Fascin inhibitors
Patent Information
- Application Number
- PCT/CN2024/098973
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-08-08
- Filing Date
- 2024-06-13
- Publication Date
- 2025-01-02
Smart Images

Figure CN2024098973_02012025_PF_FP_ABST
Abstract
Description
Fascin inhibitorsCross-References to Related ApplicationsThis application claims the benefit of priority to PCT / CN2023 / 104448, filed on June 30, 2023; and PCT / CN2023 / 111636, filed on August 08, 2023, all of which are hereby incorporated herein by reference in their entireties.Technical 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 of formula (I) :a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof, wherein the definition of each of variables is defined as below.Also provided herein is intermediates to prepare the compound of the present invention.Also provided herein is a process to prepare compounds of the present invention.Also provided herein is a pharmaceutical composition comprising an effectively therapeutic amount of the compound of the present invention, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof, and at least one pharmaceutically acceptably excipient.Also provided herein is a use of the compound of the present invention, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof or the pharmaceutical composition of the present invention for the manufacture of a medicament for the treatment of cancer relating to the overexpression of Fascin.Also provided herein is a method of treating a subject having cancer relating to the overexpression of Fascin. said method comprising administering to the subject a therapeutically effective amount of the compound of the present invention, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof.Also provided herein is a compound of the present invention, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof, or the pharmaceutical composition of the present invention for use in the treatment of cancer relating to the overexpression of Fascin.Detailed DescriptionProvided herein are the following disclosures:[1] . A compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:Wherein,R1 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R1 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;R2 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R2 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;Optionally, R1 and R2 together with the atoms to which they are respectively attached lead to the moiety offormingwhen the moiety ofisX1 is selected from N or CR7;X2 is selected from N or CR8;X3 is selected from N or CR9;X4 is selected from N or CR10;R7 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R7 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;R8 is selected from hydrogen, -C (=O) N (R81) 2, -NHC (=O) (R81) , -S (=O) N (R81) 2, -NHS (=O) (R81) , -S (=O) 2N (R81) 2 or -NHS (=O) 2 (R81) ;said R81 is each independently selected from 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;R9 is selected from hydrogen, - (C1-6alkylene) -R91, -C (=O) (OR92) , -S (=O) (OR92) , -S (=O) 2 (OR92) , -C (=O) -NHR92, -S (=O) -NHR92, -S (=O) 2-NHR92, -C (=O) (R93) , -S (=O) (R93) , -S (=O) 2 (R93) , -OC (=O) (R93) , -OS (=O) (R93) , -OS (=O) 2 (R93) , -NH-C (=O) (R93) , -NH-S (=O) (R93) , -NH-S (=O) 2 (R93) ,said R91 at each occurrence is independently selected from -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;said R92 is each independently selected from 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R92 is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;said R93 at each occurrence is independently selected from halogen, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;X2 and X3 are not N at the same time;when X2 is CR8 and X3 is CR9, only one of R8 and R9 is hydrogen;R10 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R10 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;when the moiety ofisn4 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;n5 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;Y2 is selected from -C (RY2) 2-, -RY2C=CRY2-, -C≡C-, -O-, -NRY3-, -S-, -C (=O) -, -S (=O) -, -S (=O) 2-, **-C (=O) O-, **-C (=O) NRY4-, **-NRY4C (=O) -, **-S (=O) NRY4-, **-NRY4S (=O) -, **-S (=O) 2NRY4-or **-NRY4S (=O) 2-; **indicates the attached point to the moiety ofRY2 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R1 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;RY3 at each occurrence is independently selected from hydrogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; said RY3 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY31;RY31 at each occurrence is independently selected from halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;RY32 at each occurrence is independently selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;RY4 at each occurrence is independently selected from hydrogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said RY4 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;R4 at each occurrence is independently selected from -H, halogen, -C1-6alkyl or haloC1-6alkyl;R5 at each occurrence is independently selected from -H, halogen, -C1-6alkyl or haloC1-6alkyl;R6 at each occurrence is independently selected from -H, halogen, -C1-6alkyl, -OC1-6alkyl or haloC1-6alkyl;said Y1 is selected from absent, -C (RY1A) 2-, -RY1AC=CRY1A-, -C≡C-, -N (RY1B) 2-, -O-, -S-, -C (=O) -, -S (=O) -, -S (=O) 2-, -C (=O) O-*, -OC (=O) -*, -N (RY1B) -C (=O) -*, -C (=O) -N (RY1B) -*, -N (RY1B) -S (=O) -*, -S (=O) -N (RY1B) -*, -N (RY1B) -S (=O) 2-*or -S (=O) 2-N (RY1B) -*; *indicates the attached point to the ring B;said RY1A is selected from -H, halogen, -C1-6alkyl or haloC1-6alkyl;said RY1B is selected from -H or -C1-6alkyl;ring B is selected from a 3-14 membered carbocyclic ring, a 3-14 membered heterocyclic ring, a 6-14 membered aryl ring or a 5-14 membered heteroaryl ring;RS1, RS2 or RS3 at each occurrence is independently selected from halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said RS1, RS2 or RS3 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;n1 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;n2 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;n3 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;said heterocyclyl at each occurrence is independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) , S (=O) 2;said heteroaryl at each occurrence is independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.[2] . A compound of formula (I-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,X1, X2, X3, X4, R4, R5, R6, ring B, Y1, Y2, RS1, RS2, RS3, n1, n2, n3, n4 and n5 have the same definitions as in [1] .[3] . A compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,X1, X2, X3, X4, R4, R5, R6, ring B, Y1, RS1, RS2, n1 and n2 have the same definitions as in [1] .[4] . The compound of formula (I) or formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [3] , wherein,X1 is selected from N or CR7; X2 is selected from N or CR8; X3 is selected from N or CR9, X4 is selected from N or CR10; and no more than one of X1, X2, X3 and X4 is N; orX1 is selected from N or CR7; X2 is selected from N or CR8; X3 is selected from N or CR9, X4 is selected from N or CR10; and no more than two of X1, X2, X3 and X4 is N; orX1 is selected from N or CR7; X2 is selected from N or CR8; X3 is selected from N or CR9, X4 is selected from N or CR10; and no more than three of X1, X2, X3 and X4 is N.[5] . The compound of formula (I) or formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [4] , wherein,X1 is selected from CR7, X2 is selected from CR8, X3 is selected from CR9 and X4 is selected from CR10; orX1 is selected from N, X2 is selected from CR8, X3 is selected from CR9 and X4 is selected from CR10; orX1 is selected from CR7, X2 is selected from N, X3 is selected from CR9 and X4 is selected from CR10; orX1 is selected from CR7, X2 is selected from CR8, X3 is selected from N and X4 is selected from CR10; orX1 is selected from CR7, X2 is selected from CR8, X3 is selected from CR9 and X4 is selected from N; orX1 is selected from N, X2 is selected from N, X3 is selected from CR9 and X4 is selected from CR10; orX1 is selected from N, X2 is selected from CR8, X3 is selected from N and X4 is selected from CR10; orX1 is selected from N, X2 is selected from CR8, X3 is selected from CR9 and X4 is selected from N; orX1 is selected from CR7, X2 is selected from N, X3 is selected from CR9 and X4 is selected from N; orX1 is selected from CR7, X2 is selected from CR8, X3 is selected from N and X4 is selected from N.[6] . The compound of formula (I) or formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [5] , wherein, the compound is selected from any one of the following formulas:wherein,R4, R5, R6, R7, R8, R9, R10, Y1, ring B, RS1, RS2, n1 and n2 have the same definitions as in [1] .[7] . A compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4, R5, R6, R7, R8, R9, R10, Y1, ring B, RS1, RS2, n1 and n2 have the same definitions as in [1] .[8] . The compound of formula (I) , formula (I-1) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [7] , wherein,R8 is selected from -H, -NHC (=O) (R81) , -NHS (=O) (R81) , -NHS (=O) 2 (R81) , -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkoxy, oxo, -CN, -OH, -SH, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl.[9] . The compound of formula (I) , formula (I-1) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [8] , wherein,R8 is selected from -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, or 5-6 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -CN, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C (=O) (OC1-3alkyl) , -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 or -NHS (=O) 2 (C1-3alkyl) ;Preferably, R8 is selected from -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl or 5-6 membered heteroaryl; said R81 is optionally substituted with one or moresubstituents selected from halogen, -CN, -C1-3alkyl or -C (=O) (OC1-3alkyl) ;More preferably, R8 is selected from -NHC (=O) (R81) , -S (=O) 2NH (R81) or -NHS (=O) 2 (R81) ; said R81 is selected fromthienyl, furanyl, pyridinyl, oxazolyl, isoxazolyl, thiazolyl or isothiazolyl; said R81 is optionally substituted with one or more substituents selected from -Cl, -F, -Br, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) or -C (=O) (OCH (CH3) 2) ; More preferably, R8 is selected fromfurther preferably, R8 is selected fromIn some embodiments, R8 isIn some embodiments, R8 is
[0010] . The compound of formula (I) , formula (I-1) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [9] , wherein,R9 is selected from -H, - (C0-3alkylene) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) or -S (=O) 2 (R93) ;said R91 is each independently selected from -C2-3alkenyl, -C2-3alkynyl, -C2-3alkoxy, haloC2-3alkoxy, oxo, -CN, -OH, -SH, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;said R92 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; said R92 is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, oxo, -CN, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;said R93 is each independently selected from halogen.
[0011] . The compound of formula (I) , formula (I-1) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0010] , wherein,R9 is selected from -H, - (C1-3alkylene) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) , -S (=O) 2 (R93) ,said R91 is each independently selected from -CN, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C (=O) OH, -C (=O) (OC1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) or -S (=O) 2N (C1-3alkyl) 2;said R92 is each independently selected from phenyl or 5-10 membered heteroaryl;said R93 is each independently selected from halogen;Preferably, R9 is selected from -H, -CH2-R91, -CH2CH2-R91, -CH2CH2CH2-R91, -CH2 (CH2) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) , -S (=O) 2 (R93) , said R91 is each independently selected from -CN, -OH, -O-CH3, -O-CH2CH3, -O-CH2CH2CH3, -O-CH (CH3) 2, -SH, -S-CH3, -S-CH2CH3, -S-CH2CH2CH3, -S-CH (CH3) 2, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -C (=O) OH, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) NH2, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) NH (CH2CH2CH3) , -S (=O) NH (CH (CH3) 2) , -S (=O) N (CH3) 2, -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2NH (CH2CH2CH3) , -S (=O) 2NH (CH (CH3) 2) or -S (=O) 2N (CH3) 2;said R92 is each independently selected from hydrogen, phenyl, pyrrolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, tetrazolyl, pyrazolyl, triazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, isoindolyl or indolizinyl;said R93 is each independently selected from -F, -Br or -Cl;More preferably, R9 is selected from -CH2-CN, -CH2-OH, -CH2-O-CH3, -CH2-O-CH2CH3, -CH2-O-CH2CH2CH3, -CH2-O-CH (CH3) 2, -CH2-SH, -CH2-S-CH3, -CH2-S-CH2CH3, -CH2-S-CH2CH2CH3, -CH2-S-CH (CH3) 2, -CH2-NH2, -CH2-NH (CH3) , -CH2-N (CH3) 2, -CH2-NH (CH2CH3) , -CH2-C (=O) OH, -CH2-C (=O) (OCH3) , -CH2-C (=O) (OCH2CH3) , -CH2-C (=O) (OCH2CH2CH3) , -CH2-C (=O) (OCH (CH3) 2) , -CH2-C (=O) NH2, -CH2-C (=O) NH2, -CH2-C (=O) NH (CH3) , -CH2-C (=O) NH (CH2CH3) , -CH2-C (=O) NH (CH2CH2CH3) , -CH2-C (=O) NH (CH (CH3) 2) , -CH2-C (=O) N (CH3) 2, -CH2-S (=O) NH2, -CH2-S (=O) NH (CH3) , -CH2-S (=O) NH (CH2CH3) , -CH2-S (=O) NH (CH2CH2CH3) , -CH2-S (=O) NH (CH (CH3) 2) , -CH2-S (=O) N (CH3) 2, -CH2-S (=O) 2NH2, -CH2-S (=O) 2NH (CH3) , -CH2-S (=O) 2NH (CH2CH3) , -CH2-S (=O) 2NH (CH2CH2CH3) , -CH2-S (=O) 2NH (CH (CH3) 2) , -CH2-S (=O) 2N (CH3) 2, -C (=O) -Cl, -S (=O) -Cl or -S (=O) 2-Cl;further preferably, R9 is selected from
[0012] . The compound of formula (I) , formula (I-1) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0011] , wherein,R7 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;Preferably, R7 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;More preferably, R7 is each independently selected from -H, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3;Further preferably, R7 is -H.
[0013] . The compound of formula (I) , formula (I-1) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0012] , wherein,R10 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;preferably, R10 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;mmore preferably, R10 is each independently selected from -H, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3;further preferably, R10 is -H.
[0014] . The compound of formula (I) , formula (I-1) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0013] , wherein,The moiety ofis selected fromPreferably, the moiety ofis selected fromIn some embodiments, the moiety ofis selected fromIn some embodiments, the moiety ofis selected fromIn some embodiments, the moiety ofisIn some embodiments, The moiety ofis
[0015] . A compound of formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4, R5, R6, Y1, ring B, Y2, RS1, RS2, RS3, n1, n2, n3, n4 and n5 have the same definitions as in [1] .
[0016] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] , wherein,Y2 is selected from -C (RY2) 2-, -O-, -NRY3-, -S-, **-C (=O) NRY4-, **-NRY4C (=O) -, **-S (=O) NRY4-, **-NRY4S (=O) -, **-S (=O) 2NRY4-or **-NRY4S (=O) 2-; **indicates the attached point to the moiety of preferably, Y2 is selected from -C (RY2) 2-, -O-, -S-, -NRY3-, **-C (=O) NRY4-or **-NRY4C (=O) ; **indicates the attached point to the moiety ofmore preferably, Y2 is selected from -NRY3-;RY2, RY3 and RY4 have the same definitions as in [1] .In some embodiments, Y2 is selected from -C (RY2) 2-.In some embodiments, Y2 is selected from -NRY3-.In some embodiments, Y2 is selected from -O-.In some embodiments, Y2 is selected from -S-.In some embodiments, Y2 is selected from **-C (=O) NRY4; **indicates the attached point to the moiety ofIn some embodiments, Y2 is selected from **-NRY4C (=O) ; **indicates the attached point to the moiety of
[0017] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0016] , wherein, the compound is selected from any one of the following formulas:wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, RY2, RY3, RY4, Y1 and ring B have the same definitions as in [1] .
[0018] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0017] , wherein,n4 is selected from 0, 1, 2, 3, 4, 5 or 6;preferably, n4 is selected from 0, 1, 2, 3 or 4;more preferably, n4 is selected from 0, 1 or 2.In some embodiments, n4 is 0.In some embodiments, n4 is 1.In some embodiments, n4 is 2.
[0019] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0018] , wherein,n5 is selected from 0, 1, 2, 3, 4, 5 or 6;preferably, n5 is selected from 0, 1, 2, 3 or 4;more preferably, n5 is selected from 0, 1 or 2.In some embodiments, n5 is 0.In some embodiments, n5 is 1.In some embodiments, n5 is 2.
[0020] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0019] , wherein,n4 is 0, and n5 is 1; orn4 is 0, and n5 is 2; orn4 is 1, and n5 is 0; orn4 is 2, and n5 is 0; orn4 is 1, and n5 is 1; orn4 is 1, and n5 is 2; orn4 is 2, and n5 is 1; orn4 is 2, and n5 is 2.
[0021] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0020] , wherein, n4 is 1, and n5 is 1.
[0022] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0021] , wherein,RY2 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;preferably, RY2 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;more preferably, RY2 is selected from -H, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;further preferably, RY2 is -H;In some embodiments, RY2 is selected from -H or -C1-3alkyl; preferably, RY2 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, or -CH (CH3) 2; more preferably, RY2 is -H.
[0023] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0022] , wherein, the moiety ofis selected frompreferably, the moiety ofis selected from
[0024] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0021] , wherein,RY3 is selected from -H, -C1-6alkyl, -C (=O) (C1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said RY3 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY31;said RY31 is each independently selected from halogen, -C1-3alkyl, -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) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-4alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-4alkyl) or -S (=O) 2N (C1-3alkyl) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -C2-3alkoxy, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) or 5-10 membered heteroaryl;preferably, RY3 is selected from -H, -C1-3alkyl, -C (=O) (C1-3alkyl) , 3-7 membered carbocyclyl or 3-7 membered heterocyclyl; said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -C1-3alkyl, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) or -C (=O) N (C1-3alkyl) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -C2-3alkoxy, -OH, -O (C1-3alkyl) or 5-10 membered heteroaryl;more preferably, RY3 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH2CH2CH3) , -C (=O) (CH (CH3) 2) , said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -OH, -O-CH3, -O-CH2CH3, -O-CH2CH2CH3, -O-CH (CH3) 2, -C (=O) CH3, -C (=O) (CH2CH3) , -C (=O) -CH (CH3) 2, -C (=O) OH, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) (OC (CH3) 3) , -C (=O) NH2, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) NH (C (CH3) 3) , -C (=O) N (CH3) 2 or -C (=O) N (CH2CH3) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -CH3-O-CH3, -CH2CH3-O-CH3, -CH2-O-CH2CH3, -CH (CH3) -O-CH3, -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, thienyl, furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl;More preferably, RY3 is selected from -H, -CH3, -CH2CH3, -C (=O) (CH3) , said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -CH3, -CH2CH3, -OH, -C (=O) CH3, -C (=O) OH, -C (=O) (OC (CH3) 3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH (CH3) 2) or -C (=O) NH (C (CH3) 3) ; said RY31 is independently optionally substituted with 1, 2 or 3 RY32;said RY32 is each independently selected from -OH, -O-CH3 or pyridinyl;Further preferably, RY3 is selected from -H, -CH3, -CH2CH3, -CH2COOH, -CH2CH2COOH, -CH2COOC (CH3) 3, -CH2CH2COOC (CH3) 3, -CH2CH2OH, -CH2-C (=O) -NH (CH3) , -CH2CH2-C (=O) -NH (CH3) , -CH2CH2-C (=O) -NH (CH2CH3) , -CH2CH2-C (=O) -NH (CH (CH3) 2) , -CH2CH2-C (=O) -NH (C (CH3) 3) , -C (=O) -CH3, Further preferably, RY3 is selected from -CH2CH2COOH, -CH2CH2OH, -C (=O) -CH3,
[0025] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] ,
[0015] -
[0021] and
[0024] , wherein,The moiety ofis selected fromPreferably, the moiety ofis selected from
[0026] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0021] , wherein,The moiety ofis selected from
[0027] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0021] , wherein,The moiety ofis selected from
[0028] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] and
[0015] -
[0021] , wherein,RY4 is selected from -H, -C1-6alkyl, -C (=O) (C1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said RY4 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-3alkyl, -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) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-4alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-4alkyl) or -S (=O) 2N (C1-3alkyl) 2;Preferably, RY4 is selected from -H, -C1-3alkyl or haloC1-3alkyl;More preferably, RY4 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;further preferably, RY4 is -H;In some embodiments, RY4 is selected from -H or -C1-3alkyl;preferably, RY4 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, or -CH (CH3) 2;more preferably, RY4 is -H.
[0029] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] ,
[0015] -
[0021] and
[0028] , wherein,The moiety ofis selected frompreferably, the moietyis selected from
[0030] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] ,
[0015] -
[0021] and
[0028] , wherein,the moietyis selected frompreferably, the moietyis selected from
[0031] . The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] - [2] ,
[0015] -
[0030] , wherein,the moiety ofis selected frompreferably, the moiety ofis selected from
[0032] . A compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -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; said R1 is optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -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;R2 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -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; said R2 is optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -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;wherein,R4, R5, R6, RS1, RS2, n1, n2, Y1 and ring B have the same definitions as in [1] .
[0033] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] and
[0032] ,wherein,R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -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, phenyl or 5-10 heteroaryl; said R1 is optionally substituted with 1, 2 or 3 substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -NHS (=O) 2 (C1-3alkyl) or 3-7 membered cycloalkyl;preferably, R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, -CN, -C (=O) OH, -C (=O) (OC1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, phenyl or 5-6 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said R1 is optionally substituted with 1, 2 or 3 substituents selected from -C1-3alkyl;more preferably, R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, -CN, -COOH, -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, or 5-6 heteroaryl containing 1 or 2 heteroatoms selected from N, O or S; said 5-6 heteroaryl is optionally substituted with 1 or 2 substituents selected from -C1-3alkyl;more preferably, R1 is each independent selected from -H, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CN, -COOH, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -C (=O) N (CH2CH3) 2, further preferably, R1 is selected from -CH3, -CN, -Br, -C (=O) -NH2, -COOH,
[0034] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] and
[0032] -
[0033] , wherein,R2 is each independent selected from -H, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -CN, -C (=O) OH, -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) NH2, -C (=O) NH (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) or 3-7 membered cycloalkyl;more preferably, R2 is each independent selected from -H, halogen, -C1-3alkyl, haloC1-3alkyl or -CN;more preferably, R2 is each independent selected from -H, -C1-3alkyl or -CN;more preferably, R2 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2 or -CN;further preferably, R2 is selected from -H, -CH3 or -CN.
[0035] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] and
[0032] -
[0034] , wherein,the moiety ofis selected from
[0036] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0035] , wherein,the moiety ofis selected from
[0037] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0036] , wherein,the moiety ofis selected from
[0038] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0037] , wherein,Y1 is selected from absent, -C (RY1A) 2-, -N (RY1B) -, -O-, -S-, -C (=O) -N (RY1B) -*, -S (=O) -N (RY1B) -*, -S (=O) 2-N (RY1B) -*, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;In some embodiments, Y1 is selected from -C (RY1A) 2-, -N (RY1B) -, -O-, -S-, -C (=O) -N (RY1B) -*, -S (=O) -N (RY1B) -*, -S (=O) 2-N (RY1B) -*, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B.In some embodiments, Y1 is selected from -N (RY1B) -, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B.In some embodiments, Y1 is selected from -N (RY1B) -or -N (RY1B) -C (=O) -*; *indicates the attached point to the ring B.In some embodiments, Y1 is selected from -N (RY1B) -C (=O) -*; *indicates the attached point to the ring B.In some embodiments, Y1 is selected from -N (RY1B) -S (=O) -*; *indicates the attached point to the ring B.In some embodiments, Y1 is selected from -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B.In some embodiments, Y1 is selected from -N (RY1B) -.Said RY1A and RY1B has the same definitions as in [1] .
[0039] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0038] , wherein, Y1 is selected from -N (RY1B) 2-; said RY1B has the same definition as in [1] .
[0040] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0038] , wherein, Y1 is selected from -N (RY1B) -C (=O) -*; *indicates the attached point to the ring B; said RY1B has the same definition as in [1] .
[0041] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0038] , wherein, Y1 is selected from -N (RY1B) -S (=O) -*; *indicates the attached point to the ring B; said RY1B has the same definition as in [1] .
[0042] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0038] , wherein, Y1 is selected from -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B; said RY1B has the same definition as in [1] .
[0043] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0042] , wherein,RY1A is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl; preferably, RY1A is selected from -H or -C1-3alkyl; more preferably, RY1A is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1A is selected from -H or -CH3;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3.
[0044] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0043] , wherein, Y1 is selected from absent, -O-, -S-, -CH2-, -CH (CH3) -, -CH (CH2CH3) -, -CH (CH2CH2CH3) -, -CH (CH (CH3) 2) -, -C (CH3) 2-, -NH2-, -NH (CH3) -, -NH (CH2CH3) -, -NH (CH2CH2CH3) -, -NH (CH (CH3) 2) -, -NH-C (=O) -*, -N (CH3) -C (=O) -*, -N (CH2CH3) -C (=O) -*, -NH (CH2CH2CH3) -C (=O) -*, -NH (CH (CH3) 2) -C (=O) -*, -NH-S (=O) -*, -N (CH3) -S (=O) -*, -N (CH2CH3) -S (=O) -*, -NH (CH2CH2CH3) -S (=O) -*, -NH (CH (CH3) 2) -S (=O) -*, -NH-S (=O) 2-*, -N (CH3) -S (=O) 2-*, -N (CH2CH3) -S (=O) 2-*, -NH (CH2CH2CH3) -S (=O) 2-*, -NH (CH (CH3) 2) -S (=O) 2-*, -C (=O) -NH-*, -C (=O) -N (CH3) -*, -C (=O) -N (CH2CH3) -*, -C (=O) -NH (CH2CH2CH3) -*, -C (=O) -NH (CH (CH3) 2) -*, -S (=O) -NH-*, -S (=O) -N (CH3) -*, -S (=O) -N (CH2CH3) -*, -S (=O) -NH (CH2CH2CH3) -*, -S (=O) -NH (CH (CH3) 2) -*, -S (=O) 2-NH-*, -S (=O) 2-N (CH3) -*, -S (=O) 2-N (CH2CH3) -*, -S (=O) 2-NH (CH2CH2CH3) -*or -S (=O) 2-NH (CH (CH3) 2) -*;In some embodiments, Y1 is selected from -NH2-, -NH (CH3) -, -NH (CH2CH3) -, -NH (CH2CH2CH3) -, -NH (CH (CH3) 2) -, -NH-C (=O) -*, -N (CH3) -C (=O) -*, -N (CH2CH3) -C (=O) -*, -NH (CH2CH2CH3) -C (=O) -*, -NH (CH (CH3) 2) -C (=O) -*, -NH-S (=O) -*, -N (CH3) -S (=O) -*, -N (CH2CH3) -S (=O) -*, -NH (CH2CH2CH3) -S (=O) -*, -NH (CH (CH3) 2) -S (=O) -*, -NH-S (=O) 2-*, -N (CH3) -S (=O) 2-*, -N (CH2CH3) -S (=O) 2-*, -NH (CH2CH2CH3) -S (=O) 2-*, -NH (CH (CH3) 2) -S (=O) 2-*; *indicates the attached point to the ring B;In some embodiments, Y1 is selected from -NH2-, -NH (CH3) -, -NH-C (=O) -*or -N (CH3) -C (=O) -*; *indicates the attached point to the ring B.
[0045] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0044] , wherein, Y1 is selected from -NH2-.
[0046] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0044] , wherein, Y1 is selected from -NH-C (=O) -*; *indicates the attached point to the ring B.
[0047] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0044] , wherein, Y1 is selected from -NH-S (=O) -*; *indicates the attached point to the ring B.
[0048] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0044] , wherein, Y1 is selected from -NH-S (=O) 2-*; *indicates the attached point to the ring B.
[0049] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0048] , wherein,R4 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl.In some embodiments, R4 is each independently selected from -H or -C1-3alkyl.In some embodiments, R4 is each independently selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2.In some embodiments, R4 is each independently selected from -H or -CH3.
[0050] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0049] , wherein, R4 is each independently selected from -H.
[0051] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0049] , wherein, R4 is each independently selected from -CH3.
[0052] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0051] , wherein,R5 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl.In some embodiments, R5 is each independently selected from -H or -C1-3alkyl.In some embodiments, R5 is each independently selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2.In some embodiments, R5 is each independently selected from -H or -CH3.
[0053] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0052] , wherein, R5 is each independently selected from -H.
[0054] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0052] , wherein, R5 is each independently selected from -CH3.
[0055] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0054] , wherein,R4 is each independently selected from -H or -C1-3alkyl; and R5 is each independently selected from -H or -C1-3alkyl;preferably, R4 is each independently selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; and R5 is each independently selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2.more preferably, R4 is each independently selected from -H or -CH3; and R5 is each independently selected from -H or -CH3.further preferably, R4 is each independently selected from -H; and R5 is each independently selected from -H.
[0056] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0054] , wherein, the compound is selected from any one of the following formulas:wherein,X1, X2, X3, X4, R1, R2, R4, R5, R6, R7, R8, R9, R10, RY2, RY3, RY4, ring B, Y2, RS1, RS2, RS3, n1, n2, n3, n4 and n5 have the same definitions as in any one of [1] -
[0055] .
[0057] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0056] , wherein,R6 at each occurrence is independently selected from -H, halogen, -C1-3alkyl, -OC1-3alkyl or haloC1-3alkyl;In some embodiments, R6 at each occurrence is independently selected from -H, -OC1-3alkyl or haloC1-3alkyl;preferably, R6 at each occurrence is independently selected from -H, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;more preferably, R6 at each occurrence is independently selected from -H, -OCH3 or -CF3.
[0058] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0057] , wherein, R6 at each occurrence is independently selected from -H.
[0059] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0057] , wherein, R6 at each occurrence is independently selected from -CF3.
[0060] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0057] , wherein, R6 at each occurrence is independently selected from -OCH3.
[0061] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0060] , wherein, the moiety ofis selected from
[0062] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0061] , wherein, the moiety ofis selected from
[0063] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0062] , wherein, the compound is selected from any one of the following formulas:wherein,X1, X2, X3, X4, R1, R2, R4, R5, R7, R8, R9, R10, RY2, RY3, RY4, ring B, Y2, RS1, RS2, RS3, n1, n2, n3, n4 and n5 have the same definitions as in any one of [1] -
[0062] .
[0064] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0063] , wherein, the moiety ofis selected from
[0065] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0064] , wherein,ring B is selected from a phenyl 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 5-6 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;In some embodiments, ring B is selected from 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.In some embodiments, ring B is selected from a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.In some embodiments, ring B is selected from 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.In some embodiments, ring B is selected from a 5 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.In some embodiments, ring B is selected from a 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S.
[0066] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0065] , wherein, ring B is selected fromIn some embodiments, ring B is selected fromIn some embodiments, ring B is selected fromIn some embodiments, ring B is selected fromIn some embodiments, ring B is selected fromIn some embodiments, ring B is selected fromIn some embodiments, ring B is selected fromIn some embodiments, ring B is selected from
[0067] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0066] , wherein,RS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, haloC2-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , oxo, -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; said RS2 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) ;preferably, RS2 is each independent selected from halogen, -C1-3alkyl, -CN, oxo, -C (=O) OH, -C (=O) (OC1-3alkyl) , -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, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-6 heteroaryl; said heterocyclyl contains 1, 2 or 3 heteroatoms selected from N, O or S; said heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S;more preferably, RS2 is each independent selected from -C1-3alkyl, oxo, -CN;more preferably, RS2 is each independent selected from -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CN or oxo;further preferably, RS2 is each independent selected from -CH3, -CH2CH3, -CH (CH3) 2, -CN or oxo.
[0068] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0067] , wherein, n2 is selected from 0, 1, 2, 3, 4, 5 or 6; preferably, n2 is selected from 0, 1, 2, 3 or 4; more preferably, n2 is selected from 0, 1, 2 or 3; further preferably, n2 is selected from 0, 1 or 2.
[0069] . The compound of formula (I) , formula (I-1) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0068] , wherein, the moiety ofis selected fromIn some embodiments, the moiety ofis selected fromIn some embodiments, the moiety ofis selected fromIn some embodiments, the moiety ofis selected fromIn some embodiments, the moiety ofis selected fromIn some embodiments, the moiety ofis selected fromIn some embodiments, the moiety ofis selected fromIn some embodiments, the moiety ofis selected from
[0070] . The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0069] , wherein, the compound is selected from any one of the following formulas:wherein,X1, X2, X3, X4, R1, R2, R4, R5, R7, R8, R9, R10, RY2, RY3, RY4, Y2, RS1, RS3, n1, n3, n4 and n5 have the same definitions as in any one of [1] -
[0069] .
[0071] . A compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,X1 is selected from N or CR7;X3 is selected from N or CR9;X4 is selected from N or CR10;R7 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;R8 is selected from -H, -NHC (=O) (R81) , -NHS (=O) (R81) , -NHS (=O) 2 (R81) , -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkoxy, oxo, -CN, -OH, -SH, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;R9 is selected from -H, - (C0-3alkylene) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) or -S (=O) 2 (R93) ;said R91 is each independently selected from -C2-3alkenyl, -C2-3alkynyl, -C2-3alkoxy, haloC2-3alkoxy, oxo, -CN, -OH, -SH, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;said R92 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; said R92 is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, oxo, -CN, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;said R93 is each independently selected from halogen;when X2 is CR8 and X3 is CR9, only one of R8 and R9 is hydrogen;R10 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;Y1 is selected from -N (RY1B) -, -O-, -S-, -C (=O) -N (RY1B) -*, -S (=O) -N (RY1B) -*, -S (=O) 2-N (RY1B) -*, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3;R6 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;R4 and R5 are each independently selected from -H or-C1-3alkyl;ring B is selected from a phenyl or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;RS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, haloC2-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , oxo, -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; said RS2 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) ;n2 is selected from 0, 1, 2, 3, 4, 5 or 6;RS1 and n1 have the same definitions as in [1] .
[0072] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of
[0071] , wherein, X1 is selected from N.
[0073] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of
[0071] , wherein, X1 is selected from CR7; R7 has the same definition as in any one of
[0012] .
[0074] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0071] -
[0073] , wherein, X3 is selected from N.
[0075] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0071] -
[0073] , wherein, X3 is selected from CR9; R9 has the same definition as in any one of
[0010] -
[0011] .
[0076] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0071] -
[0075] , wherein, X4 is selected from N.
[0077] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0071] -
[0075] , wherein, X4 is selected from CR10; R10 has the same definition as in
[0013] .
[0078] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0071] -
[0077] , wherein,X1 is selected from N or CR7; X3 is selected from N or CR9, X4 is selected from N or CR10; and no more than two of X1, X3 and X4 is N; orX1 is selected from N or CR7; X2 is selected from N or CR8; X3 is selected from N or CR9, X4 is selected from N or CR10; and no more than one of X1, X3 and X4 is N.
[0079] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0071] -
[0078] , wherein,X1 is selected from N, X3 is selected from CR9 and X4 is selected from CR10; orX1 is selected from N, X3 is selected from N and X4 is selected from CR10; orX1 is selected from N, X3 is selected from CR9 and X4 is selected from N; orX1 is selected from CR7, X3 is selected from N and X4 is selected from CR10; orX1 is selected from CR7, X3 is selected from CR9 and X4 is selected from N; orX1 is selected from CR7, X3 is selected from N and X4 is selected from N; orX1 is selected from CR7, X3 is selected from CR9 and X4 is selected from CR10.
[0080] . The compound of formula (Ⅱ) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0071] -
[0079] , wherein, the compound is selected from any one of the following formulas:
[0081] . A compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4 and R5 are each independently selected from -H or-C1-3alkyl;R6 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;R7 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;R8 is selected from -H, -NHC (=O) (R81) , -NHS (=O) (R81) , -NHS (=O) 2 (R81) , -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkoxy, oxo, -CN, -OH, -SH, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;R9 is selected from -H, - (C0-3alkylene) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) or -S (=O) 2 (R93) ;said R91 is each independently selected from -C2-3alkenyl, -C2-3alkynyl, -C2-3alkoxy, haloC2-3alkoxy, oxo, -CN, -OH, -SH, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;said R92 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; said R92 is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, oxo, -CN, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;said R93 is each independently selected from halogen;when X2 is CR8 and X3 is CR9, only one of R8 and R9 is hydrogen;R10 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;Y1 is selected from -N (RY1B) -, -O-, -S-, -C (=O) -N (RY1B) -*, -S (=O) -N (RY1B) -*, -S (=O) 2-N (RY1B) -*, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3;ring B is selected from a phenyl or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;RS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, haloC2-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , oxo, -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; said RS2 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) ;n2 is selected from 0, 1, 2, 3, 4, 5 or 6;RS1 and n1 have the same definitions as in [1] .
[0082] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of
[0080] , wherein, R7 has the same definition as in
[0012] .
[0083] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0082] , wherein, R8 has the same definition as in any one of [8] - [9] .
[0084] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0083] , wherein, R9 has the same definition as in any one of
[0010] -
[0011] .
[0085] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0084] , wherein, R10 has the same definition as in
[0013] .
[0086] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0085] , wherein, R4 and R5 has the same definitions as in any one of
[0049] -
[0055] .
[0087] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0086] , wherein, R6 has the same definition as in any one of
[0057] -
[0060] .
[0088] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0087] , wherein, Y1 has the same definition as in any one of
[0038] -
[0048] .
[0089] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0088] , wherein, the moiety of is selected frompreferably, the moiety ofis selected from
[0090] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0089] , wherein, ring B has the same definition as in any one of
[0065] -
[0066] .
[0091] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0090] , wherein,RS2 has the same definition as in
[0067] ;n2 has the same definition as in
[0068] .
[0092] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0091] , wherein,the moiety ofhas the same definition as in
[0069] .
[0093] . The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0081] -
[0092] , wherein, the compound is any one of the following formulas:
[0094] . A compound of formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,Y2 is selected from -C (RY2) 2-, -O-, -NRY3-, -S-, **-C (=O) NRY4-, **-NRY4C (=O) -, **-S (=O) NRY4-, **-NRY4S (=O) -, **-S (=O) 2NRY4-or **-NRY4S (=O) 2-; **indicates the attached point to the moiety ofRY2 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;RY3 is selected from -H, -C1-6alkyl, -C (=O) (C1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said RY3 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY31;said RY31 is each independently selected from halogen, -C1-3alkyl, -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) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-4alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-4alkyl) or -S (=O) 2N (C1-3alkyl) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -C2-3alkoxy, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) or 5-10 membered heteroaryl;RY4 is selected from -H, -C1-6alkyl, -C (=O) (C1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said RY4 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-3alkyl, -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) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-4alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-4alkyl) or -S (=O) 2N (C1-3alkyl) 2;n4 is selected from 0, 1, 2, 3 or 4;n5 is selected from 0, 1, 2, 3 or 4;Y1 is selected from -N (RY1B) -, -O-, -S-, -C (=O) -N (RY1B) -*, -S (=O) -N (RY1B) -*, -S (=O) 2-N (RY1B) -*, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3;R6 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;R4 and R5 are each independently selected from -H or-C1-3alkyl;ring B is selected from a phenyl or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;RS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, haloC2-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , oxo, -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; said RS2 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) ;n2 is selected from 0, 1, 2, 3, 4, 5 or 6;RS1, n1, RS3 and n3 have the same definitions as in [1] .
[0095] . A compound of formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, RY2, Y1 and ring B have the same definitions as in
[0094] .
[0096] . The compound of formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of
[0095] , wherein,RY2 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;preferably, RY2 is selected from -H, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;more preferably, RY2 is -H;In some embodiments, RY2 is selected from -H or -C1-3alkyl; preferably, RY2 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, or -CH (CH3) 2; more preferably, RY2 is -H.
[0097] . A compound of formula (I-2-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, RY3, Y1 and ring B have the same definitions as in
[0094] .
[0098] . The compound of formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of
[0097] , wherein,RY3 is selected from -H, -C1-3alkyl, -C (=O) (C1-3alkyl) , 3-7 membered carbocyclyl or 3-7 membered heterocyclyl; said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -C1-3alkyl, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) or -C (=O) N (C1-3alkyl) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -C2-3alkoxy, -OH, -O (C1-3alkyl) or 5-10 membered heteroaryl;preferably, RY3 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH2CH2CH3) , -C (=O) (CH (CH3) 2) , said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -OH, -O-CH3, -O-CH2CH3, -O-CH2CH2CH3, -O-CH (CH3) 2, -C (=O) CH3, -C (=O) (CH2CH3) , -C (=O) -CH (CH3) 2, -C (=O) OH, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) (OC (CH3) 3) , -C (=O) NH2, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) NH (C (CH3) 3) , -C (=O) N (CH3) 2 or -C (=O) N (CH2CH3) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -CH3-O-CH3, -CH2CH3-O-CH3, -CH2-O-CH2CH3, -CH (CH3) -O-CH3, -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, thienyl, furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl;More preferably, RY3 is selected from -H, -CH3, -CH2CH3, -C (=O) (CH3) , said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -CH3, -CH2CH3, -OH, -C (=O) CH3, -C (=O) OH, -C (=O) (OC (CH3) 3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH (CH3) 2) or -C (=O) NH (C (CH3) 3) ; said RY31 is independently optionally substituted with 1, 2 or 3 RY32;said RY32 is each independently selected from -OH, -O-CH3 or pyridinyl;more preferably, RY3 is selected from -H, -CH3, -CH2CH3, -CH2COOH, -CH2CH2COOH, -CH2COOC (CH3) 3, -CH2CH2COOC (CH3) 3, -CH2CH2OH, -CH2-C (=O) -NH (CH3) , -CH2CH2-C (=O) -NH (CH3) , -CH2CH2-C (=O) -NH (CH2CH3) , -CH2CH2-C (=O) -NH (CH (CH3) 2) , -CH2CH2-C (=O) -NH (C (CH3) 3) , -C (=O) -CH3, Further preferably, RY3 is selected from -CH2CH2COOH, -CH2CH2OH, -C (=O) -CH3,
[0099] . A compound of formula (I-2-3) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, Y1 and ring B have the same definitions as in
[0094] .
[0100] . A compound of formula (I-2-4) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, Y1 and ring B have the same definitions as in
[0094] .
[0101] . A compound of formula (I-2-5) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, RY4, Y1 and ring B have the same definitions as in
[0094] .
[0102] . A compound of formula (I-2-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, RY4, Y1 and ring B have the same definitions as in
[0094] .
[0103] . The compound of formula (I-2-5) and formula (I-2-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0101] and
[0102] , wherein,RY4 is selected from -H, -C1-3alkyl or haloC1-3alkyl;preferably, RY4 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;more preferably, RY4 is -H;In some embodiments, RY4 is selected from -H or -C1-3alkyl;preferably, RY4 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, or -CH (CH3) 2;more preferably, RY4 is -H.
[0104] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] and
[0103] , wherein, n4 and n5 have the same definitions as in any one of
[0018] -
[0021] .
[0105] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] and
[0104] , wherein, R4 and R5 has the same definitions as in any one of
[0049] -
[0055] .
[0106] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] and
[0105] , wherein, R6 has the same definition as in any one of
[0057] -
[0060] .
[0107] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] and
[0106] , wherein, Y1 has the same definition as in any one of
[0038] -
[0048] .
[0108] . The compound of formula (I-2) and formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] -
[0096] , and
[0104] -
[0107] , wherein,The moiety ofis selected from
[0109] . The compound of formula (I-2) and formula (I-2-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] ,
[0097] -
[0098] , and
[0104] -
[0107] , wherein,the moiety ofis selected fromPreferably, the moiety ofis selected from
[0110] . The compound of formula (I-2) and formula (I-2-3) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] ,
[0099] and
[0104] -
[0107] , wherein,the moiety ofis selected frompreferably, the moiety ofis selected from
[0111] . The compound of formula (I-2) and formula (I-2-4) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] ,
[0100] and
[0104] -
[0107] , wherein,wherein, the moiety ofis selected frompreferably, the moiety ofis selected from
[0112] . The compound of formula (I-2) and formula (I-2-5) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] ,
[0101] ,
[0103] -
[0107] , wherein, the moiety ofis selected from
[0113] . The compound of formula (I-2) and formula (I-2-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] ,
[0102] -
[0107] , wherein, the moiety ofis selected from
[0114] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] -
[0113] , wherein,The moiety ofis selected from
[0115] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] -
[0114] , wherein, ring B has the same definition as in any one of
[0065] -
[0066] .
[0116] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] -
[0115] , wherein,RS2 has the same definition as in
[0067] ;n2 has the same definition as in
[0068] .
[0117] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] -
[0116] , wherein,the moiety ofhas the same definition as in
[0069] .
[0118] . The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) , formula (I-2-3) , formula (I-2-4) , formula (I-2-5) and formula (I-6) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of
[0094] -
[0117] , wherein, the compound is any one of the following formulas:
[0119] . A compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof:wherein,R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -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, phenyl or 5-10 heteroaryl; said R1 is optionally substituted with 1, 2 or 3 substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -NHS (=O) 2 (C1-3alkyl) or 3-7 membered cycloalkyl;R2 is each independent selected from -H, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -CN, -C (=O) OH, -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) NH2, -C (=O) NH (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) or 3-7 membered cycloalkyl;R4 and R5 are each independently selected from -H or-C1-3alkyl;R6 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;Y1 is selected from -N (RY1B) -, -O-, -S-, -C (=O) -N (RY1B) -*, -S (=O) -N (RY1B) -*, -S (=O) 2-N (RY1B) -*, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3;ring B is selected from a phenyl or a 5-10 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;RS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, haloC2-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , oxo, -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; said RS2 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) ;n2 is selected from 0, 1, 2, 3, 4, 5 or 6;RS1 and n1 have the same definitions as in [1] .
[0120] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] , wherein,R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, -CN, -C (=O) OH, -C (=O) (OC1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, phenyl or 5-6 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said R1 is optionally substituted with 1, 2 or 3 substituents selected from -C1-3alkyl;more preferably, R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, -CN, -COOH, -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, or 5-6 heteroaryl containing 1 or 2 heteroatoms selected from N, O or S; said 5-6 heteroaryl is optionally substituted with 1 or 2 substituents selected from -C1-3alkyl;more preferably, R1 is each independent selected from -H, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CN, -COOH, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -C (=O) N (CH2CH3) 2, further preferably, R1 is selected from -CH3, -CN, -Br, -C (=O) -NH2, -COOH,
[0121] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0120] , wherein,R2 is each independent selected from -H, halogen, -C1-3alkyl, haloC1-3alkyl or -CN;preferably, R2 is each independent selected from -H, -C1-3alkyl or -CN;more preferably, R2 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2 or -CN;further preferably, R2 is selected from -H, -CH3 or -CN.
[0122] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0121] , wherein, R4 and R5 has the same definitions as in any one of
[0062] -
[0066] .
[0123] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0122] , wherein, R6 has the same definition as in any one of
[0062] -
[0066] .
[0124] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0123] , wherein, Y1 has the same definition as in any one of
[0062] -
[0066] .
[0125] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0124] , wherein, the moiety ofis selected from
[0126] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0125] , wherein, ring B has the same definition as in any one of
[0065] -
[0066] .
[0127] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0126] , wherein,RS2 has the same definition as in
[0067] ;n2 has the same definition as in
[0068] .
[0128] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0127] , wherein, the moiety ofhas the same definition as in
[0069] .
[0129] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] ,
[0032] -
[0069] and
[0119] -
[0128] , wherein, the compound is any one of the following formulas:
[0130] . The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] -
[0129] , wherein, the compound is any one of the following formulas:
[0131] . An intermediate selected from any one of the following formulas:Wherein, the definition of R4, R5, R6, R7, R9, R10, RY2, Y1, ring B, RS1, RS2, RS3, n1, n2, n3, n4 or n5 in each of formulas is same as any one of [1] to
[0130] ;LG6 in each of formulas is a leaving group, which is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf;Y4 in each of formulas is -C (=O) -, -S (=O) -or -S (=O) 2-;LG2 in each of formulas is a leaving group or a group that can be converted to the leaving group; said the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; said the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf;Poc2 is the protecting group of the nitrogen atom, which includes but is not limited to t-Butyloxycarbonyl;preferably, the intermediate is selected from:
[0132] . A process for preparing the compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] and
[0130] , comprising the following Scheme 1 or Scheme 2:The definition of R4, R5, R6, R7, R8, R9, R10, R81, Y1, ring B, RS1, RS2, n1 or n2 in each of formulas is same as any one of [1] to
[0130] ;Said LG3 in theLG4 in theLG5 in the (LG1 in the LG1-Y3-R81) or (LG2 in the Formula (I-1-1E’) ) is a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf;LG6 in formula (I-1-1A’) , formula (I-1-1B’) , formula (I-1-1C’) is a leaving group, which is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf;LG7 is a leaving group that is capable of detaching from the Formula (I-1-1D’) during the subsequent reaction, such as benzyl or methyl;(Y3 in the (LG1-Y3-R81) ) or (Y4 in the Formula (I-1-1E’) ) is selected from -C (=O) -, -S (=O) -or -S (=O) 2-;Y5 is -C (=O) -, -S (=O) -or -S (=O) 2-;Y6 is -S-or -CH2-; when -Y6-is -CH2-, which is oxidized to form Y4 (-C (=O) -) in the Formula (I-1-1E’) ; when -Y6-is -S-, which is oxidized to form Y4 (-S (=O) -or -S (=O) 2-) in the Formula (I-1-1E’) .
[0133] . A process for preparing the compound of formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] and
[0130] , comprising the following Scheme 3:The definition of R4, R5, R6, RY2, Y1, ring B, RS1, RS2, RS3, n1, n2, n3, n4 or n5 in each of formulas is same as any one of [1] to
[0130] ;Said LG3 in theLG4 in theand LG5 in theis a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf;Said Poc1 is the protecting group of the -NH2, preferably, Poc1 isY5 is -C (=O) -, -S (=O) -or -S (=O) 2-.
[0134] . A process for preparing the compound of formula (I-2-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] and
[0130] , comprising the following Scheme 4:The definition of R4, R5, R6, RY3, Y1, ring B, RS1, RS2, RS3, n1, n2, n3, n4 or n5 in each of formulas is same as any one of [1] to
[0130] ;Said LG3 in theLG4 in theand LG5 in theis a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf;Y5 is -C (=O) -, -S (=O) -or -S (=O) 2-;Said Poc1 is the protecting group of the -NH2, preferably, Poc1 isPoc2 in the protecting group of the nitrogen atom; prefetably, Poc2 is t-Butyloxycarbonyl.
[0135] . A pharmaceutical composition comprising the compound, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] to
[0130] , and at least one pharmaceutically acceptable excipient.
[0136] . 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, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] to
[0130] ; or the pharmaceutical composition of
[0135] ; 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.
[0137] . A use of a compound, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] to
[0130] ; or a pharmaceutical composition of
[0135] for the manufacture of a mesicament 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.
[0138] . A compound, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of [1] to
[0130] ; or a pharmaceutical composition of
[0135] 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 aboven-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 aboved-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 moncyclic heterocyclyl ring, bicyclic heterocyclyl ring, bridged heterocyclyl ring, fused heterocyclyl ring (including a non-aromatic ring system fused with an aromatic ring system) or sipro 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 (cabons 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 ring and the carbon atom adjacent to the N heteroatom is substituted with -OH, tautomers may exist.The term “carbocyclic” refers to a substituted or unsubstituted monocyclic ring, bicyclic ring, bridged ring, fused ring, sipiro 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. Examplary “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 ploycyclic ring, such as a fused ring, a brideged ring or a sprio ring, each of substituents may be respectively independently substituted on every ring atom of the ploycyclic 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 prcesses 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 inventon 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.ExamplesThe 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:General Synthesis ProcedureThe definition of R4, R5, R6, R7, R8, R9, R10, R81, RY2, Y1, ring B, RS1, RS2, RS3, n1, n2, n3, n4 or n5 at each occurrence in Formula (I-1-1) , Formula (I-1-1A) , Formula (I-1-1B) , Formula (I-1-1C) , Formula (I-1-1D) , Formula (I-1-1A’) , Formula (I-1-1B’) , Formula (I-1-1C’) , Formula (I-1-1D’) , Formula (I-1-1E’) , Formula (I-2-1) , Formula (I-2-1A) , Formula (I-2-1B) , Formula (I-2-1C) , Formula (I-2-1D) , Formula (I-2-1E) , Formula (I-2-2) , Formula (I-2-2A) , Formula (I-2-2B) , Formula (I-2-2C) , Formula (I-2-2D) , Formula (I-2-2E) or Formula (I-2-2G) , as defined in this invention.The preparing of Formula (I-1-1)Compounds of Formula (I-1-1) can be prepared according to Step A or Step B or other methods described herein.Said (LG1 in the LG1-Y3-R81) or (LG2 in the Formula (I-1-1E’) ) is a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs, -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf;Said (Y3 in the LG1-Y3-R81) or (Y4 in the Formula (I-1-1E’) ) is -C (=O) -, -S (=O) -or -S (=O) 2-. The preparing of Formula (I-1-1D)Compounds of Formula (I-1-1D) can be prepared from Compounds of Formula (I-1-1A) according to Scheme 1 or other methods described herein.Compounds of Formula (I-1-1B) can be prepared from through a substitution reaction between Compounds Formula (I-1-1A) andCompounds of Formula (I-1-1C) can be prepared from through a condensation reaction between Compounds Formula (I-1-1B) andsaid Y5 is -C (=O) -, -S (=O) -or -S (=O) 2-; or Compounds of Formula (I-1-1C) can be prepared from through a substitution reaction between Compounds Formula (I-1-1B) andor Compounds of Formula (I-1-1C) can be prepared from through a coupling reaction between Compounds Formula (I-1-1B) andin the presence of a catalyst; said the catalyst including, but is not limited to monovalent copper catalyst, Palladium (0) catalyst or Palladium (2) catalyst; the monovalent copper catalyst include, but are not limited to CuI; the Palladium (0) catalyst include, but is not limited to Pd (PPh) 4, Pd2 (dba) 3 or Pd (dba) 2; Palladium (2) catalyst include, but is not limited to Pd (TFA) 2, Pd (OAc) 2, PdCl2, Pd (PPh) 3Cl2 or Pd (OTf) 2.Compounds of Formula (I-1-1D) can be prepared from through a reduction reaction between Compounds Formula (I-1-1C) and reducing agent; said reducing agent including but not limited to palladium on carbon (Pd / C) with hydrogen, or iron powder.Said LG3 in theLG4 in theand LG5 in theis a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf.The preparing of Formula (I-1-1E’)Compounds of Formula (I-1-1E’) can be prepared from Compounds of Formula (I-1-1A’) according to Scheme 2 or other methods described herein.Compounds of Formula (I-1-1B’) can be prepared from through a substitution reaction between Compounds Formula (I-1-1A’) andCompounds of Formula (I-1-1C’) can be prepared from through a condensation reaction between Compounds Formula (I-1-1B’) andSaid Y5 is -C (=O) -, -S (=O) -or -S (=O) 2-; or Compounds of Formula (I-1-1C’) can be prepared from through a substitution reaction between Compounds Formula (I-1-1B’) andor Compounds of Formula (I-1-1C’) can be prepared from through a coupling reaction between Compounds Formula (I-1-1B’) andin the presence of a catalyst; said the catalyst including, but is not limited to monovalent copper catalyst, Palladium (0) catalyst or Palladium (2) catalyst; the monovalent copper catalyst include, but are not limited to CuI; the Palladium (0) catalyst include, but is not limited to Pd (PPh) 4, Pd2 (dba) 3 or Pd (dba) 2; Palladium (2) catalyst include, but is not limited to Pd (TFA) 2, Pd (OAc) 2, PdCl2, Pd (PPh) 3Cl2 or Pd (OTf) 2.LG6 in Formula (I-1-1A’) , Formula (I-1-1B’) , Formula (I-1-1C’) is a leaving group, which is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf.Compounds of Formula (I-1-1D’) can be prepared from through a coupling reaction between Compounds Formula (I-1-1C’) and H-Y6-LG7 in the presence of a catalyst; said the catalyst including, but is not limited to Palladium (0) catalys; the Palladium (0) catalyst include, but is not limited to Pd(PPh) 4, Pd2 (dba) 3 or Pd (dba) 2; preferably, the Palladium (0) catalyst is Pd2 (dba) 3. Y6 is -S-or -CH2-; LG7 is a leaving group that is capable of detaching from the Formula (I-1-1D’) during the subsequent oxidation reaction, such as benzyl or methyl;Compounds of Formula (I-1-1E’) are obtained by oxidizing Compounds of Formula (I-1-1D’) in the presence of an oxidizing agent; said the oxidizing agent includes but is not limited to NCS or 1, 3-dichloro-5, 5-dimethylhydantoin, and it also provides the leaving group -LG2 during the oxidation reaction; when -Y6-is -CH2-, which is oxidized to form -C (=O) -; when -Y6-is -S-, which is oxidized to form -S (=O) -or -S (=O) 2-.Said LG3 in theLG4 in theand LG5 in theis a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf.The preparing of Formula (I-2-1)Compounds of Formula (I-2-1) can be prepared from Compounds of Formula (I-2-1A) according to Scheme 3 or other methods described herein.Compounds of Formula (I-2-1) can be prepared from through a condensation reaction between Compounds of Formula (I-2-1E) andSaid Y5 is -C (=O) -, -S (=O) -or -S (=O) 2-; or Compounds of Formula (I-2-1) can be prepared from through a substitution reaction between Compounds Formula (I-2-1E) andor Compounds of Formula (I-2-1) can be prepared from through a coupling reaction between Compounds Formula (I-2-1E) andin the presence of a catalyst; said the catalyst including, but is not limited to monovalent copper catalyst, Palladium (0) catalyst or Palladium (2) catalyst; the monovalent copper catalyst include, but are not limited to CuI; the Palladium (0) catalyst include, but is not limited to Pd (PPh) 4, Pd2 (dba) 3 or Pd (dba) 2; Palladium (2) catalyst include, but is not limited to Pd (TFA) 2, Pd (OAc) 2, PdCl2, Pd (PPh) 3Cl2 or Pd (OTf) 2.Compounds of Formula (I-2-1E) is obtained through a deprotection reaction of Formula (I-2-1D) .Compounds of Formula (I-2-1D) can be prepared from through a substitution reaction between Compounds Formula (I-2-1C) andCompounds of Formula (I-2-1C) is obtained through Formula (I-2-1B) in the presence of an amino protecting reagent, said the amino protecting reagent is a protecting reagent of a primary amine or a secondary amine; preferably, the amino protecting reagent is a primary amine protecting agent, including, but is not limited toSaid Poc1 is the protecting group of -NH2, preferably, Poc1 isCompounds of Formula (I-2-1B) can be prepared from Compounds of Formula (I-2-1A) and hydrazine.Said LG3 in theLG4 in theand LG5 in theis a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf.The preparing of Formula (I-2-2)Compounds of Formula (I-2-2) can be prepared from Compounds of Formula (I-2-2G) according to Step C or other methods described herein.Compounds of Formula (I-2-2) can be prepared from through substitution reaction / condensation reaction / alkylation reaction / arylation reaction between Compounds of Formula (I-2-2G) and RY3-X; said X includes, but is not limited to halogen (such as -Cl, -Br, -I) , -OH, -OMs, -OTs or -OTf.Compounds of Formula (I-2-2G) can be prepared from Compounds of Formula (I-2-2A) according to Scheme 4 or other methods described herein.Compounds of Formula (I-2-2G) is obtained through a deprotection reaction of Poc2 in Formula (I-2-2F) .Compounds of Formula (I-2-2F) can be prepared from through a condensation reaction between Compounds of Formula (I-2-2E) andSaid Y5 is -C (=O) -, -S (=O) -or -S (=O) 2-; or Compounds of Formula (I-2-2F) can be prepared from through a substitution reaction between Compounds Formula (I-2-2E) andor Compounds of Formula (I-2-2F) can be prepared from through a coupling reaction between Compounds Formula (I-2-2E) andin the presence of a catalyst; said the catalyst including, but is not limited to monovalent copper catalyst, Palladium (0) catalyst or Palladium (2) catalyst; the monovalent copper catalyst include, but are not limited to CuI; the Palladium (0) catalyst include, but is not limited to Pd (PPh) 4, Pd2 (dba) 3 or Pd (dba) 2; Palladium (2) catalyst include, but is not limited to Pd (TFA) 2, Pd (OAc) 2, PdCl2, Pd (PPh) 3Cl2 or Pd (OTf) 2.Compounds of Formula (I-2-2E) is obtained through a deprotection reaction of Poc1 in the Formula (I-2-2D) .Compounds of Formula (I-2-2D) can be prepared from through a substitution reaction between Compounds Formula (I-2-2C) andCompounds of Formula (I-2-2C) is obtained through Formula (I-2-2B) in the presence of an amino protecting reagent, said the amino protecting reagent is a protecting reagent of a primary amine or a secondary amine; preferably, the amino protecting reagent is a primary amine protecting agent, including, but is not limited toSaid Poc1 is the protecting group of -NH2, preferably, Poc1 isCompounds of Formula (I-2-2B) can be prepared from Compounds of Formula (I-2-2A) and hydrazine.Poc2 in the Formula (I-2-2A) , Formula (I-2-2B) , Formula (I-2-2C) , Formula (I-2-2D) , Formula (I-2-2E) and Formula (I-2-2F) , which includes but is not limited to t-Butyloxycarbonyl, is the protecting group of the nitrogen atom.LG3 in theLG4 in theand LG5 in theis a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf.Intermediate 1 (INT 1)At 20 ℃, KOH (5.04 g, 2.00 eq) was added to a solution of 5-nitro-1H-indazol-3-amine (8.00 g, 1.00 eq) in DMSO (80.0 mL) . After stirring for 10 mins, 1- (bromomethyl) -4- (trifluoromethyl) benzene (11.3 g, 1.05 eq) in DMSO (8.00 mL) was added dropwise. The reaction mixture was stirred at 20 ℃for 1h, diluted with H2O (100 mL) and then extracted with EA (200 mL) . The combined organic layers were washed with brine (50 mL) , dried over Na2SO4, and concentrated under reduced pressure to give a residue which was purified with silica gel column chromatography (eluting with PE / EA) to afford INT 1-1 (4.77 g) as a solid. LCMS: m / z = 337.1 [M+1] + .To a solution of INT 1-1 (4.70 g, 1.00 eq) in pyridine (28.2 mL) was added EDCI (4.02 g, 1.50 eq) and 2-methylfuran-3-carboxylic acid (1.94 g, 1.10 eq) . The reaction mixture was stirred at 20 ℃ for 12 hrs., diluted with H2O (100 mL) and then extracted with EA (100 mL) . The combined organic layers were concentrated under reduced pressure to obtain a residue which was purified with silica gel column chromatography (eluting with PE / EA) afford INT 1-2 (5.10 g) was obtained as a solid. LCMS: m / z =445.1 [M+1] + .To a solution of INT 1-2 (1.00 g, 1.00 eq) in EtOH (10.0 mL) H2O (10.0 mL) was added NH4Cl (963 mg, 8.00 eq) and iron powder (628 mg, 5.00 eq) . The reaction mixture was stirred at 80 ℃ for 2 hrs., diluted with H2O (50 mL) and then extracted with EA (80 mL) . The combined organic layers were washed with brine (50 mL) , dried over Na2SO4, and concentrated under reduced pressure to afford INT 1 (800 mg, 85.9%yield) as a solid. LCMS: m / z = 415.1 [M+1] +.1HNMR (400 MHz, DMSO-d6) : δ 10.15 (s, 1H) , 7.69 (d, J = 8.4 Hz, 2H) , 7.59 (d, J = 1.6 Hz, 1H) , 7.46 -7.36 (m, 3H) , 7.13 (s, 1H) , 6.86 (dd, J = 8.8 Hz, J = 1.6 Hz, 1H) , 6.78 (s, 1H) , 5.60 (s, 2H) , 5.44 (s, 2H) , 2.56 (s, 3H) .Intermediate 2 (INT 2)To a mixture of 2-oxocyclopentane-1-carbonitrile (4.00 g, 1.0 eq) in H2O (8.00 mL) and EtOH (80.0 mL) was added hydrazine monohydrochloride (5.02 g, 2.0 eq) at 25 ℃. The reaction mixture was stirred at 80 ℃ for 2 hrs. and then concentrated under reduced pressure to afford a crude product of INT 2-1 (7.20g) which was used in the next step without further purification. LCMS: m / z = 124.2 [M+1] +.To a mixture of the crude product of INT 2-1 (3.00g) in 1, 4-dioxane (30.0 mL) was added molcular sieve (0.5 g) and isobenzofuran-1, 3-dione (5.05 g, 1.4 eq) . The reaction mixture was stirred at 100 ℃for 10 hrs. and then concentrated under reduced pressure to afford INT 2-2 (5.00 g, 81.1%yield) as a solid. LCMS: m / z = 254.2 [M+1] +.To a solution of INT 2-2 (2.00 g, 1.0 eq) and K2CO3 (2.18 g, 2.0 eq) in ACN (20.0 mL) was added 1- (bromomethyl) -4- (trifluoromethyl) benzene (4.72 g, 2.5 eq) at 25 ℃. The reaction mixture was stirred at 50 ℃ for 18 hrs. and then filtered. The filtrate was concentrated under reduced pressure to afford a crude product of INT 2-3 (3.50 g) which was used in the next step without further purification. LCMS: m / z = 412.1 [M+1] +.To a mixture of a crude product of INT 2-3 (3.50 g) in EtOH (20.0 mL) was added NH2-NH2·H2O (3.68 g, 9.0 eq) at 25 ℃. The mixture was stirred at 80 ℃ for 10 hrs., and then filtered. The filtrate was concentrated under reduced pressure to afford a residue which was purified with silica gel column chromatography (eluting with PE / EA) to afford INT 2 (300 mg, 13.5%yield) as a solid. LCMS: m / z =282.1 [M+1] +.1HNMR (400 MHz, MeOH-d4) : δ 7.62 (d, J = 8.4 Hz, 2H) , 7.31 (d, J = 8.0 Hz, 2H) , 5.07 (s, 2H) , 2.58 -2.55 (m, 2H) , 2.53 -2.49 (m, 4H) .The intermediates in the following table could be synthesized using the procedure or modification procedure of INT 2, with the corresponding starting material.Intermediate 8 (INT 8)To a mixture of INT 8-1 (50.0 g, 237 mmol) in EtOH (1.00 L) was added NH2NH2·HCl (16.7 g, 237 mmol) at 15 ℃. The reaction mixture was stirred for 5 hrs. at 60 ℃ and then concentrated under reduced pressure to obtain a residue. The residue was dissolved in aq. NaHCO3 (300 mL) and extracted with EtOAc (300 mL*3) . The combined organic layers were washed with brine (100 mL) , dried over Na2SO4, and then concentrated under reduced pressure to obtain a crude product of INT 8-2 (40.0 g) which was used in next step without further purification. LCMS: m / z = 225.1 [M+1] +.1HNMR: (400 MHz, DMSO-d6) δ 5.92 -5.14 (m, 3H) , 4.31 (d, J = 16.5 Hz, 2H) , 4.21 (d, J = 11.1 Hz, 2H) , 1.43 (s, 9H)At 15 ℃, DMF-DMA (42.5 g, 357 mmol, 47.4 mL, 2.00 eq) was added to a mixture of the crude product of INT 8-2 (40.0 g, 178 mmol) in toluene (400 mL) . The reaction mixture was stirred for 2 hrs. at 110 ℃, and then concentrated under reduced pressure to obtain a residue. The residue was purified with silica gel column chromatography (The gradient of eluent is PE / EA= 100 / 1 to 0 / 1) to afford INT 8-3 (20.0 g, 67.6 mmol, 37.9%yield) as a brown oil. LCMS: m / z = 280.3 [M+1] +.1HNMR (400 MHz, DMSO-d6) δ 11.91 (s, 1H) , 7.77 (d, J = 5.5 Hz, 1H) , 4.37 (d, J = 3.2 Hz, 2H) , 4.20 (d, J = 10.7 Hz, 2H) , 3.03 (s, 3H) , 2.90 (s, 3H) , 1.46 (d, J = 2.7 Hz, 9H) .To a mixture of INT 8-3 (20.0 g, 71.6 mmol) in MeCN (400 mL) was added K2CO3 (24.7 g, 179 mmol) and 4- (Trifluoromethyl) benzyl bromide (25.6 g, 107 mmol, 16.6 mL) at 15 ℃. The reaction mixture was stirred at 80 ℃ for 12 hrs., and then filtered. The filtrate was concentrated under reduce pressure to obtain a residue. The residue was purified with silica gel column chromatography (The gradient of eluent is EA / MeOH= 100 / 1 to 0 / 1) to afford INT 8-4 (20.0 g, 40.7 mmol, 56.8%yield) as a light yellow solid. LCMS: m / z = 438.2 [M+1] +.To a mixture of INT 8-4 (18.0 g, 41.2 mmo) in MeCN (180 mL) was added NH2NH2·H2O (20.6 g, 329 mmol, 19.9 mL, 80%purity, 8.00 eq) at 15 ℃. The reaction mixture was stirred at 60 ℃ for 16 hrs., and then concentrated under reduced pressure to obtain a residue. The residue was purified with silica gel column chromatography (The gradient of eluent is PE / EA= 100 / 1 to 0 / 1) to afford INT 8 (13.0 g, 33.3 mmol, 80.97%yield) as white solid. LCMS: m / z = 383.1 [M+1] +.1HNMR (400 MHz, CDCl3) δ 7.58 -7.48 (m, 2H) , 7.23 (d, J = 8.0 Hz, 2H) , 4.98 (d, J = 3.3 Hz, 2H) , 4.26 -4.07 (m, 4H) , 1.40 (d, J = 6.1 Hz, 9H) .Intermediate 9 (INT 9)At 20 ℃, to a solution of 5-bromo-1H-indazol-3-amine (2.00 g, 9.43 mmol) in DMSO (20.0 mL) was added KOH (1.06 g, 18.8 mmol) , and then 1- (bromomethyl) -4- (trifluoromethyl) benzene (2.37 g, 9.90 mmol, 1.53 mL) in DMSO (2.00 mL) was added dropwise. The reaction mixture was stirred at 20 ℃for 2 hrs., diluted with H2O (20 mL) and then extracted with DCM (50 mL) . The combined organic layers were washed with brine (10 mL) , dried over Na2SO4, and concentrated under reduced pressure to afford a residue which was purified with silica gel column chromatography (eluting with PE / EA) to afford INT 9-1 (3.00 g, 8.10 mmol) as a solid. LCMS: m / z = 370.1 / 372.1 [M+1] +.To a solution of INT 9-1 (3.00 g, 8.10 mmol) in pyridine (15.0 mL) was added EDCI (2.33 g, 12.1 mmol, 1.50 eq) and 2-methylfuran-3-carboxylic acid (1.12 g, 8.91 mmol, 1.10 eq) . The reaction mixture was stirred at 20 ℃ for 12 hrs.. The reaction mixture was diluted with H2O (100 mL) and extracted with DCM (200 mL) . The combined organic layers were washed with brine (100 mL) , dried over Na2SO4, and concentrated under reduced pressure to obtain a residue which was purified with silica gel column chromatography (eluting with PE / EA) to afford INT 9-2 (2.50 g, 5.23 mmol) as a solid. LCMS: m / z =500.0 / 502.0 [M+1] +.To a solution of INT 9-2 (1.50 g, 3.14 mmol) in dioxane (15.0 mL) was added DIEA (810 mg, 6.27 mmol, 1.09 mL, 2.00 eq) , Xantphos (181 mg, 313 umol, 0.10 eq) , BnSH (0.73 g, 5.88 mmol, 688 uL, 1.87 eq) and Pd2 (dba) 3 (143 mg, 156 umol, 0.05 eq) . The reaction mixture was stirred at 90 ℃ for 4 hrs., diluted with H2O (20 mL) and extracted with DCM (50 mL) . The combined organic layers were washed with brine (10 mL) , dried over Na2SO4, and then concentrated under reduced pressure to obtain a residue which was purified with silica gel column chromatography (eluting with PE / EA) to afford INT 9-3 (1.20 g, 2.30 mmol) as an oil. LCMS: m / z = 522.1 [M+1] +.1HNMR (400 MHz, CDCl3) δ 8.17 (s, 1H) , 7.57 (s, 1H) , 7.56 (d, J = 8.0 Hz, 2H) , 7.26-7.34 (m, 5H) , 7.13-7.16 (m, 4H) , 6.58 (d, J = 2.0 Hz, 1H) , 5.50 (s, 2H) , 4.13 (s, 2H) , 2.69 (s, 3H) .DCDMH (113 mg, 575 μmol) was added to a solution of INT 9-3 (200 mg, 383.47 μmol, 1.00 eq) dissolved in a mixed solvent of ACN (4.00 mL) , H2O (0.50 mL) and AcOH (0.80 mL) . The mixture was stirred at 0 ℃ for 1 hr, diluted with H2O (8 mL) and extracted with EA (10 mL*3) . The combined organic layers were washed with aq. NaHCO3 (10 mL) , dried over Na2SO4, and concentrated under reduced pressure to obtain INT 9 (250 mg) which was used in next step without further purification.Intermediate 10 (INT 10)At 20 ℃, KOH (2.65 g, 47.1 mmol) was added to a solution of 6-bromo-1H-indazol-3-ylamine (5.00 g, 23.5 mmol, 1.00 eq) in DMSO (100 mL) . After stirring at 20 ℃ for 10 mins, 1- (bromomethyl) -4- (trifluoromethyl) benzene (5.92 g, 24.7 mmol, 3.82 mL) in DMSO (6.00 mL) was added dropwise. The reaction mixture was stirred at 20 ℃ for 2 hrs., diluted with H2O (50 mL) and extracted with EA (200 mL) . The combined organic layers were washed with brine (50 mL) , dried over Na2SO4, and then concentrated under reduced pressure to obtain a residue. The residue was purified with silica gel column chromatography (The gradient of eluent is PE / EA= 10 / 1 to 0 / 1) to afford INT 10-1 (4.00 g, 10.8 mmol, 45.8%yield) as a yellow solid. 1HNMR (400 MHz, DMSO-d6) δ 7.82 (s, 1H) , 7.64-7.82 (m, 3H) , 7.35 (d, J = 8.0 Hz, 2H) , 7.06 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H) , 5.67 (s, 2H) , 5.42 (s, 2H) .To a solution of INT 10-1 (4.00 g, 10.8 mmol, 1.00 eq) in pyridine (24.0 mL) was added EDCI (3.11 g, 16.2 mmol, 1.50 eq) and 2-methylfuran-3-carboxylic acid (1.50 g, 11.8 mmol, 1.10 eq) . The reaction mixture was stirred at 20 ℃ for 12 hrs., diluted with H2O (50 mL) and extracted with EA (200 mL) . The combined organic layers were washed with brine (50 mL) , dried over Na2SO4, and concentrated under reduced pressure to obtain a residue. The residue was purified with silica gel column chromatography (The gradient of eluent is PE / EA= 10 / 1 to 0 / 1) to afford INT 10-2 (3.00 g, 6.27 mmol, 58.0%yield) as a yellow solid.Under an atmosphere of nitrogen, Pd (dppf) Cl2 (458 mg, 627 umol, 0.1 eq) and TEA (1.90 g, 18.8 mmol, 3.00 eq) were added to a solution of INT 10-2 (3.00 g, 6.27 mmol) in MeOH (18.0 mL) . The reaction mixture was purged with CO several times and then maintained under a CO (50 psi) atmosphere, stirred at 70 ℃ for 12 hrs., and then filtered. The filtrate was concentrated under reduced pressure to obtain a residue which was purified with silica gel column chromatography (The gradient of eluent is PE / EA= 10 / 1 to 0 / 1) to afford INT 10-3 (1.40 g, 46.3%yield) as a yellow solid. 1HNMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.8 Hz, 1H) , 8.08 (s, 1H) , 8.04 (s, 1H) , 7.82 (d, J = 8.8 Hz, 1H) , 7.57 (d, J = 8.4 Hz, 2H) , 7.28-7.34 (m, 3H) , 6.59 (d, J = 2.0 Hz, 1H) , 5.59 (s, 2H) , 3.96 (s, 3H) , 2.68 (s, 3H) .To a solution of INT 10-3 (0.80 g, 1.75 mmol, 1.00 eq) in THF (16.0 mL) was added LAH (331 mg, 8.75 mmol, 5.00 eq) . The reaction mixture was stirred at 0 ℃ for 2 hrs., quenched with H2O (5 mL) at 0 ℃, and then extracted with EA (100 mL) . The combined organic layers were washed with brine (10 mL) , dried over Na2SO4, and concentrated under reduced pressure to obtain a crude product of INT 10-4 (0.52 g) which was used into the next step without further purification. 1HNMR (400 MHz, DMSO-d6) δ . 10.39 (s, 1H) , 7.69-7.72 (m, 3H) , 7.60 (d, J = 2.8 Hz, 2H) , 7.40 (d, J = 8.0 Hz, 2H) , 7.16 (s, 1H) , 7.08-7.09 (m, 1H) , 5.70 (s, 2H) , 5.31 (t, J = 5.6 Hz, 1H) , 4.62 (d, J = 5.6 Hz, 2H) , 2.57 (s, 3H) .To a solution of INT 10-4 (0.30 g, 698 μmol, 1.00 eq) in DCM (3.00 mL) was added NBS (248 mg, 1.40 mmol, 2.00 eq) and PPh3 (274 mg, 1.05 mmol, 1.50 eq) . The reaction mixture was stirred at 20 ℃ for 3 hrs., and then concentrated under reduced pressure to give a residue. The residue was purified with prep-TLC (SiO2, the gradient of eluent is PE / EA= 3 / 1) to obtain INT 10-5 (200 mg, 406 μmol, 58.1%yield) as a yellow oil.To a solution of INT 10-5 (200 mg, 406 μmol, 1.00 eq) in ACN (2.00 mL) was added TMSCN (80.6 mg, 812 μmol, 101 μL, 2.00 eq) and K2CO3 (140 mg, 1.02 mmol, 2.50 eq) . The reaction mixture was stirred at 80 ℃ for 12 hrs., diluted with H2O (5 mL) and extracted with EA (20 mL) . The combined organic layers were washed with brine (5 mL) , dried over Na2SO4, and then concentrated under reduced pressure to obtain a residue which was purified with prep-TLC (SiO2, the gradient of eluent is PE / EA=3 / 1) to afford INT 10 (120 mg, 273 μmol, 67.3%yield) as a yellow oil.Intermediate 11 (INT 11)To a solution of INT 8 (780 mg, 2.04 mmol, 1.00 eq) in pyridine (8 mL) was added EDCI (626 mg, 3.26 mmol, 1.60 eq) and 2-methylfuran-3-carboxylic acid (334.42 mg, 2.65 mmol, 1.3 eq) . The reaction mixture was stirred at 20 ℃ for 12 hrs., poured into water (20.0 mL) and extracted with EtOAc (30.0 mL*3) . The combined organic layers were washed with brine (20.0 mL) , dried with Na2SO4 and concentrated under reduced pressure to obtain a residue which was purified with silica gel column chromatography (The gradient of eluent is PE / EA= 50 / 1 to 1 / 1) to afford INT 11-1 (780 mg, 1.27 mmol, 62.4%yield) as a yellow solid.To a solution of INT 11-1 (730 mg, 1.49 mmol, 1.00 eq) in DCM (4.0 mL) was added TFA (1.54 g, 13.5 mmol, 1.00 mL, 9.07 eq) at 20 ℃. The reaction mixture was stirred at 20 ℃ for 12 hrs., and then concentrated under reduced pressure to obtain INT 11 (1.00 g) as a yellow solid.Intermediate 12 (INT 12)To a solution of INT 11 (100 mg, 256 μmol) and tert-butyl-3-oxoazetidine-1-carboxylate (65.7 mg, 384 μmol) in MeOH (1.00 mL) was added AcOH (1.54 mg, 25.6 μmol, 1.47 μL, 0.100 eq) and NaBH3CN (40.2 mg, 640 μmol, 2.50 eq) at 20 ℃. The reaction mixture was stirred at 50 ℃ for 12 hrs., and then concentrated under reduced pressure to obtain a residue which was purified with prep-TLC (SiO2, the gradient of eluent is DCM / MeOH = 10 / 1) to afford INT 12-1 (70.0 mg, 128 μmol, 50.09%yield) as a yellow solid.INT 12-1 (70.0 mg, 128 μmol, 1.00 eq) was dispersed in HCl / dioxane (700 μL) at 20 ℃. The mixture was stirred at 20 ℃ for 1 h and then concentrated under reduced pressure to afford a residue. The residue was purified by prep-HPLC (Column: Phenomenex Luna C18 100*30 mm*3 um; Mobile phase: H2O (0.04%HCl) / ACN; The gradient of mobile phase: 5%-40%ACN; Flow Rate: 8.0 mins) to afford a HCl salt of INT 12 (35.59 mg, 77.1 μmol, 60.1%yield) as a white solid.1HNMR (400 MHz, DMSO-d6) δ 10.71 (s, 1H) , 9.67 (d, J = 2.3 Hz, 1H) , 9.24 -9.08 (m, 1H) , 7.75 (d, J = 8.2 Hz, 2H) , 7.56 (d, J = 2.0 Hz, 1H) , 7.49 (d, J = 7.9 Hz, 2H) , 7.16 (d, J = 2.0 Hz, 1H) , 5.34 (s, 2H) , 4.80 -4.32 (m, 7H) , 4.26 -4.17 (m, 2H) , 2.54 (s, 3H) .Intermediate 13 (INT 13)At 20 ℃, t-BuONa (377 mg, 3.92 mmol, 3.00 eq) was added to a solution of INT 8 (500 mg, 1.31 mmol) and 3-bromo-5-methylpyridine (269 mg, 1.57 mmol) in dioxane (5.00 mL) , and then BrettPhos Pd G3 (118 mg, 130 μmol, 0.100 eq) was added at 20 ℃ under an atmosphere of N2. The reaction mixture was stirred at 100 ℃ for 12 hrs., and then filtered. The filtrate was concentrated under reduced pressure to obtain a residue which was purified with silica gel column chromatography (The gradient of eluent is DCM / MeOH = 100 / 1 to 10 / 1) to afford INT 13-1 (210 mg, 443 μmol, 33.9%yield) as a brown oil. 1HNMR (400 MHz, CDCl3) δ 8.18 -8.08 (m, 1H) , 7.92 (br s, 1H) , 7.62 -7.49 (m, 3H) , 7.29 (d, J = 7.9 Hz, 2H) , 7.23 (d, J = 8.1 Hz, 1H) , 5.10 (d, J = 3.1 Hz, 2H) , 4.26 -4.17 (m, 4H) , 2.23 (d, J = 4.0 Hz, 3H) , 1.39 (s, 9H)The solution of INT 13-1 (50.0 mg, 105 μmol, 1.00 eq) in HCl / 1, 4-dioxane (4M, 500 μL) was stirred at 20 ℃ for 1 h and then concentrated under reduced pressure to obtain a residue. The residue was purified with prep-HPLC (Column: Waters Xbridge Prep OBD C18 150*40 mm*10 um; Mobile phase: H2O (0.05%NH3H2O+10 mM NH4HCO3) / ACN; The gradient of mobile phase: 10%-40%ACN; Flow Rate: 8.0 mins) to afford INT 13 (13.79 mg, 36.9 μmol, 34.9%yield) as a white solid.1HNMR (400 MHz, DMSO-d6) δ 8.70-8.47 (m, 1H) , 8.37-8.24 (m, 1H) , 7.83-7.71 (m, 3H) , 7.59-7.42 (m, 3H) , 5.31-5.18 (m, 2H) , 4.38-4.21 (m, 1H) , 3.76 (d, J = 14.7 Hz, 3H) , 2.24-2.18 (m, 3H) .Example 1To a solution of INT 9 (0.150 g, 301 μmol) in THF (1.00 mL) was added TEA (183 mg, 1.81 mmol, 252 μL, 6.00 eq) and cyclopropanamine (25.8 mg, 452 μmol, 31.3 μL, 1.50 eq) . The reaction mixture was stirred at -30 ℃ for 1 h, diluted with H2O (10 mL) and extracted with EA (15 mL) . The combined organic layers were washed with brine (10 mL) , dried over Na2SO4, and concentrated under reduced pressure to give a residue, which was purified with prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 1 (45.0 mg, 28.5%yield) as a solid. LCMS: m / z = 519.1 [M+1] +.1HNMR (400 MHz, DMSO-d6) : δ 10.67 (s, 1H) , 8.40 (d, J = 1.2 Hz, 1H) , 7.97 (d, J = 8.8 Hz, 1H) , 7.86 (d, J = 2.4 Hz, 1H) , 7.80 (dd, J = 8.8 Hz, J = 1.6 Hz, 1H) , 7.72 (d, J = 8.0 Hz, 2H) , 7.61 (d, J = 2.0 Hz, 1H) , 7.46 (d, J = 8.0 Hz, 2H) , 7.16 (d, J = 2.0 Hz, 1H) , 5.78 (s, 2H) , 2.58 (s, 3H) , 2.05-2.12 (m, 1H) , 0.44-0.46 (m, 2H) , 0.35-0.39 (m, 2H) .Example 2To a solution of INT 9 (0.150 g, 301 μmol, 1.00 eq) in THF (1.00 mL) was added TEA (183 mg, 1.81 mmol, 252 μL, 6.00 eq) and cyclohexylamine (44.8 mg, 452 μmol, 1.50 eq) . The mixture was stirred at -30 ℃ for 1 h, diluted with H2O (10 mL) and extracted with EA (15 mL) . The combined organic layers were washed with brine (10 mL) , dried over Na2SO4, and concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Waters Xbridge Prep OBD C18 150*40mm*10um; Mobile phase: H2O (NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 45%-75%ACN; Flow Rate: 8.0 mins) to afford Compound 3 (39.0 mg, 66.8 μmol, 22.2%yield) as a pink solid.1HNMR (400 MHz, DMSO-d6) δ 10.65 (s, 1H) , 8.36 (s, 1H) , 7.94 (d, J = 9.2 Hz, 1H) , 7.81 (dd, J = 8.8 Hz, J = 1.2 Hz, 1H) , 7.72 (d, J = 8.0 Hz, 2H) , 7.56-7.63 (m, 2H) , 7.46 (d, J = 8.0 Hz, 2H) , 7.18 (d, J = 1.6 Hz, 1 H) , 5.77 (s, 2H) , 2.94 (d, J = 1.6 Hz, 1H) , 2.59 (s, 3H) , 1.50-1.64 (m, 4H) , 1.42 (d, J = 11.2 Hz, 1H) , 0.98-1.18 (m, 5H) .The compounds in the following table could be synthesized using the procedure or modification procedure of Compound 1 or Compound 3, with the corresponding starting material and corresponding intermediate INT 9.Example 3To a solution of INT 1 (50.0 mg, 1.00 eq) and 3-methylisoxazole-4-carboxylic acid (16.9 mg, 1.10 eq) in pyridine (0.5 mL) was added EDCI (37.0 mg, 1.60 eq) . The mixture was stirred at 20 ℃ for 2hrs., concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 13 (31.6 mg, 50.03%yield) as a solid. LCMS: m / z = 524.2 [M+1] +.1HNMR (400 MHz, MeOH-d4) : δ 10.40 (s, 1H) , 10.27 (s, 1H) , 9.44 (s, 1H) , 7.99 (s, 1H) , 7.74 -7.68 (m, 4H) , 7.61 (d, J = 2.0 Hz, 1H) , 7.44 (d, J = 8.0 Hz, 2H) , 7.15 (d, J = 1.6 Hz, 1H) , 5.71 (s, 2H) , 2.57 (s, 3H) , 2.42 (s, 3H) .The compounds in the following table could be synthesized using the procedure or modification procedure of Compound 13, with the corresponding starting material and corresponding intermediate INT 1.Example 4To a solution of INT 1 (40.0 mg, 1.00 eq) in pyridine (0.8 mL) was added 1, 3-thiazole-5-sulfonyl chloride (53.2 mg, 3.00 eq) . The mixture was stirred at 25 ℃ for 8 hrs., diluted with H2O (5.0 mL) and extracted with EA (50 mL) . The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to give a residue which was purified with Prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 18 (7.52 mg, 13.9%yield) as a solid. LCMS: m / z = 562.9 [M+1] +.1HNMR (400 MHz, MeOH-d4) : δ 9.11 (s, 1H) , 8.13 (s, 1H) , 7.61 -7.57 (m, 3H) , 7.47 (d, J = 9.2 Hz, 1H) , 7.44 (d, J = 2.0 Hz, 1H) , 7.39 (d, J = 8.0 Hz, 2H) , 7.24 (dd, J = 2.0 Hz, J = 8.8 Hz, 1H) , 6.91 (s, 1H) , 5.64 (s, 2H) , 2.60 (s, 3H) .The compounds in the following table could be synthesized using the procedure or modification procedure of Compound 18, with the corresponding starting material and corresponding intermediate INT 1.Example 5To a mixture of INT 2 (99.3 mg, 1.0 eq) and 2-methylfuran-3-carboxylic acid (48.97 mg, 1.1 eq) in pyridine (2.50 mL) was added EDCI (81.2 mg, 1.2 eq) at 25 ℃. The mixture was stirred at 80 ℃ for 10 hrs., and then concentrated under reduced pressure to afford a residue which was purified with prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 22 (15.0 mg, 10.9%yield) as a solid. LCMS: m / z = 390.1 [M+1] +.1HNMR (400MHz, MeOH-d4) δ 7.64 (d, J = 8.0 Hz, 2H) , 7.38 (d, J = 8.0 Hz, 2H) , 7.39 (s, 1H) , 6.81 (d, J = 3.2 Hz, 1H) , 5.24 (s, 2H) , 2.78 -2.75 (m, 2H) , 2.68 -2.64 (m, 2H) , 2.56 (s, 3H) , 2.58 -2.51 (m, 2H) .The compounds in the following table could be synthesized using the procedure or modification procedure of Compound 22, with the corresponding starting material and corresponding intermediates.Example 6At 20 ℃, to a solution of INT11 (300 mg, 1.00 eq) and HCHO (37.0%purity, 3.12 g, 2.86 mL, 50.0 eq) in MeOH (5.00 mL) was added AcOH (110 mg, 105 μL, 2.40 eq) and NaBH3CN (72.4 mg, 1.50 eq) . The mixture was stirred at 20 ℃ for 1 h and then concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 43 (120 mg, 38.7%yield) as a solid. LCMS: m / z = 405.2 [M+1] +.1HNMR (400 MHz, MeOH-d4) δ 7.67 (d, J = 8.1 Hz, 2H) , 7.43 (d, J = 8.0 Hz, 2H) , 7.40 (d, J = 2.1 Hz, 1H) , 6.83 (d, J = 2.0 Hz, 1H) , 5.28 (s, 2H) , 3.98 (s, 2H) , 3.74 (t, J = 1.7 Hz, 2H) , 2.59 (s, 3H) , 2.57 (s, 3H) .Example 7To a mixture of INT 11 (133 mg, 0.34 mmol, 1.00 eq) and (1-ethoxycyclopropoxy) trimethylsilane (356 mg, 2.041 mmol, 6 eq) in MeOH (5 mL) was added AcOH (200 μL, 3.4 mmol, 10 eq) . After stirring at 25 ℃ for 0.5 h, and then NaBH3CN (107 mg, 1.7 mmol, 5 eq) was added. The reaction mixture was stirred at 50 ℃ for 12 hrs., diluted with H2O (100 mL) and extracted with EtOAc (100 mL*3) . The combined organic layers were washed with brine (100 mL) , dried over with Na2SO4, and concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (C18 column, eluted with H2O / CH3CN) to afford Compound 63 (59.8 mg, 0.139 mmol, 40.8%yield) as a white solid. LCMS: m / z = 431.5 [M+H] +.1HNMR (400 MHz, DMSO-d6) δ 10.30 (s, 1H) , 7.74 (d, J = 8.0 Hz, 2H) , 7.52 (d, J = 2.1 Hz, 1H) , 7.42 (d, J = 7.9 Hz, 2H) , 7.14 (d, J = 2.1 Hz, 1H) , 5.25 (s, 2H) , 3.89 (d, J = 38.5 Hz, 4H) , 2.52 (s, 3H) , 2.16 (s, 1H) , 0.40 (m, 4H) .Example 8At 0 ℃, TEA (51.8 mg, 512 μmol, 2.50 eq) and acetyl chloride (24.1 mg, 307 μmol, 1.50 eq) were added to a solution of INT 11 (80.0 mg, 205 μmol, 1.00 eq) in DCM (0.80 mL) . The reaction mixture was stirred at 25 ℃ for 12 hrs., and then concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Waters Xbridge BEH C18 100*30 mm*10 um; Mobile phase: H2O (NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 15%-45%ACN; Flow Rate: 8.0 mins) to afford Compound 64 (32 mg, 74.00 μmol, 28.8%yield) as a white solid.1HNMR (400 MHz, DMSO-d6) δ 10.58-10.51 (m, 1H) , 7.80 (d, J = 8.2 Hz, 2H) , 7.61-7.57 (m, 1H) , 7.52 (d, J = 8.1 Hz, 2H) , 7.21 (s, 1H) , 5.41-5.33 (m, 2H) , 4.75 (br s, 2H) , 4.59-4.46 (m, 2H) , 2.60 (s, 3H) , 2.11-2.04 (m, 3H) .Example 9At 20 ℃, K2CO3 (70.8 mg, 512 μmol) was added to a solution of INT 11 (100 mg, 256 μmol) and 2- (2-bromoethoxy) tetrahydro-2H-pyran (58.9 mg, 281 μmol, 42.5 μL) in MeCN (1.00 mL) . The reaction mixture was stirred at 50 ℃ for 12 hrs., and then filtered. The filtrate was concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Waters Xbridge BEH C18 100*30 mm*10 um;Mobile phase: H2O (NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 45%-75%ACN; Flow Rate: 8.0 mins) to afford Compound 66-1 (40.0 mg, 77.1 μmol, 30.1%yield) as a white solid.The solution of Compound 66-1 (40.0 mg, 77.1 μmol, 1.00 eq) in HCl / dioxane (4.00 M, 5.19 eq) was stirred at 25 ℃ for 16 hrs., and then concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Waters Xbridge BEH C18 100*30 mm*10 um; Mobile phase: H2O (NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 25%-60%ACN; Flow Rate: 8.0 mins) to afford Compound 66 (23.4 mg, 54.0 μmol, 70.0%yield) as a white solid.1H NMR: (400 MHz, DMSO-d6) δ 10.28 (s, 1H) , 7.74 (d, J = 8.1 Hz, 2H) , 7.52 (d, J = 2.0 Hz, 1H) , 7.42 (d, J = 8.0 Hz, 2H) , 7.13 (d, J = 1.9 Hz, 1H) , 5.25 (s, 2H) , 4.52-4.46 (m, 1H) , 3.86 (s, 2H) , 3.77 (s, 2H) , 3.50 (q, J = 6.0 Hz, 2H) , 2.77 (t, J = 6.2 Hz, 2H) , 2.52 (s, 3H)Example 10To a mixture of INT 11 (50.0 mg, 128 μmol, 1.00 eq) and 1-methyl-azetidin-3-one (16.4 mg, 192 μmol, 1.50 eq) in MeOH (500 μL) was added AcOH (769 μg, 12.81 μmol, 0.10 eq) . After stirring at 20 ℃for 0.5 h, and then NaBH3CN (20.1 mg, 320 μmol, 2.50 eq) was added. The reaction mixture was stirred at 50 ℃ for 12 hrs., and then concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Waters Xbridge Prep OBD C18 150*40 mm*10 um; Mobile phase: H2O (0.05%NH3H2O+NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 10%-55%ACN; Flow Rate: 8.0 mins) to afford Compound 67 (25.0 mg, 54.41 μmol, 42.48%yield) as a white solid.1HNMR (400 MHz, DMSO-d6) δ 7.68 (d, J = 8.1 Hz, 2H) , 7.46-7.38 (m, 3H) , 6.84 (d, J = 2.0 Hz, 1H) , 5.28 (s, 2H) , 3.96 (s, 2H) , 3.74 (s, 2H) , 3.67-3.58 (m, 3H) , 3.18-3.11 (m, 2H) , 2.57 (s, 3H) , 2.42 (s, 3H) .Example 11At 20 ℃, MeCHO (31.6 mg, 560 μmol, 40%purity, 3.00 eq) , AcOH (1.12 mg, 18.6 μmol, 0.10 eq) and NaBH3CN (29.3 mg, 466 μmol, 2.50 eq) were added to a solution of INT 12 (90.0 mg, 186 μmol, 1.00 eq) in MeOH (2.70 mL) . The reaction mixture was stirred at 50 ℃ for 12 hrs., and then concentrated under reduced pressure to give a residue which was purified with prep-HPLC (Column: Waters Xbridge Prep OBD C18 150*40 mm*10 um; Mobile phase: H2O (0.05%NH3H2O+NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 15%-45%ACN; Flow Rate: 8.0 mins) to afford Compound 70 (34.3 mg, 72.5 μmol, 38.8%yield) as a white solid.1HNMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H) , 7.75 (d, J = 8.1 Hz, 2H) , 7.53 (d, J = 2.0 Hz, 1H) , 7.42 (d, J = 8.1 Hz, 2H) , 7.14 (d, J = 2.0 Hz, 1H) , 5.26 (s, 2H) , 3.84-3.72 (m, 4H) , 3.52 (t, J = 6.3 Hz, 1H) , 3.39 (d, J = 6.8 Hz, 4H) , 2.93 (br s, 2H) , 2.49-2.35 (m, 3H) , 0.88 (t, J = 7.2 Hz, 3H) .Example 12At 20 ℃, AcOH (1.25 mg, 20.7 μmol, 1.19 μL, 0.100 eq) and NaBH3CN (32.6 mg, 518 μmol, 2.50 eq) were successively added to a solution of INT 12 (100 mg, 207 μmol, 1.00 eq) and (tert-ButyldiMethylsilyloxy) acetaldehyde (54.2 mg, 311 μmol, 59.3 μL, 1.50 eq) in MeOH (3.00 mL) . After stirring at 50 ℃ for 12 hrs., aq. HCl (12 M, 1.00 mL) was added. The reaction mixture was stirred at 20 ℃ for 1 h, and then concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Waters Xbridge Prep OBD C18 150*40 mm*10 um; Mobile phase: H2O (0.05%NH3H2O+NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 15%-45%ACN; Flow Rate: 8.0 mins) to afford Compound 71 (43.37 mg, 88.6 μmol, 42.7%yield) as a yellow solid.1HNMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H) , 7.75 (d, J = 8.1 Hz, 2H) , 7.53 (d, J = 2.0 Hz, 1H) , 7.43 (d, J = 7.9 Hz, 2H) , 7.14 (d, J = 1.8 Hz, 1H) , 5.26 (s, 2H) , 4.36 (t, J = 5.3 Hz, 1H) , 3.80 (br s, 2H) , 3.74 (br s, 2H) , 3.51 (t, J = 6.3 Hz, 2H) , 3.39 (t, J = 7.0 Hz, 4H) , 2.94 (t, J = 6.8 Hz, 2H) , 2.49 -2.44 (m, 3H) .The compounds in the following table could be synthesized using the procedure or modification procedure of any one of Compound 5 to Compound 10, with the corresponding starting material and corresponding intermediates.Example 13DIEA (662 mg, 892 μL, 2.00 eq) was added to a solution of INT 11 (1.00 g, 1.00 eq) in MeCN (20.0 mL) at 20 ℃, and then a solution of tert-butyl 2-bromoacetate (549 mg, 416 μL, 1.10 eq) in MeCN (1.00 mL) was dropwise added at 0 ℃. The reaction mixture was stirred at 0 ℃ for 4 hrs., poured into water (50.0 mL) and then extracted with EA (15.0 mLx4) . The combined organic layers were washed with brine (20.0 mL) , dried with Na2SO4, and concentrated under reduced pressure to obtain a crude product which was purified with silica gel column chromatography (eluting with PE / EA) to afford Compound 73 (700 mg, 54.2%yield) as a solid. LCMS: m / z = 505.2 [M+1] +. 1HNMR (400 MHz, CDCl3) δ 7.93 (s, 1H) , 7.52 (d, J = 8.1 Hz, 2H) , 7.23 -7.18 (m, 3H) , 6.41 (d, J = 1.9 Hz, 1H) , 5.04 (s, 2H) , 4.21 (br s, 2H) , 3.86 (br s, 2H) , 3.44 (s, 2H) , 2.53 (s, 3H) , 1.38 (s, 9H) .To a solution of Compound 73 (700 mg, 1.00 eq) in DCM (7.00 mL) was added HCl / 1, 4-dioxane (4 M, 1.75 mL, 5.05 eq) at 20 ℃. The reaction mixture was stirred at 25 ℃ for 16 hrs., and then concentrated under reduced pressure below 45 ℃ to obtain Compound 74 (650 mg) as a solid. LCMS: m / z = 449.1 [M+1] +.At 20 ℃, to a solution of Compound 74 (100 mg, 1.00 eq) in DMF (2.00 mL) was added HATU (127 mg, 1.50 eq) , DIEA (86.4 mg, 116 μL, 3.00 eq) and pyridin-3-amine (104 mg, 5.00 eq) . The reaction mixture was stirred at 20 ℃ for 16 hrs., and then purified with prep-HPLC (C18 column, eluting with H2O / CH3CN) to afford Compound 75 (43.0 mg, 36.8%yield) as a solid. LCMS: m / z = 525.2 [M+1] +. 1HNMR (400 MHz, CDCl3) δ 9.15 (s, 1H) , 8.62 (d, J = 2.4 Hz, 1H) , 8.39 (dd, J = 1.4, 4.7 Hz, 1H) , 8.29 -8.22 (m, 1H) , 7.89 (s, 1H) , 7.66 (d, J = 8.1 Hz, 2H) , 7.38 -7.29 (m, 4H) , 6.51 (d, J = 2.0 Hz, 1H) , 5.18 (s, 2H) , 4.32 (s, 2H) , 3.91 (s, 2H) , 3.62 (s, 2H) , 2.63 (s, 3H) .The compounds in the following table could be synthesized using the procedure or modification procedure of Compound 75, with the corresponding starting material and corresponding intermediate INT 11.Example 14At 20 ℃, DBU (2.34 g, 2.50 eq) and 2-methylpropan-2-yl prop-2-enoate (1.18 g, 1.50 eq) were added to a solution of INT11 (2.4 g, 1.00 eq) in MeOH (25.00 mL) . The reaction mixture was stirred at 20 ℃ for 12 hrs., poured into water (100 mL) and extracted with EA (120 mL*4) . The combined organic layers were washed with brine (100 mL) , dried with Na2SO4, and concentrated under reduced pressure to give a residue which was purified with prep-TLC (eluting with PE / EA) to afford Compound 77 (320.0 mg) as a solid. LCMS: m / z = 519.2 [M+1] +.To a solution of Compound 77 (320 mg, 1.00 eq) in DCM (1.60 mL) was added TFA (494 mg, 0.320 mL) at 20 ℃. The reaction mixture was stirred at 20 ℃ for 2 hrs., and then concentrated under reduced pressure to give a crude which was purified with prep-HPLC (C18 column, eluting with H2O / CH3CN) to afford Compound 78 (100 mg, 34.9%yield) as a solid. LCMS: m / z = 463.2 [M+1] +.1HNMR (400 MHz, MeOH-d4) : δ 7.68 (d, J = 8.4 Hz, 2H) , 7.47 (d, J = 8.0 Hz, 2H) , 7.39 (d, J =2.0 Hz, 1H) , 6.83 (d, J = 2.0 Hz, 1H) , 5.31 (s, 2H) , 4.56 (s, 2H) , 4.35 (s, 2H) , 3.46 (t, J = 6.4 Hz, 2H) , 2.58-2.59 (m, 2H) , 2.56 (s, 3H)To a mixture of Compound 78 (100 mg, 1.00 eq) and 2-methylpropan-2-amine (15.8 mg, 1.05 eq) in DMF (1.00 mL) was added NMI (35.5 mg, 2.00 eq) and TCFH (72.8 mg, 259 μmol, 1.20 eq) at 25 ℃. The reaction mixture was stirred at 25 ℃ for 2 hrs., and then purified with prep-HPLC (C18 column, eluting with H2O / CH3CN) to afford Compound 79 (34.1 mg, 30.5%yield) as a solid. LCMS: m / z =518.1 [M+1] +.1HNMR (400 MHz, DMSO-d6) δ 10.31 (s, 1H) , 7.74 (d, J = 8.0 Hz, 2H) , 7.57 (s, 1H) , 7.53 (d, J =2.0 Hz, 1H) , 7.41 (d, J = 7.9 Hz, 2H) , 7.15 (d, J = 1.9 Hz, 1H) , 5.26 (s, 2H) , 3.83 (s, 2H) , 3.73 (s, 2H) , 2.87 (t, J = 6.9 Hz, 2H) , 2.53 (s, 3H) , 2.22 (t, J = 7.2 Hz, 2H) , 1.23 (s, 9H) .The compounds in the following table could be synthesized using the procedure or modification procedure of Compound 79, with the corresponding starting material and corresponding intermediate INT 11.Example 15At 20 ℃, t-BuONa (377 mg, 3.00 eq) was added to a solution of INT 8 (500 mg, 1.00 eq) and 5-bromo-3-methylpyridine (269 mg, 1.20 eq) in dioxane (5.00 mL) , and then BrettPhos Pd G3 (118 mg, 0.100 eq) was added under an atmosphere of N2. The reaction mixture was stirred at 100 ℃ for 12 hrs., and then filtered. The filtrate was concentrated under reduced pressure to obtain a residue which was purified with silica gel column chromatography (The gradient of eluent is DCM / MeOH = 100 / 1 to 0 / 1) to afford Compound 83-1 (210 mg) as an oil. LCMS: m / z = 474.2 [M+1] +. 1HNMR (400 MHz, CDCl3) δ 8.18-8.08 (m, 1H) , 7.92 (br s, 1H) , 7.62 -7.49 (m, 3H) , 7.29 (d, J = 7.9 Hz, 2H) , 7.23 (d, J = 8.1 Hz, 1H) , 5.10 (d, J = 3.1 Hz, 2H) , 4.26-4.17 (m, 4H) , 2.23 (d, J = 4.0 Hz, 3H) , 1.39 (s, 9H) .A solution of Compound 83-1 (50.0 mg, 1.00 eq) in HCl / dioxane (500 μL) was stirred at 20 ℃ for 1 h and the concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Waters Xbridge Prep OBD C18 150*40 mm*10 um; Mobile phase: H2O (0.05%NH3H2O+NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 10%-40%ACN; Flow Rate: 8.0 mins) to afford Compound 83 (13.79 mg, 34.9%yield) as a solid. LCMS: m / z = 374.1 [M+1] +. 1H NMR (400 MHz, DMSO-d6) : δ 8.70-8.47 (m, 1H) , 8.37-8.24 (m, 1H) , 7.83-7.71 (m, 3H) , 7.59 -7.42 (m, 3H) , 5.31-5.18 (m, 2H) , 4.38-4.21 (m, 1H) , 3.76 (br d, J = 14.7 Hz, 3H) , 2.24-2.18 (m, 3H) .At 20 ℃, HCHO (22.8 mg, 20.9 μL, 37%purity, 1.50 eq) , AcOH (1.13 mg, 1.07 μL, 0.100 eq) and NaBH3CN (29.4 mg, 2.50 eq) were added successively to a solution of Compound 83 (70.0 mg, 1.00 eq) in MeOH (1.40 mL) . The reaction mixture was stirred at 50 ℃ for 12 hrs., and then concentrated under reduced pressure to obtain a residue. The residue was purified with prep-HPLC (Column: Phenomenex Gemini-NX 80*40mm*3um; Mobile phase: H2O (NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 30%-50%ACN; Flow Rate: 8.0 mins) to afford Compound 84 (18.8 mg, 25.9%yield) as a solid. LCMS: m / z = 388.2 [M+1] +.1H NMR (400 MHz, DMSO-d6) : δ 8.52 (s, 1H) , 8.29 (d, J = 2.3 Hz, 1H) , 7.78 (s, 1H) , 7.74 (d, J =8.1 Hz, 2H) , 7.46 (d, J = 5.6 Hz, 2H) , 7.44 (s, 1H) , 5.23 (s, 2H) , 3.65 (s, 2H) , 3.58 (s, 2H) , 2.47 (s, 3H) , 2.21 (s, 3H) .Example 16At 0 ℃, NaBH3CN (29.4 mg, 468 μmol, 2.50 eq) and AcOH (1.13 mg, 18.7 μmol, 1.07 μL, 0.100 eq) were added to a solution of INT 13 (70.0 mg, 187 μmol, 1.00 eq) in MeOH (700 μL) , and then 1-ethoxy-1- (trimethylsiloxy) cyclopropane (49.0 mg, 281 μmol, 56.5 μL, 1.50 eq) was dropwise added. The reaction mixture was stirred at 65 ℃ for 12 hrs., and then concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Waters Xbridge BEH C18 100*30 mm*10 um; Mobile phase: H2O (NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 25%-70%ACN; Flow Rate: 8.0 mins) to afford Compound 85 (16.36 mg, 39.5 μmol, 21.1%yield) as a white solid.1HNMR: (400 MHz, DMSO-d6) δ 8.51 (s, 1H) , 8.29 (d, J = 2.4 Hz, 1H) , 7.78 (s, 1H) , 7.74 (d, J =8.0 Hz, 2H) , 7.47 (d, J = 4.1 Hz, 2H) , 7.44 (s, 1H) , 5.23 (s, 2H) , 3.80 (s, 2H) , 3.71 (s, 2H) , 2.20 (s, 3H) , 2.19-2.14 (m, 1H) , 0.47-0.41 (m, 2H) , 0.38 (d, J = 2.8 Hz, 2H)The compounds in the following table could be synthesized using the procedure or modification procedure of Compound 84 or Compound 85, with the corresponding starting material and corresponding intermediates.Example 17To a solution of INT 10 (40.0 mg, 91.2 μmol, 1.00 eq) in MeOH (0.4 mL) and H2O (0.1 mL) was added KOH (15.4 mg, 274 μmol, 3.00 eq) . The mixture was stirred at 100 ℃ for 3 hrs., diluted with HCl (2 N) until the pH=4 and then extracted with DCM (20 mL) . The combined organic layers were washed with brine (2 mL) , dried over Na2SO4, and concentrated under reduced pressure to obtain a residue which was purified with prep-HPLC (Column: Phenomenex C18 75*30mm*3um; Mobile phase: H2O (NH4HCO3 (10 mM) ) / ACN; The gradient of mobile phase: 5%-35%ACN; Flow Rate: 8.0 mins) to afford Compound 119 (5.95 mg, 12.7 μmol, 13.9%yield) as a white solid and Compound 120 (5.77 mg, 12.6 μmol, 13.8%yield) as a white solid.The compounds in the following table were synthesized using the above procedures or modification procedures:Pharmacological Experiments1. Fascin and F-actin bundling assayThe Materials and Reagents of the F-actin bundling assay as shown in the following Table 1:Table 1Each compound to be tested of the invention were reconstituted to a concentration 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 compound 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 compound 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 compound 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 results of Inhibitory rate of compounds (30uM) to be tested in the Presence are shown in Table 2:Table 2 The Inhibitory rate of the compounds (30uM)From Table 2, It can be seen that the representative compounds of the present invention have good inhibitory effect on Actin bundling.2. Boyden-chamber Cell Migration AssayBoyden chamber assays for cell migration can be used to confirm that the compounds described here inhibit tumor cells activity in migration (such as breast tumor cells) .The Materials, Reagents, Plates and Instrumentation of the Boyden-chamber Cell Migration Assay as shown in the following Table 3:Table 3The 4T1 cell line was incubated in DMEM medium containing 10%fetal bovine serum and 1%Penicillin-Streptomycin, and subsequently continued to be cultured until cell confluency reached 60-80%. The medium was removed and the cells was washed with PBS. The 4T1 cells was then incubated overnight in serum-free DMEM culture medium at 37 ℃ at an atmosphere of CO2 (5%) . The following day, cells was trypsinized and resuspended in FBS-free culture medium. The cells were counted and diluted to a density of 2 x 105 cells / mL with serum-free medium. The cell suspension (200 μL) was seeded into the upper chamber of an insert to achieve a final cell density was 4 x 104 cells / well. Each compound to be tested was reconstituted to a concentration of 9 mM using DMSO. Each compound to be tested was either diluted with serum-free DMEM medium to obtain a concentration of 90 μM, or diluted with DMEM medium containing 10%FBS to obtain a concentration of 30 μM to obtain the test medium. 100 μL of the test medium without FBS was added to the upper chamber of the Transwell, and 600 μL of the test medium with FBS was added to the lower chamber. The cells were incubated at 37 ℃at an atmosphere of CO2 (5%) for 6 hrs. Wells containing same percent of DMSO served as vehicle control;Transwell inserts were washed and fixed for 15 min with 4%paraformaldehyde. Migrated Cells were stained with Crystal violet staining solution for 10 min and cells on the upper side of the insert were removed with a cotton swab. Five randomly selected fields (10x Objective lens) on the lower side of the insert were photographed, and the migrated cells were counted. Migration index was expressed as relative number of migrated cells in the presence of compound over in the absence of compound (DMSO) .The Migration index data in the Boyden-chamber Cell Migration Assay are shown in the following Table 1:Table 4From Table 4, it can be seen that the representative compounds of the present invention have strong inhibition of cell migration.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, a deuterated derivative 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 deuterated derivative thereof: Wherein,R1 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R1 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;R2 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R2 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;Optionally, R1 and R2 together with the atoms to which they are respectively attached lead to the moiety offormingwhen the moiety ofisX1 is selected from N or CR7;X2 is selected from N or CR8;X3 is selected from N or CR9;X4 is selected from N or CR10;R7 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R7 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;R8 is selected from hydrogen, -C (=O) N (R81) 2, -NHC (=O) (R81) , -S (=O) N (R81) 2, -NHS (=O) (R81) , -S (=O) 2N (R81) 2 or -NHS (=O) 2 (R81) ;said R81 is each independently selected from 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;R9 is selected from hydrogen, - (C1-6alkylene) -R91, -C (=O) (OR92) , -S (=O) (OR92) , -S (=O) 2 (OR92) , -C (=O) -NHR92, -S (=O) -NHR92, -S (=O) 2-NHR92, -C (=O) (R93) , -S (=O) (R93) , -S (=O) 2 (R93) , -OC (=O) (R93) , -OS (=O) (R93) , -OS (=O) 2 (R93) , -NH-C (=O) (R93) , -NH-S (=O) (R93) , -NH-S (=O) 2 (R93) ,said R91 at each occurrence is independently selected from -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;said R92 is each independently selected from 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R92 is optionally substituted with one or more substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;said R93 at each occurrence is independently selected from halogen, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;X2 and X3 are not N at the same time;when X2 is CR8 and X3 is CR9, only one of R8 and R9 is hydrogen;R10 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R10 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;when the moiety ofisn4 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;n5 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;Y2 is selected from -C (RY2) 2-, -RY2C=CRY2-, -C≡C-, -O-, -NRY3-, -S-, -C (=O) -, -S (=O) -, -S (=O) 2-, **-C (=O) O-, **-C (=O) NRY4-, **-NRY4C (=O) -, **-S (=O) NRY4-, **-NRY4S (=O) -, **-S (=O) 2NRY4-or **-NRY4S (=O) 2-; **indicates the attached point to the moiety ofRY2 at each occurrence is independently selected from hydrogen, halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said R1 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;RY3 at each occurrence is independently selected from hydrogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; said RY3 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY31;RY31 at each occurrence is independently selected from halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -N3, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;RY32 at each occurrence is independently selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;RY4 at each occurrence is independently selected from hydrogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , -C (=O) (C1-6alkyl) , -C (=O) NH2, -C (=O) NH (C1-6alkyl) , -C (=O) N (C1-6alkyl) 2, 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said RY4 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;R4 at each occurrence is independently selected from -H, halogen, -C1-6alkyl or haloC1-6alkyl;R5 at each occurrence is independently selected from -H, halogen, -C1-6alkyl or haloC1-6alkyl;R6 at each occurrence is independently selected from -H, halogen, -C1-6alkyl, -OC1-6alkyl or haloC1-6alkyl;said Y1 is selected from absent, -C (RY1A) 2-, -RY1AC=CRY1A-, -C≡C-, -N (RY1B) 2-, -O-, -S-, -C (=O) -, -S (=O) -, -S (=O) 2-, -C (=O) O-*, -OC (=O) -*, -N (RY1B) -C (=O) -*, -C (=O) -N (RY1B) -*, -N (RY1B) -S (=O) -*, -S (=O) -N (RY1B) -*, -N (RY1B) -S (=O) 2-*or -S (=O) 2-N (RY1B) -*; *indicates the attached point to the ring B;said RY1A is selected from -H, halogen, -C1-6alkyl or haloC1-6alkyl;said RY1B is selected from -H or -C1-6alkyl;ring B is selected from a 3-14 membered carbocyclic ring, a 3-14 membered heterocyclic ring, a 6-14 membered aryl ring or a 5-14 membered heteroaryl ring;RS1, RS2 or RS3 at each occurrence is independently selected from halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl; wherein, said RS1, RS2 or RS3 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-6alkyl, haloC1-6alkyl, -C2-6alkoxy, haloC2-6alkoxy, -C2-6alkenyl, -C2-6alkynyl, -CN, -NO2, -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) , -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) , 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, 6-12 membered aryl or 5-10 membered heteroaryl;n1 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;n2 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;n3 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;said heterocyclyl at each occurrence is independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S (=O) , S (=O) 2;said heteroaryl at each occurrence is independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S.2.A compound of formula (I-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,R4, R5, R6, R7, R8, R9, R10, ring B, Y1, Y2, RS1, RS2, RS3, n1, n2, n3, n4 and n5 have the same definitions as in claim 1.3.A compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,R8 is selected from -H, -NHC (=O) (R81) , -NHS (=O) (R81) , -NHS (=O) 2 (R81) , -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-10 membered carbocyclyl, 3-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, haloC1-3alkoxy, oxo, -CN, -OH, -SH, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;R9 is selected from -H, - (C0-3alkylene) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) or -S (=O) 2 (R93) ;said R91 is each independently selected from -C2-3alkenyl, -C2-3alkynyl, -C2-3alkoxy, haloC2-3alkoxy, oxo, -CN, -OH, -SH, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;said R92 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; said R92 is optionally substituted with one or more substituents selected from halogen, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, oxo, -CN, -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) , -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;said R93 is each independently selected from halogen;only one of R8 and R9 is hydrogen;R7 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;R10 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;R4, R5, R6, Y1, ring B, RS1, RS2, n1 and n2 have the same definitions as in claim 1.4.The compound of formula (I) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-3, wherein,R8 is selected from -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, or 5-6 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -CN, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C (=O) (OC1-3alkyl) , -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 or -NHS (=O) 2 (C1-3alkyl) ;preferably, R8 is selected from -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl or 5-6 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -CN, -C1-3alkyl or -C (=O) (OC1-3alkyl) ;more preferably, R8 is selected from -NHC (=O) (R81) , -S (=O) 2NH (R81) or -NHS (=O) 2 (R81) ;said R81 is selected fromthienyl, furanyl, pyridinyl, oxazolyl, isoxazolyl, thiazolyl or isothiazolyl; said R81 is optionally substituted with one or more substituents selected from -Cl, -F, -Br, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) or -C (=O) (OCH (CH3) 2) ;More preferably, R8 is selected fromfurther preferably, R8 is selected from5.The compound of formula (I) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-4, wherein,R9 is selected from -H, - (C1-3alkylene) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) , -S (=O) 2 (R93) ,said R91 is each independently selected from -CN, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C (=O) OH, -C (=O) (OC1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) or -S (=O) 2N (C1-3alkyl) 2;said R92 is each independently selected from phenyl or 5-10 membered heteroaryl;said R93 is each independently selected from halogen;Preferably, R9 is selected from -H, -CH2-R91, -CH2CH2-R91, -CH2CH2CH2-R91, -CH2 (CH2) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) , -S (=O) 2 (R93) ,said R91 is each independently selected from -CN, -OH, -O-CH3, -O-CH2CH3, -O-CH2CH2CH3, -O-CH (CH3) 2, -SH, -S-CH3, -S-CH2CH3, -S-CH2CH2CH3, -S-CH (CH3) 2, -NH2, -NH (CH3) , -N (CH3) 2, -NH (CH2CH3) , -C (=O) OH, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) NH2, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -S (=O) NH2, -S (=O) NH (CH3) , -S (=O) NH (CH2CH3) , -S (=O) NH (CH2CH2CH3) , -S (=O) NH (CH (CH3) 2) , -S (=O) N (CH3) 2, -S (=O) 2NH2, -S (=O) 2NH (CH3) , -S (=O) 2NH (CH2CH3) , -S (=O) 2NH (CH2CH2CH3) , -S (=O) 2NH (CH (CH3) 2) or -S (=O) 2N (CH3) 2;said R92 is each independently selected from hydrogen, phenyl, pyrrolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, tetrazolyl, pyrazolyl, triazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, isoindolyl or indolizinyl;said R93 is each independently selected from -F, -Br or -Cl;More preferably, R9 is selected from -CH2-CN, -CH2-OH, -CH2-O-CH3, -CH2-O-CH2CH3, -CH2-O-CH2CH2CH3, -CH2-O-CH (CH3) 2, -CH2-SH, -CH2-S-CH3, -CH2-S-CH2CH3, -CH2-S-CH2CH2CH3, -CH2-S-CH (CH3) 2, -CH2-NH2, -CH2-NH (CH3) , -CH2-N (CH3) 2, -CH2-NH (CH2CH3) , -CH2-C (=O) OH, -CH2-C (=O) (OCH3) , -CH2-C (=O) (OCH2CH3) , -CH2-C (=O) (OCH2CH2CH3) , -CH2-C (=O) (OCH (CH3) 2) , -CH2-C (=O) NH2, -CH2-C (=O) NH2, -CH2-C (=O) NH (CH3) , -CH2-C (=O) NH (CH2CH3) , -CH2-C (=O) NH (CH2CH2CH3) , -CH2-C (=O) NH (CH (CH3) 2) , -CH2-C (=O) N (CH3) 2, -C (=O) -Cl, -S (=O) -Cl or -S (=O) 2-Cl;further preferably, R9 is selected from6.The compound of formula (I) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-5, wherein,R7 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;preferably, R7 is each independently selected from -H, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3;more preferably, R7 is -H.7.The compound of formula (I) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-6, wherein,R10 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;preferably, R10 is each independently selected from -H, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3;more preferably, R10 is -H.8.The compound of formula (I) or formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-7, wherein,The moiety ofis selected fromPreferably, the moiety ofis selected from9.A compound of formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,Y2 is selected from -C (RY2) 2-, -O-, -NRY3-, -S-, **-C (=O) NRY4-, **-NRY4C (=O) -, **-S (=O) NRY4-, **-NRY4S (=O) -, **-S (=O) 2NRY4-or **-NRY4S (=O) 2-; **indicates the attached point to the moiety ofRY2 is selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C1-3alkoxy, -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 carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl;RY3 is selected from -H, -C1-6alkyl, -C (=O) (C1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said RY3 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY31;said RY31 is each independently selected from halogen, -C1-3alkyl, -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) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-4alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-4alkyl) or -S (=O) 2N (C1-3alkyl) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -C2-3alkoxy, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) or 5-10 membered heteroaryl;RY4 is selected from -H, -C1-6alkyl, -C (=O) (C1-6alkyl) , -S (=O) (C1-6alkyl) , -S (=O) 2 (C1-6alkyl) , 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; said RY4 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from halogen, -C1-3alkyl, -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) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-4alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-4alkyl) or -S (=O) 2N (C1-3alkyl) 2;n4 is selected from 0, 1, 2, 3, 4, 5 or 6;n5 is selected from 0, 1, 2, 3, 4, 5 or 6;R4, R5, R6, Y1, ring B, RS1, RS2, RS3, n1, n2 and n3 have the same definitions as in claim 1.10.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9, wherein,Y2 is selected from -C (RY2) 2-, -O-, -S-, -NRY3-, **-C (=O) NRY4-or **-NRY4C (=O) ; **indicates the attached point to the moiety ofPreferably, Y2 is selected from -C (RY2) 2-, -O-, -S-or -NRY3-.11.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-10, wherein, the compound is selected from any one of the following formulas: wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, RY2, RY3, RY4, Y1 and ring B have the same definitions as in claim 1.12.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-11, wherein,n4 is selected from 0, 1, 2, 3 or 4;preferably, n4 is selected from 0, 1 or 2.13.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-12, wherein,n5 is selected from 0, 1, 2, 3 or 4;preferably, n5 is selected from 0, 1 or 2.14.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-13, wherein,n4 is 0, and n5 is 1; orn4 is 0, and n5 is 2; orn4 is 1, and n5 is 0; orn4 is 2, and n5 is 0; orn4 is 1, and n5 is 1; orn4 is 1, and n5 is 2; orn4 is 2, and n5 is 1; orn4 is 2, and n5 is 2.15.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-14, wherein, n4 is 1, and n5 is 1.16.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-15, wherein,RY2 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;preferably, RY2 is selected from -H, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;more preferably, RY2 is -H.17.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-16, wherein, the moiety of is selected from preferably, the moiety ofis selected from18.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-15, wherein,RY3 is selected from -H, -C1-3alkyl, -C (=O) (C1-3alkyl) , 3-7 membered carbocyclyl or 3-7 membered heterocyclyl; said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -C1-3alkyl, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) or -C (=O) N (C1-3alkyl) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -C2-3alkoxy, -OH, -O (C1-3alkyl) or 5-10 membered heteroaryl;preferably, RY3 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH2CH2CH3) , -C (=O) (CH (CH3) 2) , said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -OH, -O-CH3, -O-CH2CH3, -O-CH2CH2CH3, -O-CH (CH3) 2, -C (=O) CH3, -C (=O) (CH2CH3) , -C (=O) -CH (CH3) 2, -C (=O) OH, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) (OC (CH3) 3) , -C (=O) NH2, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) NH (C (CH3) 3) , -C (=O) N (CH3) 2 or -C (=O) N (CH2CH3) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -CH3-O-CH3, -CH2CH3-O-CH3, -CH2-O-CH2CH3, -CH (CH3) -O-CH3, -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, thienyl, furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl;More preferably, RY3 is selected from -H, -CH3, -CH2CH3, -C (=O) (CH3) , said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -CH3, -CH2CH3, -OH, -C (=O) CH3, -C (=O) OH, -C (=O) (OC (CH3) 3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH (CH3) 2) or -C (=O) NH (C (CH3) 3) ; said RY31 is independently optionally substituted with 1, 2 or 3 RY32;said RY32 is each independently selected from -OH, -O-CH3 or pyridinyl;More preferably, RY3 is selected from -H, -CH3, -CH2CH3, -CH2COOH, -CH2CH2COOH, -CH2COOC (CH3) 3, -CH2CH2COOC (CH3) 3, -CH2CH2OH, -CH2-C (=O) -NH (CH3) , -CH2CH2-C (=O) -NH (CH3) , -CH2CH2-C (=O) -NH (CH2CH3) , -CH2CH2-C (=O) -NH (CH (CH3) 2) , -CH2CH2-C (=O) -NH (C (CH3) 3) , -C (=O) -CH3, Further preferably, RY3 is selected from -CH2CH2COOH, -CH2CH2OH, -C (=O) -CH3, 19.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-15 and 18, wherein,The moiety ofis selected fromPreferably, the moiety ofis selected from20.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-15, wherein,The moiety ofis selected from21.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-15, wherein,The moiety ofis selected from22.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-15, wherein,RY4 is selected from -H, -C1-3alkyl or haloC1-3alkyl;preferably, RY4 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;more preferably, RY4 is -H.23.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-15 and 22, wherein,The moiety ofis selected frompreferably, the moiety ofis selected from24.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-2 and 9-15 and 22-23, wherein,the moiety ofis selected frompreferably, the moiety ofis selected from25.The compound of formula (I) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of any one of 1-24, wherein,the moiety ofis selected frompreferably, the moiety ofis selected from26.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-25, wherein,the moiety ofis selected from27.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-26, wherein,Y1 is selected from absent, -C (RY1A) 2-, -N (RY1B) -, -O-, -S-, -C (=O) -N (RY1B) -*, -S (=O) -N (RY1B) -*, -S (=O) 2-N (RY1B) -*, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;preferably, Y1 is selected from -N (RY1B) -, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;more preferably, Y1 is selected from -N (RY1B) -or -N (RY1B) -C (=O) -*; *indicates the attached point to the ring B;RY1A is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl; preferably, RY1A is selected from -H or -C1-3alkyl; more preferably, RY1A is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1A is selected from -H or -CH3;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3.28.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-27, wherein,Y1 is selected from absent, -O-, -S-, -CH2-, -CH (CH3) -, -NH2-, -NH (CH3) -, -NH-C (=O) -*, -N (CH3) -C (=O) -*, -NH-S (=O) -*, -N (CH3) -S (=O) -*, -NH-S (=O) 2-*, -N (CH3) -S (=O) 2-*, -C (=O) -NH-*, -C (=O) -N (CH3) -*, -S (=O) -NH-*, -S (=O) -N (CH3) -*, -S (=O) 2-NH-*, -S (=O) 2-N (CH3) -*;preferably, Y1 is selected from -NH2-, -NH (CH3) -, NH-C (=O) -*, -N (CH3) -C (=O) -*, -NH-S (=O) -*, -N (CH3) -S (=O) -*, -NH-S (=O) 2-*, -N (CH3) -S (=O) 2-*; *indicates the attached point to the ring B;more preferably, Y1 is selected from -NH2-, -NH (CH3) -, -NH-C (=O) -*or -N (CH3) -C (=O) -*; *indicates the attached point to the ring B.29.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-28, wherein, Y1 is selected from -NH2-.30.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-28, wherein, Y1 is selected from -NH-C (=O) -*; *indicates the attached point to the ring B.31.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-30, wherein,R4 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;preferably, R4 is each independently selected from -H or -C1-3alkyl;more preferably, R4 is each independently selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2;further preferably, R4 is each independently selected from -H or -CH3.32.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-31, wherein,R5 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;preferably, R5 is each independently selected from -H or -C1-3alkyl;more preferably, R5 is each independently selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2;further preferably, R5 is each independently selected from -H or -CH3.33.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-32, wherein,R4 is each independently selected from -H or -C1-3alkyl; and R5 is each independently selected from -H or -C1-3alkyl;preferably, R4 is each independently selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; and R5 is each independently selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2;more preferably, R4 is each independently selected from -H or -CH3; and R5 is each independently selected from -H or -CH3;further preferably, R4 is each independently selected from -H; and R5 is each independently selected from -H.34.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-33, wherein, the compound is selected from any one of the following formulas: wherein,R1, R2, R4, R5, R6, R7, R8, R9, R10, RY2, RY3, RY4, ring B, Y2, RS1, RS2, RS3, n1, n2, n3, n4 and n5 have the same definitions as in any one of claims 1-33.35.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-34, wherein,R6 at each occurrence is independently selected from -H, halogen, -C1-3alkyl, -OC1-3alkyl or haloC1-3alkyl;preferably, R6 at each occurrence is independently selected from -H, -OC1-3alkyl or haloC1-3alkyl;more preferably, R6 at each occurrence is independently selected from -H, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;further preferably, R6 at each occurrence is independently selected from -H, -OCH3 or -CF3.36.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-35, wherein, R6 at each occurrence is independently selected from -CF3.37.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-36, wherein, the moiety of is selected from 38.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-37, wherein, the moiety of is selected from 39.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-38, wherein, the compound is selected from any one of the following formulas: wherein,X1, X2, X3, X4, R1, R2, R4, R5, R7, R8, R9, R10, RY2, RY3, RY4, ring B, Y2, RS1, RS2, RS3, n1, n2, n3, n4 and n5 have the same definitions as in any one of claims 1-38.40.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-39, wherein,ring B is selected from a phenyl 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 5-6 membered heteroaryl ring containing 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S;more preferablyring B is selected from 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) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-40, wherein,ring B is selected frompreferably, ring B is selected frommore preferably, ring B is selected fromfurther preferably, ring B is selected from42.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-41, wherein,RS2 is each independent selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, haloC2-3alkoxy, -C2-3alkenyl, -C2-3alkynyl, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , oxo, -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; said RS2 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) ;preferably, RS2 is each independent selected from halogen, -C1-3alkyl, -CN, oxo, -C (=O) OH, -C (=O) (OC1-3alkyl) , -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, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-6 heteroaryl; said heterocyclyl contains 1, 2 or 3 heteroatoms selected from N, O or S; said heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S;more preferably, RS2 is each independent selected from -C1-3alkyl, oxo, -CN;more preferably, RS2 is each independent selected from -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CN or oxo;further preferably, RS2 is each independent selected from -CH3, -CH2CH3, -CH (CH3) 2, -CN or oxo.43.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-42, wherein, n2 is selected from 0, 1, 2, 3, 4, 5 or 6; preferably, n2 is selected from 0, 1, 2, 3 or 4; more preferably, n2 is selected from 0, 1, 2 or 3; further preferably, n2 is selected from 0, 1 or 2.44.The compound of formula (I) , formula (I-1-1) or formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-43, wherein, the moiety of is selected from preferably, the moiety ofis selected frommore preferably, the moiety ofis selected fromfurther preferably, the moiety ofis selected from45.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-44, wherein, the compound is selected from any one of the following formulas: wherein,R1, R2, R4, R5, R7, R8, R9, R10, RY2, RY3, RY4, Y2, RS1, RS3, n1, n3, n4 and n5 have the same definitions as in any one of claims 1-44.46.A compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,R4 and R5 are each independently selected from -H or -C1-3alkyl;R6 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;R7 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;R8 is selected from -C (=O) N (R81) 2, -C (=O) NH (R81) , -S (=O) N (R81) 2, -S (=O) NH (R81) , -S (=O) 2N (R81) 2 or -S (=O) 2NH (R81) ;said R81 is each independently selected from 3-7 membered carbocyclyl, 3-7 membered heterocyclyl, or 5-6 membered heteroaryl; said R81 is optionally substituted with one or more substituents selected from halogen, -CN, -C1-3alkyl, -C2-3alkenyl, -C2-3alkynyl, -C (=O) (OC1-3alkyl) , -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 or -NHS (=O) 2 (C1-3alkyl) ;R9 is selected from -H, - (C1-3alkylene) -R91, -C (=O) -N (R92) 2, -S (=O) -N (R92) 2, -S (=O) 2-N (R92) 2, -C (=O) (R93) , -S (=O) (R93) , -S (=O) 2 (R93) ,said R91 is each independently selected from -CN, -OH, -O (C1-3alkyl) , -SH, -S (C1-3alkyl) , -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -C (=O) OH, -C (=O) (OC1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) or -S (=O) 2N (C1-3alkyl) 2;said R92 is each independently selected from phenyl or 5-10 membered heteroaryl;said R93 is each independently selected from halogen;only one of R8 and R9 is hydrogen;R10 is each independently selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;Y1 is selected from -N (RY1B) -, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3;ring B is selected from a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S;RS2 is each independent selected from halogen, -C1-3alkyl, -CN, oxo, -C (=O) OH, -C (=O) (OC1-3alkyl) , -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, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-6 heteroaryl; said heterocyclyl contains 1, 2 or 3 heteroatoms selected from N, O or S; said heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S;n2 is selected from 0, 1, 2 or 3;RS1 and n1 have the same definitions as in claim 1.47.The compound of formula (I-1-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of claim 46, wherein,the moiety ofis selected frompreferably, the moiety ofis selected from48.A compound of formula (I-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,Y2 is selected from -C (RY2) 2-, -O-, -NRY3-, -S-, **-C (=O) NRY4-, **-NRY4C (=O) -, **-S (=O) NRY4-, **-NRY4S (=O) -, **-S (=O) 2NRY4-or **-NRY4S (=O) 2-; **indicates the attached point to the moiety ofRY2 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;RY3 is selected from -H, -C1-3alkyl, -C (=O) (C1-3alkyl) , 3-7 membered carbocyclyl or 3-7 membered heterocyclyl; said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -C1-3alkyl, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) or -C (=O) N (C1-3alkyl) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -C2-3alkoxy, -OH, -O (C1-3alkyl) or 5-10 membered heteroaryl;RY4 is selected from -H, -C1-3alkyl or haloC1-3alkyl;n4 is selected from 0, 1, 2, 3 or 4;n5 is selected from 0, 1, 2, 3 or 4;Y1 is selected from -N (RY1B) -, -O-, -S-, -C (=O) -N (RY1B) -*, -S (=O) -N (RY1B) -*, -S (=O) 2-N (RY1B) -*, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3;R4 and R5 are each independently selected from -H or-C1-3alkyl;R6 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;Y1 is selected from -N (RY1B) -, -N (RY1B) -C (=O) -*, -N (RY1B) -S (=O) -*or -N (RY1B) -S (=O) 2-*; *indicates the attached point to the ring B;RY1B is selected from -H or -C1-3alkyl; more preferably, RY1B is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3 or -CH (CH3) 2; more preferably, RY1B is selected from -H or -CH3;ring B is selected from a 5-6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms selected from N, O or S;RS2 is each independent selected from halogen, -C1-3alkyl, -CN, oxo, -C (=O) OH, -C (=O) (OC1-3alkyl) , -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, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, 3-7 membered cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-6 heteroaryl; said heterocyclyl contains 1, 2 or 3 heteroatoms selected from N, O or S; said heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S;n2 is selected from 0, 1, 2 or 3;RS1, n1, RS3 and n3 have the same definitions as in claim 1.49.A compound of formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, RY2, Y1 and ring B have the same definitions as in claim 48.50.The compound of formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of claim 49, wherein,RY2 is selected from -H, halogen, -C1-3alkyl or haloC1-3alkyl;preferably, RY2 is selected from -H, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3 or -CF2CH3;more preferably, RY2 is -H.51.The compound of formula (I-2) and formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 49-50:wherein,The moiety ofis selected from52.A compound of formula (I-2-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, RY3, Y1 and ring B have the same definitions as in claim 48.53.The compound of formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of claim 52, wherein,RY3 is selected from -H, -C1-3alkyl, -C (=O) (C1-3alkyl) , 3-7 membered carbocyclyl or 3-7 membered heterocyclyl; said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -C1-3alkyl, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -C (=O) OH, -C (=O) (OC1-4alkyl) , -C (=O) NH2, -C (=O) NH (C1-4alkyl) or -C (=O) N (C1-3alkyl) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -C2-3alkoxy, -OH, -O (C1-3alkyl) or 5-10 membered heteroaryl;preferably, RY3 is selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -C (=O) (CH3) , -C (=O) (CH2CH3) , -C (=O) (CH2CH2CH3) , -C (=O) (CH (CH3) 2) , said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -OH, -O-CH3, -O-CH2CH3, -O-CH2CH2CH3, -O-CH (CH3) 2, -C (=O) CH3, -C (=O) (CH2CH3) , -C (=O) -CH (CH3) 2, -C (=O) OH, -C (=O) (OCH3) , -C (=O) (OCH2CH3) , -C (=O) (OCH2CH2CH3) , -C (=O) (OCH (CH3) 2) , -C (=O) (OC (CH3) 3) , -C (=O) NH2, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) NH (C (CH3) 3) , -C (=O) N (CH3) 2 or -C (=O) N (CH2CH3) 2; said RY31 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 RY32;said RY32 is each independently selected from -CH3-O-CH3, -CH2CH3-O-CH3, -CH2-O-CH2CH3, -CH (CH3) -O-CH3, -OH, -O-CH3, -O-CH2CH3, -O-CH (CH3) 2, thienyl, furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl;More preferably, RY3 is selected from -H, -CH3, -CH2CH3, -C (=O) (CH3) , said RY3 is independently optionally substituted with 1, 2 or 3 RY31;said RY31 is each independently selected from -CH3, -CH2CH3, -OH, -C (=O) CH3, -C (=O) OH, -C (=O) (OC (CH3) 3) , -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH (CH3) 2) or -C (=O) NH (C (CH3) 3) ; said RY31 is independently optionally substituted with 1, 2 or 3 RY32;said RY32 is each independently selected from -OH, -O-CH3 or pyridinyl;more preferably, RY3 is selected from -H, -CH3, -CH2CH3, -CH2COOH, -CH2CH2COOH, -CH2COOC (CH3) 3, -CH2CH2COOC (CH3) 3, -CH2CH2OH, -CH2-C (=O) -NH (CH3) , -CH2CH2-C (=O) -NH (CH3) , -CH2CH2-C (=O) -NH (CH2CH3) , -CH2CH2-C (=O) -NH (CH (CH3) 2) , -CH2CH2-C (=O) -NH (C (CH3) 3) , -C (=O) -CH3, Further preferably, RY3 is selected from -CH2CH2COOH, -CH2CH2OH, -C (=O) -CH3, 54.The compound of formula (I-2) and formula (I-2-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 52-53, wherein,the moiety ofis selected fromPreferably, the moiety ofis selected from55.A compound of formula (I-2-3) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,R4, R5, R6, RS1, RS2, RS3, n1, n2, n3, n4, n5, Y1 and ring B have the same definitions as in claim 48.56.The compound of formula (I-2) and formula (I-2-3) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of claim 55, wherein,the moiety ofis selected frompreferably, the moiety ofis selected from57.The compound of formula (I-2) , formula (I-2-1) , formula (I-2-2) and formula (I-2-3) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-56, wherein,The moiety ofis selected from58.A compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof: wherein,R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -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, phenyl or 5-10 heteroaryl; said R1 is optionally substituted with 1, 2 or 3 substituents selected from halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -CN, -NH2, -NH (C1-3alkyl) , -N (C1-3alkyl) 2, -OH, -O (C1-3alkyl) , -C (=O) (C1-3alkyl) , -S (=O) (C1-3alkyl) , -S (=O) 2 (C1-3alkyl) , -C (=O) OH, -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -NHC (=O) (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -NHS (=O) (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -NHS (=O) 2 (C1-3alkyl) or 3-7 membered cycloalkyl;R2 is each independent selected from -H, halogen, -C1-3alkyl, haloC1-3alkyl, -C2-3alkoxy, -CN, -C (=O) OH, -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) NH2, -C (=O) NH (C1-3alkyl) , -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) or 3-7 membered cycloalkyl;wherein,R4, R5, R6, RS1, RS2, n1, n2, Y1 and ring B have the same definitions as in claim 1.59.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of claim 58,wherein,R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, -CN, -C (=O) OH, -C (=O) (OC1-3alkyl) , -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, -S (=O) NH2, -S (=O) NH (C1-3alkyl) , -S (=O) N (C1-3alkyl) 2, -S (=O) 2NH2, -S (=O) 2NH (C1-3alkyl) , -S (=O) 2N (C1-3alkyl) 2, phenyl or 5-6 heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; said R1 is optionally substituted with 1, 2 or 3 substituents selected from -C1-3alkyl;preferably, R1 is each independent selected from hydrogen, halogen, -C1-3alkyl, -CN, -COOH, -C (=O) NH2, -C (=O) NH (C1-3alkyl) , -C (=O) N (C1-3alkyl) 2, or 5-6 heteroaryl containing 1 or 2 heteroatoms selected from N, O or S; said 5-6 heteroaryl is optionally substituted with 1 or 2 substituents selected from -C1-3alkyl;more preferably, R1 is each independent selected from -H, -F, -Cl, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, -CN, -COOH, -C (=O) NH2, -C (=O) NH (CH3) , -C (=O) NH (CH2CH3) , -C (=O) NH (CH2CH2CH3) , -C (=O) NH (CH (CH3) 2) , -C (=O) N (CH3) 2, -C (=O) N (CH2CH3) 2, further preferably, R1 is selected from -CH3, -CN, -Br, -C (=O) -NH2, -COOH, 60.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 58-59, wherein,R2 is each independent selected from -H, halogen, -C1-3alkyl, haloC1-3alkyl or -CN;preferably, R2 is each independent selected from -H, -C1-3alkyl or -CN;more preferably, R2 is each independent selected from -H, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2 or -CN;further preferably, R2 is selected from -H, -CH3 or -CN.61.The compound of formula (I) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 58-60, wherein,the moiety ofis selected from62.The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 58-61, wherein, the moiety of is selected from 63.The compound of formula (I-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-62, wherein, the compound is any one of the following formulas: 64.An intermediate selected from any one of the following formulas: Wherein, the definition of R4, R5, R6, R7, R9, R10, RY2, Y1, ring B, RS1, RS2, RS3, n1, n2, n3, n4 or n5 in each of formulas is same as any one of [1] to [130] ;LG6 in each of formulas is a leaving group, which is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf;Y4 in each of formulas is -C (=O) -, -S (=O) -or -S (=O) 2-;LG2 in each of formulas is a leaving group or a group that can be converted to the leaving group; said the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; said the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf;Poc2 is the protecting group of the nitrogen atom, which includes but is not limited to t-Butyloxycarbonyl;preferably, the intermediate is selected from:65.A process for preparing the compound of formula (I-2-1) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-63, comprising the following Scheme 3:Scheme 3The definition of R4, R5, R6, RY2, Y1, ring B, RS1, RS2, RS3, n1, n2, n3, n4 or n5 in each of formulas is same as any one of [1] to [130] ;Said LG3 in theLG4 in theand LG5 in theis a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf;Said Poc1 is the protecting group of the -NH2, preferably, Poc1 isY5 is -C (=O) -, -S (=O) -or -S (=O) 2-.66.A process for preparing the compound of formula (I-2-2) , a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-63, comprising the following Scheme 4:Scheme 4The definition of R4, R5, R6, RY3, Y1, ring B, RS1, RS2, RS3, n1, n2, n3, n4 or n5 in each of formulas is same as any one of [1] to [130] ;Said LG3 in theLG4 in theand LG5 in theis a leaving group or a group that can be converted to the leaving group; In some embodiments, the leaving group is selected from halogen (such as -Cl, -Br or -I) , -OMs, -OTs or -OTf; In some embodiments, the group that can be converted to the leaving group is selected from -OH, which can be transformed into leaving groups including, but is not limited to -Cl, -Br, -I, -OMs, -OTs or -OTf;Y5 is -C (=O) -, -S (=O) -or -S (=O) 2-;Said Poc1 is the protecting group of the -NH2, preferably, Poc1 isPoc2 in the protecting group of the nitrogen atom; prefetably, Poc2 is t-Butyloxycarbonyl.67.A pharmaceutical composition comprising the compound, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-63, and at least one pharmaceutically acceptable excipient.68.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, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-63; or the pharmaceutical composition of claim 67; 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.69.A use of a compound, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-63; or the pharmaceutical composition of claim 67 for the manufacture of a mesicament 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.70.A compound, a stereoisomer thereof, a tautomer thereof, a deuterated derivative 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 deuterated derivative thereof of any one of claims 1-63; or the pharmaceutical composition of claim 69 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.
Citation Information
Patent Citations
Methods for inhibiting fascin
CN104736202A
Compounds and methods for inhibiting fascin
CN106232583A
4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine compounds as CBP and / or EP300 inhibitors
CN107531690A
Fascin binding compounds for spinogenesis
CN112912141A