Inhibitor containing quinoline derivative as well as preparation method and application thereof

Abstract

The invention relates to an inhibitor containing quinoline derivatives as well as a preparation method and application of the inhibitor. In particular, the present invention relates to a compound containing quinoline derivatives, a preparation method thereof, a pharmaceutical composition containing the compound, and a use thereof in treatment of cancer diseases.

Description

Technical Field

[0001] The present invention belongs to the field of drug synthesis, and in particular relates to a quinoline derivative inhibitor, a preparation method and an application thereof. Background Art

[0002] Protein arginase methyltransferases (PRMTs) are divided into three major categories based on catalytic activity and product type: types I, II, and III. Type I primarily includes PRMT1 / 2 / 3 / 4 / 6 / 8, which catalyze the formation of asymmetric dimethylarginine (ADMA) from substrates; type II includes PRMT5 / 9, which catalyze the formation of symmetric dimethylarginine (SDMA) from substrates; and type III, which only includes PRMT7, is responsible for catalyzing the formation of monomethylarginine (MMA) from substrates. PRMT5 uses S-adenosyl-L-methionine (SAM) as a methyl donor to transfer methyl groups to substrates such as DNA, RNA, and histones. Arginine residues on the substrates undergo symmetrical dimethylation to form SDMA, which regulates multiple key cellular processes, including transcription, translation, and DNA repair, maintaining cellular homeostasis. It also participates in regulating tumor cell growth and survival pathways and promotes tumorigenesis and progression. Elevated PRMT5 expression has also been shown to be associated with poor prognosis in various cancers, making it a highly promising epigenetic target.

[0003] Methylthioadenosine phosphorylase (MTAP) catalyzes the conversion of methylthioadenosine (MTA) to methionine, which is essential for maintaining normal cellular function. Loss of the MTAP gene leads to intracellular accumulation of MTA. MTA competes with the PRMT5 substrate SAM, reducing PRMT5 activity and generating a large number of PRMT5-MTA complexes. Loss of the MTAP gene increases tumor dependence on PRMT5. Inhibiting PRMT5 can lead to a "synthetic lethality" effect in MTAP-deficient tumors. PARP inhibitors, based on this "synthetic lethality" theory, have achieved significant success in precision medicine for oncology. The MTAP gene is adjacent to the most common tumor suppressor gene in human cancers, CDKN2A, and is frequently co-deleted with CDKN2A. This co-deletion occurs in 10%-15% of all cancers, primarily in non-small cell lung cancer (12%-20%), glioma (53%), pancreatic cancer (30%), and DLBCL (20%), suggesting significant market potential.

[0004] Currently, there are no PRMT5 inhibitors on the market. Early PRMT5 inhibitors were non-selective, substrate-competitive inhibitors of SAM, which resulted in severe hematologic side effects and a narrow safety window. First-generation PRMT5 inhibitors GSK-3326595, JNJ-64619178, and PF-06939999 have made poor clinical progress. A new generation of PRMT5 inhibitors targeting the PRMT5-MTA complex is only effective against tumors with MTAP deficiency and MTA enrichment, with high selectivity for wild-type MTAP. This mechanistically reduces hematologic toxicity and has been validated in preclinical studies, potentially significantly increasing the safety window.

[0005] This patent relates to a novel, selective PRMT5-MTA inhibitor that is active only against MTAP-deficient cells and exhibits minimal inhibition against wild-type MTAP cells. This approach avoids the hematologic toxicity and other side effects associated with clinically unselective PRMT5 inhibitors. As a novel PRMT5-MTA inhibitor, the highly selective PRMT5-MTA inhibitor can be used to treat various tumors, cancers, and other diseases. Summary of the Invention

[0006] The present invention aims to provide a compound represented by the general formula (I), (IA) or (IB), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound represented by the general formula (I), (IA) or (IB) has the following structure:

[0007]

[0008] in:

[0009] M1 is selected from N or CR a ;

[0010] M2 is selected from N or CR b ;

[0011] M3 is selected from N or CR c ;

[0012] M8 is selected from O, S, N, -NR i -or-CR i R j -, R i and R j Can exist simultaneously or only one;

[0013] M9 is selected from O, S, N, -NR k -or-CR k R l -, R k and R l Can exist simultaneously or only one;

[0014] L1 is selected from a bond, -O-, -S-, -NR N -, -C(O)-, -S(O)-, -S(O)2-, -CONR N -、-NR N CO-、-S(O)2NR N -、-NR N S(O)2-、C 1-3 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-10 Cycloalkylene, 3-10 membered heterocyclylene, C 6-10 Arylene or 5-10 membered heteroarylene, the C 1-3 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene C 3-10 Cycloalkylene, 3-10 membered heterocyclylene, C 6-10 Arylene and 5-10 membered heteroarylene, optionally substituted by hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions in aryl, 5-6 membered heteroaryl; preferably bond, -O-, -S-, -NR N -, -C(O)-, -S(O)-, -S(O)2-, -CONR N -、-NR N CO-、-S(O)2NR N -、-NR N S(O)2-、C 1-3 Alkylene, C 2-4 Alkenylene or C 2-4 Alkynylidene, the C 1-3 Alkylene, C 2-4 Alkenylene or C 2-4 The alkynylene group is optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl, 5-6 membered heteroaryl; more preferably bond, -C(O)-, -CONR N -or-NR N CO-;

[0015] L2 is selected from a bond, -O-, -S-, -NR N -, -C(O)-, -S(O)-, -S(O)2-, -CONR N -、-NR N CO-、-S(O)2NR N -、-NR N S(O)2-、C 1-3 Alkylene, C 2-4 Alkenylene or C 2-4 Alkynylidene, the C 1-3 Alkylene, C 2-4 Alkenylene or C 2-4 The alkynylene group is optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl, 5-6 membered heteroaryl; preferably -C(O)-;

[0016] Or, L1 and CR b Link Form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0017] R1 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0018] R2 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-P(O)R b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, one or more substitutions; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0019] Alternatively, R1 and R2 are linked to form C3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may optionally be further substituted with 1, 2, 3 or 4 R d Optionally, the ring may be further linked to L1 to form a C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0020] Or R2 and R i Link Form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may optionally be further substituted with 1, 2, 3 or 4 R d substituted by a substituent;

[0021] R3 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, -(CR a3 Ra4 ) n1 -C 3-12 Cycloalkyl, -(CR a3 R a4 ) n1 -3-12 membered heterocyclic group, -(CR a3 R a4 ) n1 -C 6-14 Aryl or -(CR a3 R a4 ) n1 -5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, one or more substitutions; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, -(CH2) n1 -C 3-12Cycloalkyl, -(CH2) n1 -3-12 membered heterocyclic group, -(CH2) n1 -C 6-14 Aryl or -(CH2) n1 -5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0022] R4 is selected from -(CR a1 R a2 ) n2 - Ring A;

[0023] Ring A is selected from C 3-14 Cycloalkyl, 3-14 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally substituted by 1, 2, 3, 4, 5 or 6 R f or, R3 and R4 are linked to form a ring B, wherein the ring B is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally substituted by 1, 2, 3, 4, 5 or 6 R e substituted by a substituent;

[0024] R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0025] R b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C1-6 Hydroxyalkyl, C 1-6 Alkylamino, -(CH2) n3 -C 3-12 Cycloalkyl, -(CH2) n3 -3-12 membered heterocyclic group, -(CH2) n3 -C 6-14 Aryl, -(CH2) n3 -5-14 membered heteroaryl, -(CH2) n3 OR b1 、-(CH2) n3 C(O)R b1 、-(CH2) n3 C(O)OR b1 、-(CH2) n3 NR b1 R b2 、-(CH2) n3 NR b3 C(O)R b1 、-(CH2) n3 C(O)NR b1 R b2 、-(CH2) n3 S(O)2R b1 、-(CH2) n3 S(O)2NR b1 R b2 、-(CH2) n3 NR b3 S(O)2R b1 、-(CH2) n3 S(O)R b1 (=NR b3 ) or -(CH2) n3 N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR b4 Sum = CR b4 CR b5 One or more substitutions in ;

[0026] R c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0027] R d Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-P(O)R b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, one or more substitutions; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0028] R e Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -SF5, -P(O)R c1 CR c2 、=N-OR c1 、=CR c1 CR c2 、-S(O)R c1 (=NR c2 ) and -N=S(O)R c1 R c2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0029] Or, two R e Link Form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, -P(O)R c3 CR c4 、=N-OR c3 、=CR c3 CR c4 、-S(O)R c3 (=NR c4 ) and -N=S(O)R c3 R c4 One or more substitutions in ;

[0030] R f Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14Aryl, 5-14 membered heteroaryl, -SF5, -P(O)R d1 CR d2 、=N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ;

[0031] Or, two R f Link Form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl and -SF5, -P(O)R d5 CR d6 、=N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 One or more substitutions in ;

[0032] R a1 and R a2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0033] Or, R a1 and R a2 Together form = O;

[0034] R a3 and R a4 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0035] R b1 、R b2 、R b3 、R b4 and R b5 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0036] R c1 、R c2 、R c3 and R c4 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0037] R d1 、R d2 、R d3 、Rd4 、R d5 and R d6 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0038] R i 、R j 、R k or R l are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0039] R N Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0040] n1 is selected from 0, 1, 2 or 3;

[0041] n2 is selected from 0, 1, 2 or 3;

[0042] n3 is selected from 0, 1, 2 or 3.

[0043] In certain embodiments of the present invention, the compound represented by general formula (I), its stereoisomers or pharmaceutically acceptable salts thereof are further represented by general formula (II):

[0044]

[0045] in:

[0046] M4 is selected from N or CR g ;

[0047] R 5a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-P(O)R b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, one or more substitutions; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0048] R 6a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0049] R 6b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0050] R g Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aryl and 5-10 membered heteroaryl.

[0051] In certain embodiments of the present invention, the compound represented by general formula (I), its stereoisomers or pharmaceutically acceptable salts thereof are further represented by general formula (III):

[0052]

[0053] in:

[0054] Ring C is selected from C 3-10 Cycloalkyl or 3-10 membered heterocyclic group;

[0055] R h Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aryl and 5-10 membered heteroaryl.

[0056] x is selected from 0, 1, 2, 3 or 4;

[0057] M4, R 5a 、R 6a and R 6b As defined in general formula (II).

[0058] In certain embodiments of the present invention, the compound represented by general formula (IB), its stereoisomers or pharmaceutically acceptable salts thereof are further represented by general formula (VI) or (VI-A):

[0059]

[0060] in:

[0061] M8 Selected from -NR i -or-CR iR j -, R i and R j Can exist simultaneously or only one;

[0062] M9 Selected from -NR k -or-CR k R l -, R k and R l Can exist simultaneously or only one;

[0063] Ring F is selected from C 3-10 Cycloalkylene, 3-10 membered heterocyclylene, C 6-10 Arylene or 5-10 membered heteroarylene; preferably 3-10 membered heterocyclylene or 5-10 membered heteroarylene;

[0064] R i 、R j 、R k or R l are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0065] L1, L2, R3, R4, R b1 、R b2 、R b3 、R b4 、R b5 、n3、M4、R 5a 、R 6a and R 6b As defined in any of the above embodiments;

[0066] M4, R 5a 、R 6a and R 6b As defined in the above embodiments.

[0067] In certain embodiments of the present invention, the compound represented by general formula (I), its stereoisomers or pharmaceutically acceptable salts thereof are further represented by general formula (IV):

[0068]

[0069] In certain embodiments of the present invention, the compound, its stereoisomer or pharmaceutically acceptable salt thereof is characterized by being represented by general formula (VII):

[0070]

[0071] in:

[0072] Ring H is selected from 3-12 membered heterocyclyl or 5-14 membered heteroaryl; preferably 5 membered heterocyclyl, 6 membered heterocyclyl, 5 membered heteroaryl or 6 membered heteroaryl;

[0073] Ring G is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl; preferably 3-8 membered heterocyclic group, 5-6 membered heteroaryl;

[0074] R 10 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0075] R 11 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0076] R 11a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0077] R 11b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl;

[0078] Or, R 11a and R 11b Formation = O;

[0079] e is selected from 0, 1, 2, 3 or 4; and

[0080] f is selected from 0, 1, 2, 3 or 4.

[0081] In certain embodiments of the present invention, R4 is selected from -(CR a1 R a2 ) n2 - Ring A;

[0082] Ring A is selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally substituted by 1, 2, 3, 4, 5 or 6 R f Substituted by a substituent; preferably C 7-10 fused cycloalkyl, 7-10 membered fused heterocyclic group, phenyl or 5-6 membered heteroaryl, optionally substituted by 1, 2, 3, 4, 5 or 6 R f substituted by a substituent;

[0083] R f Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, -P(O)R d1 CR d2 、=N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)Rd1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ;

[0084] Or, two R f Link Form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10Aryl, 5-10 membered heteroaryl, -SF5, -P(O)R d5 CR d6 、=N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 One or more substitutions in .

[0085] In certain embodiments of the present invention, R4 is selected from -(CR a1 R a2 ) n2 -R5;

[0086] R5 is selected from

[0087] X is selected from O or CH2;

[0088] M4 is selected from CH or N;

[0089] M5 is selected from CH or N;

[0090] M6 is selected from CH or N;

[0091] M7 is selected from CH or N;

[0092] Ring D is selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0093] R 7a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ;

[0094] Or, two R 7a Link Form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 One or more substitutions in ;

[0095] R 7b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 ;

[0096] n4 is selected from 0, 1 or 2;

[0097] n5 is selected from 0, 1 or 2;

[0098] a is selected from 0, 1, 2, 3 or 4;

[0099] b is selected from 0, 1, 2, 3 or 4.

[0100] In certain embodiments of the present invention, the compound, its stereoisomer or pharmaceutically acceptable salt thereof is characterized by being further represented by general formula (V-1) or (V-2):

[0101]

[0102] X1 is selected from O or CH2;

[0103] X2 is selected from N or CR 9d ;

[0104] R 9bSelected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ;

[0105] R 9c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4One or more substitutions in ;

[0106] R 9d Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CRd3 CR d4 One or more substitutions in ;

[0107] R 9e Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ;

[0108] Or, two R 9e Link Form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 One or more substitutions in ;

[0109] n6 is selected from 0, 1 or 2;

[0110] n7 is selected from 0, 1 or 2;

[0111] X, M4, M5, M6, M7, Ring D, R 7a 、R 7b , n4, n5, a and b are as defined in the above embodiments.

[0112] In certain embodiments of the present invention, R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, -(CH2) n1 -C 3-10 Cycloalkyl, -(CH2) n1 -3-10 membered heterocyclic group, -(CH2) n1 -C 6-10 Aryl or -(CH2) n1 -5-10 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aryl and 5-10 membered heteroaryl.

[0113] In certain embodiments of the present invention, R 5a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-P(O)R b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, one or more substitutions; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, one or more substitutions; more preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group.

[0114] In certain embodiments of the present invention, R 6a Selected from hydrogen, deuterium, C 1-3 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group; preferably hydrogen.

[0115] In certain embodiments of the present invention, R 6b Selected from hydrogen, deuterium, C 1-3 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group; preferably hydrogen.

[0116] In certain embodiments of the present invention, R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group.

[0117] In certain embodiments of the present invention, R b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, -(CH2) n3 -C 3-10Cycloalkyl, -(CH2) n3 -3-10 membered heterocyclic group, -(CH2) n3 -C 6-10 Aryl, -(CH2) n3 -5-10 membered heteroaryl, -(CH2) n3 OR b1 、-(CH2) n3 C(O)R b1 、(CH2) n3 C(O)OR b1 、-(CH2) n3 NR b1 R b2 、-(CH2) n3 NR b3 C(O)R b1 、-(CH2) n3 C(O)NR b1 R b2 、-(CH2) n3 S(O)2R b1 、-(CH2) n3 S(O)2NR b1 R b2 、-(CH2) n3 NR b3 S(O)2R b1 、-(CH2) n3 S(O)R b1 (=NR b3 ) or -(CH2) n3 N=S(O)R b1 R b2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR b4 Sum = CR b4 CR b5 One or more substitutions in .

[0118] In certain embodiments of the present invention, R c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably R c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group.

[0119] The present invention further relates to a pharmaceutical composition comprising a therapeutically effective dose of a compound shown in any one of the embodiments, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, or excipients.

[0120] The present invention further relates to the use of the compound shown in any embodiment, its stereoisomer or pharmaceutically acceptable salt, or the pharmaceutical composition in the preparation of PRMT5 inhibitor drugs.

[0121] The present invention further relates to the use of the compound shown in any embodiment, its stereoisomer or pharmaceutically acceptable salt, or its pharmaceutical composition in the preparation of a drug for treating cancer, wherein the cancer is selected from MTAP-related cancers.

[0122] The present invention further relates to a method for preparing a compound, a stereoisomer or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as shown in any embodiment for treating cancer, wherein the cancer is selected from MTAP-related cancers.

[0123] In some embodiments, the cancer is selected from lung cancer, hepatocellular carcinoma, breast cancer, skin cancer, bladder cancer, liver cancer, pancreatic cancer, head and neck cancer, glioma, glioblastoma, esophageal cancer, pancreatic cancer, mesothelioma, melanoma, astrocytoma, undifferentiated pleomorphic sarcoma, diffuse large B-cell lymphoma, leukemia, gastric adenocarcinoma, myxofibrosarcoma, cholangiosarcoma, brain cancer, gastric cancer, kidney cancer, endometrial cancer, ovarian tumor, prostate cancer, lymphoma, non-Hodgkin lymphoma, urinary tract cancer, soft tissue cancer, pleural cancer, colorectal cancer, colorectal cancer or bile duct cancer; the lung cancer is selected from non-small cell lung cancer, squamous cell lung carcinoma or lung adenocarcinoma; the esophageal cancer is selected from esophageal squamous cell carcinoma or esophageal adenocarcinoma; the glioma is selected from brain glioma.

[0124] The present invention also relates to a method for preventing and / or treating cancer, comprising administering to a patient a therapeutically effective dose of a compound shown in any embodiment, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0125] The present invention also relates to a method of treating cancer in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt, ester, prodrug, solvate, hydrate or derivative thereof.

[0126] In certain embodiments of the present invention, the pharmaceutical composition, calculated as the free base, has a weight percentage of the compound, its stereoisomer or a pharmaceutically acceptable salt thereof of 0.1% to 95%, preferably 90%, 85%, 80%, 75%, 70%, 60% or 50%.

[0127] In certain embodiments of the present invention, the pharmaceutical composition is selected from tablets, capsules, liquid preparations or injections, and preferably further comprises a filler, optionally a disintegrant, or further comprises one or more of a glidant or a lubricant.

[0128] In certain embodiments of the present invention, the pharmaceutical composition is a rapid-release formulation or a sustained-release formulation.

[0129] In certain embodiments of the present invention, the pharmaceutical composition, calculated as the free base, the unit dose of the compound, its stereoisomer or a pharmaceutically acceptable salt thereof is 1-1000 mg, preferably 1-500 mg, or preferably 1 mg, 2 mg, 3 mg, 5 mg, 10 mg, 20 mg, 40 mg, 50 mg, 60 mg, 80 mg, 100 mg, 200 mg, 300 mg, 400 mg or 500 mg.

[0130] In certain embodiments of the present invention, the compound, its stereoisomer or a pharmaceutically acceptable salt thereof, can be administered by any convenient method, for example, by oral, parenteral, buccal, sublingual, nasal, rectal, intrathecal or transdermal administration, and the pharmaceutical composition adjusted accordingly.

[0131] In certain embodiments of the present invention, the compound, its stereoisomers or pharmaceutically acceptable salts thereof can be formulated into liquid or solid preparations, such as syrups, suspensions, emulsions, tablets, capsules, powders, granules, or lozenges.

[0132] In some embodiments, the present method relates to the treatment of conditions such as lung cancer, hepatocellular carcinoma, breast cancer, skin cancer, bladder cancer, liver cancer, pancreatic cancer, head and neck cancer, glioma, glioblastoma, esophageal cancer, pancreatic cancer, mesothelioma, melanoma, astrocytoma, undifferentiated pleomorphic sarcoma, diffuse large B-cell lymphoma, leukemia, gastric adenocarcinoma, myxofibrosarcoma, cholangiosarcoma, brain cancer, gastric cancer, kidney cancer, endometrial cancer, ovarian tumor, prostate cancer, lymphoma, non-Hodgkin lymphoma, urinary tract cancer, soft tissue cancer, pleural cancer, colon cancer, colorectal cancer, or bile duct cancer.

[0133] In some embodiments, the lung cancer is selected from non-small cell lung cancer, lung squamous cell carcinoma, or lung adenocarcinoma; the esophageal cancer is selected from esophageal squamous cell carcinoma or esophageal adenocarcinoma; and the glioma is selected from brain glioma.

[0134] Detailed Description of the Invention

[0135] Unless otherwise stated, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art. Specifically, the terms used in the specification and claims have the following meanings.

[0136] The term "alkyl" refers to a straight or branched saturated aliphatic hydrocarbon group, which may be optionally substituted with one or more substituents. In a specific embodiment, an alkyl group refers to a saturated aliphatic hydrocarbon group having 1 to 20 (C 1-20 ), 1 to 15 (C 1-15 ), 1 to 12 (C 1-12 ), 1 to 10 (C 1-10 ), 1 to 8 (C 1-8 ), 1 to 6 (C 1-6 ) or 1 to 3 (C 1-3 ) carbon atoms, or a straight-chain saturated hydrocarbon group having 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 ) carbon atoms. The straight chain C 1-6 Alkyl and branched C 3-6 Alkyl groups are also called "lower alkyl". For example, C 1-6 Alkyl refers to a linear saturated monovalent hydrocarbon group having 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon group having 3 to 6 carbon atoms. 1-6Alkyl groups contain 1 to 6 (e.g., 1, 2, 3, 4, 5, 6) carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2, 3-Dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl and various branched chain isomers thereof, etc. In one embodiment, the alkyl group is an optionally substituted alkyl group as described elsewhere herein.

[0137] The term "alkylene" refers to an alkyl group with one hydrogen atom further substituted, wherein "alkyl" is as defined above. Non-limiting examples of "alkylene" include: methylene (-CH2-), ethylene (-(CH2)2-), propylene (-(CH2)3-), or butylene (-(CH2)4-). In one embodiment, the alkylene is an optionally substituted alkyl group as described elsewhere herein.

[0138] The term "alkenyl" refers to a straight or branched unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon double bond, which may be located at any position within the alkenyl group, and which may be optionally substituted with one or more substituents. In a particular embodiment, the alkenyl group is an unsaturated aliphatic hydrocarbon group having 2 to 20 (C 2-20 ), 2 to 15 (C 2-15 ), 2 to 12 (C 2-12 ), 2 to 10 (C 2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ) or 2 to 4 (C 2-4 ) carbon atoms, or a straight-chain unsaturated hydrocarbon group having 3 to 20 (C 3-20 ), 3 to 15 (C3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 ) carbon atoms. Unless otherwise specified, the term "alkenyl" as used herein includes both straight-chain and branched alkenyl groups. For example, C 2-6 Alkenyl refers to a straight chain unsaturated hydrocarbon group having 2 to 6 carbon atoms or a branched unsaturated hydrocarbon group having 3 to 6 carbon atoms. 2-6 Alkenyl groups contain 2 to 6 (e.g., 2, 3, 4, 5, 6) carbon atoms. Non-limiting examples of alkenyl groups include: One of ordinary skill in the art will appreciate that the term "alkenyl" may also include groups having "cis" and "trans" configurations, or alternatively, groups having "E" and "Z" configurations. In one embodiment, the alkenyl is an optionally substituted alkenyl described elsewhere herein.

[0139] The term "alkynyl" refers to a straight or branched unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon triple bond, which may be located at any position within the alkynyl group, and which may be optionally substituted with one or more substituents. In a particular embodiment, the alkynyl group is a 2 to 20 (C 2-20 ), 2 to 15 (C 2-15 ), 2 to 12 (C 2-12 ), 2 to 10 (C 2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ) or 2 to 4 (C 2-4 ) carbon atoms, or a straight-chain unsaturated hydrocarbon group having 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 Unless otherwise indicated, the term "alkynyl" as used herein includes both straight-chain and branched alkynyl groups. For example, C 2-6 Alkynyl refers to a straight chain unsaturated hydrocarbon group having 2 to 6 carbon atoms or a branched unsaturated hydrocarbon group having 3 to 6 carbon atoms. 2-6 Alkynyl groups contain 2 to 6 (e.g., 2, 3, 4, 5, 6) carbon atoms. Non-limiting examples of alkynyl groups include: In one embodiment, the alkynyl group is an optionally substituted alkynyl group described elsewhere herein.

[0140] The term "cycloalkyl" refers to a saturated or partially unsaturated aliphatic hydrocarbon monocyclic, polycyclic (two or more) cyclic group, which may be optionally substituted with one or more substituents. In a particular embodiment, the cycloalkyl ring contains 3 to 20 (C 3-20 ), 3 to 12 (C 3-12 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 ) carbon atoms; in one embodiment, the cycloalkyl ring contains 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 ) carbon atoms; it may contain one or more double bonds, but does not have a completely conjugated π electron system. Non-limiting examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl or cyclooctyl, etc.; polycyclic cycloalkyls include spirocycloalkyl, fused cycloalkyl and bridged cycloalkyl in one embodiment. In one embodiment, the cycloalkyl is an optionally substituted cycloalkyl described elsewhere herein or a cycloalkyl optionally fused to a heterocyclyl, aryl or heteroaryl group, non-limiting examples of which include indanyl, tetrahydronaphthyl, benzocycloheptanyl, etc.

[0141] The term "spiroalkyl" refers to an aliphatic hydrocarbon polycyclic group in which the monocyclic rings share a carbon atom (called a spiro atom), which may contain one or more double bonds, but no ring has a completely conjugated π electron system. In a specific embodiment, the spiroalkyl group contains 5 to 20 (C 5-20 ), 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 ) (e.g., 7, 8, 9, 10) carbon atoms. Spirocycloalkyl is divided into mono-, di-, or poly-spirocycloalkyl according to the number of shared spiro atoms between the rings, and in one embodiment, is mono- and di-spirocycloalkyl. In one embodiment, it is a 4-, 3-, 5-, 4-, 5-, 4-, 6-, 5-, or 5-membered mono-spirocycloalkyl. In one embodiment, the spirocycloalkyl is an optionally substituted spirocycloalkyl described elsewhere herein. Non-limiting examples of spirocycloalkyl include:

[0142]

[0143] The term "fused cycloalkyl" refers to an all-carbon polycyclic group in which each ring in the system shares a pair of adjacent carbon atoms with other rings in the system, wherein one or more rings may contain one or more double bonds, but no ring has a completely conjugated π electron system. In a specific embodiment, the fused cycloalkyl group comprises 5 to 20 (C 5-20), 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 ) (e.g., 7, 8, 9, 10) carbon atoms. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused cycloalkyl groups, and in one embodiment, it is bicyclic or tricyclic, and further in one embodiment, it is a 3-membered / 5-membered, 4-membered / 5-membered, 5-membered / 5-membered or 5-membered / 6-membered bicyclic alkyl group. In one embodiment, the fused cycloalkyl group is an optionally substituted fused cycloalkyl group described elsewhere herein or a fused cycloalkyl group optionally fused with a heterocyclic group, an aryl group or a heteroaryl group. Non-limiting examples of fused cycloalkyl groups include:

[0144]

[0145] The term "bridged cycloalkyl" refers to a full-carbon polycyclic group in which any two rings share two carbon atoms that are not directly connected, which may contain one or more double bonds, but no ring has a completely conjugated π electron system. In a specific embodiment, the bridged cycloalkyl group comprises 5 to 20 (C 5-20 ), 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 ) (e.g., 7, 8, 9, 10) carbon atoms. Depending on the number of constituent rings, the bridged cycloalkyl group may be bicyclic, tricyclic, tetracyclic, or polycyclic, preferably bicyclic or tricyclic. In one embodiment, the bridged cycloalkyl group is an optionally substituted bridged cycloalkyl group described elsewhere herein. Non-limiting examples of bridged cycloalkyl groups include:

[0146]

[0147] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon group, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, wherein the nitrogen, phosphorus or sulfur atom may be optionally oxidized, the nitrogen atom may be optionally quaternized, the ring carbon atoms may be optionally substituted with oxygen, but does not include the ring portion of -OO- or -OS-, and the remaining ring atoms are carbon, which may contain one or more double bonds but does not have a completely conjugated π electron system. In certain embodiments, the heterocyclyl group contains 3 to 20, 3 to 12, 3 to 8, or 3 to 6 ring atoms, of which 1 to 4 are heteroatoms; in one embodiment, the heterocyclyl group contains 3 to 6, 4 to 6, 3 to 8, 3 to 10, 6 to 10, or 7 to 11 ring atoms; in one embodiment, the heterocyclyl group contains 3 to 8 (e.g., 3, 4, 5, 6, 7, 8) ring atoms. The limiting examples of monocyclic heterocyclic radical include tetrahydropyrrolyl, azetidinyl, oxetanyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl and pyranyl etc..Polycyclic heterocyclic radical includes spiro heterocyclic radical, condensed heterocyclic radical and bridged heterocyclic radical.In one embodiment, described heterocyclic radical is the optionally substituted described elsewhere herein, or the heterocyclic radical further and ring-connected with other cycloalkyl, heterocyclic radical, aryl and heteroaryl by any two or more atoms on the ring.

[0148] The term "spiroheterocyclyl" refers to a polycyclic heterocyclic group in which one atom (called a spiro atom) is shared between the rings, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, and the remaining ring atoms are carbon, which may contain one or more double bonds, but no ring has a completely conjugated π electron system. In a specific embodiment, the spiroheterocyclyl comprises 5 to 20 or 6 to 14 ring atoms; in one embodiment, it comprises 7 to 11 (e.g., 7, 8, 9, 10, 11) ring atoms; the spiroheterocyclyl is divided into a monospiroheterocyclyl, a bispiroheterocyclyl or a polyspiroheterocyclyl according to the number of spirohetero atoms shared between the rings; monospiroheterocyclyl and bispiroheterocyclyl are preferred; in one embodiment, the spiroheterocyclyl is a 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered or 5-membered / 6-membered monospiroheterocyclyl; in one embodiment, the spiroheterocyclyl is an optionally substituted spiroheterocyclyl described elsewhere herein; non-limiting examples of spiroheterocyclyls include:

[0149]

[0150] The term "fused heterocyclyl" refers to a polycyclic heterocyclic group in which each ring in the system shares a pair of adjacent atoms with the other rings in the system, one or more rings may contain one or more double bonds, but no ring has a completely conjugated π electron system, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, and the remaining ring atoms are carbon. In a specific embodiment, the fused heterocyclyl is a heterocyclic group containing 5 to 20 or 6 to 14 ring atoms, and in one embodiment contains 7 to 10 (e.g., 7, 8, 9, 10) ring atoms; according to the number of constituent rings, it can be divided into a bicyclic, tricyclic, tetracyclic or polycyclic fused heterocyclyl; preferably a bicyclic or tricyclic group; in one embodiment, it is a 5-membered / 5-membered or 5-membered / 6-membered bicyclic fused heterocyclyl; in one embodiment, the fused heterocyclyl is an optionally substituted or fused heterocyclyl described elsewhere herein, or a cycloalkyl, heterocyclyl, aryl or heteroaryl group; non-limiting examples of fused heterocyclyls include:

[0151]

[0152] The term "bridged heterocyclic group" refers to a polycyclic heterocyclic group in which any two rings share two atoms that are not directly connected, which may contain one or more double bonds, but no ring has a completely conjugated π electron system, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, and the remaining ring atoms are carbon. In specific embodiments, the bridged heterocyclic group contains 5 to 20 or 6 to 14 ring atoms; in one embodiment, it contains 7 to 10 (e.g., 7, 8, 9, 10) ring atoms; according to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocyclic groups; preferably bicyclic, tricyclic or tetracyclic; in one embodiment, it is bicyclic or tricyclic; in one embodiment, the bridged heterocyclic group is an optionally substituted bridged heterocyclic group described elsewhere herein; non-limiting examples of bridged heterocyclic groups include:

[0153]

[0154] The term "aryl" refers to an all-carbon monocyclic or fused polycyclic (i.e., rings that share adjacent pairs of carbon atoms) group containing at least one conjugated π electron system, which may be optionally substituted with one or more substituents. In specific embodiments, the aryl group contains 6 to 20, 6 to 14, or 6 to 10 ring atoms; in one embodiment, the aryl group may further refer to a bicyclic, tricyclic, or tetracyclic ring system, wherein at least one ring is aromatic and the other rings may be saturated, partially unsaturated, or a ring containing one or more heteroatoms independently selected from O, S, and N; in one embodiment, the aryl group is selected from a benzo 5-10 membered heteroaryl group, a benzo 3-10 membered cycloalkyl group, or a benzo 3-10 membered heterocyclyl group. In one embodiment, the aryl group is selected from a benzo 5-6 membered heteroaryl group, a benzo 3-6 membered cycloalkyl group, or a benzo 3-6 membered heterocyclyl group, wherein the heterocyclyl group is a heterocyclyl group containing 1-3 nitrogen atoms, oxygen atoms, or sulfur atoms. Non-limiting examples include phenyl, naphthyl, fluorenyl, azulenyl, anthracenyl, phenanthrenyl, pyrenyl, biphenyl, terphenyl, dihydronaphthyl, indenyl, tetrahydronaphthyl (tetralinyl),

[0155] The term "arylene group" refers to a divalent aromatic group formed by further replacing one hydrogen atom of an aryl group, wherein the arylene group is optionally substituted or unsubstituted, and the aryl group is as defined above.

[0156] The term "heteroaryl" refers to an optionally substituted monocyclic, polycyclic group or ring system comprising at least one aromatic ring, wherein the aromatic ring has one or more heteroatoms independently selected from O, S and N. In particular embodiments, the heteroaryl group contains 5 to 20, 5 to 15 or 5 to 10 ring atoms, of which 1 to 4 are heteroatoms; in one embodiment, the heteroaryl group contains 5 or 6 ring atoms; in particular embodiments, the heteroaryl group may further refer to a bicyclic, tricyclic or tetracyclic ring, wherein at least one ring is an aromatic ring having one or more heteroatoms independently selected from O, S and N, and the other rings may be saturated, partially unsaturated carbocyclic rings or rings containing one or more heteroatoms independently selected from O, S and N. In one embodiment, the heteroaryl group is selected from a heteroaryl group with 6-10 members, a heteroaryl group with 3-10 members, or a heteroaryl group with 3-10 members, and a heterocyclyl group with 3-10 members. In another embodiment, the heteroaryl group is selected from a 5- or 6-membered heteroaryl group with 6-10 members, a 5- or 6-membered heteroaryl group with 3-6 members, and a 5- or 6-membered heterocyclyl group, wherein the heterocyclyl group is a heterocyclyl group containing 1-3 nitrogen atoms, oxygen atoms, or sulfur atoms. Non-limiting examples include furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl, triazolyl, benzofuranyl, benzimidazolyl, benzisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiophenyl, benzothienyl, benzotriazolyl, imidazopyridinyl, imidazothiazolyl , indolizinyl, indolyl, indazolyl, isobenzofuranyl, isobenzothiophenyl, isoindolyl, isoquinolinyl, naphthyridinyl, oxazolopyridinyl, phthalazinyl, pteridinyl, purinyl, pyridopyridinyl, pyrrolopyridinyl, quinolinyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidinyl, thienopyridinyl, acridinyl, benzindolyl, carbazolyl, bibenzofuranyl, phenanthrolinyl, phenanthridinyl, phenpyrazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl,

[0157] The term "heteroarylene" refers to a divalent heteroaryl group formed by further replacing one hydrogen atom of a cycloalkyl group, wherein the heteroarylene group is optionally substituted or unsubstituted, and the heteroaryl group is as defined above.

[0158] The term "heteroalkyl" refers to a stable straight or branched chain, or cyclic hydrocarbon radical, or a combination thereof, consisting of the indicated number of carbon atoms and one or more (in one embodiment, one to three) heteroatoms selected from O, N, Si, and S, and wherein the nitrogen and sulfur atoms are optionally oxidized and the nitrogen heteroatom is optionally quaternized. In one embodiment, the heteroatoms O, N, and S can be placed at any interior position of the heteroalkyl group. In one embodiment, the heteroatom Si can be placed at any position (e.g., interior or terminal position) of the heteroalkyl group, including the position where the alkyl group is attached to the remainder of the molecule. Non-limiting examples include: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2-S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, and -CH=CH-N(CH3)-CH3. Up to two heteroatoms can be consecutive, for example, -CH2-NH-O-CH3 and -CH2-O-Si(CH3)3. In a particular embodiment, the heteroalkyl group is an optionally substituted heteroalkyl group described elsewhere herein.

[0159] The term "alkoxy" refers to -O-(alkyl) and -O-(unsubstituted cycloalkyl), wherein alkyl or cycloalkyl are as defined above. Non-limiting examples of alkoxy include methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, or cyclohexyloxy. In one embodiment, the alkoxy is an optionally substituted alkoxy described elsewhere herein.

[0160] The term "alkylacyl" refers to a -C(O)-alkyl group, wherein alkyl is as previously defined.

[0161] The term "haloalkyl" refers to an alkyl group substituted by one or more halogens, wherein the definition of alkyl is the same as above. Non-limiting examples of the haloalkyl group include: trifluoromethyl, -CH2CF3,

[0162] The term "haloalkoxy" refers to an alkoxy group substituted with one or more halogen groups, wherein alkoxy is as defined above.

[0163] The term "hydroxyalkyl" refers to an alkyl group substituted with a hydroxy group, wherein alkyl is as defined above.

[0164] The term "alkylthio" refers to -S-(alkyl) and -S-(unsubstituted cycloalkyl), wherein alkyl or cycloalkyl are as defined above. Non-limiting examples of alkylthio include methylthio, ethylthio, propylthio, butylthio, cyclopropylthio, cyclobutylthio, cyclopentylthio, or cyclohexylthio. In one embodiment, the alkylthio is an optionally substituted alkylthio described elsewhere herein.

[0165] The term "haloalkylthio" refers to an alkylthio group substituted with one or more halogen groups, wherein alkylthio is as defined above.

[0166] The term "alkenylcarbonyl" refers to -C(O)-(alkenyl), wherein alkenyl is as defined above. Non-limiting examples of alkenylcarbonyl include vinylcarbonyl, propenylcarbonyl, or butenylcarbonyl. In one embodiment, the alkenylcarbonyl is an optionally substituted alkenylcarbonyl described elsewhere herein.

[0167] The term "aminocarbonyl" refers to NH2-C(O)-.

[0168] The term "alkylaminocarbonyl" refers to an aminocarbonyl (NH2-C(O)-) group in which one or both of the hydrogen atoms are replaced by an alkyl group, wherein the alkyl group is as defined above.

[0169] The term "alkylamino" refers to an amino group in which one or both of the hydrogen atoms are replaced by an alkyl group, wherein the alkyl group has the same definition as above.

[0170] The term "carbonyl" refers to a -C(O)-, -(CO)-, or -C(=O)- group. All notations are used interchangeably in the specification.

[0171] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0172] The term "oxo" or "oxo" refers to =0.

[0173] The term "hydrogen" includes protons ( 1 H), deuterium ( 2 H), tritium ( 3 H) and / or mixtures thereof. In a particular embodiment, one or more positions occupied by hydrogen in the compound may be enriched with deuterium and / or tritium. Such isotopically enriched analogs may be prepared by appropriately isotopically labeled starting materials obtained from commercial sources or by known literature procedures.

[0174] The alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylene, heteroaryl, heteroarylene, heteroalkyl, alkoxy, alkylthio, hydroxyalkyl, alkenylcarbonyl, aminocarbonyl, alkylaminocarbonyl, alkylamino, and alkylacyl may be substituted or unsubstituted. In one embodiment, the substituents are selected from one or more of the following groups: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, alkylacyl, halogen, sulfhydryl, hydroxyl, nitro, cyano, azido, oxime, phosphate, oxo, thio, carboxyl, carboxylate, cycloalkyl, heterocyclyl, aryl, heteroaryl, heterocycloalkyloxy, cycloalkylthio, or heterocycloalkylthio.

[0175] Different expressions such as “X is selected from A, B, or C”, “X is selected from A, B and C”, “X is A, B or C”, and “X is A, B and C” all express the same meaning, that is, X can be any one or more of A, B, and C.

[0176] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, "a heterocyclic group optionally substituted with an alkyl group" means that the alkyl group may but need not be present, and that the description includes instances where the heterocyclic group is substituted with an alkyl group and instances where the heterocyclic group is not substituted with an alkyl group.

[0177] In various parts of the present invention, linking substituents are described. When the structure clearly requires a linking group, the Markush variable listed for that group should be understood to be a linking group. For example, if the structure requires a linking group and the Markush group definition for that variable lists "alkyl" or "aryl", it should be understood that the "alkyl" or "aryl" represents a linking alkylene group or arylene group, respectively.

[0178] " substituted " refers to that any one or more hydrogen atoms on a particular atom are replaced by a substituent, as long as the valence state of the particular atom is normal and the substituted compound is stable in one embodiment in one embodiment. When a substituent is an oxo (i.e., =O), it means that two hydrogen atoms are replaced. The term "optionally substituted" refers to that it may be substituted or not, and unless otherwise specified, the type and number of the substituent may be arbitrary on the basis of chemical achievable. It goes without saying that the substituent is only in its possible chemical position, and those skilled in the art can determine (by experiment or theory) possible or impossible substitution without paying too much effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (such as olefinic) bond.

[0179] In this specification and the claims, the indefinite articles "a" and "an" and the definite article "the" include plural as well as singular, unless stated to the contrary.

[0180] A "pharmaceutical composition" refers to a mixture containing one or more compounds described herein, or their physiologically / pharmaceutically acceptable salts or prodrugs, together with other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitating absorption of the active ingredient and thereby exerting its biological activity.

[0181] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present invention, which are safe and effective when used in mammals and have the desired biological activity.

[0182] "Stereoisomers" encompass all enantiomerically / diastereomerically / stereomerically pure and enantiomerically / diastereomerically / stereomerically enriched forms of the compounds of the invention.

[0183] "Stereomerically pure" refers to a composition comprising one stereoisomer of a compound and being substantially free of another stereoisomer of the compound. For example, a stereomerically pure composition of a compound having one chiral center will be substantially free of the opposite enantiomer of the compound. A stereomerically pure composition of a compound having two chiral centers will be substantially free of other diastereomers of the compound. A typical stereoisomerically pure compound comprises greater than about 80% by weight of one stereoisomer of the compound and less than about 20% by weight of another stereoisomer of the compound, greater than about 90% by weight of one stereoisomer of the compound and less than about 10% by weight of another stereoisomer of the compound, greater than about 95% by weight of one stereoisomer of the compound and less than about 5% by weight of another stereoisomer of the compound, greater than about 97% by weight of one stereoisomer of the compound and less than about 3% by weight of another stereoisomer of the compound, or greater than about 99% by weight of one stereoisomer of the compound and less than about 1% by weight of another stereoisomer of the compound.

[0184] "Stereoisomerically enriched" refers to a composition comprising greater than about 55% by weight, greater than about 60% by weight, greater than about 70% by weight, or greater than about 80% by weight of one stereoisomer of a compound.

[0185] "Enantiomerically pure" refers to a stereomerically pure composition of a compound having one chiral center. Similarly, the term "enantiomerically enriched" refers to a stereomerically enriched composition of a compound having one chiral center.

[0186] "Optically active" and "enantiomeric active" refer to a combination of molecules having an enantiomeric or diastereomeric excess of not less than about 50%, not less than about 70%, not less than about 80%, not less than about 90%, not less than about 91%, not less than about 92%, not less than about 93%, not less than about 94%, not less than about 95%, not less than about 96%, not less than about 97%, not less than about 98%, not less than about 99%, not less than about 99.5%, or not less than about 99.8%. In certain embodiments, the compound comprises about 95% or more of the desired enantiomer or diastereomer and about 5% or less of the less preferred enantiomer or diastereomer, based on the total weight of the racemate.

[0187] When describing an optically active compound, the prefixes R and S are used to denote the absolute configuration of the molecule about its chiral center. (+) and (-) are used to denote the optical rotation of the compound, i.e., the direction of the plane of polarized light rotated by the optically active compound. The prefix (-) indicates that the compound is levorotatory, i.e., the compound rotates the plane of polarized light to the left, or counterclockwise. The prefix (+) indicates that the compound is dextrorotatory, i.e., the compound rotates the plane of polarized light to the right, or clockwise. However, the signs of the optical rotations (+) and (-) have nothing to do with the absolute configuration, R or S, of the molecule. DETAILED DESCRIPTION

[0188] The present invention is further described below with reference to the following examples, but these examples are not intended to limit the scope of the present invention.

[0189] Example

[0190] The structures of the compounds of the present invention are determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). -6 The unit of ppm is given. NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD), with tetramethylsilane (TMS) as the internal standard.

[0191] MS was measured using a FINNIGAN LCQAd (ESI) mass spectrometer (manufacturer: Thermo, model: Finnigan LCQadvantage MAX).

[0192] HPLC determination was performed using an Agilent 1200DAD high pressure liquid chromatograph (Sunfire C 18

[0193] 150×4.6 mm chromatographic column) and Waters 2695-2996 high pressure liquid chromatograph (Gimini C 18150×4.6mm chromatographic column).

[0194] Average kinase inhibition rate and IC 50 The values ​​were determined using a NovoStar microplate reader (BMG, Germany).

[0195] The thin layer chromatography silica gel plate uses Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plate. The specification of the silica gel plate used in thin layer chromatography (TLC) is 0.15mm~0.2mm, and the specification used for thin layer chromatography separation and purification products is 0.4mm~0.5mm.

[0196] Column chromatography generally uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier.

[0197] The known starting materials of the present invention can be synthesized by methods known in the art, or can be purchased from ABCR GmbH & Co. KG, Acros Organics, Aldrich Chemical Company, AccelaChemBio Inc, Darui Chemicals, and other companies.

[0198] Unless otherwise specified in the examples, all reactions can be carried out under an argon atmosphere or a nitrogen atmosphere.

[0199] Argon atmosphere or nitrogen atmosphere means that the reaction bottle is connected to an argon or nitrogen balloon with a capacity of about 1 L.

[0200] Hydrogen atmosphere means that the reaction bottle is connected to a hydrogen balloon with a capacity of about 1L.

[0201] The pressurized hydrogenation reaction uses a Parr 3916EKX hydrogenator and a Qinglan QL-500 hydrogen generator or an HC2-SS hydrogenator.

[0202] The hydrogenation reaction is usually carried out by evacuating the chamber and filling it with hydrogen, and the operation is repeated three times.

[0203] A CEM Discover-S 908860 microwave reactor was used for the microwave reaction.

[0204] Unless otherwise specified in the examples, the solution refers to an aqueous solution.

[0205] Unless otherwise specified in the examples, the reaction temperature is room temperature, 20°C to 30°C.

[0206] The reaction progress in the examples was monitored by thin layer chromatography (TLC). The developing solvent systems used in the reactions were: A: dichloromethane and methanol system, B: n-hexane and ethyl acetate system, C: petroleum ether and ethyl acetate system, and D: acetone. The volume ratio of the solvents was adjusted according to the polarity of the compounds.

[0207] The eluent system for column chromatography and the developing solvent system for thin-layer chromatography used to purify the compound include: A: n-hexane and ethyl acetate system, B: n-hexane and tetrahydrofuran system. The volume ratio of the solvent is adjusted according to the polarity of the compound, and a small amount of alkaline or acidic reagents such as triethylamine and acetic acid can also be added for adjustment.

[0208] Example 1

[0209] (2-Amino-3-cyclopropylquinolin-6-yl)(2-(trifluoromethyl)-7,8,9,10-tetrahydro-10,5-(epoxymethoxy)pyrido[3,2-c]oxazin-6(5H)-yl)methanone

[0210]

[0211] Step 1: Dissolve tert-butyl N-but-3-ynylcarbamate (4.30 g, 25.41 mmol), methyl 2-bromo-6-(trifluoromethyl)pyridine-3-carboxylate 1a (4.81 g, 16.94 mmol), triethylamine (3.42 g, 33.88 mmol), cuprous iodide (646 mg, 3.39 mmol), and ditriphenylphosphine palladium dichloride (1.19 g, 1.69 mmol) in tetrahydrofuran (100 mL), replace the atmosphere with nitrogen, and stir at 50°C under nitrogen for 16 hours. The reaction mixture was filtered to remove solid impurities, and the organic phase was concentrated. The residue was purified using eluent system C to afford methyl 2-(4-((tert-butoxycarbonyl)amino)but-1-yn-1-yl)-6-(trifluoromethyl)nicotinate 1b (5.60 g) in 88.8% yield.

[0212] MS m / z(ESI):373.2[M+1] + .

[0213] Step 2: Disperse methyl 2-(4-((tert-Butoxycarbonyl)amino)but-1-yn-1-yl)-6-(trifluoromethyl)nicotinate 1b (5.00 g, 13.44 mmol) and palladium on carbon (5.00 g, 10% palladium, 55% water) in tetrahydrofuran (10 mL). Stir at room temperature under a hydrogen atmosphere for 1 hour. The reaction mixture was filtered, the filtrate was concentrated, and the residue was purified using Eluent System C to afford methyl 2-(4-((tert-Butoxycarbonyl)amino)butyl)-6-(trifluoromethyl)nicotinate 1b (4.82 g) in a 96.1% yield.

[0214] MS m / z(ESI):377.2[M+1] + .

[0215] Step 3: Methyl 2-(4-((tert-Butoxycarbonyl)amino)butyl)-6-(trifluoromethyl)nicotinate 1c (19.31 g, 51.22 mmol) was dissolved in carbon tetrachloride (100 mL), and NBS (10.03 g, 56.34 mmol) and AIBN (841 mg, 5.12 mmol) were added. The reaction was stirred at 80°C for 16 h. Water (100 mL) was added to the reaction solution, and the mixture was extracted with dichloromethane (200 mL × 3). The combined organic phases were washed with saturated brine (200 mL × 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified using eluent System C to afford methyl 2-(1-bromo-4-((tert-Butoxycarbonyl)amino)butyl)-6-(trifluoromethyl)nicotinate 1d (16.10 g) in a yield of 69.1%.

[0216] MS m / z(ESI):455.1[M+1] + .

[0217] Step 4: Sodium hydride (510 mg, 12.76 mmol, 60% purity) was added to a solution of methyl 2-hydroxyacetate (766 mg, 8.51 mmol) in DMF (3 mL) at 0°C. After stirring at 0°C for 20 minutes, methyl 2-(1-bromo-4-((tert-butoxycarbonyl)amino)butyl)-6-(trifluoromethyl)nicotinate 1d (1.93 g, 4.25 mmol) was added to the reaction mixture and stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate, washed with water and brine, and the organic phase was concentrated. The residue was purified using eluent system C to afford tert-butyl (3-(5-oxo-2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-8-yl)propyl)carbamate 1e (930 mg) in a 58.3% yield.

[0218] MS m / z(ESI):375.2[M+1] + .

[0219] Step 5: Dissolve tert-butyl (3-(5-oxo-2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-8-yl)propyl)carbamate 1e (1.20 g, 3.20 mmol) and a dioxane solution of hydrochloric acid (2 mL, 4 M) in methanol (5 mL) and stir at room temperature for 16 hours; the reaction solution is concentrated to obtain 8-(3-aminopropyl)-2-(trifluoromethyl)-6H-pyrano[3,4-b]pyridin-5(8H)-one 1f (710 mg) with a yield of 81.0%.

[0220] MS m / z(ESI):275.1[M+1]

[0221] Step 6: Dissolve 8-(3-aminopropyl)-2-(trifluoromethyl)-6H-pyrano[3,4-b]pyridin-5(8H)-one 1f (710 mg, 2.59 mmol) in trifluoroethanol (3 mL). The reaction mixture was stirred at room temperature for 3 hours. Sodium borohydride (98 mg, 2.59 mmol) was added to the reaction mixture and stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, washed with water and brine, and the organic phase was concentrated. The concentrated residue was purified with eluent system C to give 2-(trifluoromethyl)-5,6,7,8,9,10-hexahydro-10,5-(epoxycarbonyl)pyrido[3,2-c]azo 1g (510 mg) in a yield of 76.1%.

[0222] MS m / z(ESI):259.1[M+1] + .

[0223] Step 7: 2-(Trifluoromethyl)-5,6,7,8,9,10-hexahydro-10,5-(epoxycarbonyl)pyrido[3,2-c]azo 1g (21 mg, 0.08 mmol) and 2-amino-3-cyclopropylquinoline-6-carboxylic acid (36 mg, 0.16 mmol) (synthesized according to WO2023 / 207556) were dissolved in N,N-dimethylformamide (2 mL), and N-methylpyrazole (20 mg, 0 0.24 mmol) and TCFH (45 mg, 0.16 mmol), and the reaction was stirred at 25°C for 16 hours; the reaction solution was directly prepared, separated and purified by Pre-HPLC to obtain (2-amino-3-cyclopropylquinolin-6-yl)(2-(trifluoromethyl)-7,8,9,10-tetrahydro-10,5-(epoxymethoxy)pyrido[3,2-c]oxazin-6(5H)-yl)methanone 1 (16 mg) with a yield of 42.6%.

[0224] MS m / z(ESI):469.2[M+1] +

[0225] The preparation of the following examples is described in Example 1:

[0226]

[0227]

[0228]

[0229]

[0230]

[0231]

[0232] Alternatively, the following examples are synthesized by the following method:

[0233] Example 4

[0234] 2-amino-3-cyclopropyl-N-methyl-N-(3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-

[0235] c]pyridin-7-yl)quinoline-6-carboxamide

[0236]

[0237] 2-Amino-3-cyclopropylquinoline-6-carboxylic acid 4a (40 mg, 0.18 mmol, synthesized using the known method "WO2023207556"), N-methyl-3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-amine 4b (48 mg, 0.18 μmol), and N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (59 mg, 0.21 mmol) were dissolved in N,N-dimethylformamide (5 mL). N-methylimidazole (45 mg, 0.54 mmol, 44 μL) was added, and the atmosphere was purged with nitrogen three times. The reaction system was stirred at 25°C for 1 hour. The reaction solution was concentrated. The residue was purified by silica gel column chromatography using eluent System A to give 2-amino-3-cyclopropyl-N-methyl-N-(3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-yl)quinoline-6-carboxamide 4 (75 mg) in 88.9% yield.

[0238] MS m / z(ESI):482[M+1]

[0239] 1 H NMR (400MHz, DMSO) δ8.48(s,1H),8.17(d,1H),7.98(d,2H),7.90–7.72(m,2H),7.66(d,1H),7.11(d,1H),5.73( s,1H),5.14(d,1H),4.88(d,1H),4.22(d,2H),2.79(s,3H),1.87(td,1H),1.09–0.98(m,2H),0.81–0.68(m,2H).

[0240] Example 7

[0241] 2-amino-3-cyclopropyl-N-methyl-N-(2'-(trifluoromethyl)-5',6'-dihydrospiro[cyclopropane-1,8'-pyrano[3,4-b]

[0242] [pyridinyl]-5'-yl)quinoline-6-carboxamide

[0243]

[0244] Step 1: Dissolve zirconocene dichloride (15.44 g, 52.81 mmol) in toluene (100 mL). Purge the nitrogen atmosphere three times and cool to 0°C. Add ethylmagnesium bromide (2 M, 52.8 mL) dropwise. After complete addition, react at 0°C for 1 hour. Then, dissolve methyl 3-bromo-6-(trifluoromethyl)picolinate (5 g, 17.60 mmol) in toluene (20 mL) and add dropwise. After complete addition, warm the system to 25°C and react for 16 hours. The reaction is quenched by adding ammonium chloride and extracted with ethyl acetate (150 mL x 3). The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is purified by silica gel column chromatography using eluent System B to afford 1-(3-bromo-6-(trifluoromethyl)pyridin-2-yl)cyclopropan-1-ol 7b (2 g) in a 40.3% yield.

[0245] MS m / z(ESI):284[M+1]

[0246] Step 2: Dissolve 1-(3-bromo-6-(trifluoromethyl)pyridin-2-yl)cyclopropane-1-ol 7b (2.2 g, 7.80 mmol), potassium ethylene trifluoroborate (2.09 g, 15.60 mmol), and potassium carbonate (2.16 g, 15.60 mmol) in water (3 mL) and 1'4-dioxane (15 mL). The atmosphere was purged with nitrogen three times, and 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (571 mg, 0.78 mmol) was added. The reaction system was stirred at 90°C for 3 hours. Cool to room temperature, quench with water, extract with ethyl acetate (80 mL x 3), wash with saturated brine, dry over anhydrous sodium sulfate, filter, and concentrate. The residue was purified by silica gel column chromatography using eluent System B to give 1-(6-(trifluoromethyl)-3-vinylpyridin-2-yl)cyclopropan-1-ol 7c (1.30 g) in 72.7% yield.

[0247] MS m / z(ESI):230[M+1]

[0248] Step 3: Dissolve 1-(6-(trifluoromethyl)-3-vinylpyridin-2-yl)cyclopropan-1-ol 7c (0.80 g, 3.49 mmol) and acetic acid (20.96 mg, 349.04 μmol, 19.98 μL) in 1'4-dioxane (140 mL) and water (140 mL). The atmosphere was purged with nitrogen three times. N-bromosuccinimide (746 mg, 4.19 mmol) dissolved in 1'4-dioxane (30 mL) and water (30 mL) was added dropwise to the reaction system. The reaction system was stirred at 40°C for 16 hours. Dilute hydrochloric acid (2 M, 0.88 mL) was added dropwise to the reaction system, and the reaction was continued at 100°C for 6 hours. The mixture was cooled to room temperature, concentrated, and extracted with ethyl acetate (100 mL x 3). The mixture was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent System B to give 2'-(trifluoromethyl)-5',6'-dihydrospiro[cyclopropane-1,8'-pyrano[3,4-b]pyridine]-5'-ol 7d (370 mg) in a 43.2% yield.

[0249] MS m / z(ESI):246[M+1]

[0250] Step 4: 2'-(Trifluoromethyl)-5',6'-dihydrospiro[cyclopropane-1,8'-pyrano[3,4-b]pyridine]-5'-ol 7d (0.45 g, 1.84 mmol) was dissolved in dichloromethane (10 mL), purged with nitrogen three times, cooled to 0°C, and N,N-diisopropylethylamine (474 ​​mg, 3.67 mmol) and methanesulfonic anhydride (480 mg, 2.75 mmol) were added. The reaction system was stirred at 25°C for 1 hour. The reaction was quenched with water, extracted with dichloromethane (50 mL x 3), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give 2'-(trifluoromethyl)-5',6'-dihydrospiro[cyclopropane-1,8'-pyrano[3,4-b]pyridine]-5'-yl methanesulfonate 7e (0.60 g, crude).

[0251] MS m / z(ESI):324[M+1]

[0252] Step 5: 2'-(Trifluoromethyl)-5',6'-dihydrospiro[cyclopropane-1,8'-pyrano[3,4-b]pyridin]-5'-yl methanesulfonate 7e (0.6 g, 1.86 mmol) was dissolved in THF (5 mL). A methanolic solution of methylamine (9.61 g, 92.80 mmol) was added. The reaction system was heated to 65°C in a microwave reactor and stirred for 12 hours. The reaction was concentrated, quenched with sodium bicarbonate, and extracted with dichloromethane / methanol = 10 / 1 (60 mL x 3). The product was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent System B to give N-methyl-2'-(trifluoromethyl)-5',6'-dihydrospiro[cyclopropane-1,8'-pyrano[3,4-b]pyridine]-5'-amine 7f (0.41 g) in 85.6% yield.

[0253] MS m / z(ESI):259[M+1]

[0254] Step 6: 2-Amino-3-cyclopropylquinoline-6-carboxylic acid 7g (60 mg, 0.26 mmol, synthesized by the known method "WO2023207556"), N-methyl-2'-(trifluoromethyl)-5',6'-dihydrospiro[cyclopropane-1,8'-pyrano[3,4-b]pyridine]-5'-amine 7f (68 mg, 0.26 mmol), and N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (89 mg, 0.32 mmol) were dissolved in N,N-dimethylformamide (5 mL), and N-methylimidazole (68 mg, 0.81 mmol) was added. The atmosphere was purged with nitrogen three times, and the reaction system was stirred at 25 ° C for 2 hours. The concentrated reaction residue was purified by silica gel column chromatography using eluent System A to give 5-amino-3-cyclopropyl-N-methyl-N-(2'-(trifluoromethyl)-5',6'-dihydrospiro[cyclopropane-1,8'-pyrano[3,4-b]pyridine]-5'-yl)quinoline-6-carboxamide 7 (55 mg) in a yield of 44.7%.

[0255] MS m / z(ESI):469[M+1]

[0256] 1 H NMR(400MHz,DMSO)δ13.65(s,1H),8.56(s,2H),8.17(s,1H),8.07(d,2H),7.88(dd,1H),7.77(p,2H),5 .93(s,1H),4.20(d,2H),2.78(s,3H),1.90(q,1H),1.49–1.22(m,4H),1.07(dt,2H),0.84–0.75(m,2H).

[0257] Example 27

[0258] N-(6-amino-5-methylpyridin-3-yl)-2-(2-(methyl-d3)-1-(3-trifluoromethyl-7,10-dihydro-8H-imidazolin-

[0259] [1,2-a]pyrano[3,4-c]pyridin-7-yl)hydrazine)-2-oxoacetamide

[0260]

[0261] Step 1: 2-Chloro-4-iodo-3-methylpyridine 27a (150 g, 591.79 mmol), palladium acetate (13.29 g, 59.18 mmol), 1,1'-bis(diphenylphosphino)ferrocene (32.75 g, 59.18 mmol), and sodium bicarbonate (149.14 g, 1.78 mol) were placed in a reactor. MeOH (500 mL) and DMF (500 mL) were added. The mixture was stirred under a CO atmosphere at 0.4 MPa and 80°C for 16 hours. The reaction mixture was added to water and extracted with EA. The organic phase was separated, dried, concentrated, and then separated by column chromatography to afford methyl 2-chloro-3-methylisonicotinate 27b (137 g) in a 62.4% yield.

[0262] MS m / z(ESI):186[M+1]

[0263] Step 2: Dissolve methyl 2-chloro-3-methylisonicotinate 27b (73.04 g, 403.00 mmol) in 1,4-Dioxane (1700 mL). Add Pd2(dba)3 (33.55 g, 36.64 mmol), Xantphos (42.40 g, 73.27 mmol), benzophenone imine (146 g, 806 mmol), and cesium carbonate (179.05 g, 549.55 mmol). Heat to 100°C under nitrogen and stir for 16 hours. The reaction mixture was cooled, filtered through celite, and the filtrate was concentrated. 400 mL of HCl (4 M in dioxane) and 200 mL of MeOH were added, and the reaction was stirred at room temperature for 16 hours. The reaction solution was directly concentrated under reduced pressure, and then adjusted to pH 8 by adding aqueous NaHCO 3 solution, extracted with ethyl acetate, and the organic phase was separated, dried, concentrated, and separated by column chromatography to give 2-amino-3-methylisonicotinate 27c (60 g) with a yield of 49.3%.

[0264] MS m / z(ESI):167[M+1]

[0265] Step 3: Dissolve methyl 2-amino-3-methylisonicotinate 27c (59 g, 284.03 mmol) in EtOH (590 mL), add 2-chloroacetaldehyde (83.61 g, 426.05 mmol) and NaHCO₃ (35.79 g, 426.05 mmol), and stir at 70°C overnight. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and separated by column chromatography to afford methyl 8-methylimidazo[1,2-a]pyridine-7-carboxylate 27d (34 g) in a 62.9% yield.

[0266] MS m / z(ESI):191[M+1]

[0267] Step 4: Dissolve 8-methylimidazo[1,2-a]pyridine-7-carboxylic acid methyl ester 27d (34 g, 178.76 mmol) in acetonitrile (500 mL), add NIS (42.23 g, 187.70 mmol), and stir at room temperature for 1 hour. The reaction mixture was filtered to obtain 3-iodo-8-methylimidazo[1,2-a]pyridine-7-carboxylic acid methyl ester 27e (56 g) as a solid, with a yield of 99.1%.

[0268] MS m / z(ESI):317[M+1]

[0269] Step 5: Methyl 3-iodo-8-methylimidazo[1,2-a]pyridine-7-carboxylate: Dissolve 27e (53 g, 167.67 mmol) and methyl 2,2-difluoro-2-fluorosulfonylacetate (96.64 g, 503.01 mmol) in DMF (600 mL). Add CuI (95.80 g, 503.01 mmol). Heat the reaction mixture to 100°C and stir for 16 h. Cool the reaction mixture, dilute it with EtOAc (200 mL), filter it, and extract the filtrate with water. The organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to afford methyl 8-methyl-3-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylate 27f (17 g) in a 99.1% yield.

[0270] MS m / z(ESI):259[M+1]

[0271] Step 6: Dissolve 8-methyl-3-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylic acid methyl ester 27f (17 g, 65.84 mmol) in carbon tetrachloride (200 mL). Add NBS (14.06 g, 79.01 mmol) and azobisisobutyronitrile (2.16 g, 13.17 mmol). The reaction is stirred at 80°C under a nitrogen atmosphere for 2 h. The reaction mixture is cooled to room temperature and filtered. The filter cake is washed with a small amount of dichloromethane. The filtrate is concentrated under reduced pressure and separated by column chromatography to obtain 8-bromomethyl-3-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylic acid methyl ester 27 g (22 g) in a yield of 99.1%.

[0272] MS m / z(ESI):337[M+1]

[0273] Step 7: Dissolve methyl 2-hydroxyacetate (16.03 g, 177.99 mmol) in DMF (100 mL) and cool to 0°C. Add NaH (7.12 g, 177.99 mmol, 60% purity) portionwise. Stir the reaction mixture at 0°C for 15 min. Then, add a solution of 27 g (20 g, 59.33 mmol) of methyl 8-bromomethyl-3-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylate in DMF (80 mL). Warm the mixture to room temperature and stir for 2 h. Pour the reaction mixture into saturated ammonium chloride solution and extract with ethyl acetate. Separate the organic phase, wash it once with saturated brine, then separate the organic phase and dry it over anhydrous sodium sulfate. Concentrate under reduced pressure and separate by column chromatography to obtain methyl 7-oxo-3-trifluoromethyl-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridine-8-carboxylate (27 h).

[0274] MS m / z(ESI):315[M+1]

[0275] Step 8: Dissolve methyl 7-oxo-3-trifluoromethyl-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridine-8-carboxylate 27h (14 g, 44.56 mmol) in EtOH (150 mL) and add HCl (12 M, 75 mL). Stir and react at 80°C for 2 h. The reaction mixture was concentrated under reduced pressure to remove ethanol. The pH was adjusted to 6 with saturated sodium bicarbonate and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to afford 3-trifluoromethyl-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7(10H)-one 27i (6.2 g) in a yield of 54.3%.

[0276] MS m / z(ESI):257[M+1]

[0277] Step 9: 3-Trifluoromethyl-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7(10H)-one 27i (2 g, 7.78 mmol) was dissolved in 20 mL of 1,1,1-trifluoroethanol, and 30% methylamine methanol solution (2 mL) was added. The mixture was stirred at room temperature for 1 hour, followed by the addition of NaBH3CN (1 g, 16 mmol). The reaction was stirred at room temperature for 12 hours. After completion of the reaction, saturated ammonium chloride solution was added to quench the reaction. The reaction solution was concentrated and extracted with ethyl acetate. The organic phase was washed with saturated brine, separated, dried, concentrated, and then separated by column chromatography to afford N-methyl-3-trifluoromethyl-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-amine 27j (1.7 g) in 80.3% yield.

[0278] MS m / z(ESI):272[M+1]

[0279] Step 10: N-methyl-3-trifluoromethyl-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-amine 27j (136 mg, 0.50 mmol) and 2-((6-amino-5-methylpyridin-3-yl)amino)-2-oxoacetic acid 27k (97 mg, 0.50 mmol, synthesized by reference to patent "WO2022026892A1") were dissolved in DMF (5 mL), HATU (228 mg, 0.60 mmol) and TEA (0.14 mL, 1 mmol) were added, and the reaction was stirred at room temperature for 1 h. After the reaction was completed, water was added to quench the mixture, and the mixture was extracted with EA. The organic phase was separated, dried, concentrated, and then separated by column chromatography to obtain N-(6-amino-5-methylpyridin-3-yl)-2-(2-(methyl-d3)-1-(3-trifluoromethyl-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-yl)hydrazine)-2-oxoacetamide 27 (32 mg) with a yield of 8.9%.

[0280] MS m / z(ESI):721[M+1]

[0281] 1 H NMR (400MHz, DMSO-d6) δ10.63(s,1H),8.55(d,1H),8.20(t,1H),8.05(s,1H),7.54(d,1H),7.11(d,1H),5. 67(s,2H),5.30(s,1H),5.13-5.07(m,1H),4.92-4.81(m,1H),4.28-4.09(m,2H),2.86(s,3H),2.72(s,3H).

[0282] Example 31

[0283] 2-2-amino-3-(dimethylphosphino)-N-methyl-N-(3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-yl)quinoline-6-carboxamide

[0284]

[0285] Step 1: 2-Amino-3-bromoquinoline-6-carboxylic acid methyl ester 31a (1 g, 3.56 mmol, synthesized using the known method "WO2023207556"), potassium phosphate (2.27 g, 10.67 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (247 mg, 0.43 mmol) were dissolved in 1'4-dioxane (20 mL). The atmosphere was purged with nitrogen three times, and dimethylphosphine oxide (417 mg, 5.34 mmol) and tris(dibenzylideneacetone)dipalladium (326 mg, 0.36 mmol) were added. The system was heated to 100°C in a microwave reactor for 2 hours. The reaction was cooled to room temperature, quenched by the addition of water, and extracted with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent System B to give methyl 2-amino-3-(dimethylphosphino)quinoline-6-carboxylate 31b (0.70 g) in 70.7% yield.

[0286] MS m / z(ESI):279[M+1]

[0287] Step 2: Methyl 2-amino-3-(dimethylphosphino)quinoline-6-carboxylate 31b (0.70 g, 2.52 mmol) and lithium hydroxide (121 mg, 5.03 mmol) were dissolved in tetrahydrofuran (3 mL), water (3 mL), and methanol (3.00 mL). The reaction was incubated at 25°C for 14 hours. The reaction mixture was concentrated, and the pH was adjusted to 3-4 by adding 1M hydrochloric acid. A large amount of solid precipitated, which was filtered. The filter cake was washed with a small amount of petroleum ether and dried to afford 2-amino-3-(dimethylphosphino)quinoline-6-carboxylic acid 31c (0.55 g) in an 82.7% yield.

[0288] MS m / z(ESI):265[M+1]

[0289] Step 3: Referring to the synthesis method of Example 4, 2-amino-3-(dimethylphosphino)-N-methyl-N-(3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-yl)quinoline-6-carboxamide 31 (87 mg) was obtained from 2-amino-3-(dimethylphosphino)quinoline-6-carboxylic acid 31c (50 mg, 0.19 mmol) and N-methyl-3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-amine 31d (51 mg, 0.19 mmol). Yield: 88.9%.

[0290] MS m / z(ESI):469[M+1]

[0291] 1 H NMR (400MHz, DMSO) δ8.76(d,2H),8.41(t,1H),8.14(s,1H),8.01(s,1H),7.94(d,1H),7.69(d,1H),7. 17–7.02(m,1H),5.66(s,1H),5.03(dd,1H),4.82(d,1H),4.25–4.03(m,2H),2.73(s,3H),1.86(d,6H).

[0292] Example 37

[0293] 2-amino-3-cyclopropyl-N-(1-(pyrimidin-2-yl)ethyl)-N-(3-(trifluoromethyl)-7,10-dihydro-8H-imidazolinone

[0294] [1,2-a]pyrano[3,4-c]pyridin-7-yl)quinoline-6-carboxamide

[0295]

[0296] Step 1: Dissolve 3-(trifluoromethyl)-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7(10H)-one 37a (150 mg, 0.59 mmol) in methanol (10 mL). The atmosphere was purged with nitrogen three times. Sodium borohydride (44 mg, 1.17 mmol) was added and the mixture was allowed to react at 25°C for 1 hour. The reaction was quenched by adding 20 mL of sodium bicarbonate and extracted with methanol / dichloromethane (1 / 10) (50 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent System B to afford 3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-ol 37b (0.13 g) in an 86.0% yield.

[0297] MS m / z(ESI):259[M+1]

[0298] Step 2: Dissolve 3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-ol 37b (0.13 g, 0.50 mmol) in dichloromethane (10 mL). The atmosphere was purged with nitrogen three times and cooled to 0°C. N,N-diisopropylethylamine (130 mg, 1.01 mmol) and methanesulfonic anhydride (132 mg, 0.76 mmol) were added, and the reaction system was stirred at 25°C for 1 hour. The reaction was quenched with water, extracted with dichloromethane (80 mL x 3), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford 3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-yl methanesulfonate 37c (0.18 g, crude).

[0299] MS m / z(ESI):337[M+1]

[0300] Step 3: 3-(Trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-yl methanesulfonate 37c (0.18 g, 0.54 mmol) and 1-pyrimidin-2-ylethylamine hydrochloride (128 mg, 0.80 mmol) were dissolved in tetrahydrofuran (5 mL). The atmosphere was purged with nitrogen three times, and triethylamine (162 mg, 1.61 mmol) was added. The reaction system was stirred at 70°C for 15 hours. The mixture was extracted with dichloromethane / methanol = 10 / 1 (30 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent System B to give N-(1-(pyrimidin-2-yl)ethyl)-3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-amine 37d (60 mg) in 30.9% yield.

[0301] MS m / z(ESI):364[M+1]

[0302] Step 4: 2-Amino-3-cyclopropylquinoline-6-carbonyl chloride 37e (102 mg, 0.41 mmol) and N-(1-(pyrimidin-2-yl)ethyl)-3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-amine 37d (50 mg, 0.14 mmol) were dissolved in THF (10 mL). N,N-diisopropylethylamine (106 mg, 0.82 mmol) was added. The atmosphere was purged with nitrogen three times, and the reaction system was stirred at 100°C for 3 hours. The reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel column chromatography using eluent System A to afford 37 (10 mg) in a 12.6% yield.

[0303] MS m / z(ESI):574[M+1]

[0304] 1 H NMR(400MHz,DMSO)δ8.90(s,1H),8.32(d,1H),8.12(d,1H),7.77(d,1H),7.61(d,1H),7.55–7.18(m,3H),6.85(d,1 H),6.62(s,2H),5.44(s,1H),5.16–4.67(m,3H),4.41(t,1H),4.23(s,1H),1.77(d,4H),0.97(dd,2H),0.66(s,2H).

[0305] Example 38

[0306] 2-amino-3-(dimethylphosphino)-N-(1-(pyrimidin-2-yl)ethyl)-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)quinoline-6-carboxamide

[0307]

[0308] Referring to the synthesis method of Example 4, 2-amino-3-(dimethylphosphino)-N-(1-(pyrimidin-2-yl)ethyl)-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)quinoline-6-carboxamide 38 (15 mg) was obtained from 2-amino-3-(dimethylphosphino)quinoline-6-carboxylic acid 38a (30 mg, 0.11 mmol) and 1-(pyrimidin-2-yl)-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)ethane-1-amine 38b (32 mg, 0.11 mmol) in a yield of 25.0%.

[0309] MS m / z(ESI):529[M+1]

[0310] 1H NMR(400MHz,DMSO)δ8.93–8.66(m,5H),8.17–8.06(m,2H),8.00(d,1H),7.75(d,1H),7.58(d,1H), 7.43(t,1H),5.75(s,1H),5.30(d,J1H),4.93(d,1H),4.50(d,1H),1.93(d,6H),1.69–1.56(m,3H).

[0311] Example 39

[0312] 3-cyano-N 6 -methyl-N 6 -(3-(Trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-yl)imidazo[1-2-a]pyridine-2,6-dicarboxamide

[0313]

[0314] Step 1: Add 6-aminopyridine-3-carboxylic acid methyl ester 39a (1 g, 6.57 mmol) and 3-bromo-2-oxopropionic acid (1.10 g, 6.57 mmol) to a single-necked flask and dissolve them in dioxane (20 mL). Stir the reaction at 110°C for 16 hours. The reaction solution was spin-dried and dissolved in 100 ml of EA. The solution was washed with water (100 ml) and saturated brine (100 ml) in that order. The organic phase was dried over anhydrous sodium sulfate and concentrated to give 6-(methoxycarbonyl)imidazo[1,2-a]pyridine-2-carboxylic acid 39b (0.9 g, 4.09 mmol). Yield: 63.2%

[0315] MS m / z(ESI):221[M+1]

[0316] Step 2: 6-(Methoxycarbonyl)imidazo[1,2-a]pyridine-2-carboxylic acid 39b (0.8 g, 3.63 mmol), ammonium chloride (583.05 mg, 10.90 mmol), N,N-diisopropylethylamine (2.35 g, 18.17 mmol, 3.16 mL), and acetonitrile (30 mL) were added to a single-necked flask under ice-water bath. After stirring, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (2.06 g, 5.45 mmol) was added and the reaction was allowed to gradually warm to room temperature and reacted at room temperature for about 2 h. The reaction solution was spin-dried and dissolved in 100 ml of ethyl acetate, washed with water (100 ml) and saturated brine (100 ml) in that order. The organic phase was dried over anhydrous sodium sulfate and concentrated to give methyl 2-aminoformyl imidazo[1,2-a]pyridine-6-carboxylate 39c (1.1 g, crude product).

[0317] MS m / z(ESI):220[M+1]

[0318] Step 3: Dissolve methyl 2-carbamoyl imidazo[1,2-a]pyridine-6-carboxylate 39c (1 g, 4.56 mmol) in acetonitrile (20 mL) at room temperature, stir until clear, and add N-iodosuccinimide (1.23 g, 5.47 mmol). The reaction is allowed to react at room temperature for approximately 16 hours. The reaction solution is spin-dried and dissolved in 100 ml of ethyl acetate, washed with water (100 ml) and saturated brine (100 ml) in that order. The organic phase is dried over anhydrous sodium sulfate and concentrated. The residue is purified by silica gel column chromatography using eluent System B to obtain a light brown solid, methyl 2-carbamoyl-3-iodo-imidazo[1,2-a]pyridine-6-carboxylate 39d (1.1 g, 3.19 mmol). Yield: 69.9%

[0319] MS m / z(ESI):346[M+1]

[0320] Step 4: Add 2-carbamoyl-3-iodo-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester 39d (0.8 g, 2.32 mmol) to a single-necked flask, stir in N,N-dimethylformamide (5 mL) until dissolved, then add cuprous cyanide (207.62 mg, 2.32 mmol). Heat to 100°C under nitrogen and stir for 16 hours. The reaction solution was diluted with 100 ml of ethyl acetate, washed with water (100 ml) and saturated brine (100 ml) in sequence, and the organic phase was dried over anhydrous sodium sulfate and concentrated to give 2-carbamoyl-3-cyanoimidazo[1,2-a]pyridine-6-carboxylic acid methyl ester 39e (410 mg, 1.68 mmol) as a light brown solid with a yield of 72.4%.

[0321] MS m / z(ESI):245[M+1]

[0322] Step 5: In a single-necked flask, methyl 2-carbamoyl-3-cyanoimidazo[1,2-a]pyridine-6-carboxylate 39e (0.4 g, 1.64 mmol) was dissolved in a mixture of water (5 mL) / tetrahydrofuran (5 mL) / methanol (5 mL). Lithium hydroxide monohydrate (343.97 mg, 8.19 mmol) was added and the reaction mixture was stirred at 25°C for 2 hours. The pH was adjusted to 7 with 1N hydrochloric acid, and the solvent was removed by concentration under reduced pressure. The mixture was filtered and dried to obtain 2-carbamoyl-3-cyanoimidazo[1,2-a]pyridine-6-carboxylic acid 39f (340 mg, 1.48 mmol) as a light brown solid with a yield of 90.2%.

[0323] MS m / z(ESI):231[M+1]

[0324] Step 6: 2-Carbamoyl-3-cyanoimidazo[1,2-a]pyridine-6-carboxylic acid 39f (0.1 g, 434.44 μmol), N-methyl-3-(trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-amine 27j (117.84 mg, 434.44 μmol), N,N-diisopropylethylamine (168.44 mg, 1.30 mmol, 227.01 μL) were added to a single-necked flask and N,N-dimethylformamide (2 ml) was added and stirred to dissolve. Then, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (245.85 mg, 651.67 μmol) was added and the reaction solution was stirred at 25°C for 1 hour. The reaction solution was diluted with 100 ml of EA, washed with water (100 ml) and saturated brine (100 ml) in sequence, the organic phase was dried over anhydrous sodium sulfate, concentrated, and purified by preparative chromatography to obtain a white solid 3-cyano-N 6 -methyl-N 6 -(3-(Trifluoromethyl)-7,10-dihydro-8H-imidazo[1,2-a]pyrano[3,4-c]pyridin-7-yl)imidazo[1-2-a]pyridine-2,6-dicarboxamide 39 (10 mg, 20.69 μmol), yield 4.8%

[0325] MS m / z(ESI):484[M+1]

[0326] 1 H NMR(400MHz,DMSO-d6)δ8.95(s,1H),8.47(d,1H),8.17(d,2H),7.98-7.87(m,2H),7.81(d,1H),7.30 (d,1H),5.72(s,1H),5.11(dd,1H),5.01-4.82(m,1H),4.35(t,1H),4.22-4.05(m,1H),2.82(s,3H).

[0327] Example 54

[0328] 1-(4-(methyl(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)carbamoyl)thiophen-2-yl)-1H-imidazole-5-carboxamide

[0329]

[0330] Step 1: 5-Nitrothiophene-3-carboxylic acid 54a (224 mg, 1.29 mmol), 4-(3,4-dimethoxybenzyl)amino)-N-methyl-2-(trifluoromethyl)-6,8-dihydro-5H-pyrano[3,4-b]pyridin-5-amine (200 mg, 0.86 mmol), N-methylimidazole (212 mg, 2.58 mmol), and N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (362 mg, 1.29 mmol) were dissolved in acetonitrile (2 mL) and stirred at room temperature for 16 h. After the reaction was completed, water was added to quench the reaction, and the mixture was concentrated and purified on a silica gel column to give N-methyl-5-nitro-N-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)thiophene-3-carboxamide 54b (306 mg) as a white solid with a yield of 91.7%.

[0331] MS m / z(ESI):388[M+1] +

[0332] Step 2: N-methyl-5-nitro-N-[2-(trifluoromethyl)-6,8-dihydro-5H-pyrano[3,4-b]pyridin-5-yl]thiophene-3-carboxamide 54b (300 mg, 0.77 mmol) and 10% palladium on carbon (300 mg, containing 10% Pd and 50% water) were dispersed in tetrahydrofuran (20 mL). The mixture was replaced with hydrogen and stirred at room temperature for 2 hours under a hydrogen atmosphere. The reaction mixture was filtered to remove solids, and the filtrate was concentrated and purified on a silica gel column to obtain 5-amino-N-methyl-N-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)thiophene-3-carboxamide 54c (220 mg) as a white solid in a yield of 79.5%.

[0333] MS m / z(ESI):358[M+1] +

[0334] Step 3: 5-Amino-N-methyl-N-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)thiophene-3-carboxamide 54c (220 mg, 0.62 mmol), potassium carbonate (170 mg, 1.23 mmol), and ethyl 2-oxoacetate (220 mg, 1.23 mmol) were dispersed in N,N-dimethylformamide (4 mL), sealed in a microwave tube under nitrogen, and stirred at 100°C for 1 hour. After the reaction was completed, water was added to quench the reaction, and the mixture was concentrated and purified on a silica gel column to obtain a brown liquid product, ethyl 1-(4-(methyl(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)carbamoyl)thiophen-2-yl)-1H-imidazole-5-carboxylate 54d (210 mg), in a yield of 71.0%.

[0335] MS m / z(ESI):481[M+1] +

[0336] Step 4: Ethyl 1-(4-(methyl(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)carbamoyl)thiophen-2-yl)-1H-imidazole-5-carboxylate 54d (210 mg, 0.44 mmol) was dissolved in ammonia in methanol (10 mL, 7 M) and stirred at 50°C for 16 h. The reaction mixture was dried to give a crude product, which was purified by prep-HPLC to give 1-(4-(methyl(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)carbamoyl)thiophen-2-yl)-1H-imidazole-5-carboxamide 54 (100 mg) as a white solid in a yield of 51.1%.

[0337] MS m / z(ESI):452[M+1] +

[0338] 1H NMR(400MHz,MeOD)δ8.02(s,2H),7.89(s,1H),7.74(m,1H),7.70(s,1H),7. 42(s,1H),5.88(s,1H),4.92(s,1H),4.77(m,1H),4.22(m,2H),2.93(m,3H).

[0339] Example 55

[0340] 1-Methyl-5-(4-(methyl(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)carbamoyl)thiophen-2-yl)-1H-pyrazole-4-carboxamide

[0341]

[0342] Step 1: 5-bromothiophene-3-carboxylic acid methyl ester (626 mg, 2.83 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-4-carbonitrile (0.6 g, 2.57 mmol), potassium phosphate (1.09 g, 5.15 mmol) and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (123 mg, 0.26 mmol) were added. The product was dissolved in water (4 mL) and 1'4-dioxane (20 mL), and the atmosphere was purged with nitrogen three times. Methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium (II) (218 mg, 0.26 mmol) was added, and the system was heated to 90°C and stirred for 16 hours. The reaction was cooled to room temperature, quenched with water, and extracted with ethyl acetate (60 mL x 3). The combined organic phases were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography with eluent System B to give methyl 5-(4-cyano-1-methyl-1H-pyrazol-5-yl)thiophene-3-carboxylate 55b (0.35 g) in a yield of 55.0%.

[0343] MS m / z(ESI):248[M+1]

[0344] Step 2: Methyl 5-(4-cyano-1-methyl-1H-pyrazol-5-yl)thiophene-3-carboxylate 55b (0.2 g, 0.81 mmol) and lithium hydroxide (39 mg, 1.62 mmol) were dissolved in tetrahydrofuran (2 mL), methanol (2 mL), and water (2 mL). The reaction was stirred at 25°C for 18 hours. The reaction was concentrated, and the pH was adjusted to 5-6 by adding 1 M dilute hydrochloric acid. The product was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to afford 5-(4-cyano-1-methyl-1H-pyrazol-5-yl)thiophene-3-carboxylic acid 55c (0.18 g, crude).

[0345] MS m / z(ESI):234[M+1]

[0346] Step 3: 5-(4-cyano-1-methyl-1H-pyrazol-5-yl)thiophene-3-carboxylic acid 55c (0.15 g, 0.64 mmol), N-methyl-2-(trifluoromethyl)-6,8-dihydro-5H-pyrano[3,4-b]pyridin-5-amine 55d (149 mg, 0.64 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (485 mg, 1.29 mmol) and N,N-diisopropylethylamine (249 mg, 1.93 mmol) were dissolved in N,N-dimethylformamide (5 mL). The atmosphere was purged with nitrogen three times and the reaction system was stirred at 25°C for 2 hours. The mixture was quenched with water and extracted with ethyl acetate (60 mL x 3). The organic phases were combined, washed with 30 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. 5-(4-Cyano-1-methyl-1H-pyrazol-5-yl)-N-methyl-N-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)thiophene-3-carboxamide 55e was obtained (0.21 g, crude).

[0347] MS m / z(ESI):448[M+1]

[0348] Step 4: 5-(4-cyano-1-methyl-1H-pyrazol-5-yl)-N-methyl-N-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)thiophene-3-carboxamide 55e (170 mg, 0.38 mmol) and sodium hydroxide (76 mg, 1.90 mmol) were dissolved in dimethyl sulfoxide (1.2 mL), water (6 mL) and ethanol (2.4 mL). Hydrogen peroxide (388 mg, 11.40 mmol, 0.35 mL) was added and the reaction system was stirred at 25 °C for 1 hour. The reaction mixture was concentrated with water, and the residue was purified by silica gel column chromatography with eluent System A to give 1-methyl-5-(4-(methyl(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)carbamoyl)thiophen-2-yl)-1H-pyrazole-4-carboxamide 55e (0.12 g, yield: 67.9%).

[0349] MS m / z(ESI):466[M+1]

[0350] 1H NMR(400MHz,DMSO-d6)δ8.13(d,1H),8.03(d,Hz,1H),7.93(s,1H),7.80(q,2H),7.55(d,1H),6.96(s,1 H),5.68(d,1H),4.88(d,1H),4.77–4.70(m,1H),4.17(d,2H),3.99(dt,1H),3.78(s,3H),2.83(d,3H).

[0351] Biological test evaluation

[0352] The present invention is further described and explained below in conjunction with test examples, but these examples are not intended to limit the scope of the present invention.

[0353] Test Example 1: Determination of the inhibitory effect of the compounds of the present invention on the proliferation activity of HCT116 and MTAP Knockout HCT116 cells

[0354] 1.1 Experimental Purpose: The purpose of this test case is to measure the inhibitory effect of compounds on the proliferation activity of HCT116 wild-type and HCT116 MTAP knockout cells.

[0355] 1.2 Experimental instruments:

[0356] Centrifuge (Eppendorf 5810R); microplate reader (BioTek Synergy H1 or PerkinElmer Envision); pipette (Eppendorf or Rainin).

[0357] 1.3 Experimental reagents:

[0358] HCT116 and MTAP Knockout HCT116 cells were purchased from Nanjing Kebai; Cell Titer-Glo was purchased from Promega, catalog number G7573; McCoy`5A was purchased from Gibco, catalog number 12330031; FBS was purchased from Gibco, catalog number 10091148; PBS was purchased from Gibco, catalog number 10010023; trypsin was purchased from Gibco, catalog number 25200056; cell culture plates were purchased from Corning, catalog number 3610.

[0359] 1.4 Experimental methods:

[0360] When HCT116 and MTAP Knockout HCT116 cells were cultured to an appropriate cell density using McCoy'5A medium containing 10% FBS, the cells were collected and adjusted to an appropriate cell concentration using complete medium. The cell suspension was plated on a 96-well plate at 90 μL per well and placed in a 37°C, 5% CO2 incubator to adhere overnight. Compound solutions of different concentrations were prepared using DMSO and culture medium, and a solvent control was set up. The compound solution was added to a 96-well plate at 10 μL per well and continued to be cultured in a 37°C, 5% CO2 incubator for 72 to 240 hours. Then, CellTiter-Glo solution was added, the plates were shaken to mix evenly, and the plates were incubated in the dark for 10 to 30 minutes. The plates were read using a Synergy H1 or Envision microplate reader.

[0361] 1.5 Experimental data processing method:

[0362] The inhibition rate was calculated using the luminescence signal value, and the concentration and inhibition rate were fitted with a nonlinear regression curve using Graphpad Prism software to obtain the IC 50 value.

[0363] 1.6 Experimental Conclusions:

[0364] The above scheme showed that the compound of the present invention showed an inhibitory effect of about 0.1nM to 100nM (IC 50 ) biological activity; preferably 0.1nM to 50nM (IC 50 ) of biological activity; more preferably 0.1nM to 20nM (IC 50 ) of biological activity; most preferably 0.1nM to 10nM (IC 50 )'s biological activity.

[0365] In some embodiments, the IC values ​​of the compounds of the present invention for HCT116 cell proliferation activity are 50 Greater than the IC for proliferation activity of HCT116 MTAP knockout cells 50 About 20 times; preferably greater than about 50 times; more preferably greater than about 70 times; and even more preferably greater than about 100 times.

Claims

1. A compound represented by general formula (I), (IA) or (IB), a stereoisomer thereof or a pharmaceutically acceptable salt thereof: in: M1 is selected from N or CR a ; M2 is selected from N or CR b ; M3 is selected from N, C(O), O or CR c ; preferably N or CR c ; M8 is selected from O, S, N, -NR i -or-CR i R j -, R i and R j Can exist simultaneously or only one; M9 is selected from O, S, N, -NR k -or-CR k R l -, R k and R l Can exist simultaneously or only one; L1 is selected from a bond, -O-, -S-, -NR N -, -C(O)-, -S(O)-, -S(O)2-, -CONR N -、-NR N CO-、-S(O)2NR N -、-NR N S(O)2-、C 1-3 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-10 Cycloalkylene, 3-10 membered heterocyclylene, C 6-10 Arylene or 5-10 membered heteroarylene, the C 1-3 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-10 Cycloalkylene, 3-10 membered heterocyclylene, C 6-10 Arylene and 5-10 membered heteroarylene, optionally substituted by hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions in aryl, 5-6 membered heteroaryl; preferably bond, -O-, -S-, -NR N -, -C(O)-, -S(O)-, -S(O)2-, -CONR N -、-NR N CO-、-S(O)2NR N -、-NR N S(O)2-、C 1-3 Alkylene, C 2-4 Alkenylene or C 2-4 Alkynylidene, the C 1-3 Alkylene, C 2-4 Alkenylene or C 2-4 The alkynylene group is optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl, 5-6 membered heteroaryl; more preferably bond, -C(O)-, -CONR N -or-NR N CO-; L2 is selected from a bond, -O-, -S-, -NR N -, -C(O)-, -S(O)-, -S(O)2-, -CONR N -、-NR N CO-、-S(O)2NR N -、-NR N S(O)2-、C 1-3 Alkylene, C 2-4 Alkenylene or C 2-4 Alkynylidene, the C 1-3 Alkylene, C 2-4 Alkenylene or C 2-4 The alkynylene group is optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl, 5-6 membered heteroaryl; preferably -C(O)-; Or, L1 and CR b Link Form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R1 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R2 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-P(O)R b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; Alternatively, R1 and R2 are linked to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may optionally be further substituted with 1, 2, 3 or 4 R d Optionally, the ring may be further linked to L1 to form a C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; Or R2 and R i Link Form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may optionally be further substituted with 1, 2, 3 or 4 R d substituted by a substituent; R3 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, -(CR a3 R a4 ) n1 -C 3-12 Cycloalkyl, -(CR a3 R a4 ) n1 -3-12 membered heterocyclic group, -(CR a3 R a4 ) n1 -C 6-14 Aryl or -(CR a3 R a4 ) n1 -5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, -(CH2) n1 -C 3-12 Cycloalkyl, -(CH2) n1 -3-12 membered heterocyclic group, -(CH2) n1 -C 6-14 Aryl or -(CH2) n1 -5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R4 is selected from -(CR a1 R a2 ) n2 - Ring A; Ring A is selected from C 3-14 Cycloalkyl, 3-14 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally substituted by 1, 2, 3, 4, 5 or 6 R f substituted by a substituent; Alternatively, R3 and R4 are linked to form a ring B, wherein the ring B is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally substituted by 1, 2, 3, 4, 5 or 6 R e substituted by a substituent; R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, -(CH2) n3 -C 3-12 Cycloalkyl, -(CH2) n3 -3-12 membered heterocyclic group, -(CH2) n3 -C 6-14 Aryl, -(CH2) n3 -5-14 membered heteroaryl, -(CH2) n3 OR b1 、-(CH2) n3 C(O)R b1 、(CH2) n3 C(O)OR b1 、-(CH2) n3 NR b1 R b2 、-(CH2) n3 NR b3 C(O)R b1 、-(CH2) n3 C(O)NR b1 R b2 、-(CH2) n3 S(O)2R b1 、-(CH2) n3 S(O)2NR b1 R b2 、-(CH2) n3 NR b3 S(O)2R b1 、-(CH2) n3 S(O)R b1 (=NR b3 ) or -(CH2) n3 N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR b4 Sum = CR b4 CR b5 One or more substitutions in ; R c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R d Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-P(O)R b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R e Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -SF5, -P(O)R c1 CR c2 、=N-OR c1 、=CR c1 CR c2 、-S(O)R c1 (=NR c2 ) and -N=S(O)R c1 R c2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; Or, two R e Link Form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, -P(O)R c3 CR c4 、=N-OR c3 、=CR c3 CR c4 、-S(O)R c3 (=NR c4 ) and -N=S(O)R c3 R c4 One or more substitutions in ; R f Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -SF5, -P(O)R d1 CR d2 、=N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ; Or, two R f Link Form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl and -SF5, -P(O)R d5 CR d6 、=N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 One or more substitutions in ; R a1 and R a2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; Or, R a1 and R a2 Together form = O; R a3 and R a4 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R b1 、R b2 、R b3 、R b4 and R b5 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R c1 、R c2 、R c3 and R c4 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R d1 、R d2 、R d3 、R d4 、R d5 and R d6 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R i 、R j 、R k or R l are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R N Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; n1 is selected from 0, 1, 2 or 3; n2 is selected from 0, 1, 2 or 3; n3 is selected from 0, 1, 2 or 3.

2. The compound according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Further as shown in general formula (II): in: M4 is selected from N or CR g ; R 5a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-P(O)R b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-14 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R 6a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; R 6b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; R g Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aryl and 5-10 membered heteroaryl.

3. The compound according to any one of claims 1 to 2, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R4 is selected from -(CR a1 R a2 ) n2 - Ring A; Ring A is selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally substituted by 1, 2, 3, 4, 5 or 6 R f Substituted by a substituent; preferably C 7-10 fused cycloalkyl, 7-10 membered fused heterocyclic group, phenyl or 5-6 membered heteroaryl, optionally substituted by 1, 2, 3, 4, 5 or 6 R f substituted by a substituent; R f Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, -P(O)R d1 CR d2 、=N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ; Or, two R f Link Form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, -P(O)R d5 CR d6 、=N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 One or more substitutions in .

4. The compound according to any one of claims 1 to 2, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R4 is selected from -(CR a1 R a2 ) n2 -R5; R5 is selected from X is selected from O or CH2; M4 is selected from CH or N; M5 is selected from CH or N; M6 is selected from CH or N; M7 is selected from CH or N; Ring D is selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; R 7a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ; Or, two R 7a Link Form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 One or more substitutions in ; R 7b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 ; n4 is selected from 0, 1 or 2; n5 is selected from 0, 1 or 2; a is selected from 0, 1, 2, 3 or 4; b is selected from 0, 1, 2, 3 or 4.

5. The compound according to any one of claims 1 to 4, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Further as shown in general formula (V-1) or (V-2): X1 is selected from O or CH2; X2 is selected from N or CR 9d ; R 9a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ; R 9b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ; R 9c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ; R 9d Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ; R 9e Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d1 、=CR d1 CR d2 、-S(O)R d1 (=NR d2 ) and -N=S(O)R d1 R d2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR d3 Sum = CR d3 CR d4 One or more substitutions in ; Or, two R 9e Link Form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -SF5, =N-OR d5 、=CR d5 CR d6 、-S(O)R d5 (=NR d6 ) and -N=S(O)R d5 R d6 One or more substitutions in ; n6 is selected from 0, 1 or 2; n7 is selected from 0, 1 or 2; X, M4, M5, M6, M7, Ring D, R 7a 、R 7b , n4, n5, a and b are as defined in claim 8.

6. The compound according to any one of claims 1 to 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R3 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, -(CH2) n1 -C 3-10 Cycloalkyl, -(CH2) n1 -3-10 membered heterocyclic group, -(CH2) n1 -C 6-10 Aryl or -(CH2) n1 -5-10 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 one or more substitutions selected from aryl and 5-10 membered heteroaryl; R 5a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-P(O)R b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -OR b1 、-C(O)R b1 、-C(O)OR b1 、-NR b1 R b2 、-NR b3 C(O)R b1 、-C(O)NR b1 R b2 、-S(O)2R b1 、-S(O)2NR b1 R b2 、-NR b3 S(O)2R b1 、-S(O)R b1 (=NR b3 ) or -N=S(O)R b1 R b2 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Alkylamino, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-14 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, one or more substitutions; more preferably selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl or 3-6 membered heterocyclic group; R 6a Selected from hydrogen, deuterium, C 1-3 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group; preferably hydrogen; R 6b Selected from hydrogen, deuterium, C 1-3 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group; preferably hydrogen; R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group; R b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, -(CH2) n3 -C 3-10 Cycloalkyl, -(CH2) n3 -3-10 membered heterocyclic group, -(CH2) n3 -C 6-10 Aryl, -(CH2) n3 -5-10 membered heteroaryl, -(CH2) n3 OR b1 、-(CH2) n3 C(O)R b1 、(CH2) n3 C(O)OR b1 、-(CH2) n3 NR b1 R b2 、-(CH2) n3 NR b3 C(O)R b1 、-(CH2) n3 C(O)NR b1 R b2 、-(CH2) n3 S(O)2R b1 、-(CH2) n3 S(O)2NR b1 R b2 、-(CH2) n3 NR b3 S(O)2R b1 、-(CH2) n3 S(O)R b1 (=NR b3 ) or -(CH2) n3 N=S(O)R b1 R b2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =N-OR b4 Sum = CR b4 CR b5 One or more substitutions in ; R c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; preferably R c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 1-3 Alkylamino, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group.

7. The compound according to any one of claims 1 to 6, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Selected from the following compounds:

8. A pharmaceutical composition comprising a therapeutically effective dose of the compound according to any one of claims 1 to 7, its stereoisomers or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.

9. Use of the compound according to any one of claims 1 to 7, its stereoisomer or pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 8 in the preparation of a PRMT5 inhibitor.

10. Use of the compound according to any one of claims 1 to 7, its stereoisomer or pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 8 in the preparation of a drug for treating cancer; wherein the cancer is an MTAP-related cancer; The cancer is selected from lung cancer, hepatocellular carcinoma, breast cancer, skin cancer, bladder cancer, liver cancer, pancreatic cancer, head and neck cancer, glioma, glioblastoma, esophageal cancer, pancreatic cancer, mesothelioma, melanoma, astrocytoma, undifferentiated pleomorphic sarcoma, leukemia, gastric adenocarcinoma, myxofibrosarcoma, bile duct sarcoma, brain cancer, gastric cancer, kidney cancer, endometrial cancer, ovarian tumor, prostate cancer, diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, urinary tract cancer, soft tissue cancer, pleural cancer, colorectal cancer, colorectal cancer or bile duct cancer; the lung cancer is selected from non-small cell lung cancer, squamous cell lung carcinoma or lung adenocarcinoma; the esophageal cancer is selected from esophageal squamous cell carcinoma or esophageal adenocarcinoma.

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