZ1cRZ1d, -NRZ1cS (=O) 2RZ1h, -NRZ1cS (=O) 2ORZ1b, -OS (=O) 2NRZ1cRZ1d, -NRZ1cS (=O) 2NRZ1cRZ1d, -P (=O) (RZ1i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R1b, R1e, R2b, R2e, R3b, R3e, R4b, R4e, R5b, R5e, R6b, R6e, R7b, R8b, R9b, RS1b, RS1e, RS2b, RS2e, RS3b, RS3e, RS4b or RS4e at each occurrence is independently selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -ORZ2b, -C (=O) RZ2f, -C (=O) ORZ2b, -S (=O) RZ2g, -S (=O) ORZ2b, -S (=O) 2RZ2h, -S (=O) 2ORZ2b, -P (=O) (RZ2i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R1c, R1d, R2c, R2d, R3c, R3d, R4c, R4d, R5c, R5d, R6c, R6d, R8c, R8d, R9c, R9d, RS1c, RS1d, RS2c, RS2d, RS3c, RS3d, RS4c or RS4d at each occurrence is independently selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) RZ3f, -C (=O) NRZ3cRZ3d, -S (=O) RZ3g, -S (=O) NRZ3cRZ3d, -S (=O) 2RZ3h, -S (=O) 2NRZ3cRZ3d, -P (=O) (RZ3i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl, 5-14 membered heteroaryl; said 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl substituted with one or more substituents selected from C1-6alkyl, haloC1-6alkyl or halogen;R1f, R1g, R1h, R1i, R2f, R2g, R2h, R2i, R3f, R3g, R3h, R3i, R4f, R4g, R4h, R4i, R5f, R5g, R5h, R5i, R6f, R6g, R6h, R6i, R7f, R7g, R7h, R7i, R8f, R8g, R8h, R8i, RS1f, RS1g, RS1h, RS1i, RS2f, RS2g, RS2h, RS2i, RS3f, RS3g, RS3h, RS3i, RS4f, RS4g, RS4h or RS4i at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -ORZ4b, -NRZ4cRZ4d, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl, 5-14 membered heteroaryl or 3-14 membered heterocyclyl optionally substituted with one or more -C (=O) ORZ4b;(R1c and R1d) , (R2c and R2d) , (R3c and R3d) , (R4c and R4d) , (R5c and R5d) , (R6c and R6d) , (R8c and R8d) , (R9c and R9d) , (Rs1c and Rs1d) , (Rs2c and Rs2d) , (Rs3c and Rs3d) or (Rs4c and Rs4d) together with the nitrogen atom to which they are both attached form 3-14 membered heterocyclyl ring or 5-14 membered heteroaryl ring; said 3-14 membered heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, SO or SO2; said 3-14 membered heteroaryl ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S; each said ring is independently optionally substituted with n7 RS5;RS5 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORZ5b, -NRZ5cRZ5d, -SRZ5e, -C (=O) RZ5f, -C (=O) ORZ5b, -OC (=O) RZ5f, -OC (=O) ORZ5b, -C (=O) NRZ5cRZ5d, -OC (=O) NRZ5cRZ5d, -C (=NRZ5c) RZ5a, -C (=NRZ5c) NRZ5cRZ5d, -NRZ5cC (=NRZ5c) NRZ5cRZ5d, -NRZ5cC (=O) RZ5f, -NRZ5cC (=O) ORZ5b, -NRZ5cC (=O) NRZ5cRZ5d, -S (=O) RZ5g, -S (=O) ORZ5b, -OS (=O) RZ5g, -OS (=O) ORZ5b, -S (=O) NRZ5cRZ5d, -NRZ5cS (=O) RZ5g, -NRZ5aS (=O) ORZ5b, -OS (=O) NRZ5cRZ5d, -NRZ5cS (=O) NRZ5cRZ5d, -S (=O) 2RZ5h, -S (=O) 2ORZ5b, -OS (=O) 2RZ5h, -OS (=O) 2ORZ5b, -S (=O) 2NRZ5cRZ5d, -NRZ5cS (=O) 2RZ5h, -NRZ5cS (=O) 2ORZ5b, -OS (=O) 2NRZ5cRZ5d, -NRZ5cS (=O) 2NRZ5cRZ5d, -P (=O) (RZ5i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl;n7 is selected from 0, 1, 2, 3, 4, 5 or 6;RZ1a or RZ5a is independently selected from hydrogen, halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NO2, -N3, oxo, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O(C1-6alkyl) , -SH, -S (C1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -OC (=O) O (C1-6alkyl) , -NHC (=O) (OC1-6alkyl) , -N (C1-6alkyl) C (=O) (OC1-6alkyl) , -OC (=O) NH (C1-6alkyl) , -OC (=O) N (C1-6alkyl) 2, -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (OC1-6alkyl) , -OS (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -OS (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -OS (=O) 2O (C1-6alkyl) , -NHS (=O) 2O (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2O (C1-6alkyl) , -OS (=O) 2NH2, -OS (=O) 2NH (C1-6alkyl) , -OS (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2NH2, -NHS (=O) 2NH (C1-6alkyl) , -NHS (=O) 2N (C1-6alkyl) 2, -N (C1-6alkyl) S (=O) 2NH2, -N (C1-6alkyl) S (=O) 2NH (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2N (C1-6alkyl) 2, -PH (C1-6alkyl) , -P (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;RZ1b, RZ1e, RZ2b, RZ4b, RZ5b or RZ5e is independently selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) (OC1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) (OC1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; RZ1c, RZ1d, RZ3c, RZ3d, RZ4c, RZ4d, RZ5c or RZ5d is independently selected from hydrogen, halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;RZ1f, RZ1g, RZ1h, RZ1i, RZ2f, RZ2g, RZ2h, RZ2i, RZ3f, RZ3g, RZ3h, RZ3i, RZ5f, RZ5g, RZ5h or RZ5i is independently selected from hydrogen, halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -OH, -O (C1-6alkyl) , -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein, said -C1-6alkyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C1-6alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -OC (=O) O (C1-3alkyl) , -NHC (=O) (OC1-3alkyl) , -N (C1-3alkyl) C (=O) (OC1-3alkyl) , -OC (=O) NH (C1-3alkyl) , -OC (=O) N (C1-3alkyl) 2, -NHC (=O) NH2, -NHC (=O) NH (C1-3alkyl) , -NHC (=O) N (C1-3alkyl) 2, -N (C1-3alkyl) C (=O) NH2, -N (C1-3alkyl) C (=O) NH (C1-3alkyl) , -N (C1-3alkyl) C (=O) N (C1-3alkyl) 2, -S (=O) (OC1-3alkyl) , -OS (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2 (OC1-3alkyl) , -OS (=O) 2 (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , -OS (=O) 2O (C1-3alkyl) , -NHS (=O) 2O (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2O (C1-3alkyl) , -OS (=O) 2NH2, -OS (=O) 2NH (C1-3alkyl) , -OS (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2NH2, -NHS (=O) 2NH (C1-3alkyl) , -NHS (=O) 2N (C1-3alkyl) 2, -N (C1-3alkyl) S (=O) 2NH2, -N (C1-3alkyl) S (=O) 2NH (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2N (C1-3alkyl) 2, -PH (C1-3alkyl) , -P (C1-3alkyl) 2, -P (=O) H (C1-3alkyl) , -P (=O) (C1-3alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6 membered aryl, 10 membered aryl or 5-6 membered heteroaryl;Each of heterocyclyl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) or S (=O) 2;Each of heteroaryl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.[2] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of [1] , wherein,Y1 is selected from -O-, -NRY13-, -S-, *-NRY13-C (=O) -, *-NRY13S (=O) -or *-NRY13S (=O) 2-;*indicates the attached point to the moiety ofRY13 has the same definition as in [1] .[3] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to [2] , wherein,Y1 is selected from -NRY13-or *-NRY13-C (=O) -;*indicates the attached point to the moiety ofRY13 has the same definition as in [1] .[4] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to [3] , wherein,Y1 is selected from -NRY13-;RY13 has the same definition as in [1] .[5] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to [3] , wherein,Y1 is selected from *-NRY13-C (=O) -;*indicates the attached point to the moiety ofRY13 has the same definition as in [1] .[6] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to [5] , wherein,RY13 is selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl;Preferably, RY13 is each independent selected from hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2 or 3-7 membered cycloalkyl;More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2;Further preferably, RY13 is each independent selected from -H.[7] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to [6] , wherein,RY13 is each independent selected from -H.[8] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to [7] , wherein,Y1 is selected from -NRY13-;RY13 is each independent selected from -H, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2 or 3-7 membered cycloalkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; Further preferably, RY13 is each independent selected from -H.[9] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of [8] , wherein, Y1 is selected from -NH-, -N (CH3) -or -N (CH2CH3) -.
[0010] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [8] to [9] , wherein, Y1 is selected from -NH-.
[0011] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to [7] , wherein,Y1 is selected from *-NRY13-C (=O) -;*indicates the attached point to the moiety ofRY13 is each independent selected from -H, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, haloC1-3alkoxy or 3-7 membered cycloalkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; Further preferably, RY13 is each independent selected from -H.
[0012] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of
[0011] , wherein,Y1 is selected from *-NH-C (=O) -, *-N (CH3) -C (=O) -or *-N (CH2CH3) -C (=O) -;*indicates the attached point to the moiety of
[0013] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0011] to
[0012] , wherein,Y1 is selected from *-NH-C (=O) -;*indicates the attached point to the moiety of
[0014] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0013] , wherein, n4 is selected from 0, 1, 2, 3, 4, 5 or 6; preferably, n4 is selected from 0, 1, 2 or 3; more preferably, n4 is selected from 0, 1 or 2; further preferably, n4 is selected from 0 or 1.
[0015] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0014] , wherein, n4 is 0.
[0016] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0014] , wherein, n4 is 1.
[0017] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0016] , wherein, X1 is N.
[0018] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0016] , wherein, X1 is CR3;R3 has the same definition as in [1] .
[0019] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0018] , wherein,R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;Preferably, R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -S-CH2CH3, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) N (CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) N (CH3) 2, -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -S (=O) 2 (OCH3) , -S (=O) 2 (OCH2CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) ,More preferably, R4 or R5 at each occurrence is independently selected from -H, -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -C (=O) NH2, Further preferably, R4 or R5 at each occurrence is independent selected from -H, -CH3 or -CH2CH3.
[0020] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0019] , wherein,R4 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2;R5 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2.
[0021] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0020] , wherein,R4 is selected from -H.
[0022] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0021] , wherein,R5 is selected from -H.
[0023] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0022] , wherein,Y1 is selected from -NRY13-or *-NRY13-C (=O) -, *indicates the attached point to the moiety of RY13 is selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; preferably, RY13 is each independent selected from hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2 or 3-7 membered cycloalkyl; More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; Further preferably, RY13 is each independent selected from -H;n4 is selected from 0, 1, 2 or 3; preferably, n4 is selected from 0, 1 or 2; more preferably, n4 is selected from 0 or 1;X1 is N or CR3, R3 has the same definition as in [1] ;R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -S-CH2CH3, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) N (CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) N (CH3) 2, -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -S (=O) 2 (OCH3) , -S (=O) 2 (OCH2CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , more preferably, R4 or R5 at each occurrence is independently selected from -H, -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -C (=O) NH2, more preferably, R4 or R5 at each occurrence is independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; further preferably, R4 is selected from -H; and R4 is selected from -H.
[0024] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0023] , wherein,The moiety ofis selected fromR1, R2 and R3 have the same definitions as in [1] .
[0025] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0024] , wherein, The moiety ofis selected fromR1, R2 and R3 have the same definitions as in [1] .
[0026] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0025] , wherein, The moiety ofis selected fromR1, R2 and R3 have the same definitions as in [1] .
[0027] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0026] , wherein, the compound is selected from formula (I-1) , formula (I-2) or formula (I-3) :Ring A, RS1, n1, Ring B, RS2, n2, R1, R2 and R3 have the same definitions as in [1] .
[0028] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0027] , wherein,R3 is each independent selected from hydrogen, halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , - (C1-6alkylene) -C (=O) R6, -C (=O) R6, -OC (=O) R6, -NHC (=O) R6, -N (C1-6alkyl) C (=O) R6, -S (=O) R6, -OS (=O) R6, -NHS (=O) R6, -N (C1-6alkyl) S (=O) R6, -S (=O) 2R6, -OS (=O) 2R6, -NHS (=O) 2R6, -N (C1-6alkyl) S (=O) 2R6, -P (=O) (R6) H, -P (=O) (R6) 2, -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) (OC1-6alkyl) , -OS (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -OS (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -PH (C1-6alkyl) , -P (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered , 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;R6 is selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -OH, -O (C1-6alkyl) , -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; said R6 is optionally substituted with one or more R6A, said R6A at each occurrence is independently selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) (OC1-6alkyl) , -OS (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -OS (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -PH (C1-6alkyl) , -P (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;Said (-C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl) of R6A is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) (OC1-6alkyl) , -OS (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -OS (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -PH (C1-6alkyl) , -P (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, -Si (C1-6alkyl) 3, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;Each of heterocyclyl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) or S (=O) 2;Each of heteroaryl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.
[0029] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0028] , wherein,R3 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , - (C1-3alkylene) -C (=O) R6, -C (=O) R6, -OC (=O) R6, -NHC (=O) R6, -N (C1-3alkyl) C (=O) R6, -S (=O) R6, -NHS (=O) R6, -N (C1-3alkyl) S (=O) R6, -S (=O) 2R6, -NHS (=O) 2R6, -N (C1-3alkyl) S (=O) 2R6, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; said -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (OC1-3alkyl) or -C (=O) (haloC1-3alkyl) ;R6 is hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -OH, -O (C1-3alkyl) , -NH2, -NH (C1-4alkyl) , -N (C1-3alkyl) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; said R6 is optionally substituted with one or more R6A, said R6A at each occurrence is independently selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl;Said (-C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl) of R6A is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (haloC1-3alkyl) , -Si (C1-3alkyl) 3;Each of heterocyclyl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) or S (=O) 2;Each of heteroaryl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.
[0030] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0029] , wherein,R3 is each independent selected from -H, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, - (C1-3alkylene) -C (=O) R6, -C (=O) R6, -NHC (=O) R6, -S (=O) 2R6 or -NHS (=O) 2R6; said -C1-3alkyl, -C2-3alkenyl or -C2-3alkynyl is optionally substituted with 0, 1, 2 or 3 substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (OC1-3alkyl) or -C (=O) (haloC1-3alkyl) ;R6 is hydrogen, -C1-3alkyl, -C2-3alkenyl, -OH, -O (C1-3alkyl) , -NH2, -NH (C1-4alkyl) , -N (C1-4alkyl) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R6 is optionally substituted with 0, 1, 2 or 3 R6A, said R6A at each occurrence is independently selected from halogen, -C1-4alkyl, -C2-3alkynyl, -CN, -C (=O) (OC1-4alkyl) , 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;Said (-C1-4alkyl, -C2-6alkynyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl) of R6A is optionally substituted with 0, 1, 2 or 3 substituents selected from -Si (C1-3alkyl) 3, -C1-3alkyl or haloC1-3alkyl;said 3-7 membered carbocyclyl is selected fromsaid 3-7 membered heterocyclyl is selected from morpholinyl, azetidinyl, tetrahydrofuranyl, thiomorpholinyl, tetrahydropyranyl, tetrahydroimidazolyl, piperidinyl, pyrrolidinyl or piperazinyl;said 5-10 membered heteroaryl is selected from furyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, quinolyl, isoquinolyl, quinazolyl, quinoxalyl, benzofuranyl, benzoxazolyl, benzisooxazolyl, benzothiazolyl, benzimidazol, indolyl, indazolyl, 1H-pyrrolo [2, 3-b] pyrazinyl, 1H-imidazo [4, 5-b] pyridinyl, 1H-imidazo [4, 5-b] pyrazinyl, 1H-pyrazolo [4, 3-c] pyridinyl, 2H-pyrazolo [3, 4-b] thiopheny1, pyrazolo [5, 1-c] [1, 2, 4] triazinyl, thiazolo [4.5-b] pyridinyl or pyrido [2, 3-b] pyridinyl.
[0031] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0030] , wherein,R3 is each independent selected from -H, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -NH2, -NH (CH3) , -NH (CH2CH3) , -N (CH3) 2, -C (=O) R6, -CH2-C (=O) R6, -CH2CH2-C (=O) R6, -CH (CH3) -C (=O) R6, -CH2CH2CH2-C (=O) R6, -NHC (=O) R6, -S (=O) 2R6 or -NHS (=O) 2R6; saidsubstituted with -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) or -C (=O) (OCH (CH3) 2) ;R6 is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -NH2, -NH (CH3) , -NH (CH2CH3) , -NH (CH (CH3) 2) , -NH (C (CH3) 3) , -N (CH3) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said (-NH2, phenyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl) of R6 is optionally substituted with 0, 1, 2 or 3 R6A, said R6A at each occurrence is independently selected from -F, -Cl, -Br, -NH2, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2,-CN, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) (OC (CH3) 3) , 5-10 membered heteroaryl;Said (-NH2 or 5-10 membered heteroaryl) of R6A is optionally substituted with 0, 1, 2 or 3 substituents selected from -F, -Cl, -Br, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -Si (CH (CH3) 2) 3;said 3-7 membered carbocyclyl is selected fromsaid 3-7 membered heterocyclyl is selected fromsaid 5-10 membered heteroaryl is selected from
[0032] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0031] , wherein,R3 is selected from -Br, -NH2,
[0033] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0032] , wherein,R1 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl;Preferably, R1 is each independent selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -S-CH2CH3, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) N (CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) N (CH3) 2, -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -S (=O) 2 (OCH3) , -S (=O) 2 (OCH2CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , More preferably, R1 is each independent selected from -H, -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -C (=O) NH2, Further preferably, R1 is each independent selected from -H, -Cl, -OH, -O-CH3, -NH (CH3) or
[0034] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0033] , wherein, R1 is each independent selected from -H, -Cl, -OH, -O-CH3, -NH (CH3) or
[0035] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0034] , wherein,R2 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;Preferably, R2 is each independent selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -S-CH2CH3, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) N (CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) N (CH3) 2, -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -S (=O) 2 (OCH3) , -S (=O) 2 (OCH2CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , More preferably, R2 is each independent selected from -H, -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -C (=O) NH2, Further preferably, R2 is each independent selected from -H, -CH3 or -CH2CH3.
[0036] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0035] , wherein, R2 is each independent selected from -H, -CH3 or -CH2CH3.
[0037] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0036] , wherein, the moiety ofis selected from
[0038] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0036] , wherein, the moiety ofis selected from
[0039] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0038] , wherein, ring A is selected from a 3-7 membered carbocyclic ring; 3-7 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; or a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.
[0040] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0039] , wherein, ring A is selected from a 3 membered carbocyclic ring; a 4 membered carbocyclic ring; a 5 membered carbocyclic ring; a 6 membered carbocyclic ring; a 7 membered carbocyclic ring; a 3 membered a heterocyclic ring containing 1 or 2 heteroatoms selected from N, O or S; a 4 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 5 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 6 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 7 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; or a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.
[0041] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0040] , wherein, ring A is selected from
[0042] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0041] , wherein, ring A is selected from
[0043] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0042] , wherein, ring A is selected from
[0044] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0043] , wherein, the compound is selected from formula (I-4) , formula (I-5) or formula (I-6) :RS1, n1, Ring B, RS2, n2, R1, R2 and R3 have the same definitions as in [1] .
[0045] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0044] , wherein,RS1 is each independent selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;Preferably, RS1 is each independent selected from -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -O (haloC1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;More preferably, RS1 is each independent selected from -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -NH (CH (CH3) 2) , -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -O-CHF2, -O-CF3, -SH, -S-CH3, -S-CH2CH3, -S-CH (CH3) 2, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -C (=O) (CF3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH (CH3) 2) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -OC (=O) (CH (CH3) 2) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -C (=O) N (CH2CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -NHC (=O) (CH (CH3) 2) , -N (CH3) C (=O) (CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) NH (CH (CH3) 2) , -S (=O) N (CH3) 2, -S (=O) N (CH3) (CH2CH3) , -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -NHS (=O) (CH (CH3) 2) , -N (CH3) S (=O) (CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2NH (CH (CH3) 2) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , -NHS (=O) 2 (CH (CH3) 2) , -CH2-OH, -CH2CH2-OH, -CH (CH3) -OH, -CH2-SH, -CH2CH2-SH, -CH (CH3) -SH, -CH2-NH2, -CH2CH2-NH2, -CH (CH3) -NH2, -CH2-CN, -CH2CH2-CN, -CH (CH3) -CN, More preferably, RS1 is each independent selected from -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -CH2-OH, -CH2CH2-OH, -OH, -O-CH3, -O-CH2CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -CH2-NH2, -CH2CH2-NH2, -O-CF3, -O-CHF2, -C (=O) NH2, Further preferably, RS1 is each independent selected from -F, -Cl, -CN, -CF3, -CH3, -CH2CH3, -O-CH3, -O-CH2CH3 or -O-CF3;n1 is selected from 0, 1, 2, 3, 4, 5 or 6; n1 is selected from 0, 1, 2, 3 or 4; n1 is selected from 0, 1, 2 or 3.
[0046] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0045] , wherein, the moiety ofis selected from
[0047] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0046] , wherein, the moiety ofis selected from
[0048] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0047] , wherein, ring B is selected from a phenyl ring; or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.
[0049] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0048] , wherein, ring B is selected from a phenyl ring; a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 7 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 8 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 9 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 10 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.
[0050] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0049] , wherein, ring B is selected from
[0051] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0050] , wherein, ring B is selected from
[0052] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0051] , wherein,RS2 is each independent selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;Preferably, RS2 is each independent selected from -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C1-3alkoxy substituted with one or more (-O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) ) , -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;More preferably, RS2 is each independent selected from -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -NH (CH (CH3) 2) , -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3, -CH2-O-CH2-O-CH2-O-CH2CH3, -O-CHF2, -O-CF3, -SH, -S-CH3, -S-CH2CH3, -S-CH (CH3) 2, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -C (=O) (CF3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH (CH3) 2) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -OC (=O) (CH (CH3) 2) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -C (=O) N (CH2CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -NHC (=O) (CH (CH3) 2) , -N (CH3) C (=O) (CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) NH (CH (CH3) 2) , -S (=O) N (CH3) 2, -S (=O) N (CH3) (CH2CH3) , -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -NHS (=O) (CH (CH3) 2) , -N (CH3) S (=O) (CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2NH (CH (CH3) 2) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , -NHS (=O) 2 (CH (CH3) 2) , -CH2-OH, -CH2CH2-OH, -CH (CH3) -OH, -CH2-SH, -CH2CH2-SH, -CH (CH3) -SH, -CH2-NH2, -CH2CH2-NH2, -CH (CH3) -NH2, -CH2-CN, -CH2CH2-CN, -CH (CH3) -CN, More preferably, RS2 is each independent selected from -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -CH2-OH, -CH2CH2-OH, -OH, -O-CH3, -O-CH2CH3, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3, -CH2-O-CH2-O-CH2-O-CH2CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -CH2-NH2, -CH2CH2-NH2, -O-CF3, -O-CHF2, -C (=O) NH2, Further preferably, RS2 is each independent selected from -F, -Cl, -CH3, -CH2CH3, -CH2CH2OH, -CH2CH2OCH2CH2OCH2CH2OCH3 or -OH;n2 is selected from 0, 1, 2, 3, 4, 5 or 6; n2 is selected from 0, 1, 2, 3 or 4; n2 is selected from 0, 1, 2 or 3.
[0053] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0052] , wherein, the compound is selected from formula (I-7) , formula (I-8) or formula (I-9) :R8 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R86, -C (=O) OR82, -C (=O) NR83R84, -S (=O) R87, -S (=O) OR82, -S (=O) NR83R84, -S (=O) 2R88, -S (=O) 2OR82, -S (=O) 2NR83R84, -P (=O) (R89) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -OR10b, -NR10cR10d, -SR10e, -C (=O) R10f, -C (=O) OR10b, -OC (=O) R10f, -OC (=O) OR10b, -C (=O) NR10cR10d, -OC (=O) NR10cR10d, -C (=NR10c) R10a, -C (=NR10c) NR10cR10d, -NR10cC (=NR10c) NR10cR10d, -NR10cC (=O) R10f, -NR10cC (=O) OR10b, -NR10cC (=O) NR10cR10d, -S (=O) R10g, -S (=O) OR10b, -OS (=O) R10g, -OS (=O) OR10b, -S (=O) NR10cR10d, -NR10cS (=O) R10g, -NR10cS (=O) OR10b, -OS (=O) NR10cR10d, -NR10cS (=O) NR10cR10d, -S (=O) 2R10h, -S (=O) 2OR10b, -OS (=O) 2R10h, -OS (=O) 2OR10b, -S (=O) 2NR10cR10d, -NR10cS (=O) 2R10h, -NR10cS (=O) 2OR10b, -OS (=O) 2NR10cR10d, -NR10cS (=O) 2NR10cR10d, -P (=O) (R10i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R82 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R7f, -C (=O) OR7b, -S (=O) R7g, -S (=O) OR7b, -S (=O) 2R7h, -S (=O) 2OR7b, -P (=O) (R7i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R83 or R84 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R8f, -C (=O) OR8b, -C (=O) NR8cR8d, -S (=O) R8g, -S (=O) OR8b, -S (=O) NR8cR8d, -S (=O) 2R8h, -S (=O) 2OR8b, -S (=O) 2NR8cR8d, -P (=O) (R8i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl;R86, R87, R88 or R89 at each occurrence is selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -OR9b, -NR9cR9d, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl;Optionally, (R83 and R84) together with the nitrogen atom to which they are both attached form 3-14 membered heterocyclyl ring or 5-14 membered heteroaryl ring; said 3-14 membered heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, SO or SO2; said 3-14 membered heteroaryl ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S; each said ring is independently optionally substituted with n6 RS4;R10a at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-10alkoxy, -ORZ1b, -NRZ1cRZ1d, -SRZ1e, -C (=O) RZ1f, -C (=O) ORZ1b, -OC (=O) RZ1f, -OC (=O) ORZ1b, -C (=O) NRZ1cRZ1d, -OC (=O) NRZ1cRZ1d, -C (=NRZ1c) RZ1a, -C (=NRZ1c) NRZ1cRZ1d, -NRZ1cC (=NRZ1c) NRZ1cRZ1d, -NRZ1cC (=O) RZ1f, -NRZ1cC (=O) ORZ1b, -NRZ1cC (=O) NRZ1cRZ1d, -S (=O) RZ1g, -S (=O) ORZ1b, -OS (=O) RZ1g, -OS (=O) ORZ1b, -S (=O) NRZ1cRZ1d, -NRZ1cS (=O) RZ1g, -NRZ1cS (=O) ORZ1b, -OS (=O) NRZ1cRZ1d, -NRZ1cS (=O) NRZ1cRZ1d, -S (=O) 2RZ1h, -S (=O) 2ORZ1b, -OS (=O) 2RZ1h, -OS (=O) 2ORZ1b, -S (=O) 2NRZ1cRZ1d, -NRZ1cS (=O) 2RZ1h, -NRZ1cS (=O) 2ORZ1b, -OS (=O) 2NRZ1cRZ1d, -NRZ1cS (=O) 2NRZ1cRZ1d, -P (=O) (RZ1i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R10b or R10e at each occurrence is independently selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) RZ2f, -C (=O) ORZ2b, -S (=O) RZ2g, -S (=O) ORZ2b, -S (=O) 2RZ2h, -S (=O) 2ORZ2b, -P (=O) (RZ2i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R10c or R10d at each occurrence is independently selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) RZ3f, -C (=O) NRZ3cRZ3d, -S (=O) RZ3g, -S (=O) NRZ3cRZ3d, -S (=O) 2RZ3h, -S (=O) 2NRZ3cRZ3d, -P (=O) (RZ3i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R10f, R10g, R10h or R10i at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -ORZ4b, -NRZ4cRZ4d, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; (R10c and R10d) together with the nitrogen atom to which they are both attached form 3-14 membered heterocyclyl ring or 5-14 membered heteroaryl ring; said 3-14 membered heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, SO or SO2; said 3-14 membered heteroaryl ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S; each said ring is independently optionally substituted with n7 RS5;n6, RS4, RZ1a, RZ1b, RZ1c, RZ1d, RZ1e, RZ1f, RZ1g, RZ1h, RZ1i, RZ2f, RZ2b, RZ2g, RZ2h, RZ2i, RZ3f, RZ3c, RZ3d, RZ3g, RZ3h, RZ3i, RZ4b, RZ4c, RZ4d, RS5 and n7 have the same definitions as in [1] ;n5 is selected from 0, 1 or 2;RS1, n1, RS2, R1, R2 and R3 have the same definitions as in [1] .
[0054] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of
[0053] , wherein,R8 is each independent selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, -C1-6alkoxy substituted with one or more (-O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) ) , haloC1-6alkyl, haloC1-6alkoxy, -C1-6alkylene-OH, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;Preferably, R8 is each independent selected from hydrogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C1-3alkylene-OH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, 3-7 membered cycloalkyl, -C1-3alkoxy, -C1-3alkoxy substituted with 0, 1 or 2 (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) ;More preferably, R8 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2CH2OH, -CH2OH, -CH (CH2) 3OH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3 or -CH2-O-CH2-O-CH2-O-CH2CH3;More preferably, R8 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2CH2OH, -CH2OH, -CH (CH2) 3OH or -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3;Further preferably, R8 is each independent selected from -CH3.
[0055] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0054] , wherein, the compound is selected from formula (I-10) , formula (I-11) or formula (I-12) :n5 is selected from 0, 1 or 2;RS1, n1, RS2, R1, R2 and R3 have the same definitions as in [1] .
[0056] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0055] , wherein, the moiety ofis selected from
[0057] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0056] , wherein, the moiety ofis selected frompreferably, the moiety ofis selected from
[0058] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0057] ,wherein,Y1 is selected from -O-, -NRY13-, -S-, *-NRY13-C (=O) -, *-NRY13S (=O) -or *-NRY13S (=O) 2-;*indicates the attached point to the moiety ofRY13 is selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl;n4 is selected from 0, 1, 2 or 3;X1 is selected from N or CR3;R1 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl;R2 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;R3 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , - (C1-3alkylene) -C (=O) R6, -C (=O) R6, -OC (=O) R6, -NHC (=O) R6, -N (C1-3alkyl) C (=O) R6, -S (=O) R6, -NHS (=O) R6, -N (C1-3alkyl) S (=O) R6, -S (=O) 2R6, -NHS (=O) 2R6, -N (C1-3alkyl) S (=O) 2R6, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; said -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (OC1-3alkyl) or -C (=O) (haloC1-3alkyl) ;R6 is hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -OH, -O (C1-3alkyl) , -NH2, -NH (C1-4alkyl) , -N (C1-3alkyl) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; said R6 is optionally substituted with one or more R6A, said R6A at each occurrence is independently selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl;Said (-C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl) of R6A is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (haloC1-3alkyl) , -Si (C1-3alkyl) 3;R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;ring A is selected from a 3-7 membered carbocyclic ring; 3-7 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; or a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S;ring B is selected from a phenyl ring; or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;RS1 is each independent selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;RS2 is each independent selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;n1 is selected from 0, 1, 2, 3, 4, 5 or 6;n2 is selected from 0, 1, 2, 3, 4, 5 or 6.
[0059] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0058] , wherein, the compound is selected from formula (II) :Y1 is selected from -NRY13-or *-NRY13-C (=O) -; *indicates the attached point to the moiety ofRY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H;n4 is selected from 0, 1 or 2; preferably, n4 is selected from 0 or 1;Ring A is selected from a 3-7 membered carbocyclic ring; 3-7 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; or a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; preferably, Ring A is selected from a 5 membered carbocyclic ring; a 6 membered carbocyclic ring; a 5 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 6 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; or a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; more preferably, ring A is selected fromFurther preferably, ring A is selected fromRS1 is each independent selected from -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -O (haloC1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS1 is each independent selected from halogen, -CN, -C1-3alkyl, haloC1-3alkyl, -OH, -O (C1-3alkyl) or -O (haloC1-3alkyl) ; more preferably, RS1 is each independent selected from -F, -Br, -Cl, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -OH, -O-CH3, -O-CH2CH3, -OCH2CH2CH3, -OCH (CH3) 2, -O-CF3, -O-CH2F, -O-CHF2, -O-CF3, -O-CH2CH2F, -O-CH2CHF2, -O-CH2CF3, -O-CHFCH3, -O-CF2CH3; further preferably, RS1 is each independent selected from -F, -Cl, -CN, -CF3, -CH3, -CH2CH3, -O-CH3, -O-CH2CH3 or -O-CF3;n1 is selected from 0, 1, 2, 3 or 4; preferably, n1 is selected from 0, 1, 2 or 3;R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl; preferably, R1 is each independent selected from hydrogen, halogen, -OH, -O (C1-3alkyl) , -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2 or 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S; more preferably, R1 is each independent selected from -H, -F, -Br, -Cl, -OH, -O-CH3, -O-CH2CH3, -OCH2CH2CH3, -OCH (CH3) 2, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) or 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S, said 3-7 membered heterocyclyl is selected fromfurther preferably, R1 is each independent selected from -H, -Cl, -OH, -O-CH3, -NH (CH3) orR2 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R2 is each independent selected from hydrogen, -C1-3alkyl; more preferably, R2 is each independent selected from -H, -CH3, -CH2CH3 or -CH (CH3) 2;R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, 3-7 membered cycloalkyl; more preferably, R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2OCH3, -CH2OCH2CH3, more preferably, R4 or R5 at each occurrence is independent selected from -H, -CH3 or -CH2CH3; Further preferably, R4 or R5 at each occurrence is independent selected from -H;ring B is selected from a phenyl ring; or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S; preferably, ring B is selected frommore preferably, ring B is selected fromRS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C1-3alkoxy substituted with one or more (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) , -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS2 is each independent selected from halogen, -C1-3alkyl, -OH, -C1-3alkylene-OH, -O (C1-3alkyl) , -C1-3alkoxy substituted with 1, 2 or 3 (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) ; more preferably, RS2 is each independent selected from -F, -Br, -Cl, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2-OH, -CH2CH2-OH, -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3, -CH2-O-CH2-O-CH2-O-CH2CH3; further preferably, RS2 is each independent selected from -F, -Cl, -CH3, -CH2CH3, -CH2CH2OH, -CH2CH2OCH2CH2OCH2CH2OCH3 or -OH;n2 is selected from 0, 1, 2, 3 or 4; preferably, n2 is selected from 0, 1, 2 or 3.
[0060] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0059] , wherein, the compound is selected from formula (II-1) :Wherein,RY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H;ring B is selected from a phenyl ring; or a 5-6 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S; preferably, ring B is selected frommore preferably, ring B is selected fromR1, R2, R4, R5, ring A, RS1, n1, RS2, n2 have the same definitions as in
[0059] .
[0061] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0060] , wherein, the compound is selected from formula (II-1-1) :Wherein,RY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3 or -CH (CH3) 2; more preferably, RY13 is each independent selected from -H;R8 is each independent selected from hydrogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C1-3alkylene-OH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, 3-7 membered cycloalkyl, -C1-3alkoxy, -C1-3alkoxy substituted with 0, 1 or 2 (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) ; preferably, R8 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2CH2OH, -CH2OH, -CH (CH2) 3OH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3 or -CH2-O-CH2-O-CH2-O-CH2CH3; More preferably, R8 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2CH2OH, -CH2OH, -CH (CH2) 3OH or -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3; Further preferably, R8 is each independent selected from -CH3;RS2 is each independent selected from -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C1-3alkoxy substituted with one or more (-O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) ) , -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS2 is each independent selected from -C1-3alkyl; more preferably, RS2 is each independent selected from -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; further preferably, RS2 is each independent selected from -CH3;n5 is selected from 0, 1, or 2;R1, R2, R4, R5, RS1 and n1 have the same definitions as in
[0059] .
[0062] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0059] , wherein, the compound is selected from formula (II-2) :RY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3 or -CH (CH3) 2; more preferably, RY13 is each independent selected from -H;n4 is selected from 0, 1 or 2; preferably, n4 is selected from 0 or 1;R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl; preferably, R1 is each independent selected from -H;R2 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R2 is each independent selected from -H;RS1 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS1 is each independent selected from halogen or haloC1-3alkyl; more preferably, RS1 is each independent selected from -F, -Br, -Cl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3; further preferably, RS1 is each independent selected from-Cl or -CF3;n1 is selected from 0, 1, or 2; preferably, n1 is selected from 1;ring B is selected from a phenyl ring; or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S; preferably, ring B is selected from a phenyl ring; a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 9 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 10 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; more preferably, ring B is selected fromRS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C1-3alkoxy substituted with one or more (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) , -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS2 is each independent selected from halogen, -C1-3alkyl, -OH, -O (C1-3alkyl) or -C1-3alkylene-OH; more preferably, RS2 is each independent selected from -F, -Br, -Cl, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2-OH, -CH2CH2-OH, -OH, -O-CH3, -O-CH2CH3, -O-CH2CH2CH3 or -O-CH (CH3) 2; further preferably, RS2 is each independent selected from -F, -Cl, -CH3, -CH2CH2OH or -OH;n2 is selected from 0, 1, or 2; preferably, n2 is selected from 1;R4 and R5 have the same definitions as in
[0059] .
[0063] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0058] , wherein, the compound is selected from formula (III) :RY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3 or -CH (CH3) 2; more preferably, RY13 is each independent selected from -H;R3 is selected from halogen, -NH2, -Y2-R7;Y2 is selected from **-C (=O) -NRY23-, **-C (=O) -O-, **-NRY23-C (=O) -, **-NRY23-S (=O) 2-, **-S (=O) 2-NRY23-, **- (C1-6alkylene) -Y3-, or **-RY21C=CRY21-;**indicates the attached point to the moiety ofRY23 or RY21 is each independent selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; preferably, RY23 or RY21 at each occurrence is selected from hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, 3-7 membered carbocyclyl, 3-7membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; more preferably, RY23 or RY21 at each occurrence is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH3-O-CH3, -CH2CH3-O-CH3, -CH3-O-CH2CH3, -CH (CH3) -O-CH3, further preferably, RY23 or RY21 at each occurrence is selected from -H, -CH3 or -CH2CH3;Y3 is selected from &-C (=O) -NRY33-, &-C (=O) -O-, &-NRY33-C (=O) -, &-NRY33-S (=O) -, &-S (=O) -NRY33-, &-NRY33-S (=O) 2-, &-S (=O) 2-NRY33-; &indicates the attached point to the moiety of **- (C1-6alkylene) ; RY33 is each independent selected from -H or -C1-3alkyl; preferably, RY33 is each independent selected from -H;R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl; preferably, R1 is each independent selected from -H;R2 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R2 is each independent selected from -H;RS1 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS1 is each independent selected from halogen or haloC1-3alkyl; more preferably, RS1 is each independent selected from -F, -Br, -Cl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3; further preferably, RS1 is each independent selected from-Cl or -CF3;n1 is selected from 0, 1, or 2; preferably, n1 is selected from 1;R7 is selected from -H; -C1-6 alkyl; -C2-6 alkenyl; -C2-6 alkynyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S; 6-10 membered aryl or 5-10 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-6 alkyl; -C2-6 alkenyl; -C2-6alkynyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl; 6-10 membered aryl or 5-10 heteroaryl is optionally substituted with one or more R9;R9 is selected from halogen, -C1-4alkyl, -CN, -C (=O) (OC1-4alkyl) , -Si (C1-3alkyl) 3, phenyl, said R9 is optionally substituted with one or more R9A;said R9A is selected from halogen, haloC1-3alkyl or -C1-3alkoxy;n5 is selected from 0, 1, or 2; preferably, n5 is selected from 0;RY13, RS2, R4 and R5 have the same definitions as in
[0058] .
[0064] . The compound of formula (III) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of
[0063] , wherein,R7 is each independent selected from -H, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; said -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl is optionally substituted with 0, 1, 2 or 3 substituents selected from halogen, -C1-3alkyl, -CN, -C (=O) (OC1-4alkyl) , -Si (C1-3alkyl) 3, or 6-10 membered aryl optionally substituted with 1, 2 or 3 substituents selected from haloC1-3alkyl;preferably, R7 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, tetrahydropyranyl, piperidinyl, furyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl or benzothiazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CN, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) (OC (CH3) 3) , -Si (CH3) 3, -Si(CH2CH3) 3, -Si (CH (CH3) 2) 3, optionally substituted with 1, 2 or 3 substituents selected from -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;more preferably, R7 is each independent selected from -H, -CH3, -CH2CH3, tetrahydropyranyl, piperidinyl, furyl, pyrrolyl, pyridinyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, benzothiazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -Cl, -Br, -CH3, -CN, -C (=O) (OCH2CH3) , -C (=O) (OC (CH3) 3) , -Si(CH (CH3) 2) 3 or
[0065] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0063] to
[0064] , wherein, R7 is selected from -H, -CH3, -CH2CH3,
[0066] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0063] to
[0065] , wherein, the compound is selected from formula (III-1) :RY23 at each occurrence is -H or -C1-3alkyl; preferably, RY23 is each independent selected from -H or -CH3;R7 is selected from -H; -C1-6 alkyl; -C2-6 alkenyl; -C2-6 alkynyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S; 6-10 membered aryl or 5-10 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-6 alkyl; -C2-6 alkenyl; -C2-6alkynyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl; 6-10 membered aryl or 5-10 heteroaryl is optionally substituted with one or more R9;R9 is selected from halogen, -C1-4alkyl, -CN, -C (=O) (OC1-4alkyl) , phenyl, said R9 is optionally substituted with one or more R9A;said R9A is selected from haloC1-3alkyl;RY13, R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in
[0063] .
[0067] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of
[0066] , wherein,R7 is selected from -C1-3 alkyl; -C2-3 alkenyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S; or 5-6 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-3 alkyl, -C2-3 alkenyl, 3-7 membered carbocyclyl, 3-7membered heterocyclyl or 5-6 membered heteroaryl is optionally substituted with 0, 1, 2 or 3 R8; said R8 is selected from -C1-3alkyl, -CN, -C (=O) (OC1-4alkyl) , phenyl optionally substituted with 1, 2 or 3 substituents selected from haloC1-3alkyl;preferably, R7 is each independent selected from -H, -CH3, -CH2CH3, tetrahydropyranyl, piperidinyl, furyl, pyrrolyl, pyridinyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -CH3, -CN, -C (=O) (OC (CH3) 3) or
[0068] . The compound of formula (III-1) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0066] to
[0067] , wherein,R7 is selected from -CH3,
[0069] . The compound of formula (III-1) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0066] to
[0068] , wherein, the moiety ofis selected from
[0070] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0063] to
[0065] , wherein, the compound is selected from formula (III-2) :RY23 at each occurrence is -H or -C1-3alkyl; preferably, RY23 is each independent selected from -H or -CH3;R7 is selected from -H; -C1-6 alkyl; 3-7 membered carbocyclyl; phenyl or 5-10 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-6 alkyl; 3-7 membered carbocyclyl; phenyl or 5-10 heteroaryl is optionally substituted with one or more R9;R9 is selected from halogen or -C1-3alkyl;RY13, R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in
[0063] .
[0071] . The compound of formula (III-2) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of
[0070] , wherein,R7 is selected from -H, -C1-3 alkyl, 3-7 membered carbocyclyl, phenyl or 5-6 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-3 alkyl, 3-7 membered carbocyclyl, phenyl or 5-6 membered heteroaryl is optionally substituted with 0, 1, 2 or 3 halogen or -C1-3alkyl;preferably, R7 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, phenyl, pyridinyl, benzothiazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -F, -Br, -Cl, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2.
[0072] . The compound of formula (III-2) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0070] to
[0071] , wherein, R7 is selected from -CH3, -CH2CH3,
[0073] . The compound of formula (III-2) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0070] to
[0072] , wherein, the moiety ofis selected from
[0074] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0063] to
[0065] , wherein, the compound is selected from formula (III-3) :RY23 at each occurrence is -H or -C1-3alkyl; preferably, RY23 is each independent selected from -H;R7 is selected from phenyl or 5-6 membered heteroaryl; said phenyl or 5-6 membered heteroaryl is optionally substituted with 0, 1, 2 or 3 substituents selected from -C1-3alkyl;R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in
[0063] .
[0075] . The compound of formula (III-3) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of
[0074] , wherein,R7 is selected from phenyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2.
[0076] . The compound of formula (III-3) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0074] to
[0075] , wherein, R7 is selected from
[0077] . The compound of formula (III-3) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0074] to
[0076] , wherein, the moiety ofis selected from
[0078] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0063] to
[0065] , wherein, the compound is selected from formula (III-4) :Y3 is selected from &-C (=O) -NRY33-or &-C (=O) -O-; &indicates the attached point to the moiety of (C1-6alkylene) ;RY33 is each independent selected from -H or -C1-3alkyl; preferably, RY33 is each independent selected from -H or -CH3;R7 is selected from hydrogen, -C1-3 alkyl or 5-10 membered heteroaryl; said -C1-3 alkyl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from -C1-3 alkyl;R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in
[0063] .
[0079] . The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of
[0078] , wherein, the compound is selected from formula (III-5) :Y3 is selected from &-C (=O) -NH-, &-C (=O) -N (CH3) -or &-C (=O) -O-;&indicates the attached point to the moiety of - (CH2) n12-;n12 is selected from 1, 2, 3, 4, 5 or 6; preferably, n12 is selected from 1, 2 or 3; more preferably, n12 is selected from 1 or 2;Y3, R7, R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in
[0078] .
[0080] . The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0078] -
[0079] , wherein, the compound is selected from formula (III-5-1) or formula (III-5-2) :n12 is selected from 1 or 2;R7, R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in
[0078] .
[0081] . The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0078] -
[0080] , wherein,R7 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, pyridyl, thiazolyl, isoxazolyl; said R7 is optionally substituted with 0, 1 or 2 substituents selected from -CH3.
[0082] . The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0078] -
[0081] , wherein, R7 is selected from -H, -CH3, -CH2CH3, -CH (CH3) 2, -C (CH3) 3,
[0083] . The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of
[0078] -
[0082] , wherein, the moiety ofis selected from
[0084] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] -
[0083] , wherein, the compound is any one of the following formulas:
[0085] . A pharmaceutical composition comprising the compound, a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0084] , and at least one pharmaceutically acceptable excipient.
[0086] . A method of treating a subject having a cancer related to overexpression of Fascin, said method comprising administering to the subject a therapeutically effective amount of the compound, a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0084] ; or the pharmaceutical composition of
[0085] ; preferably, the cancer is selected from breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, esophagus cancer, tongue cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, mesothelioma, melanoma, fibrosarcoma, bladder cancer, rectal cancer, lymphoma, cervical cancer, head and neck cancer, upperaerodigestive cancer, colorectal cancer, urinary tract cancer, or colon cancer; more preferably, each cancer is independently selected from adenocarcinoma, squamous cell carcinoma, mixed adenosquamous carcinoma, undifferentiated carcinoma. More preferably, the ovarian cancer comprises high grade ovarian serious adenocarcinoma, ovarian mucinous cystadenocarcinoma or malignant ovarian Brenner tumor; the kidney cancer comprises clear cell renal cell carcinoma; the tongue cancer comprises tongue squamous cell carcinoma; the lung cancer comprises lung adenocarcinoma, lung adenosquamous carcinoma, squamous cell lung carcinoma, large cell lung carcinoma, small cell lung carcinoma, papillary adenocarcinoma of the lung or non-small cell lung carcinoma; the pancreatic cancer comprises pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma; the esophagus cancer comprises esophageal squamous cell carcinoma; the mesothelioma comprises biphasic mesothelioma; the cancer of the central nervous system comprises neuroglioma, glioblastoma or glioblastoma multiforme; the stomach cancer comprises gastric adenocarcinoma; the breast cancer comprises ductal breast carcinoma, breast adenocarcinoma or HR+ breast cancer; the bladder cancer comprises bladder squamous cell carcinoma; the melanoma comprises malignant melanoma; the colon cancer comprises colon adenocarcinoma; the head and neck cancer comprises head and neck small squamous cell cancer.
[0087] . A use of a compound, a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0084] ; or a pharmaceutical composition of
[0085] for the manufacture of a medicament for the treatment of cancer related to overexpression of Fascin; preferably, the cancer the cancer is selected from breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, esophagus cancer, tongue cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, mesothelioma, melanoma, fibrosarcoma, bladder cancer, rectal cancer, lymphoma, cervical cancer, head and neck cancer, upperaerodigestive cancer, colorectal cancer, urinary tract cancer, or colon cancer; more preferably, each cancer is independently selected from adenocarcinoma, squamous cell carcinoma, mixed adenosquamous carcinoma, undifferentiated carcinoma; more preferably, the ovarian cancer comprises high grade ovarian serious adenocarcinoma, ovarian mucinous cystadenocarcinoma or malignant ovarian Brenner tumor; the kidney cancer comprises clear cell renal cell carcinoma; the tongue cancer comprises tongue squamous cell carcinoma; the lung cancer comprises lung adenocarcinoma, lung adenosquamous carcinoma, squamous cell lung carcinoma, large cell lung carcinoma, small cell lung carcinoma, papillary adenocarcinoma of the lung or non-small cell lung carcinoma; the pancreatic cancer comprises pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma; the esophagus cancer comprises esophageal squamous cell carcinoma; the mesothelioma comprises biphasic mesothelioma; the cancer of the central nervous system comprises neuroglioma, glioblastoma or glioblastoma multiforme; the stomach cancer comprises gastric adenocarcinoma; the breast cancer comprises ductal breast carcinoma, breast adenocarcinoma or HR+breast cancer; the bladder cancer comprises bladder squamous cell carcinoma; the melanoma comprises malignant melanoma; the colon cancer comprises colon adenocarcinoma; the head and neck cancer comprises head and neck small squamous cell cancer.
[0088] . A compound, a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of [1] to
[0084] ; or a pharmaceutical composition of
[0085] for use in the treatment of cancer related to overexpression of Fascin; preferably, the cancer the cancer is selected from breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, esophagus cancer, tongue cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, mesothelioma, melanoma, fibrosarcoma, bladder cancer, rectal cancer, lymphoma, cervical cancer, head and neck cancer, upperaerodigestive cancer, colorectal cancer, urinary tract cancer, or colon cancer; more preferably, each cancer is independently selected from adenocarcinoma, squamous cell carcinoma, mixed adenosquamous carcinoma, undifferentiated carcinoma; more preferably, the ovarian cancer comprises high grade ovarian serious adenocarcinoma, ovarian mucinous cystadenocarcinoma or malignant ovarian Brenner tumor; the kidney cancer comprises clear cell renal cell carcinoma; the tongue cancer comprises tongue squamous cell carcinoma; the lung cancer comprises lung adenocarcinoma, lung adenosquamous carcinoma, squamous cell lung carcinoma, large cell lung carcinoma, small cell lung carcinoma, papillary adenocarcinoma of the lung or non-small cell lung carcinoma; the pancreatic cancer comprises pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma; the esophagus cancer comprises esophageal squamous cell carcinoma; the mesothelioma comprises biphasic mesothelioma; the cancer of the central nervous system comprises neuroglioma, glioblastoma or glioblastoma multiforme; the stomach cancer comprises gastric adenocarcinoma; the breast cancer comprises ductal breast carcinoma, breast adenocarcinoma or HR+ breast cancer; the bladder cancer comprises bladder squamous cell carcinoma; the melanoma comprises malignant melanoma; the colon cancer comprises colon adenocarcinoma; the head and neck cancer comprises head and neck small squamous cell cancer.DefinitionThe term “halogen” or “halo” , as used interchangeably herein, unless otherwise indicated, means fluoro, chloro, bromo or iodo. The preferred halogen groups include -F, -Cl and -Br.The term “alkyl” , as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight or branched. For example, alkyl radicals include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, 3- (2-methyl) butyl, 2-pentyl, 2-methylbutyl, neopentyl, n-hexyl, 2-hexyl and 2-methylpentyl. C1-6, in -C1-6alkyl is defined to identify the group having 1, 2, 3, 4, 5 or 6 carbon atoms in a linear or branched arrangement.The term “haloalkyl” , as used herein, unless otherwise indicated, means the above-mentioned alkyl substituted with one or more (for 1, 2, 3, 4, 5, or 6) halogen (-F, -Cl or -Br) . In some embodiment, the haloalkyl is interchangeable haloC1-6alkyl or haloC1-6alkyl, wherein, C1-6 in the -C1-6haloaklyl or haloC1-6alkyl indicates that the total carbon atoms of the alkyl is 1 to 6. In some embodiments, the haloC1-6alkyl is the haloC1-3alkyl. In some embodiments, the haloC1-3alkyl is (methyl, ethyl, propyl or isopropyl) substituted with 1, 2, 3, 4, 5, or 6 -F; preferably, the haloC1-3alkyl is -CF3.The term “alkylene” means a difunctional group obtained by removal of an additional hydrogen atom from an alkyl group defined above. For example, methylene (i.e., -CH2-) , ethylene (i.e., -CH2-CH2-or -CH (CH3) -) and propylene (i.e., -CH2-CH2-CH2-, -CH (-CH2-CH3) -or -CH2-CH (CH3) -) .The term “alkenyl” means a straight or branch-chained hydrocarbon radical containing one or more double bonds and typically from 2 to 20 carbon atoms in length. For example, “-C2-6alkenyl” contains from 2 to 6 carbon atoms. Alkenyl group include, but are not limited to, for example, ethenyl, propenyl, butenyl, 2-methyl-2-buten-1-yl, hepetenyl, octenyl and the like.The term “alkynyl” contains a straight or branch-chained hydrocarbon radical containing one or more triple bonds and typically from 2 to 20 carbon atoms in length. For example, “C2-6alkynyl” contains from 2 to 6 carbon atoms. Representative alkynyl groups include, but are not limited to, for example, ethynyl, 1-propynyl, 1-butynyl, heptynyl, octynyl and the like.The term “alkoxy” radicals are oxygen ethers formed from the previously described alkyl groups. alkoxy refers to alkyl substituted with -O-alkyl or -OH substituted with alkyl, e.g., alkoxy referring to alkyl substituted with -O-alkyl includes, but is not limited to -CH2-O-CH3, -CH2CH2-O-CH3, -CH2-O-CH2CH3, -CH2 (CH3) -O-CH3 and -CH2CH2-O-CH2CH2; alkoxy referring to hydroxyl (-OH) substituted with alkyl includes, but is not limited to -O-CH3, -O-CH2CH3 and -O-CH (CH3) 2.In present invention, -O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) , e.g., -CH2-O-CH3-O-CH3, -CH2CH2-O-CH2-O-CH3, -CH2CH2-O-CH2CH2-O-CH2CH3.The term “haloalkoxy” , as used herein, unless otherwise indicated, means the above-mentioned alkoxy substituted with one or more (for 1, 2, 3, 4, 5, or 6) halogen (-F, -Cl or -Br) . In some embodiment, the haloalkoxy is interchangeable -C1-6haloalkoxy or haloC1-6alkoxy, wherein, C1-6 in the -C1-6haloakloxy or haloC1-6alkoxy indicates that the total carbon atoms of the alkoxy is 1 to 6. In some embodiments, the -C1-6haloalkoxy is the -C1-3haloalkoxy. In some embodiments, the -C1-3haloalkoxy is (methoxy, ethoxy, propoxy or isopropoxy) substituted with 1, 2, 3, 4, 5, or 6 -F; preferably, the -C1-3haloalkoxy is includes but is not limited to -OCF3, -CH2-O-CF3 and -CHF-O-CH3.The term “aryl” , as used herein, unless otherwise indicated, refers to an unsubstituted or substituted mono or polycyclic aromatic ring system containing carbon ring atoms. The preferred aryls are mono cyclic or bicyclic 6-10 membered aromatic ring systems. Phenyl and naphthyl are preferred aryls.The interchangeable term “heterocyclyl” or “heterocyclic” , as used herein, unless otherwise indicated, refers to unsubstituted and substituted mono or polycyclic non-aromatic ring system containing one or more heteroatoms, which comprising monocyclic heterocyclyl ring, bicyclic heterocyclyl ring, bridged heterocyclyl ring, fused heterocyclyl ring or spiro heterocyclyl ring. Preferred heteroatoms include N, O, and S, including N-oxides, sulfur oxides, and dioxides. Preferably, the ring is three to ten membered and is either fully saturated or has one or more degrees of unsaturation. Multiple degrees of substitution, preferably one, two or three, are included within the present definition. Examples of such heterocyclyl groups include, but are not limited to azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxopiperazinyl, oxopiperidinyl, oxetanyl, oxoazepinyl, azepinyl, tetrahydrofuranyl, dioxolanyl, tetrahydroimidazolyl, tetrahydrothiazolyl, pyrrolidinyl, tetrahydrooxazolyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiamorpholinylsulfoxide, thiamorpholinylsulfone and oxadiazolyl.The term “heteroaryl” , as used herein, unless otherwise indicated, represents an aromatic ring system containing carbon (s) and at least one heteroatom. Heteroaryl may be monocyclic or polycyclic, substituted or unsubstituted. A monocyclic heteroaryl group may have 1 to 4 heteroatoms in the ring, while a polycyclic heteroaryl may contain 1 to 10 heteroatoms. A polycyclic heteroaryl ring may contain fused, spiro or bridged ring junction, for example, bycyclicheteroaryl is a polycyclic heteroaryl. Bicyclic heteroaryl rings may contain from 8 to 12 member atoms. Monocyclic heteroaryl rings may contain from 5 to 8 member atoms (carbons and heteroatoms) . Examples of heteroaryl groups include, but are not limited to thienyl, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, triazolyl, pyridyl (pyridinyl) , pyridazinyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, benzofuranyl, benzothienyl, benzisoxazolyl, benzoxazolyl, benzopyrazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyladeninyl, quinolinyl or isoquinolinyl.In pyridinyl, tautomers may exist when the carbon atom next to the N heteroatom is substituted with -OH or -NH2, e.g., In present invention, when ring B is a pyridine ringand the carbon atom adjacent to the N heteroatom is substituted with -OH, tautomersmay exist.The term “carbocyclic” refers to a substituted or unsubstituted monocyclic ring, bicyclic ring, bridged ring, fused ring, spiro ring non-aromatic ring system only containing carbon atoms. Preferably, the ring is three to ten membered and is either fully saturated or has one or more degrees of unsaturation. Multiple degrees of substitution, preferably one, two or three, are included within the present definition. The carbocyclic includes but not be limited cycloalkly, cycloalkenyl and cycloalkynyl. Exemplary “cycloalkyl” groups includes but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.The term “one or more” refers to one or more than one. In some embodiments, “one or more” refers to 1, 2, 3, 4, 5 or 6. In some embodiments, “one or more” refers to 1, 2, 3 or 4. In some embodiments, “one or more” refers to 1, 2, or 3. In some embodiments, “one or more” refers to 1 or 2. In some embodiments, “one or more” refers to 1. In some embodiments, “one or more” refers to 2. In some embodiments, “one or more” refers to 3. In some embodiments, “one or more” refers to 4. In some embodiments, “one or more” refers to 5. In some embodiments, “one or more” refers to 6.When one or more substituents are substituted on a ring in the present invention, it means that each of substituents may be respectively independently substituted on every ring atom of the ring including but not limited to a ring carbon atom or a ring nitrogen atom. In addition, when the ring is a polycyclic ring, such as a fused ring, a bridged ring or a spiro ring, each of substituents may be respectively independently substituted on every ring atom of the polycyclic ring.The term “oxo” refers to oxygen atom together with the attached carbon atom forms the groupThe term “composition” , as used herein, is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combinations of the specified ingredients in the specified amounts. Accordingly, pharmaceutical compositions containing the compounds of the present invention as the active ingredient as well as methods of preparing the instant compounds are also part of the present invention. Furthermore, some of the crystalline forms for the compounds may exist as polymorphs and as such are intended to be included in the present invention. In addition, some of the compounds may form solvates with water (i.e., hydrates) or common organic solvents and such solvates are also intended to be encompassed within the scope of this invention.The term “pharmaceutically acceptable salts” refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids. When the compound of the present invention is acidic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic bases, including inorganic bases and organic bases. When the compound of the present invention is basic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Since the compounds in the present invention are intended for pharmaceutical use they are preferably provided in substantially pure form, for example at least 60%pure, more suitably at least 75%pure, especially at least 98%pure (%are on a weight for weight basis) .The present invention includes within its scope the prodrugs of the compounds of this invention. In general, such prodrugs will be functional derivatives of the compounds that are readily converted in vivo into the required compound. Thus, in the methods of treatment of the present invention, the term “administering” shall encompass the treatment of the various disorders described with the compound specifically disclosed or with a compound which may not be specifically disclosed, but which converts to the specified compound in vivo after administration to the subject. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in “Design of Prodrugs” , ed. H. Bundgaard, Elsevier, 1985.It is intended that the definition of any substituent or variable at a particular location in a molecule be independent of its definitions elsewhere in that molecule. It is understood that substituents and substitution patterns on the compounds of this invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques know in the art as well as those methods set forth herein.The present invention includes compounds described can contain one or more asymmetric centers and may thus give rise to diastereomers and optical isomers. The present invention includes all such possible diastereomers as well as their racemic mixtures, their substantially pure resolved enantiomers, all possible geometric isomers, and pharmaceutically acceptable salts thereof.The present invention includes all stereoisomers of the compound and pharmaceutically acceptable salts thereof. Further, mixtures of stereoisomers as well as isolated specific stereoisomers are also included. During the course of the synthetic procedures used to prepare such compounds or in using racemization or epimerization procedures known to those skilled in the art, the products of such procedures can be a mixture of stereoisomers.The term “stereoisomer” as used in the present invention refers to an isomer in which atoms or groups of atoms in the molecule are connected to each other in the same order but differ in spatial arrangement, including conformational isomers and conformational isomers. The configuration isomers include geometric isomers and optical isomers, and optical isomers mainly include enantiomers and diastereomers. The invention includes all possible stereoisomers of the compound.Certain of the compounds provided herein may exist as atropisomers, which are conformational stereoisomers that occur when rotation about a single bond in the molecule is prevented, or greatly slowed, as a result of steric interactions with other parts of the molecule. The compounds provided herein include all atropisomers, both as pure individual atropisomer preparations, enriched preparations of each, or a non-specific mixture of each. Where the rotational barrier about the single bond is high enough, and interconversion between conformations is slow enough, separation and isolation of the isomeric species may be permitted.The present invention is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include deuterium and tritium. The isotopes of hydrogen can be denoted as 1H (hydrogen) , 2H (deuterium) and 3H (tritium) . They are also commonly denoted as D for deuterium and T for tritium. In the application, CD3 denotes a methyl group wherein all of the hydrogen atoms are deuterium. Isotopes of carbon include 13C and 14C. Isotopically-labeled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described herein, using an appropriate isotopically-labeled reagent in place of the non-labeled reagent.The term “deuterated derivative” , used herein, unless otherwise indicated, refers to a compound having the same chemical structure as a reference compound, but with one or more hydrogen atoms replaced by a deuterium atom ( “D” ) . It will be recognized that some variation of natural isotopic abundance occurs in a synthesized compound depending on the origin of chemical materials used in the synthesis. The concentration of naturally abundant stable hydrogen isotopes, notwithstanding this variation is small and immaterial as compared to the degree of stable isotopic substitution of deuterated derivative described herein. Thus, unless otherwise stated, when a reference is made to a "deuterated derivative" of a compound of the disclosure, at least one hydrogen is replaced with deuterium at well above its natural isotopic abundance (which is typically about 0.015%) In some embodiments, the deuterated derivative of the disclosure have an isotopic enrichment factor for each deuterium atom, of at least 3500 (52.5%deuterium incorporation at each designated deuterium) at least 4500, (67.5 %deuterium incorporation) , at least 5000 (75%deuterium incorporation) at least 5500 (82.5%deuterium incorporation) , at least 6000 (90%deuterium incorporation) , at lease 6333.3 (95%deuterium incorporation, at least 6466.7 (97%deuterium incorporation, or at least 6600 (99%deuterium incorporation) .When a tautomer of the compound in the present invention exists, the present invention includes any possible tautomers and pharmaceutically acceptable salts thereof, and mixtures thereof, except where specifically stated otherwise.The pharmaceutical compositions of the present invention comprise a compound in present invention (or a pharmaceutically acceptable salt thereof) as an active ingredient, a pharmaceutically acceptable carrier and optionally other therapeutic ingredients or adjuvants. The compositions include compositions suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions may be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy.In practice, the compounds in present invention or a prodrug or a metabolite or pharmaceutically acceptable salts thereof, of this invention can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g. oral or parenteral (including intravenous) . Thus, the pharmaceutical compositions of the present invention can be presented as discrete units suitable for oral administration such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient. Further, the compositions can be presented as a powder, as granules, as a solution, as a suspension in an aqueous liquid, as a non-aqueous liquid, as an oil-in-water emulsion or as a water-in-oil liquid emulsion. In addition to the common dosage forms set out above, the compound represented by Formula I or a pharmaceutically acceptable salt thereof, may also be administered by controlled release means and / or delivery devices. The compositions may be prepared by any of the methods of pharmacy. In general, such methods include a step of bringing into association the active ingredient with the carrier that constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both. The product can then be conveniently shaped into the desired presentation.Thus, the pharmaceutical compositions of this invention may include a pharmaceutically acceptable carrier and a compound or a pharmaceutically acceptable salt. The compounds of Formula I or pharmaceutically acceptable salts thereof, can also be included in pharmaceutical compositions in combination with one or more other therapeutically active compounds.The pharmaceutical carrier employed can be, for example, a solid, liquid or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. Examples of liquid carriers are sugar syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen. In preparing the compositions for oral dosage form, any convenient pharmaceutical media may be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like may be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like may be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical carriers are employed. Optionally, tablets may be coated by standard aqueous or nonaqueous techniques.A tablet containing the composition of this invention may be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants. Compressed tablets may be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. Each tablet preferably contains from about 0.05mg to about 5g of the active ingredient and each cachet or capsule preferably containing from about 0.05mg to about 5g of the active ingredient. For example, a formulation intended for the oral administration to humans may contain from about 0.5mg to about 5g of active agent, compounded with an appropriate and convenient amount of carrier material which may vary from about 0.05 to about 95 percent of the total composition. Unit dosage forms will generally contain between from about 0.0lmg to about 2g of the active ingredient, typically 0.01mg, 0.02mg, 1mg, 2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, 10mg, 25mg, 50mg, l00mg, 200mg, 300mg, 400mg, 500mg, 600mg, 800mg, l000mg, 1500mg or 2000mg.Pharmaceutical compositions of the present invention suitable for parenteral administration may be prepared as solutions or suspensions of the active compounds in water. A suitable surfactant can be included such as, for example, hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Further, a preservative can be included to prevent the detrimental growth of microorganisms.Pharmaceutical compositions of the present invention suitable for injectable use include sterile aqueous solutions or dispersions. Furthermore, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. In all cases, the final injectable form must be sterile and must be effectively fluid for easy syringability. The pharmaceutical compositions must be stable under the conditions of manufacture and storage; thus, preferably should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol) , vegetable oils, and suitable mixtures thereof.Pharmaceutical compositions of the present invention can be in a form suitable for topical use such as, for example, an aerosol, cream, ointment, lotion, dusting powder or the like. Further, the compositions can be in a form suitable for use in transdermal devices. These formulations may be prepared, utilizing a compound represented by Formula I of this invention or a pharmaceutically acceptable salt thereof, via conventional processing methods. As an example, a cream or ointment is prepared by admixing hydrophilic material and water, together with about 0.05wt%to about 10wt%of the compound, to produce a cream or ointment having a desired consistency.Pharmaceutical compositions of this invention can be in a form suitable for rectal administration wherein the carrier is a solid. It is preferable that the mixture forms unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppositories may be conveniently formed by first admixing the composition with the softened or melted carrier (s) followed by chilling and shaping in molds.In addition to the aforementioned carrier ingredients, the pharmaceutical formulations described above may include, as appropriate, one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface-active agents, thickeners, lubricants, preservatives (including antioxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient. Compositions containing a compound described by Formula I or pharmaceutically acceptable salts thereof, may also be prepared in powder or liquid concentrate form.Generally, dosage levels on the order of from about 0.001mg / kg to about 150mg / kg of body weight per day are useful in the treatment of the above-indicated conditions or alternatively about 0.05mg to about 7g per patient per day. For example, inflammation, cancer, psoriasis, allergy / asthma, disease and conditions of the immune system, disease and conditions of the central nervous system (CNS) , may be effectively treated by the administration of from about 0.001 to 50mg of the compound per kilogram of body weight per day or alternatively about 0.05mg to about 3.5g per patient per day.It is understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and the severity of the particular disease undergoing therapy.Unless otherwise apparent from the context, when a value is expressed as “about” X or “approximately” X, the stated value of X will be understood to be accurate to ±10%, preferably, ±5%, ±2%.These and other aspects will become apparent from the following written description of the invention.METHODS OF PREPRATIONCompounds of the present invention can be synthesized from commercially available reagents using the synthetic methods and reaction schemes described herein. The examples which outline specific synthetic route, and the generic schemes below are meant to provide guidance to the ordinarily skilled synthetic chemist, who will readily appreciate that the solvent, concentration, reagent, protecting group, order of synthetic steps, time, temperature, and the like can be modified as necessary, well within the skill and judgment of the ordinarily skilled artisan.ExamplesExamplesThe following Examples are provided to better illustrate the present invention. All parts and percentages are by weight and all temperatures are degrees Celsius, unless explicitly stated otherwise. The following abbreviations have been used in the examples:Intermediate 1 (INT 1)To a solution of 3-amino-5-bromopyridin-2 (1H) -one (25.0 g, 1.00 eq) in DMA (250 mL) was added NaH (5.29 g, 60%purity, 1.00 eq) at 0 ℃ over 30 mins, and then 1- (bromomethyl) -3-chloro-benzene (28.5 g, 1.05 eq) in DMA (10.0 mL) was added dropwise at 0 ℃. The resulting mixture was stirred at 25 ℃ for 3 hrs, quenched with water (700 mL) at 0 ℃, and then extracted with EtOAc (250 mL *3, 150 mL *3) . The combined organic layers were washed with brine (500 mL *2) , dried over Na2SO4, and then concentrated under reduced pressure to obtain a residue which was purified with column chromatography (SiO2, eluted with PE / EA) to afford INT 1-1 (20.0 g) as a solid. LCMS: m / z = 312.9, 314.9 (Br isotope, [M+H] +) .To a solution of INT 1-1 (20.0 g, 1.00 eq) in Py (200 mL) was added EDCI (19.5 g, 1.60 eq) and 3-methylimidazole-4-carboxylic acid (12.1 g, 1.50 eq) . The reaction mixture was stirred at 80 ℃ for 12 hrs, diluted with H2O (500 mL) and extracted with EtOAc (400 mL *2 or 200 mL *4) . The combined organic layers were washed with brine (600 mL *2) , dried over Na2SO4, and then concentrated under reduced pressure to afford a residue which was purified with column chromatography (SiO2, eluted with PE / EA) to afford INT 1-2 (16.0 g) as a solid. LCMS: m / z = 421.0, 423.0 (Br isotope, [M+H] +) .Under an atmosphere of N2, Compound INT 1-2 (2.0 g, 1.0 eq) , diphenylmethanimine (1.29 g, 1.19 mL, 1.5 eq) , BINAP (590.66 mg, 0.2 eq) , Cs2CO3 (4.64 g, 3.0 eq) and Pd2 (dba) 3 (868.65 mg, 0.2 eq) were successively added into dioxane (20 mL) at 20 ℃. The reaction mixture was stirred at 110 ℃ for 16 hrs under an atmosphere of N2, diluted with EtOAc (50 mL) , and then filtered. The combined filtrate was concentrated under reduced pressure to afford a residue which was purified with column chromatography (SiO2, eluted with PE / EA) to afford INT 1-3 (1.33 g) as an oil.1H NMR (400 MHz, DMSO-d6) : δ 8.99 (s, 1H) , 7.93 (d, J = 2.4 Hz, 1H) , 7.84 (s, 1H) , 7.73 (s, 1H) , 7.66 (d, J = 7.3 Hz, 2H) , 7.57 -7.51 (m, 1H) , 7.50 -7.44 (m, 2H) , 7.42 -7.37 (m, 3H) , 7.36 -7.29 (m, 2H) , 7.24 -7.15 (m, 3H) , 7.02 (d, J = 2.4 Hz, 1H) , 6.87 (br d, J = 7.1 Hz, 1H) , 5.00 (s, 2H) , 3.82 (s, 3H) . Repeat this step for eight times to obtain INT 1-3 11g.HCl (12 M, 35.0 mL, 20.2 eq) was added into a solution of INT 1-3 (10.64 g, 1.00 eq) in THF (250.0 mL) . The mixture was stirred at 20 ℃ for 30 mins, diluted with THF, and then HCl (12 M) was added. The reaction mixture was stirred at 20 ℃ for 30 mins and filtered. The filter cake was washed with THF (500 mL) and EtOAc (500 mL) , dispersed in NaHCO3 aqueous solution, and the resulting mixture was filtered a filter cake which was washed by H2O (1000 mL) and dried in vacuo to afford compound INT 1 (7.3 g, 100%yield) as a solid. LCMS: m / z = 358.1 [M+H] +.1H NMR (400 MHz, DMSO-d6) : δ 9.85 (s, 1H) , 9.09 (s, 1H) , 8.47 (s, 1H) , 8.30 (s, 1H) , 7.81 (s, 1H) , 7.40 (s, 3H) , 7.30 (d, J = 6.4 Hz, 1H) , 5.26 (s, 2H) , 3.99 (s, 3H) .Intermediate 2 (INT 2)To a mixture of 3-amino-5-bromopyridin-2 (1H) -one (2.5 g, 1.00 eq) in DMA (25 mL) was added NaH (0.530 g, 60%purity, 1.00 eq) in portions at 0 ℃. The mixture was stirred for 30 mins, and then 1-(bromomethyl) -4- (trifluoromethyl) benzene (3.32 g, 1.05 eq) in DMA (25 mL) was added dropwise at 0 ℃. The reaction mixture was stirred for 2 hrs at 20 ℃, quenched with aq. NH4Cl (20 mL) , diluted with EtOAc (10 mL) , and then extracted with EtOAc (15 mL *3) . The combined organic layers were washed with aq.NaCl (15 mL *1) , dried over with Na2SO4, and then concentrated under reduced pressure to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford INT 2-1 (2.9 g) as a solid. LCMS: m / z = 347.1, 349.1 (Br isotope, [M+H] +) .NMI (1.37 g, 3.00 eq) was added into a mixture of 1-methyl-1H-imidazole-5-carboxylic acid (1.06 g, 1.00 eq) and INT 2-1 (2.9 g, 1.00 eq) in DMF (30 mL) , and then TCFH (2.81 g, 1.50 eq) was added in portions at 0 ℃ under an atmosphere of N2. The reaction mixture was stirred for 12 hrs at 20 ℃, diluted with H2O (160 mL) and extracted with EtOAc (50 mL *3) . The combined organic layers were washed with aq.NaCl (100 mL *1) , dried over with Na2SO4, and then concentrated under reduced pressure to afford a residue which was purified by column chromatography (SiO2, eluted with EA / MeOH) to afford INT 2 (2.04 g, 53.2%yield) as a solid. LCMS: m / z = 455.1, 457.1 (Br isotope, [M+H] +) .1H NMR (400 MHz, CDCl3) : δ 8.89 (s, 1H) , 8.56 (d, J = 2.4 Hz, 1H) , 7.71 -7.64 (m, 3H) , 7.59 (s, 1H) , 7.44 (d, J = 8.1 Hz, 2H) , 7.21 (d, J = 2.4 Hz, 1H) , 5.23 (s, 2H) , 3.99 (s, 3H) .Intermediate 3 (INT 3)To a mixture of 5-aminopyrimidin-4 (3H) -one compound (5.0 g, 1.00 eq) in DMA (50 mL) was added NaH (1.8 g, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 20 ℃ for 30 mins, then 3-Chlorobenzyl bromide (9.71 g, 1.05 eq) in DMA (50 mL) at 20 ℃. The mixture was stirred at 20 ℃for 3 hrs. The reaction mixture was added H2O (300 mL) , and then diluted with EtOAc (100 mL) and extracted with EtOAc (200 mL *3) . The combined organic layers were washed with brine (100 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford INT 3 (3.4 g, 32.1%yield) as a solid. LCMS: m / z = 236.8 [M+H] +.1H NMR: (400 MHz, CHCl3-d) δ 7.46 (s, 1H) , 7.14 (s, 1H) , 7.10 -7.04 (m, 3H) , 7.01 -6.96 (m, 1H) , 4.88 (s, 2H) , 3.86 (br s, 2H) .Example 1Under an atmosphere of N2, NaH (203 mg, 60%purity, 1.13 eq) in portions to a mixture of 5-aminopyrimidin-4 (3H) -one (0.50 g, 1.00 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 0 ℃ for 30 mins, then (bromomethyl) benzene (692 mg, 0.90 eq) in DMA (1 mL) was added at 0 ℃. The reaction mixture was stirred at 15 ℃ for 3 hrs, H2O (10 mL) was added, diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, and then concentrated to obtain a residue which was purified with column chromatography (SiO2, eluted with PE / EA) to afford Compound 1-1 (0.10 g) as a solid.1H NMR (400 MHz, CDCl3) : δ 7.70 (s, 1H) , 7.32-7.38 (m, 6H) , 5.14 (s, 2H) , 4.06 (s, 2H) .To a solution of Compound 1-1 (60.0 mg, 1.00 eq) in Py (2 mL) was added EDCI (68.5 mg, 1.20 eq) and 1-methyl-1H-imidazole-2-carboxylic acid (49.0 mg, 1.30 eq) . The reaction mixture was stirred at 50 ℃for 5 hrs, and then filtered. The filtrate was concentrated under reduced pressure to afford a residue which was purified with Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 1 (0.03 g, 32.5%yield) as a solid. LCMS: m / z = 310.0 [M+H] +.1H NMR (400 MHz, CDCl3) : δ 9.02 (s, 1H) , 8.53 (s, 1H) , 7.99 (s, 1H) , 7.66 (s, 1H) , 7.57 (s, 1H) , 7.33 -7.42 (m, 5H) , 5.18 (s, 2H) , 3.97 (s, 3H) .Example 2To a solution of Compound INT 3 (160.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (112.0 mg, 0.387 mmol, 1.30 eq) and NMI (560 mg, 10.00 eq) in DMF (2 mL) was added TCFH (574.1 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 13 (48.0 mg, 20.6%yield) as a solid. LCMS: m / z = 344.1 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.26 (s, 1H) , 8.57 (d, J = 3.4 Hz, 2H) , 7.85 (d, J = 10.1 Hz, 2H) , 7.47 (t, J = 1.9 Hz, 1H) , 7.42 -7.37 (m, 2H) , 7.35 -7.32 (m, 1H) , 5.18 (s, 2H) , 3.83 (s, 3H) .Example 3To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.50 g, 1.00 eq) in DMA (1 mL) was added NaH (203 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 4-Chlorobenzyl bromide (833 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 14-1 (0.31 g) as a solid. LCMS: m / z = 236.9 [M+H] +.To a solution of Compound 14-1 (310.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (499.0 mg, 1.30 eq) and NMI (1.084 g, 10.00 eq) in DMF (5 mL) was added TCFH (1.113 g, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 14 (242.0 mg, 53.7%yield) as a solid. LCMS: m / z = 344.1 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.25 (s, 1H) , 8.56 (s, 2H) , 7.90 -7.78 (m, 2H) , 7.47 -7.37 (m, 4H) , 5.17 (s, 2H) , 3.83 (s, 3H) .Example 4To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.40 g, 1.00 eq) in DMA (1 mL) was added NaH (163 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 2-Chloro-5-fluorobenzyl bromide (726 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 15-1 (0.215 g) as a solid. LCMS: m / z = 254.8 [M+H] +.To a solution of Compound 15-1 (200.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (129.4 mg, 1.30 eq) and NMI (648.6 mg, 10.00 eq) in DMF (5 mL) was added TCFH (666.0 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 15 (130.0 mg, 45.7%yield) was obtained as a solid. LCMS: m / z = 362.1 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.20 (s, 1H) , 8.55 (s, 1H) , 8.49 (s, 1H) , 7.80 (d, J = 10.6 Hz, 2H) , 7.55 -7.48 (m, 1H) , 7.28 -7.22 (m, 1H) , 7.19 (t, J = 7.9 Hz, 1H) , 5.22 (s, 2H) , 3.79 (s, 3H) .Example 5To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.30 g, 1.00 eq) in DMA (1 mL) was added NaH (123 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 2, 4-Difluorobenzyl bromide (503 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 23-1 (0.15 g) as a solid. LCMS: m / z =238.3 [M+H] +.To a solution of Compound 23-1 (130.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (89.8 mg, 1.30 eq) and NMI (449.9 mg, 10.00 eq) in DMF (5 mL) was added TCFH (462.0 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 23 (30.0 mg, 15.9%yield) as a solid. LCMS: m / z = 346.0 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.23 (s, 1H) , 8.56 (s, 1H) , 8.49 (s, 1H) , 7.83 (d, J = 12.1 Hz, 2H) , 7.44 -7.40 (m, 1H) , 7.30 -7.27 (m, 1H) , 7.11 -7.08 (m, 1H) , 5.19 (s, 2H) , 3.83 (s, 3H) .Example 6To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.30 g, 1.00 eq) in DMA (1 mL) was added NaH (123 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 3, 4-Difluorobenzyl bromide (503 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 25-1 (0.20 g) as a solid. LCMS: m / z = 238.3 [M+H] +.To a solution of Compound 25-1 (180.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (124.3 mg, 1.30 eq) and NMI (622.9 mg, 10.00 eq) in DMF (5 mL) was added TCFH (639.7 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 25 (60.0 mg, 22.9%yield) as a solid. LCMS: m / z = 346.0 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.25 (s, 1H) , 8.56 (d, J = 1.4 Hz, 2H) , 7.84 (d, J = 8.8 Hz, 2H) , 7.55 -7.47 (m, 1H) , 7.47 -7.40 (m, 1H) , 7.27 -7.22 (m, 1H) , 5.15 (s, 2H) , 3.83 (s, 3H) .Example 7To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.40 g, 1.00 eq) in DMA (1 mL) was added NaH (163 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 3-Chloro-2-fluorobenzyl bromide (726 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 26-1 (0.20 g) as a solid. LCMS: m / z =254.8 [M+H] +.To a solution of Compound 26-1 (200.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (129.4 mg, 1.30 eq) and NMI (648.6 mg, 10.00 eq) in DMF (5 mL) was added TCFH (666.0 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 26 (35.0 mg, 12.3%yield) as a solid. LCMS: m / z = 362.0 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.24 (s, 1H) , 8.58 (s, 1H) , 8.52 (s, 1H) , 7.87 -7.78 (m, 2H) , 7.60 -7.49 (m, 1H) , 7.33 -7.26 (m, 1H) , 7.24 -7.20 (m, 1H) , 5.26 (s, 2H) , 3.83 (s, 3H) .Example 8To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.363 g, 1.00 eq) in DMA (1 mL) was added NaH (148 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 4-Chloro-2-fluorobenzyl bromide (658.8 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 28-1 (0.30 g) as a solid. LCMS: m / z =254.8 [M+H] +.To a solution of Compound 28-1 (100.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (65.0 mg, 1.30 eq) and NMI (324.3 mg, 10.00 eq) in DMF (5 mL) was added TCFH (333.0 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 28 (52.0 mg, 36.6%yield) as a solid. LCMS: m / z = 362.0 [M+1] +.1H NMR (600 MHz, DMSO-d6) δ 9.23 (s, 1H) , 8.57 (s, 1H) , 8.50 (s, 1H) , 7.83 (d, J = 13.3 Hz, 2H) , 7.51 -7.44 (m, 1H) , 7.36 (t, J = 8.3 Hz, 1H) , 7.33 -7.27 (m, 1H) , 5.20 (s, 2H) , 3.83 (s, 3H) .Example 9To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.363 g, 1.00 eq) in DMA (1 mL) was added NaH (148 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 4- (bromomethyl) -2-fluoro-1-methoxybenzene (644.7 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 38-1 (0.30 g) as a solid. LCMS: m / z =250.3 [M+H] +.To a solution of Compound 38-1 (165.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (108.4 mg, 1.30 eq) and NMI (543.5 mg, 10.00 eq) in DMF (5 mL) was added TCFH (558.1 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 38 (68.2 mg, 43.4%yield) as a solid. LCMS: m / z = 358.0 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.23 (s, 1H) , 8.54 (s, 2H) , 7.84 (d, J = 9.1 Hz, 2H) , 7.33 -7.27 (m, 1H) , 7.21 -7.12 (m, 2H) , 5.09 (s, 2H) , 3.83 (s, 3H) , 3.81 (s, 3H) .Example 10To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.363 g, 1.00 eq) in DMA (1 mL) was added NaH (148 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 4- (bromomethyl) -1, 2-dichlorobenzene (700.2 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 39-1 (0.34 g) as a solid. LCMS: m / z =270.9 [M+H] +.To a solution of Compound 39-1 (340.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (207.0 mg, 1.30 eq) and NMI (1.038 g, 10.00 eq) in DMF (5 mL) was added TCFH (1.066 g, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 39 (190 mg, 40.0%yield) as a solid. LCMS: m / z = 378.0 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.26 (s, 1H) , 8.57 (s, 2H) , 7.84 (d, J = 11.3 Hz, 2H) , 7.71 -7.67 (m, 1H) , 7.65 -7.61 (m, 1H) , 7.39 -7.35 (m, 1H) , 5.16 (s, 2H) , 3.83 (s, 3H) .Example 11To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.363 g, 1.00 eq) in DMA (1 mL) was added NaH (148 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 4-methylbenzyl bromide (544.7 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 47-1 (0.3 g) as a solid. LCMS: m / z =216.4 [M+H] +.To a solution of Compound 47-1 (150.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (114.7 mg, 1.30 eq) and NMI (574.7 mg, 10.00 eq) in DCM (15 mL) was added TCFH (590.1 mg, 3.00 eq) slowly at room temperature. Then the reaction mixture was concentrated by reduced pressure to afford the residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 47 (35.5 mg, 15.8%yield) as a solid. LCMS: m / z = 324.2 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.22 (s, 1H) , 8.54 (d, J = 10.6 Hz, 2H) , 7.84 (d, J = 10.2 Hz, 2H) , 7.26 (d, J = 8.1 Hz, 2H) , 7.16 (d, J = 8.3 Hz, 2H) , 5.13 (s, 2H) , 3.83 (s, 3H) , 2.27 (s, 3H) .Example 12To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.363 g, 1.00 eq) in DMA (1 mL) was added NaH (148 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 4- (trifluoromethoxy) benzyl bromide (747.6 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added with H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 49-1 (0.23 g) as a solid. LCMS: m / z =286.4 [M+H] +.To a solution of Compound 49-1 (150.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (86.2 mg, 1.30 eq) and NMI (431.8 mg, 10.00 eq) in DCM (15 mL) and TCFH (443.4 mg, 3.00 eq) were added slowly at room temperature. The mixture was stirred at room temperature for overnight. Then the reaction mixture was concentrated by reduced pressure to afford the residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 49 (52.5 mg, 25.4%yield) as a solid. LCMS: m / z = 394.0 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.24 (s, 1H) , 8.58 (d, J = 3.7 Hz, 2H) , 7.84 (d, J = 11.1 Hz, 2H) , 7.50 (d, J = 8.6 Hz, 2H) , 7.37 (d, J = 8.3 Hz, 2H) , 5.21 (s, 2H) , 3.83 (s, 3H) .Example 13To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.363 g, 1.00 eq) in DMA (1 mL) was added NaH (148 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 5- (bromomethyl) -1, 2, 3-trifluorobenzene (659.1 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 52-1 (0.21 g) as a solid. LCMS: m / z =256.4 [M+H] +.To a solution of Compound 52-1 (150.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (96.3 mg, 1.30 eq) and NMI (482.7 mg, 10.00 eq) in DCM (15 mL) was added TCFH (495.7 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight. Then the reaction mixture was concentrated by reduced pressure to afford the residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 52 (49.6 mg, 23.2%yield) as a solid. LCMS: m / z = 364.0 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.25 (s, 1H) , 8.55 (d, J = 21.8 Hz, 2H) , 7.84 (d, J = 10.0 Hz, 2H) , 7.44 -7.37 (m, 2H) , 5.14 (s, 2H) , 3.83 (s, 3H) .Example 14To a solution of methyl 4-formyl-1H-pyrrole-2-carboxylate (2.00 g, 1.00 eq) in DMF (40.0 mL) was added NaH (1.04 g, 26.1 mmol, 60.0%purity, 2.50 eq) at 0 ℃. Then the reaction mixture was stirred 0 ℃for 0.5 hr. And then MeI (2.78 g, 19.6 mmol, 1.22 mL, 1.50 eq) was added dropwise to the reaction mixture at 0 ℃ and stirred at 0 ℃ for 0.5 hr. The reaction mixture was quenched by H2O (45 mL) , and extracted by EtOAc (100 mL *2) . The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO2, PE / EA) to afford Compound 70-1 (1.70 g) as a solid. LCMS: m / z = 168.3 [M+H] +.To a solution Compound 70-1 (1.70 g, 1.00 eq) in DCM (17.0 mL) was added NaBH4 (192 mg, 5.08 mmol, 0.2 eq) at -78 ℃ in portions. The reaction was stirred at 0 ℃ for 2 hrs. The reaction mixture was quenched by aq. NH4Cl (10 mL) and extracted with DCM (15 mL *2) . The combined organic layers were washed by brine (5.00 mL *2) , dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give Compound 70-2 (1.50 g, crude) as an oil which was used into next step without further purification.To a mixture of Compound 70-2 (1.50 g, 1.00 eq) in DMF (7.50 mL) was added DIEA (2.86 g, 3.86 mL, 2.50 eq) and 2- (trimethylsilyl) ethoxymethyl chloride (2.22 g, 1.50 eq) in one portion at 0 ℃. The reaction mixture was stirred at 25 ℃ for 4 hrs. The reaction mixture was quenched by H2O (10 mL) and extracted by DCM (15.0 mL *2) . The combined organic layers were washed by brine (10.0 mL *2) , dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give Compound 70-3 (2.50 g, crude) as an oil which was used into next step without further purification.To a solution of Compound 70-3 (1.50 g, 1 eq) in THF (7.50 mL) and H2O (7.50 mL) was added LiOH (300 mg, 2.00 eq) at 25 ℃. The reaction mixture was stirred at 45 ℃ for 3 hrs. The pH of the mixture was adjusted to ~5 by aq. HCl (2 N) . Then the mixture was extracted by EtOAc (10 mL *2) . The combined organic layers were washed with brine (5 mL *2) , dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford Compound 70-4 (1.20 g, crude) as a solid. LCMS: m / z = 284.1 [M-H] -. 1H NMR: (400 MHz, CHCl3-d) δ 7.03 (d, J = 1.7 Hz, 1H) , 6.83 (d, J = 1.2 Hz, 1H) , 4.68 (s, 2H) , 4.42 (s, 2H) , 3.87 (s, 3H) , 3.65 -3.59 (m, 2H) , 0.99 -0.89 (m, 2H) , 0.00 (s, 9H)To a solution of Compound 70-4 (500 mg, 1.00 eq) in Py (5.00 mL) was added Compound INT 3 (248 mg, 1.00 eq) and EDCI (840 mg, 2.50 eq) in one portion at 25 ℃. The reaction mixture was stirred at 80 ℃ for 12 hrs. The reaction mixture was quenched by H2O (10 mL) and extracted by EtOAc (5 mL *2) . The combined organic layers were washed by brine (5 mL *2) , dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 70-5 (80.0 mg) as a solid. LCMS: m / z = 503.2 [M+H] +.A solution of Compound 70-5 (80.0 mg, 159 μmol, 1.00 eq) in HCl / MeOH (0.200 mL) was stirred at 25 ℃ for 16 hrs. The reaction mixture was concentrated under reduced pressure to give a residue which was purified by prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 70 (11.0 mg, 9.9%yield) as a solid. LCMS: m / z = 371.1 [M-H] -.1H NMR (600 MHz, DMSO-d6) δ 8.76 (s, 1H) , 8.64 (s, 1H) , 8.52 (s, 1H) , 7.48 (s, 1H) , 7.42 -7.38 (m, 2H) , 7.34 (br d, J = 6.6 Hz, 1H) , 6.97 (s, 1H) , 6.88 (s, 1H) , 5.19 (s, 2H) , 4.80 (t, J = 5.4 Hz, 1H) , 4.30 (d, J = 5.4 Hz, 2H) , 3.83 (s, 3H) .Example 15To a mixture of 5-aminopyrimidin-4 (3H) -one compound (2.2 g, 1.00 eq) in DMA (10 mL) was added NaH (0.895 g, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 1- (bromomethyl) -3- (trifluoromethyl) benzene (4.243 g, 0.90 eq) in DMA (10 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (30 mL) , and then diluted with EtOAc (30 mL) and extracted with EtOAc (50.0 mL *3) . The combined organic layers were washed with brine (50 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 72-1 (1.2 g) as a solid. LCMS: m / z =254.8 [M+H] +.To a solution of Compound 72-1 (1.83 g, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (1.114 mg, 1.30 eq) and NMI (5.576 g, 10.00 eq) in DMF (20 mL) was added TCFH (5.712 g, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight and then was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 72 (1.531 g, 58.5%yield) as a solid. LCMS: m / z = 362.3 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.25 (s, 1H) , 8.57 (d, J = 4.3 Hz, 2H) , 7.88 -7.75 (m, 2H) , 7.69 -7.59 (m, 1H) , 7.50 -7.34 (m, 2H) , 5.15 (s, 2H) , 3.83 (s, 3H) .Example 16To a mixture of 5-aminopyrimidin-4 (3H) -one compound (0.333 g, 1.00 eq) in DMA (1 mL) was added NaH (135.5 mg, 60%purity, 1.13 eq) in portion at 0 ℃ under N2. The mixture was stirred at 0 ℃ for 30 mins, then 1- (bromomethyl) -3- (trifluoromethyl) benzene (642.2 mg, 0.90 eq) in DMA (1 mL) at 0 ℃. The mixture was stirred at 15 ℃ for 3 hrs. The reaction mixture was added H2O (10 mL) , and then diluted with EtOAc (10 mL) and extracted with EtOAc (20.0 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, filtered concentrated to obtain a residue which was purified by column chromatography (SiO2, eluted with PE / EA) to afford Compound 73-1 (0.438 g) as a solid. LCMS: m / z =270.4 [M+H] +.To a solution of Compound 73-1 (200.0 mg, 1.00 eq) , 1-methyl-1H-imidazole-5-carboxylic acid (121.7 mg, 1.30 eq) and NMI (609.5 mg, 10.00 eq) in DMF (15 mL) was added TCFH (624.3 mg, 3.00 eq) slowly at room temperature. The mixture was stirred at room temperature for overnight. Then the reaction mixture was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 73 (21.8 mg, 7.8%yield) as a solid. LCMS: m / z = 378.6 [M+H] +.1H NMR (600 MHz, DMSO-d6) δ 9.25 (s, 1H) , 8.62 (s, 1H) , 8.58 (s, 1H) , 7.86 -7.77 (m, 3H) , 7.72 -7.58 (m, 3H) , 5.26 (s, 2H) , 3.83 (s, 3H) .The following compounds were synthesized using the above procedure or modification procedure using the corresponding intermediates.Example 17Under an atmosphere of N2, NaH (405 mg, 60.0%purity, 1.13 eq) was added in portion to a solution of 5-aminopyrimidin-4 (3H) -one (1.00 g, 1.00 eq) in DMA (6 mL) at 0 ℃. The mixture was stirred at 0 ℃for 30 mins, then 1- (bromomethyl) -4- (trifluoromethyl) benzene (2.15 g, 1.00 eq) in DMA (6 mL) was added at 0 ℃. The reaction mixture was stirred at 15 ℃ for 3 hours, H2O (10 mL) was added, and then extracted with EtOAc (20 mL *3) . The combined organic layers were washed with brine (20 mL *2) , dried over Na2SO4, and then concentrated under reduced pressure to obtain a residue which was purified with column chromatography (SiO2, eluted with Petroleum ether / Ethyl acetate) to afford Compound 74-1 (1.05 g) as a solid. LCMS: m / z = 270.1 [M+H] +.Under an atmosphere of N2, t-BuONa (145 mg, 3.00 eq) , BINAP (63 mg, 0.2 eq) and Pd2 (dba) 3 (46 mg, 0.1 eq) were added subsequently at 25 ℃ to a solution of Compound 74-1 (135 mg, 1.00 eq) and 2-iodopyridine (123 mg, 1.2 eq) in toluene (5 mL) . The reaction mixture was purged with N2 for 3 times, stirred at 110 ℃ for 2 hrs, quenched with H2O (10 mL) and extracted with EtOAc (10 mL *2) . The combined organic layers were washed with brine (5 mL *2) , dried over by Na2SO4 and concentrated under reduced pressure to afford a residue which was purified with Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 74 (60 mg, 11.5%yield) as a solid. LCMS: m / z = 347.6 [M+H] +.1H NMR (600 MHz, DMSO-d6) : δ 9.18 (s, 1H) , 8.62 (s, 1H) , 8.32 (s, 1H) , 8.26 -8.19 (m, 1H) , 7.77 -7.69 (m, 2H) , 7.63 -7.51 (m, 3H) , 7.30 -7.23 (m, 1H) , 6.86 -6.78 (m, 1H) , 5.29 (s, 2H) .Example 18The solution of INT 3 (150 mg, 1.00 eq) and 3-bromo-5-methylpyridine (130.9 mg, 1.2 eq) in toluene (3 mL) was added t-BuONa (183.7 mg, 3.00 eq) , BINAP (79.4 mg, 0.2 eq) and Pd2 (dba) 3 (58.3 mg, 0.1 eq) in one portion at 25 ℃ under N2. The reaction mixture was degassed with N2 for 3 times and stirred at 110 ℃ for 2 hrs. The reaction mixture was quenched by H2O (10 mL) and extracted by EtOAc (10 mL *2) . The combined organic layers were washed with brine (5 mL *2) , dried over by Na2SO4 and concentrated under reduced pressure to give a residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 75 (91 mg, 43.7%yield) as a solid. LCMS: m / z = 327.5 [M+H] +. 1H NMR (400 MHz, DMSO-d6) δ 8.34 -8.27 (m, 2H) , 7.98 -7.91 (m, 2H) , 7.84 (s, 1H) , 7.51 -7.45 (m, 1H) , 7.45 -7.31 (m, 4H) , 5.17 (s, 2H) , 2.30 -2.22 (m, 3H) .Example 19The solution of Compound 74-1 (100 mg, 1.00 eq) and 3-bromopyridine (69.9 mg, 1.2 eq) in toluene (3 mL) was added t-BuONa (107.1 mg, 3.00 eq) , BINAP (46.2 mg, 0.2 eq) and Pd2 (dba) 3 (34.0 mg, 0.1 eq) in one portion at 25 ℃ under N2. The reaction mixture was degassed with N2 for 3 times and stirred at 110 ℃ for 2 hrs. The reaction mixture was quenched by H2O (10 mL) and extracted by EtOAc (10 mL *2) . The combined organic layers were washed with brine (5 mL *2) , dried over by Na2SO4 and concentrated under reduced pressure to give a residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 94 (14.9 mg, 10.1%yield) as a solid. LCMS: m / z = 347.5 [M+H] +. 1H NMR (600 MHz, DMSO-d6) δ 8.47 (d, J = 2.7 Hz, 1H) , 8.32 (s, 1H) , 8.10 (d, J = 4.6 Hz, 1H) , 8.01 (s, 1H) , 7.85 (s, 1H) , 7.74 (d, J = 8.0 Hz, 2H) , 7.62 -7.54 (m, 3H) , 7.29 -7.24 (m, 1H) , 5.28 (s, 2H) .The following compounds were synthesized using the above procedure or modification procedure using the corresponding intermediates.Example 20Under an atmosphere of N2, TEA (0.85 g, 3.00 eq) , tris-o-tolylphosphane (171 mg, 0.300 eq) and Pd(OAc) 2 (126.0 mg, 0.100 eq) were added into a mixture of INT-2 (2.04 g, 1.00 eq) and Ethyl acrylate (2.35 g, 10.0 eq) in DMF (15.0 mL) at 20 ℃. The reaction mixture was stirred for at 110 ℃ 12 hrs, diluted with H2O (30 mL) and extracted with EtOAc (30 mL *3) . The combined organic layers were washed with brine (30 mL *1) , dried over with Na2SO4, and concentrated under reduced pressure to afford a residue which was purified with column chromatography (SiO2, EA / MeOH) to afford Compound 96-1 (0.893 g) as a solid. LCMS: m / z = 475.2 [M+H] +.1H NMR (400 MHz, CDCl3) : δ 8.90 -8.86 (m, 1H) , 8.74 (d, J = 2.3 Hz, 1H) , 7.70 (s, 1H) , 7.66 (d, J = 8.1 Hz, 2H) , 7.59 (s, 1H) , 7.47 -7.38 (m, 3H) , 7.25 -7.19 (m, 1H) , 6.35 (d, J = 15.8 Hz, 1H) , 5.30 -5.21 (m, 2H) , 4.26 (q, J = 7.1 Hz, 2H) , 4.01 -3.97 (m, 3H) , 1.34 (t, J = 7.1 Hz, 3H) .To a mixture of Pd / C (0.45 g, 10%purity) in EtOH (30 mL) was added Compound 96-1 (0.895 g, 1.00 eq) at 15 ℃. The suspension was purged with H2 (30.0 psi) for 3 times and stirred for 4 hrs at 30 ℃ under H2 (30.0 psi) . The reaction mixture was filtered and concentrated under reduced pressure to afford a crude product (0.810 g) of Compound 96-2 as a solid which was used in next step without further purification. LCMS: m / z = 477.2 [M+H] +.To the reaction mixture of Compound 96-2 (0.81 g, 1.00 eq) in THF (10 mL) and H2O (10.0 mL) was added LiOH. H2O (0.18 g, 2.50 eq) in one portion at 15 ℃. The reaction mixture was stirred at 15 ℃ for 2 hrs, diluted with EtOAc (20 mL) and extracted with EtOAc (20 mL *3) . The pH of the aqueous phase was adjusted to about 6 by HCl (12 N) and then filtrated, the filter cake was dried in vacuo to afford Compound 96-3 (0.4 g) as a solid. LCMS: m / z = 449.1 [M+H] +.1H NMR (400 MHz, CDCl3) : δ 12.56 -11.90 (m, 1H) , 9.07 (s, 1H) , 8.16 (d, J = 2.1 Hz, 1H) , 7.86 (s, 1H) , 7.77 -7.69 (m, 3H) , 7.56 -7.48 (m, 3H) , 5.25 (s, 2H) , 3.86 (s, 3H) , 2.69 -2.61 (m, 2H) , 2.50 -2.47 (m, 2H) .DIEA (86.5 mg, 3.00 eq) and HATU (127 mg, 1.50 eq) was added at 15 ℃ to a mixture of Compound 96-3 (100 mg, 1.00 eq) in DMF (2.00 mL) , and then pyridin-3-amine (105 mg, 5.00 eq) was added. The reaction mixture was stirred at 15 ℃ for 2 hrs. The mixture was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 96 (82.0 mg, 69.5%yield) as a solid. LCMS: m / z = 525.2 [M+H] +.1H NMR (400 MHz, DMSO-d6) : δ 10.18 (s, 1H) , 9.07 (s, 1H) , 8.73 (d, J = 2.4 Hz, 1H) , 8.28 -8.20 (m, 2H) , 8.05 -7.98 (m, 1H) , 7.86 (s, 1H) , 7.75 (s, 1H) , 7.60 (d, J = 8.2 Hz, 2H) , 7.54 (d, J = 2.0 Hz, 1H) , 7.46 (br d, J = 8.1 Hz, 2H) , 7.32 (dd, J = 4.7, 8.3 Hz, 1H) , 5.25 (s, 2H) , 3.86 (s, 3H) , 2.80 -2.73 (m, 2H) , 2.66 -2.60 (m, 2H) .The following compounds were synthesized using the above procedure or modification procedure using the corresponding intermediates.Example 21To a solution of INT 1 (50.0 mg, 1.00 eq) in Py (1.00 mL) was added EDCI (42.9 mg, 1.60 eq) and 2-methylfuran-3-carboxylic acid (26.4 mg, 1.50 eq) . The reaction mixture was stirred at 25 ℃ for 12 hrs. The resulting mixture was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 109 (14.16 mg, 21.1%yield) as a solid. LCMS: m / z = 466.1 [M+H] +.1H NMR: (400 MHz, MeOH-d4) : δ 8.62 (d, J = 2.8 Hz, 1H) , 8.08 (d, J = 2.6 Hz, 1H) , 7.81 -7.83 (m, 2H) , 7.41 (d, J = 2.0 Hz, 2H) , 7.31 -7.36 (m, 3H) , 6.87 (d, J = 2.0 Hz, 1H) , 5.27 (s, 2H) , 3.98 (s, 3H) , 2.57 (s, 3H) .Example 22To a solution of INT 1 (100 mg, 1.00 eq) in Py (1.00 mL) was added EDCI (85.7 mg, 1.60 eq) and 1-methyl-1H-imidazole-5-carboxylic acid (52.9 mg, 1.50 eq) . The mixture was stirred at 20 ℃ for 12 hrs. The reaction mixture was concentrated under reduced pressure to afford a residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 115 (8.6 mg, 6.6%yield) as a solid. LCMS: m / z = 466.1 [M+1] +.1H NMR (400 MHz, DMSO-d6) δ 10.02 (s, 1H) , 9.16 (s, 1H) , 8.54 (d, J = 2.4 Hz, 1H) , 8.19 (d, J = 2.7 Hz, 1H) , 7.88 (s, 1H) , 7.86 -7.78 (m, 3H) , 7.46 -7.36 (m, 3H) , 7.33 -7.27 (m, 1H) , 5.25 (s, 2H) , 3.87 (s, 3H) , 3.84 (s, 3H) .Example 23To a solution of INT 1 (50.0 mg, 1.00 eq) in Py (1.00 mL) was added EDCI (42.9 mg, 1.60 eq) and 3-methylisoxazole-4-carboxylic acid (26.6 mg, 1.50 eq) . The mixture was stirred at 25 ℃ for 12 hrs. The reaction mixture was concentrated under reduced pressure to afford a residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 118 (14.8 mg, 22.7%yield) as a solid. LCMS: m / z = 467.1 [M+H] +.1H NMR (400 MHz, MeOH-d4) δ 9.15 (s, 1H) , 8.59 (d, J = 2.6 Hz, 1H) , 8.16 (d, J = 2.6 Hz, 1H) , 7.81-7.83 (m, 2H) , 7.40 (s, 1H) , 7.30-7.36 (m, 3H) , 5.27 (s, 2H) , 3.98 (s, 3H) , 2.48 (s, 3H)Example 24To a solution of compound INT 1 (0.10 g, 1.00 eq) in Py (1.00 mL) was added 4-methyloxazole-5-carboxylic acid (53.3 mg, 1.50 eq) and EDCI (85.7 mg, 1.60 eq) . The mixture was stirred at 80 ℃ for 12 hrs. The residue was diluted with H2O 10 mL and extracted with DCM / MeOH 100 mL. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 122 (13.1 mg, 10.0%yield) as a solid. LCMS: m / z = 467.1 [M+H] +.1H NMR (400 MHz, MeOH-d4) δ 8.64 (d, J = 2.4 Hz, 1H) , 8.23 (s, 1H) , 8.10 (d, J = 2.4 Hz, 1H) , 7.82 (d, J = 4.8 Hz, 2H) , 7.42 (s, 1H) , 7.36-7.31 (m, 3H) , 5.28 (s, 2H) , 3.98 (s, 3H) , 2.49 (s, 3H) .Example 25To a solution of INT 1 (50.0 mg, 1.00 eq) in Py (1.00 mL) was added EDCI (42.9 mg, 1.60 eq) and 4-methylthiazole-5-carboxylic acid (30.0 mg, 1.50 eq) . The mixture was stirred at 25 ℃ for 12 hrs. The reaction mixture was concentrated under reduced pressure to afford a residue. Then the residue was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 126 (15.55 mg, 23.0%yield) as a solid. LCMS: m / z = 483.1 [M+H] +.1H NMR (400 MHz, MeOH-d4) δ 9.01 (s, 1H) , 8.60 (s, 1H) , 8.10 (s, 1H) , 7.82 (d, J = 4.0 Hz, 2H) , 7.42 (s, 1H) , 7.30-7.38 (m, 3H) , 5.28 (s, 2H) , 3.98 (s, 3H) , 2.69 (s, 3H)The following compounds were synthesized using the above procedure or modification procedure using the corresponding intermediates.Example 26TEA (14.1 mg, 2.50 eq) and methanesulfonyl chloride (10.0 mg, 1.50 eq) was added at 0 ℃ to a solution of INT 1 (20.0 mg, 1.00 eq) in DCM (1.00 mL) . The reaction mixture was stirred at 0 ℃ for 1 h, quenched with H2O (3.00 mL) at 0 ℃, and extracted with EtOAc (1.00 mL *3) . The combined organic layers were washed with brine (5.00 mL *3) , dried over Na2SO4, and concentrated under reduced pressure to afford a residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 139 (9.03 mg, 37.5%yield) as a solid. LCMS: m / z = 436.1 [M+H] +.1H NMR: (400 MHz, MeOH-d4) δ 8.44 (d, J = 2.6 Hz, 1H) , 7.81 (d, J = 9.2 Hz, 2H) , 7.50 (d, J = 2.8 Hz, 1H) , 7.40 (s, 1H) , 7.28 -7.37 (m, 3H) , 5.25 (s, 2H) , 3.97 (s, 3H) , 2.98 (s, 3H) .The following compounds were synthesized using the above procedure or modification procedure using the corresponding intermediates.Example 27Under an atmosphere of N2, Potassium vinyltrifluoroborate (4.4 g, 2.50 eq) , Na2CO3 (4.2 g, 3.00 eq) , H2O (6.0 mL) and Pd (dppf) Cl2 (1.93 g, 0.20 eq) were added successively to a mixture of compound INT 2 (6.0 g, 1.00 eq) in dioxane (60 mL) at 20 ℃. The reaction mixture was stirred at 100 ℃ for 12 hrs under an atmosphere of N2 and then filtered. The filtrate was concentrated under reduce pressure to afford a residue which was purified by column chromatography (SiO2, EA / MeOH) to afford Compound 148-1 (3.84 g) as a solid. LCMS: m / z = 403.1 [M+H] +.A solution of Compound 147-1 (3.84 g, 1.00 eq) in THF (65 mL) was dropwise added at 20 ℃ to a solution of BH3-Me2S (10.0 M, 1.91 mL, 2.00 eq) in THF (13.0 mL) . The reaction mixture was stirred for 2 hrs, then cooled to 0 ℃, aq. NaOH (3.00 M, 6.36 mL, 2.00 eq) and H2O2 (2.17 g, 30%purity, 2.00 eq) was added at 0 ℃. The resulting mixture was stirred at 20 ℃ for 12 hrs, poured into aq. Na2SO3 (70 mL) and then extracted with EtOAc (80 mL *2) . The combined organic layers were concentrated under reduce pressure to give a residue which was purified by column chromatography (SiO2, eluted with DCM / MeOH) to afford Compound 148-2 (3.50 g) as a solid. LCMS: m / z = 421.2 [M+H] +.To the mixture of Compound 147-2 (3.50 g, 1.00 eq) in DCM (175.0 mL) was added PhI (OAc) 2 (6.71 g, 2.50 eq) , TEMPO (65 mg, 0.05 eq) and H2O (525.0 mg, 29.15 mmol, 3.50 eq) at 20 ℃. The reaction mixture was stirred for 12 hrs and then concentrated under reduce pressure to afford a residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 148-3 (320 mg) as a solid. LCMS: m / z = 435.2 [M+H] +.1H NMR (400MHz, DMSO-d6) : δ 13.19 -11.68 (m, 1H) , 9.61 (s, 1H) , 8.94 (s, 1H) , 8.37 (s, 1H) , 8.17 (d, J = 2.1 Hz, 1H) , 7.75 (d, J = 8.1 Hz, 2H) , 7.66 (d, J = 2.1 Hz, 1H) , 7.51 (d, J = 8.0 Hz, 2H) , 5.28 (s, 2H) , 3.98 (s, 3H) , 3.44 (s, 2H) .To a solution of Compound 148-3 (100 mg, 1.00 eq) in DMF (1.00 mL) was added pyridin-3-amine (108 mg, 5.00 eq) , DIEA (89.2 mg, 3.00 eq) and HATU (131 mg, 1.50 eq) at 20 ℃. The reaction mixture was stirred at 20 ℃ for 12 hrs and then concentrated under reduce pressure to afford a residue which was purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 148 (34.0 mg, 28.3%yield) as a solid. LCMS: m / z = 511.1 [M+H] +.1H NMR (400MHz, DMSO-d6) : δ 10.39 (s, 1H) , 9.10 (s, 1H) , 8.75 (d, J = 2.4 Hz, 1H) , 8.30 -8.24 (m, 2H) , 8.08 -8.00 (m, 1H) , 7.86 (s, 1H) , 7.78 -7.72 (m, 3H) , 7.59 (d, J = 2.1 Hz, 1H) , 7.53 (d, J = 8.3 Hz, 2H) , 7.35 (dd, J = 4.8, 8.3 Hz, 1H) , 5.30 (s, 2H) , 3.85 (s, 3H) , 3.54 (s, 2H) .The following compounds were synthesized using the above procedure or modification procedure using the corresponding intermediates.Example 28H2SO4 (12.0 M, 40.0 mL, 8.83 eq) was added into a mixture of 5-nitro-6-oxo-1, 6-dihydropy-r-idine-3-carboxylic acid (10 g, 1.00 eq) in EtOH (200 mL) at 0 ℃. The reaction mixture was stirred for 30 mins at 0 ℃, subsequently stirred for 30 mins at room temperature, and then refluxed for 3 hrs at 110 ℃. The reaction mixture was slowly cooled down to room temperature, stirring for overnight and filtered. The filter cake was washed by cold EtOH (3*100 mL) and dried in vacuo to afford Compound 150-1 (7.0 g) as a solid. LCMS: m / z = 213.2 [M+H] +.1-(bromomethyl) -3-chloro-benzene (10.1 g, 1.91 eq) in DMF (60.0 mL) was added dropwise to a mixture of Compound 150-1 (7.0 g, 1.0 eq) and K2CO3 (13.66 g, 3.00 eq) in DMF (100 mL) at room temperature over 30 mins, and stirring for 3 hrs. The reaction mixture was quenched by addition water (700 mL) , and then extracted with EtOAc (250 mL *3, 150 mL *3) . The combined organic layers were washed with brine 500 mL (500 mL *2) , dried over Na2SO4 filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO2, PE / EA) to afford Compound 150-2 (10.0 g) as a solid. LCMS: m / z = 337.2 [M+H] +.To the mixture of Compound 150-2 (10.0 g, 1.00 eq) in MeOH (90.0 mL) was added Fe (11.4 g, 6.84 eq) , NH4Cl (21.8 g, 13.82 eq) and H2O (30.0 g, 56.00 eq) at room temperature. Then the mixture was warmed up to 80 ℃, stirring for 2 hrs and filtered. The filter was extracted with EtOAc (250 mL *3, 150 mL *3) . The combined organic layers were washed with brine (500 mL *2) , dried over Na2SO4 filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO2, PE / EA) to afford Compound 150-3 (4.3 g) as a solid. LCMS: m / z=307.3 [M+H] +.To a mixture of Compound 150-3 (4.3 g, 1.00 eq) and 1-methyl-1H-imidazole-5-carboxylic acid (3.5 g, 1.98 eq) in DMF (45 mL) was added NMI (11.5 g, 9.97 eq) at room temperature and stirring for 30 mins. Then TCFH (11.8 g, 2.99 eq) was added to the mixture in portions at room temperature. The mixture was stirred for 12 hrs at room temperature. The reaction mixture was directly purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 150-4 (2.1 g) as a solid. LCMS: m / z = 415.3 [M+H] +.1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H) , 8.59 (d, J = 2.3 Hz, 1H) , 8.54 (d, J = 2.3 Hz, 1H) , 7.89 -7.80 (m, 2H) , 7.45 -7.43 (m, 1H) , 7.40 -7.36 (m, 2H) , 7.31 -7.28 (m, 1H) , 5.31 (s, 2H) , 4.30 (q, J = 7.1 Hz, 2H) , 3.85 (d, J = 0.5 Hz, 3H) , 1.31 (t, J = 7.1 Hz, 3H) .To the reaction mixture of Compound 150-4 (2.1 g, 1.00 eq) in THF (20 mL) and H2O (10.0 mL) was added LiOH. H2O (0.6 g, 2.80 eq) in one portion at 20 ℃ and stirring for 3 hrs. The reaction mixture was diluted with EtOAc (20 mL) and the aqueous layer was extracted with EtOAc (20 mL *3) . The pH of the aqueous phase was adjust to ~6 by HCl 2 N and then filtrated, the filter cake was dried in vacuo to afford Compound 150-5 (1.1 g) as a solid. LCMS: m / z = 387.2 [M+H] +.To a mixture of Compound 150-5 (100.0 mg, 1.00 eq) and thiazol-2-amine (38 mg, 1.46 eq) in DMF (3 mL) was added NMI (212.0 mg, 9.93 eq) at room temperature and stirring for 15 mins. Then TCFH (217.0 g, 2.97 eq) was added to the mixture in portions at room temperature. The mixture was stirred for 2 hrs at room temperature. The reaction mixture was directly purified by Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 150 (57.5 mg, 46.1%yield) as a solid. LCMS: m / z = 469.3 [M+H] +.1H NMR: (400 MHz, DMSO-d6) δ 12.56 (s, 1H) , 9.21 (s, 1H) , 8.78 -8.67 (m, 2H) , 7.85 (d, J = 14.2 Hz, 2H) , 7.61 -7.49 (m, 2H) , 7.46 -7.35 (m, 3H) , 7.26 (d, J = 3.6 Hz, 1H) , 5.25 (s, 2H) , 3.87 (s, 3H) .The following compounds were synthesized using the above procedure or modification procedure using the corresponding intermediates.Example 29To a solution of INT 3 (240 mg, 1.00 eq) and 3-methoxybenzaldehyde (151 mg, 1.1 eq) in MeOH (10.00 mL) was added AcOH (2 mL) . After stirring at 20 ℃ for 1 hr, NaBH3CN (190 mg, 3.0 eq) was added. The mixture was stirred at 20 ℃ for overnight. The mixture was filtered. The filter cake was washed by cold MeOH (5.0 mL) to afford Compound 161 (13.5 mg, 3.72%) as a solid. LCMS: m / z = 356.2 [M+H] +.1H NMR: (400 MHz, DMSO-d6) δ 7.96 (s, 1H) , 7.42 -7.35 (m, 3H) , 7.30 -7.19 (m, 2H) , 6.91 -6.86 (m, 3H) , 6.81 -6.77 (m, 1H) , 6.16 (t, J = 6.4 Hz, 1H) , 5.10 (s, 2H) , 4.24 (d, J = 6.4 Hz, 2H) , 3.71 (s, 3H) .The following compounds were synthesized using the above procedure or modification procedure.The following compounds in Table 1 were synthesized using the above procedures or modification procedures:Pharmacological Experiments1. Fascin and F-actin bundling assayThe Materials, Reagents, Plates and Instrumentation of the F-actin bundling assay as shown in the following Table 1:Table 1Each compounds to be tested of the invention were reconstituted to a concentrations of 10 mM by DMSO, and then diluted with DMSO to obtain the concentrations of 3 mM, 120 uM and 12 uM.Actin-bundling activity was measured by low-speed centrifugation assay.1uM Monomeric rabbit G-actin was induced to polymerize at 25 ℃ in F-actin buffer (20 mM Tris-HCl at pH 8.0, 1 mM ATP, 1 mM DTT, 2 mM MgCl2 and 100 mM KCl) . Each compounds to be tested were diluted with F-actin buffer to obtain the following concentrations of 120 uM, 12uM, 1.2 uM and 0 uM, and then 0.25uM Recombinant Fascin proteins was added to obtain the final concentrations of 30 uM, 3uM, 0.3 uM and 0 uM. The resulting solution of each compounds to be tested were incubated for 30 min at 25 ℃and centrifuged for 30 min at 10, 000 g in an Eppendorf 5810 tabletop centrifuge. Both supernatants and pellets were dissolved in an equivalent volume of SDS sample buffer, and the amount of Fascin was determined by SDS-PAGE. The intensities of fascin proteins in Coomassie-stained gels was measured and then the gel imaging is taken using a multifunctional imaging system. Image J analyzes the gray value of the image at each concentration of each compounds to be tested and then calculated the relative actin-bundling activity (P) .The Inhibitory rate (%) was calculate according to the following formula:Inhibitory rate (%) =100-P (30uM)P (30uM) represents the inhibition rate at the concentration of 30uM.The data were analyzed by fitting with a 4-parameter logistic model using GraphPad Prism 8.0 tocalculated IC50 values.The results of IC50 values or Inhibitory rate of compounds to be tested are shown in Table 2:Table 2From Table 2, It can be seen that the representative compounds of the present invention have good inhibitory effect on Actin bundling.2. Mouse Pharmacokinetic StudyThe purpose of this study was to evaluate the pharmacokinetic properties of compounds in ICR mouse (♂) following single dose administration. Six mice were needed for each compound and the six mice were divided into two groups (n=3 / group) , group A and group B. Mice in group A were treated with a single 5 mg / kg dose of compound (i. v. ) . Mice in group B were treated with a single 10 mg / kg dose of compound (p.o. ) . For each mouse in group A and Group B, blood samples were collected at the time point of 0.25, 0.5, 1, 2, 4, 8 and 24 h post-dose. Blood samples were placed on ice until centrifugation to obtain plasma samples. The plasma samples were stored at -80℃ until analysis. The concentration of compound in plasma samples was determined using a LC-MS / MS method.The results are in the following Table 3:Table 3From Table 3, it can be seen that the representative compounds of the present invention have good pharmacokinetic properties.It is to be understood that, if any prior art publication is referred to herein; such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art in any country.The disclosures of all publications, patents, patent applications and published patent applications referred to herein by an identifying citation are hereby incorporated herein by reference in their entirety.Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is apparent to those skilled in the art that certain minor changes and modifications will be practiced. Therefore, the description and Examples should not be construed as limiting the scope of the invention.
Claims
1.A compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof: Wherein,X1 is selected from N or CR3;R1 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR12, -NR13R14, -SR15, -C (=O) R16, -C (=O) OR12, -OC (=O) R16, -C (=O) NR13R14, -NR13C (=O) R16, -S (=O) R17, -S (=O) OR12, -OS (=O) R17, -S (=O) NR13R14, -NR13S (=O) R17, -S (=O) 2R18, -S (=O) 2OR12, -OS (=O) R18, -S (=O) 2NR13R14, -NR13S (=O) 2R18, -P (=O) (R19) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, oxo, -OR1b, -NR1cR1d, -SR1e, -C (=O) R1f, -C (=O) OR1b, -OC (=O) R1f, -OC (=O) OR1b, -C (=O) NR1cR1d, -OC (=O) NR1cR1d, -C (=NR1c) R1a, -C (=NR1c) NR1cR1d, -NR1cC (=NR1c) NR1cR1d, -NR1cC (=O) R1f, -NR1cC (=O) OR1b, -NR1cC (=O) NR1cR1d, -S (=O) R1g, -S (=O) OR1b, -OS (=O) R1g, -OS (=O) OR1b, -S (=O) NR1cR1d, -NR1cS (=O) R1g, -NR1cS (=O) OR1b, -OS (=O) NR1cR1d, -NR1cS (=O) NR1cR1d, -S (=O) 2R1h, -S (=O) 2OR1b, -OS (=O) 2R1h, -OS (=O) 2OR1b, -S (=O) 2NR1cR1d, -NR1cS (=O) 2R1h, -NR1cS (=O) 2OR1b, -OS (=O) 2NR1cR1d, -NR1cS (=O) 2NR1cR1d, -P (=O) (R1i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R2 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR22, -NR23R24, -SR25, -C (=O) R26, -C (=O) OR22, -OC (=O) R26, -C (=O) NR23R24, -NR23C (=O) R26, -S (=O) R27, -S (=O) OR22, -OS (=O) R27, -S (=O) NR23R24, -NR23S (=O) R27, -S (=O) 2R28, -S (=O) 2OR22, -OS (=O) 2R28, -S (=O) 2NR23R24, -NR23S (=O) 2R28, -P (=O) (R29) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, oxo, -OR2b, -NR2cR2d, -SR2e, -C (=O) R2f, -C (=O) OR2b, -OC (=O) R2f, -OC (=O) OR2b, -C (=O) NR2cR2d, -OC (=O) NR2cR2d, -C (=NR2c) R2a, -C (=NR2c) NR2cR2d, -NR2cC (=NR2c) NR2cR2d, -NR2cC (=O) R2f, -NR2cC (=O) OR2b, -NR2cC (=O) NR2cR2d, -S (=O) R2g, -S (=O) OR2b, -OS (=O) R2g, -OS (=O) OR2b, -S (=O) NR2cR2d, -NR2cS (=O) R2g, -NR2cS (=O) OR2b, -OS (=O) NR2cR2d, -NR2cS (=O) NR2cR2d, -S (=O) 2R2h, -S (=O) 2OR2b, -OS (=O) 2R2h, -OS (=O) 2OR2b, -S (=O) 2NR2cR2d, -NR2cS (=O) 2R2h, -NR2cS (=O) 2OR2b, -OS (=O) 2NR2cR2d, -NR2cS (=O) 2NR2cR2d, -P (=O) (R2i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R3 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR32, -NR33R34, -SR35, -C (=O) R36, -C (=O) OR32, -OC (=O) R36, -C (=O) NR33R34, -NR33C (=O) R36, -N (R33) -C (=O) -C2-6alkenyl-R31, -S (=O) R37, -S (=O) OR32, -OS (=O) R37, -S (=O) NR33R34, -NR33S (=O) R37, -S (=O) 2R38, -S (=O) 2OR32, -OS (=O) R38, -S (=O) 2NR33R34, -NR33S (=O) 2R38, -P (=O) (R39) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, oxo, -OR3b, -NR3cR3d, -SR3e, -C (=O) R3f, -C (=O) OR3b, -OC (=O) R3f, -OC (=O) OR3b, -C (=O) NR3cR3d, -OC (=O) NR3cR3d, -C (=NR3c) R3a, -C (=NR3c) NR3cR3d, -NR3cC (=NR3c) NR3cR3d, -NR3cC (=O) R3f, -NR3cC (=O) OR3b, -NR3cC (=O) NR3cR3d, -S (=O) R3g, -S (=O) OR3b, -OS (=O) R3g, -OS (=O) OR3b, -S (=O) NR3cR3d, -NR3cS (=O) R3g, -NR3cS (=O) OR3b, -OS (=O) NR3cR3d, -NR3cS (=O) NR3cR3d, -S (=O) 2R3h, -S (=O) 2OR3b, -OS (=O) 2R3h, -OS (=O) 2OR3b, -S (=O) 2NR3cR3d, -NR3cS (=O) 2R3h, -NR3cS (=O) 2OR3b, -OS (=O) 2NR3cR3d, -NR3cS (=O) 2NR3cR3d, -P (=O) (R3i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R4 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR42, -NR43R44, -SR45, -C (=O) R46, -C (=O) OR42, -OC (=O) R46, -C (=O) NR43R44, -NR43C (=O) R46, -S (=O) R47, -S (=O) OR42, -OS (=O) R47, -S (=O) NR43R44, -NR43S (=O) R47, -S (=O) 2R48, -S (=O) 2OR42, -OS (=O) R48, -S (=O) 2NR43R44, -NR43S (=O) 2R48, -P (=O) (R49) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, oxo, -OR4b, -NR4cR4d, -SR4e, -C (=O) R4f, -C (=O) OR4b, -OC (=O) R4f, -OC (=O) OR4b, -C (=O) NR4cR4d, -OC (=O) NR4cR4d, -C (=NR4c) R4a, -C (=NR4c) NR4cR4d, -NR4cC (=NR4c) NR4cR4d, -NR4cC (=O) R4f, -NR4cC (=O) OR4b, -NR4cC (=O) NR4cR4d, -S (=O) R4g, -S (=O) OR4b, -OS (=O) R4g, -OS (=O) OR4b, -S (=O) NR4cR4d, -NR4cS (=O) R4g, -NR4cS (=O) OR4b, -OS (=O) NR4cR4d, -NR4cS (=O) NR4cR4d, -S (=O) 2R4h, -S (=O) 2OR4b, -OS (=O) 2R4h, -OS (=O) 2OR4b, -S (=O) 2NR4cR4d, -NR4cS (=O) 2R4h, -NR4cS (=O) 2OR4b, -OS (=O) 2NR4cR4d, -NR4cS (=O) 2NR4cR4d, -P (=O) (R4i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R5 is selected from selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -OR52, -NR53R54, -SR55, -C (=O) R56, -C (=O) OR52, -OC (=O) R56, -C (=O) NR53R54, -NR53C (=O) R56, -S (=O) R57, -S (=O) OR52, -OS (=O) R57, -S (=O) NR53R54, -NR53S (=O) R57, -S (=O) 2R58, -S (=O) 2OR52, -OS (=O) R58, -S (=O) 2NR53R54, -NR53S (=O) 2R58, -P (=O) (R59) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, oxo, -OR5b, -NR5cR5d, -SR5e, -C (=O) R5f, -C (=O) OR5b, -OC (=O) R5f, -OC (=O) OR5b, -C (=O) NR5cR5d, -OC (=O) NR5cR5d, -C (=NR5c) R5a, -C (=NR5c) NR5cR5d, -NR5cC (=NR5c) NR5cR5d, -NR5cC (=O) R5f, -NR5cC (=O) OR5b, -NR5cC (=O) NR5cR5d, -S (=O) R5g, -S (=O) OR5b, -OS (=O) R5g, -OS (=O) OR5b, -S (=O) NR5cR5d, -NR5cS (=O) R5g, -NR5cS (=O) OR5b, -OS (=O) NR5cR5d, -NR5cS (=O) NR5cR5d, -S (=O) 2R5h, -S (=O) 2OR5b, -OS (=O) 2R5h, -OS (=O) 2OR5b, -S (=O) 2NR5cR5d, -NR5cS (=O) 2R5h, -NR5cS (=O) 2OR5b, -OS (=O) 2NR5cR5d, -NR5cS (=O) 2NR5cR5d, -P (=O) (R5i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;Optionally, R4 and R5 together with the atoms to which they are both attached form a 3-14 membered carbocyclic ring, a 3-14 membered heterocyclic ring, a 6-12 membered aryl ring or a 5-14 membered heteroaryl ring; each said ring is independent optionally substituted with n3 RS3;RS3 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS32, -NRS33RS34, -SRS35, -C (=O) RS36, -C (=O) ORS32, -OC (=O) RS36, -OC (=O) ORS32, -C (=O) NRS33RS34, -OC (=O) NRS33RS34, -C (=NRS33) RS31, -C (=NRS33) NRS33RS34, -NRS33C (=NRS33) NRS33RS34, -NRS33C (=O) RS36, -NRS33C (=O) ORS32, -NRS33C (=O) NRS33RS34, -S (=O) RS37, -S (=O) ORS32, -OS (=O) RS37, -OS (=O) ORS32, -S (=O) NRS33RS34, -NRS33S (=O) RS37, -NRS33S (=O) ORS32, -OS (=O) NRS33RS34, -NRS33S (=O) NRS33RS34, -S (=O) 2RS38, -S (=O) 2ORS32, -OS (=O) 2RS38, -OS (=O) 2ORS32, -S (=O) 2NRS33RS34, -NRS33S (=O) 2RS38, -NRS33S (=O) 2ORS32, -OS (=O) 2NRS33RS34, -NRS33S (=O) 2NRS33RS34, -P (=O) (RS39) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein said -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-10alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS3b, -NRS3cRS3d, -SRS3e, -C (=O) RS3f, -C (=O) ORS3b, -OC (=O) RS3f, -OC (=O) ORS3b, -C (=O) NRS3cRS3d, -OC (=O) NRS3cRS3d, -C (=NRS3c) RS3a, -C (=NRS3c) NRS3cRS3d, -NRS3cC (=NRS3c) NRS3cRS3d, -NRS3cC (=O) RS3f, -NRS3cC (=O) ORS3b, -NRS3cC (=O) NRS3cRS3d, -S (=O) RS3g, -S (=O) ORS3b, -OS (=O) RS3g, -OS (=O) ORS3b, -S (=O) NRS3cRS3d, -NRS3cS (=O) RS3g, -NRS3aS (=O) ORS3b, -OS (=O) NRS3cRS3d, -NRS3cS (=O) NRS3cRS3d, -S (=O) 2RS3h, -S (=O) 2ORS3b, -OS (=O) 2RS3h, -OS (=O) 2ORS3b, -S (=O) 2NRS3cRS3d, -NRS3cS (=O) 2RS3h, -NRS3cS (=O) 2ORS3b, -OS (=O) 2NRS3cRS3d, -NRS3cS (=O) 2NRS3cRS3d, -P (=O) (RS3i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;n3 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;n4 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;Y1 is selected from -C (RY11) 2-, -RY11C=CRY11-, -C≡C-, -C (=O) -, -O-, -NRY13-, -S-, -S (=O) -, -S (=O) 2-, -P (=O) RY19-, *-C (=O) O-, *-OC (=O) -, *-C (=O) NRY13-, *-NRY13C (=O) -, *-S (=O) O-, *-OS (=O) -, *-S (=O) NRY13-, *-NRY13S (=O) -, *-S (=O) 2O-, *-OS (=O) 2-, *-S (=O) 2NRY13-, *-NRY13S (=O) 2- or *-NRY13P (=O) RY19-;* indicates the attached point to the moiety ofRing A is selected from a 3-14 membered carbocyclic ring, 3-14 membered heterocyclic ring, 6-14 membered aryl ring or 5-14 membered heteroaryl ring; said heterocyclic ring at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) , S (=O) 2; said heteroaryl ring at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;RS1 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS12, -NRS13RS14, -SRS15, -C (=O) RS16, -C (=O) ORS12, -OC (=O) RS16, -OC (=O) ORS12, -C (=O) NRS13RS14, -OC (=O) NRS13RS14, -C (=NRS13) RS11, -C (=NRS13) NRS13RS14, -NRS13C (=NRS13) NRS13RS14, -NRS13C (=O) RS16, -NRS13C (=O) ORS12, -NRS13C (=O) NRS13RS14, -S (=O) RS17, -S (=O) ORS12, -OS (=O) RS17, -OS (=O) ORS12, -S (=O) NRS13RS14, -NRS13S (=O) RS17, -NRS13S (=O) ORS12, -OS (=O) NRS13RS14, -NRS13S (=O) NRS13RS14, -S (=O) 2RS18, -S (=O) 2ORS12, -OS (=O) 2RS18, -OS (=O) 2ORS12, -S (=O) 2NRS13RS14, -NRS13S (=O) 2RS18, -NRS13S (=O) 2ORS12, -OS (=O) 2NRS13RS14, -NRS13S (=O) 2NRS13RS14, -P (=O) (RS19) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein said -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-10alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS1b, -NRS1cRS1d, -SRS1e, -C (=O) RS1f, -C (=O) ORS1b, -OC (=O) RS1f, -OC (=O) ORS1b, -C (=O) NRS1cRS1d, -OC (=O) NRS1cRS1d, -C (=NRS1c) RS1a, -C (=NRS1c) NRS1cRS1d, -NRS1cC (=NRS1c) NRS1cRS1d, -NRS1cC (=O) RS1f, -NRS1cC (=O) ORS1b, -NRS1cC (=O) NRS1cRS1d, -S (=O) RS1g, -S (=O) ORS1b, -OS (=O) RS1g, -OS (=O) ORS1b, -S (=O) NRS1cRS1d, -NRS1cS (=O) RS1g, -NRS1aS (=O) ORS1b, -OS (=O) NRS1cRS1d, -NRS1cS (=O) NRS1cRS1d, -S (=O) 2RS1h, -S (=O) 2ORS1b, -OS (=O) 2RS1h, -OS (=O) 2ORS1b, -S (=O) 2NRS1cRS1d, -NRS1cS (=O) 2RS1h, -NRS1cS (=O) 2ORS1b, -OS (=O) 2NRS1cRS1d, -NRS1cS (=O) 2NRS1cRS1d, -P (=O) (RS1i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;n1 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;Ring B is selected from a 3-14 membered carbocyclic ring, 3-14 membered heterocyclic ring, 6-14 membered aryl ring or 5-14 membered heteroaryl ring; said heterocyclic ring at each occurrence independently contains 1, 2, 3 or 4 heteroatoms selected from N, O, S, S (=O) , S (=O) 2; said heteroaryl ring at each occurrence independently contains 1, 2 or 3 heteroatoms selected from N, O or S;RS2 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS22, -NRS23RS24, -SRS25, -C (=O) RS26, -C (=O) ORS22, -OC (=O) RS26, -OC (=O) ORS22, -C (=O) NRS23RS24, -OC (=O) NRS23RS24, -C (=NRS23) RS21, -C (=NRS23) NRS23RS24, -NRS23C (=NRS23) NRS23RS24, -NRS23C (=O) RS26, -NRS23C (=O) ORS22, -NRS23C (=O) NRS23RS24, -S (=O) RS27, -S (=O) ORS22, -OS (=O) RS27, -OS (=O) ORS22, -S (=O) NRS23RS24, -NRS23S (=O) RS27, -NRS23S (=O) ORS22, -OS (=O) NRS23RS24, -NRS23S (=O) NRS23RS24, -S (=O) 2RS28, -S (=O) 2ORS22, -OS (=O) 2RS28, -OS (=O) 2ORS22, -S (=O) 2NRS23RS24, -NRS23S (=O) 2RS28, -NRS23S (=O) 2ORS22, -OS (=O) 2NRS23RS24, -NRS23S (=O) 2NRS23RS24, -P (=O) (RS29) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; wherein said -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-10alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS2b, -NRS2cRS2d, -SRS2e, -C (=O) RS2f, -C (=O) ORS2b, -OC (=O) RS2f, -OC (=O) ORS2b, -C (=O) NRS2cRS2d, -OC (=O) NRS2cRS2d, -C (=NRS2c) RS2a, -C (=NRS2c) NRS2cRS2d, -NRS2cC (=NRS2c) NRS2cRS2d, -NRS2cC (=O) RS2f, -NRS2cC (=O) ORS2b, -NRS2cC (=O) NRS2cRS2d, -S (=O) RS2g, -S (=O) ORS2b, -OS (=O) RS2g, -OS (=O) ORS2b, -S (=O) NRS2cRS2d, -NRS2cS (=O) RS2g, -NRS2aS (=O) ORS2b, -OS (=O) NRS2cRS2d, -NRS2cS (=O) NRS2cRS2d, -S (=O) 2RS2h, -S (=O) 2ORS2b, -OS (=O) 2RS2h, -OS (=O) 2ORS2b, -S (=O) 2NRS2cRS2d, -NRS2cS (=O) 2RS2h, -NRS2cS (=O) 2ORS2b, -OS (=O) 2NRS2cRS2d, -NRS2cS (=O) 2NRS2cRS2d, -P (=O) (RS2i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;n2 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;R31, RS11, RS21 or RY11 at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -OR6b, -NR6cR6d, -SR6e, -C (=O) R6f, -C (=O) OR6b, -OC (=O) R6f, -OC (=O) OR6b, -C (=O) NR6cR6d, -OC (=O) NR6cR6d, -C (=NR6c) R6a, -C (=NR6c) NR6cR6d, -NR6cC (=NR6c) NR6cR6d, -NR6cC (=O) R6f, -NR6cC (=O) OR6b, -NR6cC (=O) NR6cR6d, -S (=O) R6g, -S (=O) OR6b, -OS (=O) R6g, -OS (=O) OR6b, -S (=O) NR6cR6d, -NR6cS (=O) R6g, -NR6cS (=O) OR6b, -OS (=O) NR6cR6d, -NR6cS (=O) NR6cR6d, -S (=O) 2R6h, -S (=O) 2OR6b, -OS (=O) 2R6h, -OS (=O) 2OR6b, -S (=O) 2NR6cR6d, -NR6cS (=O) 2R6h, -NR6cS (=O) 2OR6b, -OS (=O) 2NR6cR6d, -NR6cS (=O) 2NR6cR6d, -P (=O) (R6i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; said 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl optionally substituted with one or more substituents selected from halogen or haloC1-6alkyl;R12, R15, R22, R25, R32, R35, R42, R45, R52, R55, RS12, RS15, RS22, RS25, RS32 or RS35 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R7f, -C (=O) OR7b, -S (=O) R7g, -S (=O) OR7b, -S (=O) 2R7h, -S (=O) 2OR7b, -P (=O) (R7i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;RY13, R13, R14, R23, R24, R33, R34, R43, R44, R53, R54, RS13, RS14, RS23, RS24, RS33 or RS34 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R8f, -C (=O) OR8b, -C (=O) NR8cR8d, -S (=O) R8g, -S (=O) OR8b, -S (=O) NR8cR8d, -S (=O) 2R8h, -S (=O) 2OR8b, -S (=O) 2NR8cR8d, -P (=O) (R8i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; said -C2-6alkynyl, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl optionally substituted with one or more substituents selected from -C1-6alkyl, Si (C1-6alkyl) 3, haloC1-6alkyl or halogen;RY19, R16, R17, R18, R19, R26, R27, R28, R29, R36, R37, R38, R39, R46, R47, R48, R49, R56, R57, R58, R59, RS16, RS17, RS18, RS19, RS26, RS27, RS28, RS29, RS36, RS37, RS38 or RS39 at each occurrence is selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -OR9b, -NR9cR9d, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; said 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl optionally substituted with one or more substituents selected from -C1-6alkyl, haloC1-6alkyl, -CN, halogen or -C (=O) O-C1-6alkyl;Optionally, (R13 and R14) , (R23 and R24) , (R33 and R34) , (R43 and R44) , (R53 and R54) , (RS13 and RS14) , (RS23 and RS24) or (RS33 and RS34) together with the nitrogen atom to which they are both attached form 3-14 membered heterocyclyl ring or 5-14 membered heteroaryl ring; said 3-14 membered heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, SO or SO2; said 3-14 membered heteroaryl ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S; each said ring is independently optionally substituted with n6 RS4;RS4 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORS4b, -NRS4cRS4d, -SRS4e, -C (=O) RS4g, -C (=O) ORS4b, -OC (=O) RS4f, -OC (=O) ORS4b, -C (=O) NRS4cRS4d, -OC (=O) NRS4cRS4d, -C (=NRS4c) RS4a, -C (=NRS4c) NRS4cRS4d, -NRS4cC (=NRS4c) NRS4cRS4d, -NRS4cC (=O) RS4f, -NRS4cC (=O) ORS4b, -NRS4cC (=O) NRS4cRS4d, -S (=O) RS4g, -S (=O) ORS4b, -OS (=O) RS4g, -OS (=O) ORS4b, -S (=O) NRS4cRS4d, -NRS4cS (=O) RS4g, -NRS4cS (=O) ORS4b, -OS (=O) NRS4cRS4d, -NRS4cS (=O) NRS4cRS4d, -S (=O) 2RS4h, -S (=O) 2ORS4b, -OS (=O) 2RS4h, -OS (=O) 2ORS4b, -S (=O) 2NRS4cRS4d, -NRS4cS (=O) 2RS4h, -NRS4cS (=O) 2ORS4b, -OS (=O) 2NRS4cRS4d, -NRS4cS (=O) 2NRS4cRS4d, -P (=O) (RS4i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;n6 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;R1a, R2a, R3a, R4a, R5a, R6a, RS1a, RS2a, RS3a or RS4a at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -ORZ1b, -NRZ1cRZ1d, -SRZ1e, -C (=O) RZ1f, -C (=O) ORZ1b, -OC (=O) RZ1f, -OC (=O) ORZ1b, -C (=O) NRZ1cRZ1d, -OC (=O) NRZ1cRZ1d, -C (=NRZ1c) RZ1a, -C (=NRZ1c) NRZ1cRZ1d, -NRZ1cC (=NRZ1c) NRZ1cRZ1d, -NRZ1cC (=O) RZ1f, -NRZ1cC (=O) ORZ1b, -NRZ1cC (=O) NRZ1cRZ1d, -S (=O) RZ1g, -S (=O) ORZ1b, -OS (=O) RZ1g, -OS (=O) ORZ1b, -S (=O) NRZ1cRZ1d, -NRZ1cS (=O) RZ1g, -NRZ1cS (=O) ORZ1b, -OS (=O) NRZ1cRZ1d, -NRZ1cS (=O) NRZ1cRZ1d, -S (=O) 2RZ1h, -S (=O) 2ORZ1b, -OS (=O) 2RZ1h, -OS (=O) 2ORZ1b, -S (=O) 2NRZ1cRZ1d, -NRZ1cS (=O) 2RZ1h, -NRZ1cS (=O) 2ORZ1b, -OS (=O) 2NRZ1cRZ1d, -NRZ1cS (=O) 2NRZ1cRZ1d, -P (=O) (RZ1i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R1b, R1e, R2b, R2e, R3b, R3e, R4b, R4e, R5b, R5e, R6b, R6e, R7b, R8b, R9b, RS1b, RS1e, RS2b, RS2e, RS3b, RS3e, RS4b or RS4e at each occurrence is independently selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -ORZ2b, -C (=O) RZ2f, -C (=O) ORZ2b, -S (=O) RZ2g, -S (=O) ORZ2b, -S (=O) 2RZ2h, -S (=O) 2ORZ2b, -P (=O) (RZ2i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R1c, R1d, R2c, R2d, R3c, R3d, R4c, R4d, R5c, R5d, R6c, R6d, R8c, R8d, R9c, R9d, RS1c, RS1d, RS2c, RS2d, RS3c, RS3d, RS4c or RS4d at each occurrence is independently selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) RZ3f, -C (=O) NRZ3cRZ3d, -S (=O) RZ3g, -S (=O) NRZ3cRZ3d, -S (=O) 2RZ3h, -S (=O) 2NRZ3cRZ3d, -P (=O) (RZ3i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl, 5-14 membered heteroaryl; said 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl substituted with one or more substituents selected from C1-6alkyl, haloC1-6alkyl or halogen;R1f, R1g, R1h, R1i, R2f, R2g, R2h, R2i, R3f, R3g, R3h, R3i, R4f, R4g, R4h, R4i, R5f, R5g, R5h, R5i, R6f, R6g, R6h, R6i, R7f, R7g, R7h, R7i, R8f, R8g, R8h, R8i, RS1f, RS1g, RS1h, RS1i, RS2f, RS2g, RS2h, RS2i, RS3f, RS3g, RS3h, RS3i, RS4f, RS4g, RS4h or RS4i at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -ORZ4b, -NRZ4cRZ4d, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl, 5-14 membered heteroaryl or 3-14 membered heterocyclyl optionally substituted with one or more -C (=O) ORZ4b;(R1c and R1d) , (R2c and R2d) , (R3c and R3d) , (R4c and R4d) , (R5c and R5d) , (R6c and R6d) , (R8c and R8d) , (R9c and R9d) , (Rs1c and Rs1d) , (Rs2c and Rs2d) , (Rs3c and Rs3d) or (Rs4c and Rs4d) together with the nitrogen atom to which they are both attached form 3-14 membered heterocyclyl ring or 5-14 membered heteroaryl ring; said 3-14 membered heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, SO or SO2; said 3-14 membered heteroaryl ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S; each said ring is independently optionally substituted with n7 RS5;RS5 at each occurrence is independently selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -ORZ5b, -NRZ5cRZ5d, -SRZ5e, -C (=O) RZ5f, -C (=O) ORZ5b, -OC (=O) RZ5f, -OC (=O) ORZ5b, -C (=O) NRZ5cRZ5d, -OC (=O) NRZ5cRZ5d, -C (=NRZ5c) RZ5a, -C (=NRZ5c) NRZ5cRZ5d, -NRZ5cC (=NRZ5c) NRZ5cRZ5d, -NRZ5cC (=O) RZ5f, -NRZ5cC (=O) ORZ5b, -NRZ5cC (=O) NRZ5cRZ5d, -S (=O) RZ5g, -S (=O) ORZ5b, -OS (=O) RZ5g, -OS (=O) ORZ5b, -S (=O) NRZ5cRZ5d, -NRZ5cS (=O) RZ5g, -NRZ5aS (=O) ORZ5b, -OS (=O) NRZ5cRZ5d, -NRZ5cS (=O) NRZ5cRZ5d, -S (=O) 2RZ5h, -S (=O) 2ORZ5b, -OS (=O) 2RZ5h, -OS (=O) 2ORZ5b, -S (=O) 2NRZ5cRZ5d, -NRZ5cS (=O) 2RZ5h, -NRZ5cS (=O) 2ORZ5b, -OS (=O) 2NRZ5cRZ5d, -NRZ5cS (=O) 2NRZ5cRZ5d, -P (=O) (RZ5i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl;n7 is selected from 0, 1, 2, 3, 4, 5 or 6;RZ1a or RZ5a is independently selected from hydrogen, halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NO2, -N3, oxo, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O(C1-6alkyl) , -SH, -S (C1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -OC (=O) O (C1-6alkyl) , -NHC (=O) (OC1-6alkyl) , -N (C1-6alkyl) C (=O) (OC1-6alkyl) , -OC (=O) NH (C1-6alkyl) , -OC (=O) N (C1-6alkyl) 2, -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (OC1-6alkyl) , -OS (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -OS (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -OS (=O) 2O (C1-6alkyl) , -NHS (=O) 2O (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2O (C1-6alkyl) , -OS (=O) 2NH2, -OS (=O) 2NH (C1-6alkyl) , -OS (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2NH2, -NHS (=O) 2NH (C1-6alkyl) , -NHS (=O) 2N (C1-6alkyl) 2, -N (C1-6alkyl) S (=O) 2NH2, -N (C1-6alkyl) S (=O) 2NH (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2N (C1-6alkyl) 2, -PH (C1-6alkyl) , -P (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;RZ1b, RZ1e, RZ2b, RZ4b, RZ5b or RZ5e is independently selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) (OC1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) (OC1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; RZ1c, RZ1d, RZ3c, RZ3d, RZ4c, RZ4d, RZ5c or RZ5d is independently selected from hydrogen, halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;RZ1f, RZ1g, RZ1h, RZ1i, RZ2f, RZ2g, RZ2h, RZ2i, RZ3f, RZ3g, RZ3h, RZ3i, RZ5f, RZ5g, RZ5h or RZ5i is independently selected from hydrogen, halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -OH, -O (C1-6alkyl) , -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein, said -C1-6alkyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C1-6alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -OC (=O) O (C1-3alkyl) , -NHC (=O) (OC1-3alkyl) , -N (C1-3alkyl) C (=O) (OC1-3alkyl) , -OC (=O) NH (C1-3alkyl) , -OC (=O) N (C1-3alkyl) 2, -NHC (=O) NH2, -NHC (=O) NH (C1-3alkyl) , -NHC (=O) N (C1-3alkyl) 2, -N (C1-3alkyl) C (=O) NH2, -N (C1-3alkyl) C (=O) NH (C1-3alkyl) , -N (C1-3alkyl) C (=O) N (C1-3alkyl) 2, -S (=O) (OC1-3alkyl) , -OS (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2 (OC1-3alkyl) , -OS (=O) 2 (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , -OS (=O) 2O (C1-3alkyl) , -NHS (=O) 2O (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2O (C1-3alkyl) , -OS (=O) 2NH2, -OS (=O) 2NH (C1-3alkyl) , -OS (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2NH2, -NHS (=O) 2NH (C1-3alkyl) , -NHS (=O) 2N (C1-3alkyl) 2, -N (C1-3alkyl) S (=O) 2NH2, -N (C1-3alkyl) S (=O) 2NH (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2N (C1-3alkyl) 2, -PH (C1-3alkyl) , -P (C1-3alkyl) 2, -P (=O) H (C1-3alkyl) , -P (=O) (C1-3alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6 membered aryl, 10 membered aryl or 5-6 membered heteroaryl;Each of heterocyclyl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) or S (=O) 2;Each of heteroaryl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.2.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 1, wherein,Y1 is selected from -O-, -NRY13-, -S-, *-NRY13-C (=O) -, *-NRY13S (=O) -or *-NRY13S (=O) 2-;*indicates the attached point to the moiety ofRY13 has the same definition as in claim 1.3.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 2, wherein,Y1 is selected from -NRY13-or *-NRY13-C (=O) -;*indicates the attached point to the moiety ofRY13 has the same definition as in claim 1.4.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 3, wherein,Y1 is selected from -NRY13-;RY13 has the same definition as in claim 1.5.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 3, wherein,Y1 is selected from *-NRY13-C (=O) -;*indicates the attached point to the moiety ofRY13 has the same definition as in claim 1.6.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 5, wherein,RY13 is selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl;Preferably, RY13 is each independent selected from hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2 or 3-7 membered cycloalkyl;More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2;Further preferably, RY13 is each independent selected from -H.7.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of 1 to 6, wherein,RY13 is each independent selected from -H.8.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 7, wherein,Y1 is selected from -NRY13-;RY13 is each independent selected from -H, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2 or 3-7 membered cycloalkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; Further preferably, RY13 is each independent selected from -H.9.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 8, wherein, Y1 is selected from -NH-, -N (CH3) -or -N (CH2CH3) -.10.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 8 to 9, wherein, Y1 is selected from -NH-.11.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 7, wherein,Y1 is selected from *-NRY13-C (=O) -;*indicates the attached point to the moiety ofRY13 is each independent selected from -H, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, haloC1-3alkoxy or 3-7 membered cycloalkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; Further preferably, RY13 is each independent selected from -H.12.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 11, wherein,Y1 is selected from *-NH-C (=O) -, *-N (CH3) -C (=O) -or *-N (CH2CH3) -C (=O) -;*indicates the attached point to the moiety of13.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 11 to 12, wherein,Y1 is selected from *-NH-C (=O) -;*indicates the attached point to the moiety of14.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 13, wherein, n4 is selected from 0, 1, 2, 3, 4, 5 or 6; preferably, n4 is selected from 0, 1, 2 or 3; more preferably, n4 is selected from 0, 1 or 2; further preferably, n4 is selected from 0 or 1.15.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 14, wherein, n4 is 0.16.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 14, wherein, n4 is 1.17.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 16, wherein, X1 is N.18.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 16, wherein, X1 is CR3;R3 has the same definition as in claim 1.19.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 18, wherein,R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;Preferably, R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -S-CH2CH3, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) N (CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) N (CH3) 2, -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -S (=O) 2 (OCH3) , -S (=O) 2 (OCH2CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) ,More preferably, R4 or R5 at each occurrence is independently selected from -H, -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -C (=O) NH2, Further preferably, R4 or R5 at each occurrence is independent selected from -H, -CH3 or -CH2CH3.20.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 19, wherein,R4 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2;R5 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2.21.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 20, wherein,R4 is selected from -H.22.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 21, wherein,R5 is selected from -H.23.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 22, wherein,Y1 is selected from -NRY13-or *-NRY13-C (=O) -, *indicates the attached point to the moiety ofRY13 is selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; preferably, RY13 is each independent selected from hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2 or 3-7 membered cycloalkyl; More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , More preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; Further preferably, RY13 is each independent selected from -H;n4 is selected from 0, 1, 2 or 3; preferably, n4 is selected from 0, 1 or 2; more preferably, n4 is selected from 0 or 1;X1 is N or CR3, R3 have the same definitions as in claim 1;R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -S-CH2CH3, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) N (CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) N (CH3) 2, -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -S (=O) 2 (OCH3) , -S (=O) 2 (OCH2CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , more preferably, R4 or R5 at each occurrence is independently selected from -H, -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -C (=O) NH2, more preferably, R4 or R5 at each occurrence is independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; further preferably, R4 is selected from -H; and R4 is selected from -H.24.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 23, wherein,The moiety ofis selected fromR1, R2 and R3 have the same definitions as in claim 1.25.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 24, wherein, The moiety of is selected from R1, R2 and R3 have the same definitions as in claim 1.26.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 25, wherein, The moiety of is selected from R1, R2 and R3 have the same definitions as in claim 1.27.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 26, wherein, the compound is selected from formula (I-1) , formula (I-2) or formula (I-3) : Ring A, RS1, n1, Ring B, RS2, n2, R1, R2 and R3 have the same definitions as in claim 1.28.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 27, wherein,R3 is each independent selected from hydrogen, halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , - (C1-6alkylene) -C (=O) R6, -C (=O) R6, -OC (=O) R6, -NHC (=O) R6, -N (C1-6alkyl) C (=O) R6, -S (=O) R6, -OS (=O) R6, -NHS (=O) R6, -N (C1-6alkyl) S (=O) R6, -S (=O) 2R6, -OS (=O) 2R6, -NHS (=O) 2R6, -N (C1-6alkyl) S (=O) 2R6, -P (=O) (R6) H, -P (=O) (R6) 2, -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) (OC1-6alkyl) , -OS (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -OS (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -PH (C1-6alkyl) , -P (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered , 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;R6 is selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -OH, -O (C1-6alkyl) , -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl; said R6 is optionally substituted with one or more R6A, said R6A at each occurrence is independently selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) (OC1-6alkyl) , -OS (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -OS (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -PH (C1-6alkyl) , -P (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;Said (-C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl) of R6A is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) (OC1-6alkyl) , -OS (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2 (OC1-6alkyl) , -OS (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -PH (C1-6alkyl) , -P (C1-6alkyl) 2, -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, -Si (C1-6alkyl) 3, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;Each of heterocyclyl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) or S (=O) 2;Each of heteroaryl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.29.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 28, wherein,R3 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , - (C1-3alkylene) -C (=O) R6, -C (=O) R6, -OC (=O) R6, -NHC (=O) R6, -N (C1-3alkyl) C (=O) R6, -S (=O) R6, -NHS (=O) R6, -N (C1-3alkyl) S (=O) R6, -S (=O) 2R6, -NHS (=O) 2R6, -N (C1-3alkyl) S (=O) 2R6, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; said -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (OC1-3alkyl) or -C (=O) (haloC1-3alkyl) ;R6 is hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -OH, -O (C1-3alkyl) , -NH2, -NH (C1-4alkyl) , -N (C1-3alkyl) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; said R6 is optionally substituted with one or more R6A, said R6A at each occurrence is independently selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl;Said (-C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl) of R6A is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (haloC1-3alkyl) , -Si (C1-3alkyl) 3;Each of heterocyclyl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) or S (=O) 2;Each of heteroaryl at each occurrence independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.30.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 29, wherein,R3 is each independent selected from -H, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, - (C1-3alkylene) -C (=O) R6, -C (=O) R6, -NHC (=O) R6, -S (=O) 2R6 or -NHS (=O) 2R6; said -C1-3alkyl, -C2-3alkenyl or -C2-3alkynyl is optionally substituted with 0, 1, 2 or 3 substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (OC1-3alkyl) or -C (=O) (haloC1-3alkyl) ;R6 is hydrogen, -C1-3alkyl, -C2-3alkenyl, -OH, -O (C1-3alkyl) , -NH2, -NH (C1-4alkyl) , -N (C1-4alkyl) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R6 is optionally substituted with 0, 1, 2 or 3 R6A, said R6A at each occurrence is independently selected from halogen, -C1-4alkyl, -C2-3alkynyl, -CN, -C (=O) (OC1-4alkyl) , 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;Said (-C1-4alkyl, -C2-6alkynyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl) of R6A is optionally substituted with 0, 1, 2 or 3 substituents selected from -Si (C1-3alkyl) 3, -C1-3alkyl or haloC1-3alkyl;said 3-7 membered carbocyclyl is selected fromsaid 3-7 membered heterocyclyl is selected from morpholinyl, azetidinyl, tetrahydrofuranyl, thiomorpholinyl, tetrahydropyranyl, tetrahydroimidazolyl, piperidinyl, pyrrolidinyl or piperazinyl;said 5-10 membered heteroaryl is selected from furyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, quinolyl, isoquinolyl, quinazolyl, quinoxalyl, benzofuranyl, benzoxazolyl, benzisooxazolyl, benzothiazolyl, benzimidazol, indolyl, indazolyl, 1H-pyrrolo [2, 3-b] pyrazinyl, 1H-imidazo [4, 5-b] pyridinyl, 1H-imidazo [4, 5-b] pyrazinyl, 1H-pyrazolo [4, 3-c] pyridinyl, 2H-pyrazolo [3, 4-b] thiopheny1, pyrazolo [5, 1-c] [1, 2, 4] triazinyl, thiazolo [4.5-b] pyridinyl or pyrido [2, 3-b] pyridinyl.31.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 30, wherein,R3 is each independent selected from -H, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -NH2, -NH (CH3) , -NH (CH2CH3) , -N (CH3) 2, -C (=O) R6, -CH2-C (=O) R6, -CH2CH2-C (=O) R6, -CH (CH3) -C (=O) R6, -CH2CH2CH2-C (=O) R6, -NHC (=O) R6, -S (=O) 2R6 or -NHS (=O) 2R6; saidsubstituted with -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) or -C (=O) (OCH (CH3) 2) ;R6 is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -NH2, -NH (CH3) , -NH (CH2CH3) , -NH (CH (CH3) 2) , -NH (C (CH3) 3) , -N (CH3) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said (-NH2, phenyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl) of R6 is optionally substituted with 0, 1, 2 or 3 R6A, said R6A at each occurrence is independently selected from -F, -Cl, -Br, -NH2, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CN, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) (OC (CH3) 3) , 5-10 membered heteroaryl;Said (-NH2 or 5-10 membered heteroaryl) of R6A is optionally substituted with 0, 1, 2 or 3 substituents selected from -F, -Cl, -Br, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -Si (CH (CH3) 2) 3;said 3-7 membered carbocyclyl is selected fromsaid 3-7 membered heterocyclyl is selected fromsaid 5-10 membered heteroaryl is selected from32.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 31, wherein,R3 is selected from -Br, -NH2, 33.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 32, wherein,R1 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl;Preferably, R1 is each independent selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -S-CH2CH3, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) N (CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) N (CH3) 2, -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -S (=O) 2 (OCH3) , -S (=O) 2 (OCH2CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , More preferably, R1 is each independent selected from -H, -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -C (=O) NH2, Further preferably, R1 is each independent selected from -H, -Cl, -OH, -O-CH3, -NH (CH3) or34.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 33, wherein, R1 is each independent selected from -H, -Cl, -OH, -O-CH3, -NH (CH3) or 35.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 34, wherein,R2 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;Preferably, R2 is each independent selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -S-CH2CH3, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) N (CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) N (CH3) 2, -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -S (=O) 2 (OCH3) , -S (=O) 2 (OCH2CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , More preferably, R2 is each independent selected from -H, -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -OH, -O-CH3, -O-CH2CH3, -SH, -S-CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -C (=O) NH2, Further preferably, R2 is each independent selected from -H, -CH3 or -CH2CH3.36.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 35, wherein, R2 is each independent selected from -H, -CH3 or -CH2CH3.37.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 36, wherein, the moiety of is selected from 38.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 36, wherein, the moiety of is selected from 39.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 38, wherein, ring A is selected from a 3-7 membered carbocyclic ring; 3-7 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; or a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.40.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 39, wherein, ring A is selected from a 3 membered carbocyclic ring; a 4 membered carbocyclic ring; a 5 membered carbocyclic ring; a 6 membered carbocyclic ring; a 7 membered carbocyclic ring; a 3 membered a heterocyclic ring containing 1 or 2 heteroatoms selected from N, O or S; a 4 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 5 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 6 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 7 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; or a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.41.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 40, wherein, ring A is selected from 42.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 41, wherein, ring A is selected from 43.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 42, wherein, ring A is selected from 44.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 43, wherein, the compound is selected from formula (I-4) , formula (I-5) or formula (I-6) : RS1, n1, Ring B, RS2, n2, R1, R2 and R3 have the same definitions as in claim 1.45.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 44, wherein,RS1 is each independent selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;Preferably, RS1 is each independent selected from -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -O (haloC1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;More preferably, RS1 is each independent selected from -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -NH (CH (CH3) 2) , -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -O-CHF2, -O-CF3, -SH, -S-CH3, -S-CH2CH3, -S-CH (CH3) 2, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -C (=O) (CF3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH (CH3) 2) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -OC (=O) (CH (CH3) 2) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -C (=O) N (CH2CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -NHC (=O) (CH (CH3) 2) , -N (CH3) C (=O) (CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) NH (CH (CH3) 2) , -S (=O) N (CH3) 2, -S (=O) N (CH3) (CH2CH3) , -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -NHS (=O) (CH (CH3) 2) , -N (CH3) S (=O) (CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2NH (CH (CH3) 2) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , -NHS (=O) 2 (CH (CH3) 2) , -CH2-OH, -CH2CH2-OH, -CH (CH3) -OH, -CH2-SH, -CH2CH2-SH, -CH (CH3) -SH, -CH2-NH2, -CH2CH2-NH2, -CH (CH3) -NH2, -CH2-CN, -CH2CH2-CN, -CH (CH3) -CN, More preferably, RS1 is each independent selected from -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -CH2-OH, -CH2CH2-OH, -OH, -O-CH3, -O-CH2CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -CH2-NH2, -CH2CH2-NH2, -O-CF3, -O-CHF2, -C (=O) NH2, Further preferably, RS1 is each independent selected from -F, -Cl, -CN, -CF3, -CH3, -CH2CH3, -O-CH3, -O-CH2CH3 or -O-CF3;n1 is selected from 0, 1, 2, 3, 4, 5 or 6; n1 is selected from 0, 1, 2, 3 or 4; n1 is selected from 0, 1, 2 or 3.46.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 45, wherein, the moiety of is selected from 47.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 46, wherein, the moiety of is selected from 48.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 47, wherein, ring B is selected from a phenyl ring; or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.49.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 48, wherein, ring B is selected from a phenyl ring; a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 7 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 8 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 9 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 10 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.50.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 49, wherein, ring B is selected from 51.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 50, wherein, ring B is selected from 52.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 51, wherein,RS2 is each independent selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;Preferably, RS2 is each independent selected from -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C1-3alkoxy substituted with one or more (-O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) ) , -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;More preferably, RS2 is each independent selected from -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CN, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -NH (CH (CH3) 2) , -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3, -CH2-O-CH2-O-CH2-O-CH2CH3, -O-CHF2, -O-CF3, -SH, -S-CH3, -S-CH2CH3, -S-CH (CH3) 2, -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , -COOH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -C (=O) (CF3) , -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH (CH3) 2) , -OC (=O) (CH3) , -OC (=O) (CH2CH3) , -OC (=O) (CH (CH3) 2) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -C (=O) N (CH2CH3) 2, -NHC (=O) (CH3) , -NHC (=O) (CH2CH3) , -NHC (=O) (CH (CH3) 2) , -N (CH3) C (=O) (CH3) , -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) NH (CH (CH3) 2) , -S (=O) N (CH3) 2, -S (=O) N (CH3) (CH2CH3) , -NHS (=O) (CH3) , -NHS (=O) (CH2CH3) , -NHS (=O) (CH (CH3) 2) , -N (CH3) S (=O) (CH3) , -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2NH (CH (CH3) 2) , -S (=O) 2N (CH3) 2, -NHS (=O) 2 (CH3) , -NHS (=O) 2 (CH2CH3) , -NHS (=O) 2 (CH (CH3) 2) , -CH2-OH, -CH2CH2-OH, -CH (CH3) -OH, -CH2-SH, -CH2CH2-SH, -CH (CH3) -SH, -CH2-NH2, -CH2CH2-NH2, -CH (CH3) -NH2, -CH2-CN, -CH2CH2-CN, -CH (CH3) -CN, More preferably, RS2 is each independent selected from -F, -Cl, -CH3, -CH2CH3, -CN, -COOH, -CH2-OH, -CH2CH2-OH, -OH, -O-CH3, -O-CH2CH3, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3, -CH2-O-CH2-O-CH2-O-CH2CH3, -CF3, -CHF2, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -CH2-NH2, -CH2CH2-NH2, -O-CF3, -O-CHF2, -C (=O) NH2, Further preferably, RS2 is each independent selected from -F, -Cl, -CH3, -CH2CH3, -CH2CH2OH, -CH2CH2OCH2CH2OCH2CH2OCH3 or -OH;n2 is selected from 0, 1, 2, 3, 4, 5 or 6; n2 is selected from 0, 1, 2, 3 or 4; n2 is selected from 0, 1, 2 or 3.53.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 52, wherein, the compound is selected from formula (I-7) , formula (I-8) or formula (I-9) : R8 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R86, -C (=O) OR82, -C (=O) NR83R84, -S (=O) R87, -S (=O) OR82, -S (=O) NR83R84, -S (=O) 2R88, -S (=O) 2OR82, -S (=O) 2NR83R84, -P (=O) (R89) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; wherein, the -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl is independently optionally substituted with one or more substituents selected from halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-10alkyl, -C1-10alkoxy, haloC1-10alkoxy, -CN, -NO2, -N3, oxo, -OR10b, -NR10cR10d, -SR10e, -C (=O) R10f, -C (=O) OR10b, -OC (=O) R10f, -OC (=O) OR10b, -C (=O) NR10cR10d, -OC (=O) NR10cR10d, -C (=NR10c) R10a, -C (=NR10c) NR10cR10d, -NR10cC (=NR10c) NR10cR10d, -NR10cC (=O) R10f, -NR10cC (=O) OR10b, -NR10cC (=O) NR10cR10d, -S (=O) R10g, -S (=O) OR10b, -OS (=O) R10g, -OS (=O) OR10b, -S (=O) NR10cR10d, -NR10cS (=O) R10g, -NR10cS (=O) OR10b, -OS (=O) NR10cR10d, -NR10cS (=O) NR10cR10d, -S (=O) 2R10h, -S (=O) 2OR10b, -OS (=O) 2R10h, -OS (=O) 2OR10b, -S (=O) 2NR10cR10d, -NR10cS (=O) 2R10h, -NR10cS (=O) 2OR10b, -OS (=O) 2NR10cR10d, -NR10cS (=O) 2NR10cR10d, -P (=O) (R10i) 2, 3-14 membered cycloalkyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R82 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R7f, -C (=O) OR7b, -S (=O) R7g, -S (=O) OR7b, -S (=O) 2R7h, -S (=O) 2OR7b, -P (=O) (R7i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R83 or R84 at each occurrence is selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) R8f, -C (=O) OR8b, -C (=O) NR8cR8d, -S (=O) R8g, -S (=O) OR8b, -S (=O) NR8cR8d, -S (=O) 2R8h, -S (=O) 2OR8b, -S (=O) 2NR8cR8d, -P (=O) (R8i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl;R86, R87, R88 or R89 at each occurrence is selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -OR9b, -NR9cR9d, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl;Optionally, (R83 and R84) together with the nitrogen atom to which they are both attached form 3-14 membered heterocyclyl ring or 5-14 membered heteroaryl ring; said 3-14 membered heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, SO or SO2; said 3-14 membered heteroaryl ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S; each said ring is independently optionally substituted with n6 RS4;R10a at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-10alkoxy, -ORZ1b, -NRZ1cRZ1d, -SRZ1e, -C (=O) RZ1f, -C (=O) ORZ1b, -OC (=O) RZ1f, -OC (=O) ORZ1b, -C (=O) NRZ1cRZ1d, -OC (=O) NRZ1cRZ1d, -C (=NRZ1c) RZ1a, -C (=NRZ1c) NRZ1cRZ1d, -NRZ1cC (=NRZ1c) NRZ1cRZ1d, -NRZ1cC (=O) RZ1f, -NRZ1cC (=O) ORZ1b, -NRZ1cC (=O) NRZ1cRZ1d, -S (=O) RZ1g, -S (=O) ORZ1b, -OS (=O) RZ1g, -OS (=O) ORZ1b, -S (=O) NRZ1cRZ1d, -NRZ1cS (=O) RZ1g, -NRZ1cS (=O) ORZ1b, -OS (=O) NRZ1cRZ1d, -NRZ1cS (=O) NRZ1cRZ1d, -S (=O) 2RZ1h, -S (=O) 2ORZ1b, -OS (=O) 2RZ1h, -OS (=O) 2ORZ1b, -S (=O) 2NRZ1cRZ1d, -NRZ1cS (=O) 2RZ1h, -NRZ1cS (=O) 2ORZ1b, -OS (=O) 2NRZ1cRZ1d, -NRZ1cS (=O) 2NRZ1cRZ1d, -P (=O) (RZ1i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R10b or R10e at each occurrence is independently selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) RZ2f, -C (=O) ORZ2b, -S (=O) RZ2g, -S (=O) ORZ2b, -S (=O) 2RZ2h, -S (=O) 2ORZ2b, -P (=O) (RZ2i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R10c or R10d at each occurrence is independently selected from hydrogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -C (=O) RZ3f, -C (=O) NRZ3cRZ3d, -S (=O) RZ3g, -S (=O) NRZ3cRZ3d, -S (=O) 2RZ3h, -S (=O) 2NRZ3cRZ3d, -P (=O) (RZ3i) 2, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;R10f, R10g, R10h or R10i at each occurrence is independently selected from hydrogen, halogen, -C1-10alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-10alkoxy, haloC1-10alkyl, haloC1-10alkoxy, -ORZ4b, -NRZ4cRZ4d, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-12 membered aryl or 5-14 membered heteroaryl;(R10c and R10d) together with the nitrogen atom to which they are both attached form 3-14 membered heterocyclyl ring or 5-14 membered heteroaryl ring; said 3-14 membered heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, SO or SO2; said 3-14 membered heteroaryl ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S; each said ring is independently optionally substituted with n7 RS5;n6, RS4, RZ1a, RZ1b, RZ1c, RZ1d, RZ1e, RZ1f, RZ1g, RZ1h, RZ1i, RZ2f, RZ2b, RZ2g, RZ2h, RZ2i, RZ3f, RZ3c, RZ3d, RZ3g, RZ3h, RZ3i, RZ4b, RZ4c, RZ4d, RS5 and n7 have the same definitions as in claim 1;n5 is selected from 0, 1 or 2;RS1, n1, RS2, R1, R2 and R3 have the same definitions as in claim 1.54.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 53, wherein,R8 is each independent selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, -C1-6alkoxy substituted with one or more (-O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) ) , haloC1-6alkyl, haloC1-6alkoxy, -C1-6alkylene-OH, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;Preferably, R8 is each independent selected from hydrogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C1-3alkylene-OH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, 3-7 membered cycloalkyl, -C1-3alkoxy, -C1-3alkoxy substituted with 0, 1 or 2 (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) ;More preferably, R8 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2CH2OH, -CH2OH, -CH (CH2) 3OH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3 or -CH2-O-CH2-O-CH2-O-CH2CH3;More preferably, R8 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2CH2OH, -CH2OH, -CH (CH2) 3OH or -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3;Further preferably, R8 is each independent selected from -CH3.55.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 54, wherein, the compound is selected from formula (I-10) , formula (I-11) or formula (I-12) : n5 is selected from 0, 1 or 2;RS1, n1, RS2, R1, R2 and R3 have the same definitions as in claim 1.56.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 55, wherein, the moiety of is selected from 57.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 56, wherein, the moiety of is selected from preferably, the moiety ofis selected from58.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 57, wherein,Y1 is selected from -O-, -NRY13-, -S-, *-NRY13-C (=O) -, *-NRY13S (=O) -or *-NRY13S (=O) 2-;*indicates the attached point to the moiety ofRY13 is selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, haloC1-6alkyl, -C1-6alkoxy, haloC1-6alkoxy, -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl;n4 is selected from 0, 1, 2 or 3;X1 is selected from N or CR3;R1 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl;R2 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;R3 is each independent selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , - (C1-3alkylene) -C (=O) R6, -C (=O) R6, -OC (=O) R6, -NHC (=O) R6, -N (C1-3alkyl) C (=O) R6, -S (=O) R6, -NHS (=O) R6, -N (C1-3alkyl) S (=O) R6, -S (=O) 2R6, -NHS (=O) 2R6, -N (C1-3alkyl) S (=O) 2R6, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; said -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (OC1-3alkyl) or -C (=O) (haloC1-3alkyl) ;R6 is hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -OH, -O (C1-3alkyl) , -NH2, -NH (C1-4alkyl) , -N (C1-3alkyl) 2, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; said R6 is optionally substituted with one or more R6A, said R6A at each occurrence is independently selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl;Said (-C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl) of R6A is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) (haloC1-3alkyl) , -Si (C1-3alkyl) 3;R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl;ring A is selected from a 3-7 membered carbocyclic ring; 3-7 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; or a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S;ring B is selected from a phenyl ring; or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;RS1 is each independent selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;RS2 is each independent selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; said -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC2-6alkenyl, haloC2-6alkynyl, haloC1-6alkoxy, -CN, -NH2, -NH (C1-6alkyl) , -N (C1-6alkyl) 2, -OH, -O (C1-6alkyl) , -O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) , -SH, -S (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) OH, -C (=O) (OC1-6alkyl) , -OC (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, -NHC (=O) (C1-6alkyl) , -N (C1-6alkyl) C (=O) (C1-6alkyl) , -NHC (=O) NH2, -NHC (=O) NH (C1-6alkyl) , -NHC (=O) N (C1-6alkyl) 2, -N (C1-6alkyl) C (=O) NH2, -N (C1-6alkyl) C (=O) NH (C1-6alkyl) , -N (C1-6alkyl) C (=O) N (C1-6alkyl) 2, -S (=O) (C1-6alkyl) , -S (=O) NH2, -S (=O) NH (C1-6alkyl) , -S (=O) N (C1-6alkyl) 2, -NHS (=O) (C1-6alkyl) , -N (C1-6alkyl) S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-6alkyl) , -S (=O) 2N (C1-6alkyl) 2, -NHS (=O) 2 (C1-6alkyl) , -N (C1-6alkyl) S (=O) 2 (C1-6alkyl) , -P (=O) H (C1-6alkyl) , -P (=O) (C1-6alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered cycloalkenyl, 3-7 membered cycloalkynyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;n1 is selected from 0, 1, 2, 3, 4, 5 or 6;n2 is selected from 0, 1, 2, 3, 4, 5 or 6.59.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 58, wherein, the compound is selected from formula (II) : Y1 is selected from -NRY13-or *-NRY13-C (=O) -; *indicates the attached point to the moiety ofRY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H;n4 is selected from 0, 1 or 2; preferably, n4 is selected from 0 or 1;Ring A is selected from a 3-7 membered carbocyclic ring; 3-7 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; or a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; preferably, Ring A is selected from a 5 membered carbocyclic ring; a 6 membered carbocyclic ring; a 5 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 6 membered a heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a phenyl ring; a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; or a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; more preferably, ring A is selected fromFurther preferably, ring A is selected fromRS1 is each independent selected from -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -O (haloC1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS1 is each independent selected from halogen, -CN, -C1-3alkyl, haloC1-3alkyl, -OH, -O (C1-3alkyl) or -O (haloC1-3alkyl) ; more preferably, RS1 is each independent selected from -F, -Br, -Cl, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -OH, -O-CH3, -O-CH2CH3, -OCH2CH2CH3, -OCH (CH3) 2, -O-CF3, -O-CH2F, -O-CHF2, -O-CF3, -O-CH2CH2F, -O-CH2CHF2, -O-CH2CF3, -O-CHFCH3, -O-CF2CH3; further preferably, RS1 is each independent selected from -F, -Cl, -CN, -CF3, -CH3, -CH2CH3, -O-CH3, -O-CH2CH3 or -O-CF3;n1 is selected from 0, 1, 2, 3 or 4; preferably, n1 is selected from 0, 1, 2 or 3;R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl; preferably, R1 is each independent selected from hydrogen, halogen, -OH, -O (C1-3alkyl) , -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2 or 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S; more preferably, R1 is each independent selected from -H, -F, -Br, -Cl, -OH, -O-CH3, -O-CH2CH3, -OCH2CH2CH3, -OCH (CH3) 2, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) or 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S, said 3-7 membered heterocyclyl is selected fromfurther preferably, R1 is each independent selected from -H, -Cl, -OH, -O-CH3, -NH (CH3) orR2 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R2 is each independent selected from hydrogen, -C1-3alkyl; more preferably, R2 is each independent selected from -H, -CH3, -CH2CH3 or -CH (CH3) 2;R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, 3-7 membered cycloalkyl; more preferably, R4 or R5 at each occurrence is independently selected from hydrogen, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2OCH3, -CH2OCH2CH3, more preferably, R4 or R5 at each occurrence is independent selected from -H, -CH3 or -CH2CH3; Further preferably, R4 or R5 at each occurrence is independent selected from -H;ring B is selected from a phenyl ring; or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S; preferably, ring B is selected frommore preferably, ring B is selected fromRS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C1-3alkoxy substituted with one or more (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) , -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS2 is each independent selected from halogen, -C1-3alkyl, -OH, -C1-3alkylene-OH, -O (C1-3alkyl) , -C1-3alkoxy substituted with 1, 2 or 3 (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) ; more preferably, RS2 is each independent selected from -F, -Br, -Cl, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2-OH, -CH2CH2-OH, -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3, -CH2-O-CH2-O-CH2-O-CH2CH3; further preferably, RS2 is each independent selected from -F, -Cl, -CH3, -CH2CH3, -CH2CH2OH, -CH2CH2OCH2CH2OCH2CH2OCH3 or -OH;n2 is selected from 0, 1, 2, 3 or 4; preferably, n2 is selected from 0, 1, 2 or 3.60.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 59, wherein, the compound is selected from formula (II-1) : Wherein,RY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H;ring B is selected from a phenyl ring; or a 5-6 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S; preferably, ring B is selected frommore preferably, ring B is selected fromR1, R2, R4, R5, ring A, RS1, n1, RS2, n2 have the same definitions as in claim 59.61.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 60, wherein, the compound is selected from formula (II-1-1) : Wherein,RY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3 or -CH (CH3) 2; more preferably, RY13 is each independent selected from -H;R8 is each independent selected from hydrogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C1-3alkylene-OH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, 3-7 membered cycloalkyl, -C1-3alkoxy, -C1-3alkoxy substituted with 0, 1 or 2 (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) ; preferably, R8 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2CH2OH, -CH2OH, -CH (CH2) 3OH, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH (CH3) 2) , -S (=O) CH3, -S (=O) (CH2CH3) , -S (=O) (CH (CH3) 2) , -S (=O) 2CH3, -S (=O) 2 (CH2CH3) , -S (=O) 2 (CH (CH3) 2) , -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3, -CH2-O-CH2CH2-O-CH2CH2-O-CH2CH3, -CH2-O-CH2-O-CH2-O-CH3 or -CH2-O-CH2-O-CH2-O-CH2CH3; More preferably, R8 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2CH2OH, -CH2OH, -CH (CH2) 3OH or -CH2CH2-O-CH2CH2-O-CH2CH2-O-CH3; Further preferably, R8 is each independent selected from -CH3;RS2 is each independent selected from -F, -Cl, -Br, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C1-3alkoxy substituted with one or more (-O (C1-6alkyl) substituted with one or more -O (C1-6alkyl) ) , -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS2 is each independent selected from -C1-3alkyl; more preferably, RS2 is each independent selected from -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; further preferably, RS2 is each independent selected from -CH3;n5 is selected from 0, 1, or 2;R1, R2, R4, R5, RS1 and n1 have the same definitions as in claim 59.62.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 59, wherein, the compound is selected from formula (II-2) : RY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3 or -CH (CH3) 2; more preferably, RY13 is each independent selected from -H;n4 is selected from 0, 1 or 2; preferably, n4 is selected from 0 or 1;R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl; preferably, R1 is each independent selected from -H;R2 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R2 is each independent selected from -H;RS1 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS1 is each independent selected from halogen or haloC1-3alkyl; more preferably, RS1 is each independent selected from -F, -Br, -Cl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3; further preferably, RS1 is each independent selected from-Cl or -CF3;n1 is selected from 0, 1, or 2; preferably, n1 is selected from 1;ring B is selected from a phenyl ring; or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S; preferably, ring B is selected from a phenyl ring; a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 9 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S, a 10 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S; more preferably, ring B is selected fromRS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, -C1-3alkoxy substituted with one or more (-O (C1-3alkyl) substituted with one or more -O (C1-3alkyl) ) , -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS2 is each independent selected from halogen, -C1-3alkyl, -OH, -O (C1-3alkyl) or -C1-3alkylene-OH; more preferably, RS2 is each independent selected from -F, -Br, -Cl, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2-OH, -CH2CH2-OH, -OH, -O-CH3, -O-CH2CH3, -O-CH2CH2CH3 or -O-CH (CH3) 2; further preferably, RS2 is each independent selected from -F, -Cl, -CH3, -CH2CH2OH or -OH;n2 is selected from 0, 1, or 2; preferably, n2 is selected from 1;R4 and R5 have the same definitions as in claim 59.63.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 58, wherein, the compound is selected from formula (III) : RY13 is each independent selected from -H or -C1-3alkyl; preferably, RY13 is each independent selected from -H, -CH3, -CH2CH3 or -CH (CH3) 2; more preferably, RY13 is each independent selected from -H;R3 is selected from halogen, -NH2, -Y2-R7;Y2 is selected from **-C (=O) -NRY23-, **-C (=O) -O-, **-NRY23-C (=O) -, **-NRY23-S (=O) 2-, **-S (=O) 2-NRY23-, **- (C1-6alkylene) -Y3-, or **-RY21C=CRY21-;**indicates the attached point to the moiety ofRY23 or RY21 is each independent selected from hydrogen, -C1-6alkyl, -C2-6alkenyl, -C2-6alkynyl, -C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, 3-14 membered carbocyclyl, 3-14 membered heterocyclyl, 6-14 membered aryl or 5-14 membered heteroaryl; preferably, RY23 or RY21 at each occurrence is selected from hydrogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, 3-7 membered carbocyclyl, 3-7membered heterocyclyl, phenyl, naphthyl or 5-10 membered heteroaryl; more preferably, RY23 or RY21 at each occurrence is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH3-O-CH3, -CH2CH3-O-CH3, -CH3-O-CH2CH3, -CH (CH3) -O-CH3, further preferably, RY23 or RY21 at each occurrence is selected from -H, -CH3 or -CH2CH3;Y3 is selected from &-C (=O) -NRY33-, &-C (=O) -O-, &-NRY33-C (=O) -, &-NRY33-S (=O) -, &-S (=O) -NRY33-, &-NRY33-S (=O) 2-, &-S (=O) 2-NRY33-; &indicates the attached point to the moiety of **- (C1-6alkylene) ; RY33 is each independent selected from -H or -C1-3alkyl; preferably, RY33 is each independent selected from -H;R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C1-3alkoxy, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl, naphthyl or 5-10 heteroaryl; preferably, R1 is each independent selected from -H;R2 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, R2 is each independent selected from -H;RS1 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -C1-3alkylene-CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C1-3alkylene-NH2, -OH, -O (C1-3alkyl) , -C1-3alkylene-OH, -O (3-7 membered cycloalkyl) , -SH, -S (C1-3alkyl) , -C1-3alkylene-SH, -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-3alkyl) , -OC (=O) (C1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -NHC (=O) (C1-3alkyl) , -N (C1-3alkyl) C (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -NHS (=O) (C1-3alkyl) , -N (C1-3alkyl) S (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, -NHS (=O) 2 (C1-3alkyl) , -N (C1-3alkyl) S (=O) 2 (C1-3alkyl) , 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; preferably, RS1 is each independent selected from halogen or haloC1-3alkyl; more preferably, RS1 is each independent selected from -F, -Br, -Cl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3; further preferably, RS1 is each independent selected from-Cl or -CF3;n1 is selected from 0, 1, or 2; preferably, n1 is selected from 1;R7 is selected from -H; -C1-6 alkyl; -C2-6 alkenyl; -C2-6 alkynyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S; 6-10 membered aryl or 5-10 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-6 alkyl; -C2-6 alkenyl; -C2-6alkynyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl; 6-10 membered aryl or 5-10 heteroaryl is optionally substituted with one or more R9;R9 is selected from halogen, -C1-4alkyl, -CN, -C (=O) (OC1-4alkyl) , -Si (C1-3alkyl) 3, phenyl, said R9 is optionally substituted with one or more R9A;said R9A is selected from halogen, haloC1-3alkyl or -C1-3alkoxy;n5 is selected from 0, 1, or 2; preferably, n5 is selected from 0;RY13, RS2, R4 and R5 have the same definitions as in claim 58.64.The compound of formula (III) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 63, wherein,R7 is each independent selected from -H, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl; said -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, 6-10 membered aryl or 5-10 heteroaryl is optionally substituted with 0, 1, 2 or 3 substituents selected from halogen, -C1-3alkyl, -CN, -C (=O) (OC1-4alkyl) , -Si (C1-3alkyl) 3, or 6-10 membered aryl optionally substituted with 1, 2 or 3 substituents selected from haloC1-3alkyl;preferably, R7 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, tetrahydropyranyl, piperidinyl, furyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl or benzothiazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CN, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) (OC (CH3) 3) , -Si (CH3) 3, -Si (CH2CH3) 3, -Si (CH (CH3) 2) 3, optionally substituted with 1, 2 or 3 substituents selected from -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;more preferably, R7 is each independent selected from -H, -CH3, -CH2CH3, tetrahydropyranyl, piperidinyl, furyl, pyrrolyl, pyridinyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, benzothiazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -Cl, -Br, -CH3, -CN, -C (=O) (OCH2CH3) , -C (=O) (OC (CH3) 3) , -Si (CH (CH3) 2) 3 or65.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 63 to 64, wherein, R7 is selected from -H, -CH3, -CH2CH3, 66.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 63 to 65, wherein, the compound is selected from formula (III-1) : RY23 at each occurrence is -H or -C1-3alkyl; preferably, RY23 is each independent selected from -H or -CH3;R7 is selected from -H; -C1-6 alkyl; -C2-6 alkenyl; -C2-6 alkynyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S; 6-10 membered aryl or 5-10 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-6 alkyl; -C2-6 alkenyl; -C2-6alkynyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl; 6-10 membered aryl or 5-10 heteroaryl is optionally substituted with one or more R9;R9 is selected from halogen, -C1-4alkyl, -CN, -C (=O) (OC1-4alkyl) , phenyl, said R9 is optionally substituted with one or more R9A;said R9A is selected from haloC1-3alkyl;RY13, R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in claim 63.67.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 66, wherein,R7 is selected from -C1-3 alkyl; -C2-3 alkenyl; 3-7 membered carbocyclyl; 3-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O or S; or 5-6 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-3 alkyl, -C2-3 alkenyl, 3-7 membered carbocyclyl, 3-7membered heterocyclyl or 5-6 membered heteroaryl is optionally substituted with 0, 1, 2 or 3 R8; said R8 is selected from -C1-3alkyl, -CN, -C (=O) (OC1-4alkyl) , phenyl optionally substituted with 1, 2 or 3 substituents selected from haloC1-3alkyl;preferably, R7 is each independent selected from -H, -CH3, -CH2CH3, tetrahydropyranyl, piperidinyl, furyl, pyrrolyl, pyridinyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -CH3, -CN, -C (=O) (OC (CH3) 3) or68.The compound of formula (III-1) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 66 to 67, wherein,R7 is selected from -CH3, 69.The compound of formula (III-1) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 66 to 68, wherein, the moiety of is selected from 70.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 63 to 65, wherein, the compound is selected from formula (III-2) : RY23 at each occurrence is -H or -C1-3alkyl; preferably, RY23 is each independent selected from -H or -CH3;R7 is selected from -H; -C1-6 alkyl; 3-7 membered carbocyclyl; phenyl or 5-10 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-6 alkyl; 3-7 membered carbocyclyl; phenyl or 5-10 heteroaryl is optionally substituted with one or more R9;R9 is selected from halogen or -C1-3alkyl;RY13, R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in claim 63.71.The compound of formula (III-2) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 70, wherein,R7 is selected from -H, -C1-3 alkyl, 3-7 membered carbocyclyl, phenyl or 5-6 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said -C1-3 alkyl, 3-7 membered carbocyclyl, phenyl or 5-6 membered heteroaryl is optionally substituted with 0, 1, 2 or 3 halogen or -C1-3alkyl;preferably, R7 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, phenyl, pyridinyl, benzothiazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -F, -Br, -Cl, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2.72.The compound of formula (III-2) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 70 to 71, wherein, R7 is selected from -CH3, -CH2CH3, 73.The compound of formula (III-2) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 70 to 72, wherein, the moiety of is selected from 74.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 63 to 65, wherein, the compound is selected from formula (III-3) : RY23 at each occurrence is -H or -C1-3alkyl; preferably, RY23 is each independent selected from -H;R7 is selected from phenyl or 5-6 membered heteroaryl; said phenyl or 5-6 membered heteroaryl is optionally substituted with 0, 1, 2 or 3 substituents selected from -C1-3alkyl;R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in claim 63.75.The compound of formula (III-3) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 74, wherein,R7 is selected from phenyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl; said R7 is optionally substituted with 0, 1, 2 or 3 substituents selected from -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2.76.The compound of formula (III-3) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 74 to 75, wherein, R7 is selected from 77.The compound of formula (III-3) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 74 to 76, wherein, the moiety of is selected from 78.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 63 to 65, wherein, the compound is selected from formula (III-4) : Y3 is selected from &-C (=O) -NRY33-or &-C (=O) -O-; &indicates the attached point to the moiety of (C1-6alkylene) ;RY33 is each independent selected from -H or -C1-3alkyl; preferably, RY33 is each independent selected from -H or -CH3;R7 is selected from hydrogen, -C1-3 alkyl or 5-10 membered heteroaryl; said -C1-3 alkyl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from -C1-3 alkyl;R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in claim 63.79.The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of claim 78, wherein, the compound is selected from formula (III-5) : Y3 is selected from &-C (=O) -NH-, &-C (=O) -N (CH3) -or &-C (=O) -O-;&indicates the attached point to the moiety of - (CH2) n12-;n12 is selected from 1, 2, 3, 4, 5 or 6; preferably, n12 is selected from 1, 2 or 3; more preferably, n12 is selected from 1 or 2;Y3, R7, R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in claim78.80.The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 78-79, wherein, the compound is selected from formula (III-5-1) or formula (III-5-2) : n12 is selected from 1 or 2;R7, R1, R2, R4, R5, RS1, n1, RS2 and n5 have the same definitions as in claim 78.81.The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 78-80, wherein,R7 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, pyridyl, thiazolyl, isoxazolyl; said R7 is optionally substituted with 0, 1 or 2 substituents selected from -CH3.82.The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 78-81, wherein, R7 is selected from -H, -CH3, -CH2CH3, -CH (CH3) 2, -C (CH3) 3, 83.The compound of formula (III-4) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 78-82, wherein, the moiety of is selected from 84.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the tautomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1-83, wherein, the compound is any one of the following formulas: 85.A pharmaceutical composition comprising the compound, a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 84, and at least one pharmaceutically acceptable excipient.86.A method of treating a subject having a cancer related to overexpression of Fascin, said method comprising administering to the subject a therapeutically effective amount of the compound, a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 84; or the pharmaceutical composition of claim 85; preferably, the cancer is selected from breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, esophagus cancer, tongue cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, mesothelioma, melanoma, fibrosarcoma, bladder cancer, rectal cancer, lymphoma, cervical cancer, head and neck cancer, upperaerodigestive cancer, colorectal cancer, urinary tract cancer, or colon cancer; more preferably, each cancer is independently selected from adenocarcinoma, squamous cell carcinoma, mixed adenosquamous carcinoma, undifferentiated carcinoma; more preferably, the ovarian cancer comprises high grade ovarian serious adenocarcinoma, ovarian mucinous cystadenocarcinoma or malignant ovarian Brenner tumor; the kidney cancer comprises clear cell renal cell carcinoma; the tongue cancer comprises tongue squamous cell carcinoma; the lung cancer comprises lung adenocarcinoma, lung adenosquamous carcinoma, squamous cell lung carcinoma, large cell lung carcinoma, small cell lung carcinoma, papillary adenocarcinoma of the lung or non-small cell lung carcinoma; the pancreatic cancer comprises pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma; the esophagus cancer comprises esophageal squamous cell carcinoma; the mesothelioma comprises biphasic mesothelioma; the cancer of the central nervous system comprises neuroglioma, glioblastoma or glioblastoma multiforme; the stomach cancer comprises gastric adenocarcinoma; the breast cancer comprises ductal breast carcinoma, breast adenocarcinoma or HR+ breast cancer; the bladder cancer comprises bladder squamous cell carcinoma; the melanoma comprises malignant melanoma; the colon cancer comprises colon adenocarcinoma; the head and neck cancer comprises head and neck small squamous cell cancer.87.A use of a compound, a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 84; or a pharmaceutical composition of claim 85 for the manufacture of a medicament for the treatment of cancer related to overexpression of Fascin; preferably, the cancer the cancer is selected from breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, esophagus cancer, tongue cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, mesothelioma, melanoma, fibrosarcoma, bladder cancer, rectal cancer, lymphoma, cervical cancer, head and neck cancer, upperaerodigestive cancer, colorectal cancer, urinary tract cancer, or colon cancer; more preferably, each cancer is independently selected from adenocarcinoma, squamous cell carcinoma, mixed adenosquamous carcinoma, undifferentiated carcinoma; more preferably, the ovarian cancer comprises high grade ovarian serious adenocarcinoma, ovarian mucinous cystadenocarcinoma or malignant ovarian Brenner tumor; the kidney cancer comprises clear cell renal cell carcinoma; the tongue cancer comprises tongue squamous cell carcinoma; the lung cancer comprises lung adenocarcinoma, lung adenosquamous carcinoma, squamous cell lung carcinoma, large cell lung carcinoma, small cell lung carcinoma, papillary adenocarcinoma of the lung or non-small cell lung carcinoma; the pancreatic cancer comprises pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma; the esophagus cancer comprises esophageal squamous cell carcinoma; the mesothelioma comprises biphasic mesothelioma; the cancer of the central nervous system comprises neuroglioma, glioblastoma or glioblastoma multiforme; the stomach cancer comprises gastric adenocarcinoma; the breast cancer comprises ductal breast carcinoma, breast adenocarcinoma or HR+breast cancer; the bladder cancer comprises bladder squamous cell carcinoma; the melanoma comprises malignant melanoma; the colon cancer comprises colon adenocarcinoma; the head and neck cancer comprises head and neck small squamous cell cancer.88.A compound, a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof of any one of claims 1 to 84; or a pharmaceutical composition of claim 85 for use in the treatment of cancer related to overexpression of Fascin; preferably, the cancer the cancer is selected from breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, esophagus cancer, tongue cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, mesothelioma, melanoma, fibrosarcoma, bladder cancer, rectal cancer, lymphoma, cervical cancer, head and neck cancer, upperaerodigestive cancer, colorectal cancer, urinary tract cancer, or colon cancer; more preferably, each cancer is independently selected from adenocarcinoma, squamous cell carcinoma, mixed adenosquamous carcinoma, undifferentiated carcinoma; more preferably, the ovarian cancer comprises high grade ovarian serious adenocarcinoma, ovarian mucinous cystadenocarcinoma or malignant ovarian Brenner tumor; the kidney cancer comprises clear cell renal cell carcinoma; the tongue cancer comprises tongue squamous cell carcinoma; the lung cancer comprises lung adenocarcinoma, lung adenosquamous carcinoma, squamous cell lung carcinoma, large cell lung carcinoma, small cell lung carcinoma, papillary adenocarcinoma of the lung or non-small cell lung carcinoma; the pancreatic cancer comprises pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma; the esophagus cancer comprises esophageal squamous cell carcinoma; the mesothelioma comprises biphasic mesothelioma; the cancer of the central nervous system comprises neuroglioma, glioblastoma or glioblastoma multiforme; the stomach cancer comprises gastric adenocarcinoma; the breast cancer comprises ductal breast carcinoma, breast adenocarcinoma or HR+ breast cancer; the bladder cancer comprises bladder squamous cell carcinoma; the melanoma comprises malignant melanoma; the colon cancer comprises colon adenocarcinoma;the head and neck cancer comprises head and neck small squamous cell cancer.