Heterocyclic carbonyl derivative modulator, preparation method therefor, and use thereof

Abstract

The present invention relates to a heterocyclic carbonyl derivative modulator, a preparation method therefor, and the use thereof. Specifically, the present invention relates to a compound represented by general formula (II-B), a preparation method therefor, a pharmaceutical composition containing said compound, and a use thereof as a modulator in the treatment of Alzheimer's disease, schizophrenia, pain, addiction, and sleep disorders, wherein each substituent in general formula (II-B) is as defined in the description.

Description

Heterocyclic carbonyl derivative regulator, preparation method and application thereof Technical Field

[0001] The present invention belongs to the field of biomedicine, and specifically relates to a heterocyclic carbonyl derivative regulator, a preparation method and an application thereof. Background Art

[0002] The object of the present invention is to provide compounds which are useful in the treatment or prevention of such diseases and which have improved therapeutic properties.

[0003] Schizophrenia is a severe, complex, and debilitating mental health disorder characterized by a range of symptoms, including delusions, hallucinations, disorganized speech or behavior, delayed speech, and blunted affect. Schizophrenia is also often accompanied by severe cognitive impairment, which further limits patients' ability to work and maintain interpersonal relationships. According to the World Health Organization, schizophrenia affects over 23 million people worldwide, with a lifetime prevalence of between 3.8 and 8.4 percent. Onset is most common in late adolescence, and treatment challenges primarily include low medication adherence and high relapse rates. Only 20% of patients report good treatment outcomes, and medication adherence is poor, with an 18-month adherence rate of approximately 60% and a discontinuation rate of 74%. Among patients who discontinue medication, relapse rates can reach as high as 77% within one year and 90% within two years. Compared to the general population, life expectancy for patients with schizophrenia is shortened by 10 to 25 years.

[0004] Muscarinic receptors belong to the acetylcholine receptor family and are typical GPCRs. There are five subtypes: M1-5. The G protein-coupled M4 is primarily expressed in the cerebral cortex, striatum, hypothalamus, and hippocampus. A 2018 genome-wide association study of schizophrenia published in Nature Genetics (11,260 cases and 24,542 controls) showed a significant correlation between M4 gene mutations and the disease.

[0005] Cholinergic neuronal transmission is crucial for cognitive function, and antagonism of its receptors can lead to severe memory impairment. In schizophrenia, excessive dopamine levels in the striatum and nucleus accumbens are thought to be associated with the disease, and blocking dopamine D2 receptors is currently an effective therapeutic strategy. Several newly developed M4-specific positive isomeric modulators (PAMs) enhance the effects of the endogenous agonist acetylcholine, revealing that muscarinic acetylcholine receptors are involved in controlling dopamine release at key synapses in the hippocampus and striatum involved in cognition.

[0006] In a recent study, M4PAMs reduced striatal dopamine release in wild-type mice after amphetamine treatment, and further in vivo studies showed that the M4PAM VU0467154 improved learning impairment induced by the NMDA receptor antagonist MK-801.

[0007] PAM CVL-231, which targets the M4 receptor, is currently in Phase II clinical trials, and its Phase Ib clinical trial showed good overall tolerability. After six weeks of administration, both the 30mg / 1 day / 1 time and 20mg / 1 day / 2 times doses showed significant antipsychotic activity. Compared with the placebo group, the Positive and Negative Syndrome Scale (PANSS) total score of the 30mg / 1 day / 1 time group decreased by an average of 19.5 points from the baseline examination, and the PANSS total score of the 20mg / 1 day / 2 times group decreased by an average of 17.9 points from the baseline, which was statistically significant and clinically meaningful.

[0008] Activating M4 receptors in the striatum and hippocampus using specific PAMs can significantly improve the high dopamine state in the striatum and the overstimulation state in the hippocampus, providing treatment for the psychotic symptoms and cognitive impairment of schizophrenia. Therefore, regulating M4 receptor activity is an effective strategy for treating or preventing schizophrenia mediated by M4 dysregulation. Summary of the Invention

[0009] Another aspect of the present invention provides a compound represented by general formula (II-A1) or (II-A2), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof:

[0010] in:

[0011] is a single bond or a double bond;

[0012] X1 is independently selected from a bond, C, CR 11 , CR 11 R 22 or N;

[0013] X2 are each independently selected from a bond, C, CR 22 , CR 11 R 22 or N;

[0014] X3 are each independently selected from a bond, C, CR 33 , CR 11 R 22 or N;

[0015] X4 are each independently selected from a bond, C, CR 44 , CR 11 R 22 or N;

[0016] L4 or L5 are each independently selected from a bond, C(R5R6), N(R5), O or S;

[0017] L1 is selected from C(CF3)R 66、C(O), C(=S), C(=NR 66 ) or S(O) n2 ;

[0018] L2 is selected from C 2-6 Alkenylene, C 2-6 Alkynylidene, C 3-12 Cycloalkylene, 3-12 membered heterocyclylene, C 6-12 Arylene or 5-12 membered heteroarylene;

[0019] R 11 、R 22 、R 33 、R 44 or R 66 each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0020] Ring B or Ring C is present or absent, and when present is each independently selected from cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0021] At least one of ring B and ring C exists;

[0022] Ring F or Ring G is each independently selected from a cycloalkyl group, a heterocyclic group, an aryl group or a heteroaryl group, and the cycloalkyl group, the heterocyclic group, the aryl group or the heteroaryl group may be further substituted with a substituent;

[0023] R1, R2, R3, R4, R5 or R6 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from deuterium, oxo, thioxo, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl or cyano-substituted alkyl;

[0024] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the carbon atoms to form a cycloalkyl or heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally substituted with one or more substituents selected from deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0025] n2 is 1 or 2.

[0026] In a preferred embodiment of the present invention:

[0027] X1 is selected from C, CR 11 or N;

[0028] X2 is selected from C, CR 22 or N;

[0029] X3 is selected from C, CR 33 or N;

[0030] X4 is selected from C, CR 44 or N.

[0031] In a preferred embodiment of the present invention,

[0032] Ring F or ring G is independently selected from cycloalkyl, heterocyclic, aryl or heteroaryl, and the cycloalkyl, heterocyclic, aryl or heteroaryl may be further R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0033] R 55 , R7, R8, R9 or R 10are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, deuterated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32 -、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0034] R 31 、R 32 、R 33 、R aa 、R bb or R cc each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0035] m1 is 0, 1, or 2;

[0036] n1 is 0, 1, or 2.

[0037] In a preferred embodiment of the present invention, the compound is further represented by formula (II-B), (II-C), (II-D) or (II-E):

[0038] X5 selected from CR 55 or N;

[0039] M1, M2, M3 or M4 are each independently selected from C or N;

[0040] When M1, M2, M3 or M4 is N, R7, R8, R9 or R 10 Does not exist; R 55 , R7, R8, R9 or R 10are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, deuterated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32 -、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0041] R 31 、R 32 、R 33 、R aa 、R bb or R cc each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0042] m1 is 0, 1, or 2;

[0043] n1 is 0, 1, or 2.

[0044] In certain embodiments of the present invention,

[0045] R 55 , R7, R8, R9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32-、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group may optionally be further substituted with one or more substituents selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0046] R 31 、R 32 、R 33 、R aa 、R bb or R cceach independently selected from deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from hydrogen, deuterium, hydroxy, halogen, cyano, amino, alkyl, haloalkyl or deuterated alkyl;

[0047] m1 is 0, 1, or 2;

[0048] n1 is 0, 1, or 2.

[0049] In certain embodiments of the present invention,

[0050] X5, M1, M2, M3 or M4 are each independently selected from CR 55 or N;

[0051] R 55 , R7, R8, R9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32 -、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 S(O)(=NRcc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group may optionally be further substituted with one or more substituents selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0052] R 31 、R 32 、R aa 、R bb or R cc each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, said amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl being optionally substituted with one or more substituents of hydrogen, deuterium, hydroxy, halogen, cyano, amino, alkyl, haloalkyl or deuterated alkyl;

[0053] m1 is 0, 1, or 2;

[0054] n1 is 0, 1, or 2;

[0055] Ring B, Ring C, X1 to X4, R1, R2, R3, and R4 are as defined in the general formula (II-A1) or (II-A2).

[0056] In a further preferred embodiment of the present invention, the compound is not of the following structure:

[0057] In certain embodiments of the present invention, the compound is further represented by formula (II) or (II-1):

[0058] in:

[0059] X1 is independently selected from a bond, C, CR 11 , CR 11 R 22 or N;

[0060] X2 are each independently selected from a bond, C, CR22 , CR 11 R 22 or N;

[0061] X3 are each independently selected from a bond, C, CR 33 or N;

[0062] X4 are each independently selected from a bond, C, CR 44 or N;

[0063] R 11 、R 22 、R 33 、R 44 R1, R2, R3, R4, R5 or R6 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0064] R 55 、R7、R8、R9、R 10 or R 12 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, C1-6 Halogenated alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0065] Ring B or Ring C is present or absent, and when present, each is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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, halogenated C1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0066] At least one of ring B and ring C exists;

[0067] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, the C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0068] R 31 、R 32 、R 33 、R aa 、R bb or R cc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, halogenated, 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, halogenated C 1-6 Alkoxy, C 1- 6-hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0069] m1 is 0, 1, or 2; and

[0070] n1 is 0, 1, or 2.

[0071] In a preferred embodiment of the present invention:

[0072] X1 is independently selected from C, CR 11 or N;

[0073] X2 is independently selected from C, CR 22 or N;

[0074] X3 are each independently selected from C, CR 33 or N;

[0075] X4 are each independently selected from C, CR 44 or N.

[0076] In certain embodiments of the present invention,

[0077] X1 is independently selected from C, CR 11 or N;

[0078] X2 is independently selected from C, CR 22 or N;

[0079] X3 are each independently selected from C, CR 33 or N;

[0080] X4 are each independently selected from C, CR 44 or N;

[0081] X5 are each independently selected from CR 55 or N;

[0082] R11 、R 22 、R 33 、R 44 R1, R2, R3, R4, R5 or R6 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0083] R 55 、R7、R8、R9、R 10 or R 12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa Rbb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , which may be further substituted with 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0084] Ring B or Ring C is present or absent, and when present, each is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally further substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0085] At least one of ring B and ring C exists;

[0086] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally further substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0087] R 31 or R 32 、R aa 、R bb or R cc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0088] m1 is 0, 1, or 2; and

[0089] n1 is 0, 1, or 2.

[0090] In a preferred embodiment of the present invention, the compound is further represented by the general formula (II-A-1), (II-A-2) or (II-A-3):

[0091] in:

[0092] is a single bond or a double bond;

[0093] X1 is independently selected from a bond, C, CR 11 , CR 11 R 22 or N;

[0094] X2 are each independently selected from a bond, C, CR 22 , CR 11 R 22 or N;

[0095] X3 are each independently selected from a bond, C, CR 33 , CR 11 R 22 or N;

[0096] X4 are each independently selected from a bond, C, CR 44 , CR 11 R 22 or N;

[0097] X5 selected from CR 55 or N;

[0098] M1, M2, M3 or M4 are each independently selected from C or N;

[0099] When M1, M2, M3 or M4 is N, R7, R8, R9 or R 10 does not exist;

[0100] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 、(CR 66 ) n2 , N or O;

[0101] L4 or L5 are each independently selected from a bond, C(R5R6), N(R5), O or S;

[0102] R 11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0103] Ring F is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0104] Ring G is independently selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-14 membered heteroaryl, optionally further R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0105] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, the C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0106] R 55 、R7、R8、R9、R 10 or R 12 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, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -O(CR aa R bb ) n1 R 31 、-N(CR aa Rbb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino group, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0107] R 31 、R 32 、R 33 、R aa 、R bb or R cc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, halogenated, 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, halogenated C 1-6 Alkoxy, C 1- 6-hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0108] m1 is 0, 1, or 2; and

[0109] n1 is 0, 1, or 2.

[0110] In a preferred embodiment of the present invention:

[0111] X1 is independently selected from C, CR 11 or N;

[0112] X2 is independently selected from C, CR 22 or N;

[0113] X3 are each independently selected from C, CR 33 or N;

[0114] X4 are each independently selected from C, CR 44 or N.

[0115] In a preferred embodiment of the present invention,

[0116] is a single bond or a double bond;

[0117] X1 is independently selected from C, CR 11 or N;

[0118] X2 is independently selected from C, CR 22 or N;

[0119] X3 are each independently selected from C, CR 33 or N;

[0120] X4 are each independently selected from C, CR 44 or N;

[0121] X5 are each independently selected from CR 55 or N;

[0122] M1, M2, M3 or M4 are each independently selected from C or N;

[0123] When M1, M2, M3 or M4 is N, R7, R8, R9 or R 10 does not exist;

[0124] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 、(CR 66 ) n2 , N or O;

[0125] L4 or L5 are each independently selected from a bond, C(R5R6), N(R5), O or S;

[0126] R 11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88 R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0127] R 55 、R7、R8、R9、R 10 or R 12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa Rbb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0128] Ring F is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0129] Ring G is independently selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-14 membered heteroaryl, optionally further R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0130] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, the C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally further substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0131] R 31 、R 32 、R 33 、R aa 、R bb or R cc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the amino, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1- 6 haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0132] m1 is 0, 1, or 2; and

[0133] n1 is 0, 1, or 2.

[0134] In certain embodiments of the present invention,

[0135] X1 is independently selected from C, CR 11 or N;

[0136] X2 is independently selected from C, CR 22 or N;

[0137] X3 are each independently selected from C, CR 33 or N;

[0138] X4 are each independently selected from C, CR 44 or N;

[0139] X5, M1, M2, M3 or M4 are each independently selected from CR 55 or N;

[0140] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 、(CR 66 ) n2 , N or O;

[0141] L4 or L5 are each independently selected from a bond, C(R5R6), N(R5), O or S;

[0142] R 11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88 R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0143] R 55 , R7, R8, R9 or R 10 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with 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, halogenated C 1-6 Alkoxy, C1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0144] Ring F is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally further substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0145] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, the C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0146] R 31 、R 32 、R aa 、R bb or R ccare 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0147] m1 is 0, 1, or 2; and

[0148] n1 is 0, 1, or 2.

[0149] In a preferred embodiment of the present invention, the compound is further represented by the general formula (II-A-a1), (II-A-a2), (II-A-a3), (II-A-a4), (II-A-a5), (II-A-a6), (II-A-a7), (II-A-a8) or (II-A-a9):

[0150] X1~X8, M1~M4, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 or R 12 As defined in general formula (II-A-1) or (II-A-2).

[0151] In a preferred embodiment of the present invention, the compound is further represented by the general formula (II-B-1), (II-B-2) or (II-B-5):

[0152] X1 is independently selected from C, CR 11 or N;

[0153] X2 is independently selected from C, CR 22 or N;

[0154] X3 are each independently selected from CR 33 or N;

[0155] X4 are each independently selected from CR 44 or N;

[0156] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 、(CR 66 ) n2 , N or O;

[0157] L4 is each independently selected from a bond, C(R5R6), N(R5), O or S;

[0158] R 11 、R 22 、R 33 、R 44 R1, R2, R3, R4, R5 or R6 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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 1-6Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0159] Ring F is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally further substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0160] Ring G is independently selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-14 membered heteroaryl, optionally further R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0161] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, the C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally further substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0162] R 55 , R7, R8, R9 or R 10 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1- 6 alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted by 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0163] R 31 、R 32 、R 33 、R aa 、R bb or R cc are each independently 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0164] m1 is 0, 1, or 2; and

[0165] n1 is 0, 1, or 2.

[0166] In a further preferred embodiment of the present invention, the compound is further represented by the general formula (II-B-a1), (II-B-a2), (II-B-a3), (II-B-a4), (II-B-a5), (II-B-a6), (II-B-a7), (II-B-a8), (II-B-a9) or (II-B-a10):

[0167] Ring F is independently selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0168] Ring G is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally further substituted by R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents.

[0169] In a further preferred embodiment of the present invention, the compound is further represented by the general formula (II-B-3), (II-B-4), (II-8), (II-9), (II-10), (II-11), (II-12), (II-13), (II-14), (II-15), (II-16), (II-17) or (II-18):

[0170] in:

[0171] X1 is independently selected from C, CR 11 or N;

[0172] X2 is independently selected from C, CR 22 or N;

[0173] X3 are each independently selected from C, CR 33 or N;

[0174] X4 are each independently selected from C, CR 44 or N;

[0175] X5 are each independently selected from CR 55 or N;

[0176] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR88 NR 88 (CR 66 R 77 ) n2 、(CR 66 ) n2 , N or O;

[0177] L4 is each independently selected from a bond, C(R5R6), N(R5), O or S;

[0178] R 11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88 R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0179] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-10Cycloalkyl or 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl or 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0180] R 55 , R7, R8, R9 or R 10 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, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) n1C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0181] R 31 、R 32 、R 33 、R aa 、R bb or R cc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C1- 6 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0182] m1 is 0, 1, or 2; and

[0183] n1 is 0, 1, or 2.

[0184] In a preferred embodiment of the present invention,

[0185] R 55 , R7, R8, R9 or R 10 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1- 6 alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0186] R 31 、R 32 、R 33 、R aa 、R bb or R cc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0187] m1 is 0, 1, or 2; and

[0188] n1 is 0, 1, or 2.

[0189] In a preferred embodiment of the present invention, the compound is further represented by the general formula (II-1), (II-2), (II-3), (II-4), (II-5), (II-6) or (II-7):

[0190] X1 is independently selected from C, CR11 or N;

[0191] X2 is independently selected from C, CR 22 or N;

[0192] X3 are each independently selected from C, CR 33 or N;

[0193] X4 are each independently selected from C, CR 44 or N;

[0194] X5 are each independently selected from CR 55 or N; X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 、(CR 66 ) n2 , N or O;

[0195] L4 is each independently selected from a bond, C(R5R6), N(R5), O or S;

[0196] R 11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88 R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0197] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-10 Cycloalkyl or 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl or 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0198] R 55 , R7, R8, R9 or R 10 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, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CRaa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0199] R 31 、R 32 、R 33 、R aa 、R bb or R cc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0200] m1 is 0, 1, or 2; and

[0201] n1 is 0, 1, or 2.

[0202] In a further preferred embodiment of the present invention,

[0203] is a single bond or a double bond;

[0204] X1 is independently selected from C, CR 11 or N;

[0205] X2 is independently selected from C, CR 22 or N;

[0206] X3 are each independently selected from C, CR 33 or N;

[0207] X4 are each independently selected from C, CR 44 or N;

[0208] X5 are each independently selected from CR 55 or N;

[0209] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 , CR 66 , N or O;

[0210] R 11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88 R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0211] R 55 、R7、R8、R9、R10 or R 12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O)m1 R 32 , 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0212] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, the C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally further substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0213] R 31 、R 32 、R 33 、R aa 、R bb or Rcc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0214] n2 is 0, 1 or 2.

[0215] In certain embodiments of the present invention,

[0216] is a single bond or a double bond;

[0217] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 , CR 66 , N or O;

[0218] R 66 、R 77 or R 88are 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0219] n2 is 0, 1, or 2;

[0220] X1, X2, R1~R 11 As defined in general formula (II).

[0221] In a preferred embodiment of the present invention,

[0222] is a single bond or a double bond;

[0223] X1 is independently selected from C, CR 11 or N;

[0224] X2 is independently selected from C, CR 22 or N;

[0225] X3 are each independently selected from C, CR 33 or N;

[0226] X4 are each independently selected from C, CR 44 or N;

[0227] X5 are each independently selected from CR 55 or N;

[0228] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 )n2 , CR 66 , N or O;

[0229] R 11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88 R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0230] R 55 、R7、R8、R9、R 10 or R 12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with 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, halogenated C1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0231] Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, the C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally further substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0232] R 31 、R 32 、R aa 、R bb or R cc 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0233] n2 is 0, 1 or 2.

[0234] In a further preferred embodiment of the present invention, the compound is further represented by the general formula (II-1a), (II-2a), (II-3a), (II-4a), (II-5a) or (II-6a):

[0235] In a further preferred embodiment of the present invention, the compound is further represented by the general formula (II-1b), (II-2b), (II-3b), (II-4b), (II-5b), (II-6b), (II-7b), (II-8b), (II-9b), (II-10b), (II-11b), (II-12b), (II-13b), (II-14b), (II-15b), (II-16b), (II-17b), (II-18b) or (II-19b):

[0236] The present invention also provides a compound represented by general formula (VIII-A), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof:

[0237] is a cycloalkyl group, a heterocyclic group, an aromatic ring or a heteroaryl group;

[0238] X1 selected from CR 11 or N; X2 is selected from CR 22 or N;

[0239] X3 selected from CR 33 or N; X4 selected from CR 44 or N;

[0240] L4 or L5 are each independently selected from a bond, C(R5R6), N(R5), O or S;

[0241] R0, R 11 、R 22 、R 33 、R 44R1, R2, R3, R4, R5 or R6 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl are optionally substituted with one or more substituents of deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0242] Moreover, R1, R2, R3, R4, R 11 、R 22 、R 33 or R 44 Any two groups in the group are linked to the connected atoms to form a cycloalkyl, heterocyclyl, aryl or heteroaryl group, and the cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with one or more substituents of deuterium, oxo, thioxo, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0243] Ring F or Ring G is present or absent, and when present, each is independently selected from cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl may be further replaced by R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0244] R 55 , R7, R8, R9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, deuterated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-OCR 31 R32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32 -、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0245] R 31 、R 32 、R 33 、R aa 、R bb or R cc each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0246] m1 is 0, 1, or 2;

[0247] n1 is 0, 1, or 2;

[0248] w is 0, 1, 2, 3, or 4.

[0249] In a preferred embodiment of the present invention, the general formula (VIII-A) is further represented by the general formula (VIII-1A), (VIII-1B) or (VIII-1C):

[0250] X1 is each independently selected from CR 11 or N; X2 are each independently selected from CR 22 or N;

[0251] X3 are each independently selected from CR 33 or N; X4 are each independently selected from CR 44 or N;

[0252] L4 or L5 are each independently selected from a bond, C(R5R6), N(R5), O or S;

[0253] X5 selected from CR 55 or N;

[0254] M1, M2, M3 or M4 are each independently selected from C or N;

[0255] When M1, M2, M3 or M4 is N, R7, R8, R9 or R 10 does not exist;

[0256] Ring F or ring G are each independently selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12Aryl or 5-12 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0257] R0, R 11 、R 22 、R 33 、R 44 R1, R2, R3, R4, R5 or R6 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0258] R 55 , R7, R8, R9 or R 10 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, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa Rbb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0259] R 31 、R 32 、R 33 、R aa 、R bb or R cc are each independently 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, halogenated, 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, halogenated C 1-6 Alkoxy, C 1- 6-hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0260] m1 is 0, 1, or 2; and

[0261] n1 is 0, 1, or 2;

[0262] The conditions are:

[0263] (1) R1 and R 44 , or R2 and R 44 Linked to the connected atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0264] Or, (2) R3 and R 11 , or R4 and R 11 Linked to the connected atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0265] Or, (3) R 22 With R 33 Linked to connected atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0266] Or, (4) R 33 With R 44 Linked to connected atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 substituted by one or more substituents in aryl or 5-12 membered heteroaryl;

[0267] Or, (4) R 11 With R 22 Linked to connected atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by deuterium, oxo, thio, 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 The aryl or 5-12 membered heteroaryl is substituted with one or more substituents.

[0268] In the above general formulas described in the present invention,

[0269] R 11 、R 22 、R 33 or R 44 are each independently 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, halogenated C 1-3 Alkoxy, C 1- 3-hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0270] Preferably, R 11 、R 22 、R 33 or R 44 Each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, oxirane, oxirane or oxirane, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 The deuterated alkyl group is substituted with one or more substituents.

[0271] In the above general formulas of the present invention, wherein:

[0272] R 55 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, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O)m1 R 32 , 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, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0273] R 31 、R 32 or R 33 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0274] Preferably, R 31 、R 32 or R 33 each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy, the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy, optionally deuterated by deuterium, hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0275] R aa 、R bb or R cc are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, the amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, optionally deuterated, hydroxy, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0276] Preferably, R aa 、R bb or R cc Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

[0277] In a further preferred embodiment of the present invention,

[0278] R 55 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0279] R 31 、R 32 or R 33are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0280] Preferably, R 31 、R 32 or R 33 each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy;

[0281] R aa 、R bb or R cc are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, optionally deuterated, hydroxy, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0282] Preferably, R aa 、R bb or R ccEach is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

[0283] In the above general formulas of the present invention, wherein:

[0284] R1 or R2 are each independently 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0285] Preferably, R1 or R2 are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy;

[0286] Alternatively, R1, R2 and the connected carbon atoms are linked to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1- 3 alkyl, C 3-10Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0287] Preferably, R1, R2 and the connected carbon atom are linked to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1- 3. The alkyl group is substituted with one or more substituents.

[0288] In the above general formulas of the present invention, wherein:

[0289] R3 or R4 are each independently 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0290] Preferably, R3 or R4 are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy;

[0291] Alternatively, R3, R4 and the connected carbon atom are linked to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1- 3 alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0292] Preferably, R3, R4 and the connected carbon atom are linked to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1- 3. The alkyl group is substituted with one or more substituents.

[0293] In the above general formulas of the present invention, wherein:

[0294] R5 or R6 are each independently 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0295] Preferably, R5 or R6 are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

[0296] Alternatively, R5, R6 and the connected carbon atom are linked to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1- 3 alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 The aryl group or the 5-10 membered heteroaryl group containing 1-3 N, O or S atoms is substituted by one or more substituents.

[0297] Preferably, R5, R6 and the connected carbon atom are linked to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, oxo, thio, 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, halogenated C1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1- 3. One or more substituents in the alkyl group;

[0298] More preferably, R5, R6 and the connected carbon atom are linked to form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group.

[0299] In the above general formulas described in the present invention,

[0300] R7, R8, R9 or R 10 are each independently 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, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl, 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0301] R 31 、R 32 or R 33 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0302] Preferably, R 31 、R 32 or R 33 each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy, the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy, optionally deuterated by deuterium, hydroxyl, fluorine, chlorine, bromine, cyano, amino, C1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0303] R aa 、R bb or R cc are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, the amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, optionally deuterated, hydroxy, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0304] Preferably, R aa 、R bb or R cc Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

[0305] In a preferred embodiment of the present invention,

[0306] R8 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0307] R 31 、R 32 or R 33 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0308] Preferably, R 31 、R 32 or R 33 each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy;

[0309] R aa 、R bb or R cc are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, optionally substituted by hydrogen, deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1- 3 haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0310] Preferably, R aa 、R bb or R cc Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

[0311] In the above general formulas of the present invention, wherein:

[0312] R7, R9 or R 10 are each independently 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 1-3Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0313] Preferably, R7, R9 or R 10 are each independently 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 One or more substituents in the alkyl group;

[0314] More preferably, R7, R9 or R 10 Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, vinyl, allyl, propenyl, ethynyl, propynyl, propargyl, deuterated methyl, deuterated ethyl, deuterated propyl, fluoromethyl, fluoroethyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, propoxy, fluorinated methoxy, fluorinated ethoxy, trifluoromethoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, 2-hydroxypropyl, cyano-substituted methyl, cyano-substituted ethyl, cyano-substituted propyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0315] In the above general formulas of the present invention, wherein:

[0316] R11 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0317] Preferably, R 11 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, C1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 One or more substituents in the alkyl group;

[0318] More preferably, R 11 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, vinyl, allyl, propenyl, ethynyl, propynyl, propargyl, deuterated methyl, deuterated ethyl, deuterated propyl, fluoromethyl, fluoroethyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, propoxy, fluorinated methoxy, fluorinated ethoxy, trifluoromethoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, 2-hydroxypropyl, cyano-substituted methyl, cyano-substituted ethyl, cyano-substituted propyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0319] In the above general formulas of the present invention, wherein:

[0320] R 12 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0321] Preferably, R 12Selected 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 One or more substituents in the alkyl group;

[0322] More preferably, R 12 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, vinyl, allyl, propenyl, ethynyl, propynyl, propargyl, deuterated methyl, deuterated ethyl, deuterated propyl, fluoromethyl, fluoroethyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, propoxy, fluorinated methoxy, fluorinated ethoxy, trifluoromethoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, 2-hydroxypropyl, cyano-substituted methyl, cyano-substituted ethyl, cyano-substituted propyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0323] In the above general formulas described in the present invention,

[0324] Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0325] Preferably, ring A is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0326] More preferably, ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl.

[0327] In the above general formulas described in the present invention,

[0328] Ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0329] Preferably, ring B is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0330] More preferably, ring B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or phenyl, optionally substituted with one or more substituents selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl;

[0331] More preferably, ring B is selected from optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl;

[0332] Indicates the site of attachment to the fused ring.

[0333] In certain embodiments of the present invention, ring B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl;

[0334] In certain embodiments of the present invention, ring B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Optionally, it may be further substituted with one or more substituents selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl.

[0335] In the above general formulas described in the present invention,

[0336] Ring C is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0337] Preferably, ring C is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0338] More preferably, ring C is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl.

[0339] In the above general formulas described in the present invention,

[0340] Ring D is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0341] Preferably, ring D is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0342] More preferably, ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl.

[0343] In the above general formulas described in the present invention,

[0344] Ring E is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms;

[0345] Preferably, ring E is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms;

[0346] More preferably, ring E is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, pyridyl,

[0347] In the above general formulas described in the present invention,

[0348] R0 is independently selected from hydrogen, deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1- 3-hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group;

[0349] Preferably, R0 is independently selected from hydrogen, deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0350] More preferably, R0 is independently substituted by one or more substituents selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl.

[0351] In the above general formulas described in the present invention,

[0352] R 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -(CR aa R bb ) n1C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, halogen, amino, hydroxyl, cyano, nitro, C1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1- 3 alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S;

[0353] R 31 、R 32 or R 33 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0354] Preferably, R 31 、R 32or R 33 each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, vinyl, propenyl, allyl, ethynyl, propynyl or propargyl;

[0355] In certain embodiments of the present invention, R 31 、R 32 or R 33 each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy;

[0356] R aa 、R bb or R cc are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, the amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, optionally deuterated, hydroxy, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0357] Preferably, R aa 、R bb or R ccEach is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

[0358] In the above general formulas described in the present invention,

[0359] R 66 、R 77 or R 88 are each independently 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0360] Preferably, R 66 、R 77 or R 88 Each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, oxirane, oxirane or oxirane, optionally substituted by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 The deuterated alkyl group is substituted with one or more substituents.

[0361] In the above general formulas described in the present invention,

[0362] L2 is selected from C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-10 Cycloalkylene, 3-10 membered heterocyclylene containing 1-3 N, O or S atoms, C 6-10 Arylene or 5-10 membered heteroarylene containing 1-3 N, O or S atoms;

[0363] Preferably, L2 is selected from C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-8 Cycloalkylene, 3-8 membered heterocyclylene containing 1-3 N, O or S atoms, C 6-10 Arylene or 5-8 membered heteroarylene containing 1-3 N, O or S atoms;

[0364] More preferably, L2 is selected from C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-6 Monocyclic cycloalkylene, C 3-8 Bridged ring cycloalkylene, C 3-8 Spirocycloalkylene, C 3-6 Condensed ring cycloalkylene, 3-6 membered monocyclic heterocyclic group containing 1-3 N, O or S atoms, 3-8 membered bridged heterocyclic group containing 1-3 N, O or S atoms, 3-8 membered spiro heterocyclic group containing 1-3 N, O or S atoms, 3-8 membered fused ring heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl, 5-8 membered monocyclic heteroarylene containing 1-3 N, O or S atoms, or 5-8 membered fused-ring heteroarylene containing 1-3 N, O or S atoms;

[0365] More preferably, L2 is selected from vinylene, ethynylene,

[0366] In the above general formulas described in the present invention,

[0367] L3 is selected from a bond, (CH2) n2 、C 2-4 Alkenylene or C 2-4 Alkynylidene;

[0368] Preferably, L2 is selected from a bond, methylene, vinylene or ethynylene.

[0369] In the above general formulas described in the present invention, ring F is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group;

[0370] Preferably, ring F is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by hydrogen, deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1- 3. One or more substituents in the alkyl group;

[0371] More preferably, ring F is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl;

[0372] In certain embodiments of the present invention, ring F is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl;

[0373] More preferably, ring F is selected from optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl;

[0374] It indicates the site connected to L4 or L5. When L4 or L5 is a bond, it indicates the site connected to the carbonyl group or ring G.

[0375] In certain embodiments of the present invention, ring F is selected from Optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl.

[0376] In the above general formulas described in the present invention, ring G is selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally replaced by R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0377] Preferably, ring G is selected from C 3-8 Cycloalkyl, 5-6 membered monocyclic heterocyclic group containing 1-3 N, O or S atoms, 6-10 membered fused ring heterocyclic group containing 1-3 N, O or S atoms, 5-10 membered spirocyclic heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl, 5-6 membered monocyclic heteroaryl containing 1-3 N, O or S atoms, or 8-10 membered fused ring heteroaryl containing 1-3 N, O or S atoms, optionally substituted by R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0378] More preferably, ring G is selected from benzene ring, naphthalene ring, pyridine, Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0379] More preferably, ring G is selected from Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0380] Indicates the site connected to L5. When L5 is a bond, it indicates the site connected to ring F. When ring F does not exist, it indicates the site connected to L4. When L4 is a bond, it indicates the site connected to C(O). In certain embodiments of the present invention, ring G is selected from benzene ring, naphthalene ring, pyridine, Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0381] In certain embodiments of the present invention, ring G is selected from Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0382] It indicates the site connected to L5. When L5 is a bond, it indicates the site connected to ring F. When ring F does not exist, it indicates the site connected to L4. When L4 is a bond, it indicates the site connected to C(O).

[0383] In certain embodiments of the present invention, ring G is selected from benzene ring, naphthalene ring, pyridine, Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0384] In certain embodiments of the present invention, ring G is selected from benzene ring, naphthalene ring, pyridine, Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0385] In certain embodiments of the present invention, ring G is selected from Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0386] It indicates the site connected to L5. When L5 is a bond, it indicates the site connected to ring F.

[0387] In certain embodiments of the present invention, ring G is selected from benzene ring, naphthalene ring, pyridine, Optionally, it may be further optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents;

[0388] In certain embodiments of the present invention, ring G is selected from Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents.

[0389] The present invention also provides a method for preparing a compound represented by general formula (II-A-a4), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, comprising the following steps:

[0390] The compound of general formula (III), its stereoisomer or a pharmaceutically acceptable salt thereof, reacts with the compound of general formula (III-A) to obtain the compound of general formula (II-A-a4);

[0391] Preferably, the reaction is carried out in a condensation reagent, and the condensation reagent is preferably 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate, 1-propylphosphoric anhydride, O-(benzotriazole-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, N,N'-carbonyldiimidazole, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1H-benzotriazole-1-yloxytripyrrolidino hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, (2-oximino-ethyl cyanoacetate)-N,N-dimethyl N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate, 2-hydroxypyridine-N-oxide, tripyrrolidinylphosphonium bromide hexafluorophosphate, bis(2-oxo-3-oxazolidinyl)phosphinoyl chloride, 2-chloro-1-methylpyridinium iodide, diethyl cyanophosphate, 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride, 2-succinimidyl-1,1,3,3-tetramethyluronium tetrafluoroborate, 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, 2-chloro-4,6-dimethoxy-1,3,5-triazine, ethyl 2-oximecyanoacetate, diphenylphosphoryl azide, bis(pentafluorophenyl)carbonate, 3-(diethoxy-o-acyloxy)-1,2,3-benzotriazin-4-one;

[0392] More preferably, the reaction is carried out in a base, and the base is preferably diisopropylethylamine, N-methylmorpholine, N-methylimidazole, 4-dimethylaminopyridine, 2,6-lutidine, potassium carbonate, potassium tert-butoxide, sodium tert-butoxide, 1,8-diazabicyclo[5.4.0]undec-7-ene, trimethylamine, triethylamine, pyridine, piperidine, morpholine, lithium diisopropylamide, lithium diethylamide, lithium bis(trimethylsilyl)amide, lithium isopropylcyclohexylamide, LiHMDS, potassium phosphate, potassium phosphate trihydrate, potassium phosphate dihydrate, potassium phosphate monohydrate, potassium acetate, sodium acetate, sodium bicarbonate, potassium bicarbonate, sodium carbonate, cesium carbonate, potassium hydroxide, sodium hydroxide, potassium hydride, sodium hydride, lithium hydroxide or 2-tert-butyl-1,1,3,3-tetramethylguanidine and mixtures thereof.

[0393] The present invention also provides a compound represented by general formula (III), a stereoisomer thereof or a pharmaceutically acceptable salt thereof,

[0394] is a single bond or a double bond;

[0395] X1 is independently selected from a bond, C, CR 11 , CR 11 R 22 or N;

[0396] X2 are each independently selected from a bond, C, CR 22 , CR 11 R 22 or N;

[0397] X3 are each independently selected from a bond, C, CR 33 or N;

[0398] X4 are each independently selected from a bond, C, CR 44 or N;

[0399] X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 、(CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 、(CR 66 ) n2 , N or O;

[0400] R L1 is selected from hydrogen, deuterium or an amino protecting group;

[0401] R11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88 R1, R2, R3 or R4 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl are optionally substituted with one or more substituents of deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0402] n2 is 1 or 2.

[0403] In a preferred embodiment of the present invention, the compound of formula (III) is further represented by formula (III-1), (III-2), (III-3), (III-4) or (III-5):

[0404] X1 is independently selected from a bond, C, CR 11 or N;

[0405] X2 are each independently selected from a bond, C, CR 22 or N;

[0406] X3 are each independently selected from a bond, CR 33 or N;

[0407] X4 are each independently selected from a bond, CR 44 or N;

[0408] R L1 is selected from hydrogen, deuterium or an amino protecting group, wherein the amino protecting group is selected from a benzyl protecting group, a carboxylate protecting group, an acyl protecting group or a silyl protecting group;

[0409] Preferably, the benzyl protecting group is selected from benzyl, 4-methoxybenzyl, 2,4-dimethoxybenzyl, 3,4-dimethoxybenzyl, 3-methoxybenzyl, 3,5-dimethoxybenzyl or 2,4,6-trimethoxybenzyl; the carboxylate protecting group is selected from allyloxycarbonyl, tert-butyloxycarbonyl, benzyloxycarbonyl, trimethylsilylethoxycarbonyl, trichloroethoxycarbonyl, 9-fluorenylmethoxycarbonyl, methoxycarbonyl or ethoxycarbonyl; the acyl protecting group is selected from acetyl, benzoyl, p-methoxybenzylcarbonyl, acetyl, toluenesulfonyl, p-nitrobenzenesulfonyl, phthaloyl, p-toluenesulfonyl or trifluoroacetyl; the silyl protecting group is selected from tert-butyldimethylsilyl or (trimethylsilyl)ethoxymethyl;

[0410] R 11 、R 22 、R 33 、R 44 、R 66 、R 77 、R 88 , R1, R2, R3 or R4 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0411] Preferably, R 11 、R 22 、R 33、R 44 、R 66 、R 77 、R 88 , R1, R2, R3 or R4 are each independently 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 haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 substituted with one or more substituents of a deuterated alkyl group;

[0412] More preferably, R 11 、R 22 、R 33 、R 44 、R 66 、R 77 or R 88 Each of the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl, optionally deuterated by deuteration, hydroxyl, halogen, cyano, amino, C1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 The deuterated alkyl group is substituted with one or more substituents.

[0413] R1, R2, R3 or R4 are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

[0414] The present invention also provides a method for preparing a compound of formula (III-1), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, comprising the following steps:

[0415] The compound of formula (III-B), its stereoisomer or a pharmaceutically acceptable salt thereof is prepared by cyclization to obtain the compound of formula (III-1);

[0416] Preferably, the reaction is carried out in the presence of a cyclization reagent, preferably trifluoroacetic anhydride, p-toluenesulfonyl chloride, methanesulfonyl chloride, p-trifluoromethylbenzenesulfonyl chloride, 1-propylphosphoric anhydride, acetic anhydride, polyphosphoric acid, Eaton's reagent, boron trifluoride ether complex, etc.

[0417] Alternatively, a method for preparing the compound of formula (III-3), its stereoisomers or pharmaceutically acceptable salts thereof comprises the following steps:

[0418] The compound of formula (III-D), its stereoisomer or a pharmaceutically acceptable salt thereof is reacted to obtain the compound of formula (III-3);

[0419] Optionally, the preparation method of the compound of formula (III-B), its stereoisomers or pharmaceutically acceptable salts thereof is as follows:

[0420] The compound of formula (III-C), its stereoisomer or a pharmaceutically acceptable salt thereof is reacted to obtain the compound of formula (III-B);

[0421] R L2 or R L3 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, halogenated C 1-6 Alkoxy, C 1-6Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 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, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0422] Preferably, R L2 or R L3 are each independently 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein 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, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally deuterated, hydroxyl, halogen, cyano, amino, C1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 The deuterated alkyl group is substituted with one or more substituents.

[0423] The present invention further relates to a pharmaceutical composition comprising a therapeutically effective dose of any compound of the general formula shown, its stereoisomers or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0424] 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 5-70%, for example 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10% or 5%.

[0425] 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.

[0426] In certain embodiments of the present invention, the pharmaceutical composition is a rapid-release formulation or a sustained-release formulation.

[0427] 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.

[0428] 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.

[0429] 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.

[0430] The present invention further relates to the use of any compound of the general formula shown, its stereoisomers or pharmaceutically acceptable salts, or the pharmaceutical composition in the preparation of drugs for treating M4-related diseases.

[0431] The present invention further relates to the use of a compound represented by the general formula, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the preparation of a medicament for treating Alzheimer's disease, schizophrenia or psychosis, pain, addiction, sleep disorders, cognitive disorders, diseases or conditions of Parkinson's disease, Parkinson's disease-levodopa-induced movement disorders, Huntington's disease, dry mouth, pulmonary hypertension, chronic obstructive pulmonary disease, asthma, urinary incontinence, glaucoma, Down syndrome, cerebral amyloid angiopathy, dementia, hereditary Dutch amyloidosis cerebral hemorrhage, Creutzfeldt-Jakob disease, prion disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, head trauma, stroke, pancreatitis, inclusion body myositis, other peripheral amyloidosis, diabetes, autism, and atherosclerosis, and more preferably in the preparation of a medicament for treating Alzheimer's disease, schizophrenia, pain, addiction, and sleep disorders.

[0432] The present invention further relates to a method for using the compound represented by the general formula, its stereoisomers or pharmaceutically acceptable salts, or its pharmaceutical composition in the preparation of drugs for treating M4-related and related diseases.

[0433] The present invention also relates to a method for treating, preventing and / or treating M4-related diseases, which comprises administering to a patient a therapeutically effective dose of a compound represented by the general formula, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0434] The present invention also provides methods of using the compounds or pharmaceutical compositions of the present invention to treat disease conditions, including but not limited to conditions associated with M4.

[0435] The present invention also relates to a method for treating an M4-related disease 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.

[0436] The compound prepared by the present invention has high M4 agonist activity and selectivity, high solubility, Ks can reach more than 200 μM in a PBS solution with a pH of 7.4, and has higher plasma freeness and brain exposure.

[0437] Detailed Description of the Invention

[0438] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0439] The term "alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 8 carbon atoms, more preferably an alkyl group containing 1 to 6 carbon atoms, and most preferably an alkyl group containing 1 to 3 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. More preferred are lower alkyl groups containing 1 to 6 carbon atoms, non-limiting examples of which 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, and the like. The alkyl group may be substituted or unsubstituted. When substituted, the substituent may be substituted at any available point of attachment. The substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate groups. Methyl, ethyl, isopropyl, tert-butyl, haloalkyl, deuterated alkyl, alkoxy-substituted alkyl and hydroxy-substituted alkyl are preferred.

[0440] The term "alkylene" refers to an alkyl group in which one hydrogen atom is further substituted, for example: "methylene" refers to -CH2-, "ethylene" refers to -(CH2)2-, "propylene" refers to -(CH2)3-, "butylene" refers to -(CH2)4-, etc. The term "alkenyl" refers to an alkyl group as defined above consisting of at least two carbon atoms and at least one carbon-carbon double bond, for example, ethenyl, 1-propenyl, 2-propenyl, 1-, 2- or 3-butenyl, etc. The alkenyl group may be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, and heterocycloalkylthio.

[0441] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent, wherein the cycloalkyl ring contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, and more preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, and the like; polycyclic cycloalkyls include spirocyclic, fused, and bridged cycloalkyls, preferably cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, and cycloheptyl.

[0442] The term "spiroalkyl" refers to a polycyclic group having a carbon atom (called a spiral atom) shared between 5 to 20 monocyclic rings, which may contain one or more double bonds, but no ring has a completely conjugated π electron system. Preferably, it is 6 to 14 yuan, more preferably 7 to 10 yuan. According to the number of spiral atoms shared between the rings, the spiroalkyl is divided into a single spiroalkyl, a double spiroalkyl or a multi-spiroalkyl, preferably a single spiroalkyl and a double spiroalkyl. More preferably, it is 3 yuan / 6 yuan, 3 yuan / 5 yuan, 4 yuan / 4 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 5 yuan or 5 yuan / 6 yuan of single spiroalkyl. Non-limiting examples of spiroalkyl include:

[0443] wait;

[0444] It also includes spirocycloalkyl groups that share a spiro atom with a heterocycloalkyl group. Non-limiting examples include:

[0445] wait.

[0446] The term "fused cycloalkyl" refers to a 5 to 20-membered, all-carbon polycyclic group in which each ring in the system shares a pair of adjacent carbon atoms with the 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. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. Depending on the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused cycloalkyl groups, preferably bicyclic or tricyclic, more preferably 5-membered / 5-membered or 5-membered / 6-membered bicyclic alkyl groups. Non-limiting examples of fused cycloalkyl groups include:

[0447] wait.

[0448] The term "bridged cycloalkyl" refers to a 5-20 membered, all-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. Preferably, it is 6-14 members, more preferably 7-10 members. Depending on the number of constituent rings, it can be classified as a bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyl group, preferably a bicyclic, tricyclic or tetracyclic group, more preferably a bicyclic or tricyclic group. Non-limiting examples of bridged cycloalkyl groups include:

[0449] The cycloalkyl ring may be fused to an aryl, heteroaryl or heterocycloalkyl ring, wherein the ring attached to the parent structure is a cycloalkyl, non-limiting examples of which include indanyl, tetrahydronaphthyl, benzocycloheptanyl, etc. The cycloalkyl group may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[0450] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing 3 to 20 ring atoms, one or more of which is selected from nitrogen, oxygen or S(O) m (wherein m is an integer from 0 to 2) heteroatoms, excluding the ring portion of -OO-, -OS- or -SS-, and the remaining ring atoms are carbon. Preferably, it contains 3 to 12 ring atoms, of which 1 to 4 are heteroatoms; more preferably, it contains 3 to 8 ring atoms; most preferably, it contains 3 to 8 ring atoms; further preferably, it is a 3-8 membered heterocyclic group containing 1-3 nitrogen atoms, optionally substituted with 1-2 oxygen atoms, sulfur atoms, or oxo groups, including nitrogen-containing monocyclic heterocyclic groups, nitrogen-containing spiro heterocyclic groups, or nitrogen-containing fused heterocyclic groups.

[0451] Non-limiting examples of monocyclic heterocyclic groups include pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, azepanyl, 1,4-diazepanyl, pyranyl, etc., preferably pyrrolidinyl, morpholinyl, piperidinyl, azepanyl, 1,4-diazepanyl and piperazinyl. Polycyclic heterocyclic groups include spirocyclic, fused and bridged heterocyclic groups; wherein the spirocyclic, fused and bridged heterocyclic groups are optionally connected to other groups by single bonds, or further connected to other cycloalkyl, heterocyclic, aryl and heteroaryl groups through any two or more atoms on the ring.

[0452] The term "spiroheterocyclyl" refers to a polycyclic heterocyclic group in which the monocyclic rings of 5 to 20 members share one atom (called a spiro atom), wherein one or more ring atoms are selected from nitrogen, oxygen or S(O) m (wherein m is an integer 0 to 2) heteroatom, and the remaining ring atoms are carbon. It may contain one or more double bonds, but no ring has a completely conjugated π electron system. It is preferably 6 to 14 yuan, more preferably 7 to 10 yuan. According to the number of shared spiral atoms between the rings, the spiral heterocyclic group is divided into a single spiral heterocyclic group, a double spiral heterocyclic group or a multi-spiral heterocyclic group, preferably a single spiral heterocyclic group and a double spiral heterocyclic group. More preferably 3 yuan / 5 yuan, 3 yuan / 6 yuan, 4 yuan / 4 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 5 yuan or 5 yuan / 6 yuan single spiral heterocyclic group. Non-limiting examples of spiral heterocyclic groups include:

[0453] wait.

[0454] The term "fused heterocyclyl" refers to a polycyclic heterocyclic group of 5 to 20 members, wherein each ring in the system shares a pair of adjacent atoms with 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 selected from nitrogen, oxygen or S(O) m (wherein m is an integer from 0 to 2) heteroatoms, the remaining ring atoms being carbon. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused heterocyclic groups, preferably bicyclic or tricyclic, more preferably 5-membered / 5-membered or 5-membered / 6-membered bicyclic fused heterocyclic groups. Non-limiting examples of fused heterocyclic groups include: wait.

[0455] The term "bridged heterocyclyl" refers to a 5- to 14-membered 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 selected from nitrogen, oxygen or S(O)m (wherein m is an integer from 0 to 2) heteroatoms, the remaining ring atoms being carbon. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. Depending on the number of constituent rings, it can be classified as a bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocyclic group, preferably a bicyclic, tricyclic or tetracyclic group, more preferably a bicyclic or tricyclic group. Non-limiting examples of bridged heterocyclic groups include: wait.

[0456] The heterocyclyl ring may be fused to an aryl, heteroaryl or cycloalkyl ring, wherein the ring attached to the parent structure is a heterocyclyl, non-limiting examples of which include:

[0457] wait.

[0458] The heterocyclyl group may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[0459] The term "aryl" refers to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of carbon atoms) group having a conjugated π electron system, preferably 6- to 12-membered, such as phenyl and naphthyl. More preferably, phenyl. The aryl ring may be fused to a heteroaryl, heterocyclic, or cycloalkyl ring, including benzo 5- to 10-membered heteroaryl, benzo 3- to 8-membered cycloalkyl, and benzo 3- to 8-membered heteroalkyl, preferably benzo 5- to 6-membered heteroaryl, benzo 3- to 6-membered cycloalkyl, and benzo 3- to 6-membered heteroalkyl, wherein the heterocyclic group is a heterocyclic group containing 1-3 nitrogen atoms, oxygen atoms, or sulfur atoms; or further comprises a three-membered nitrogen-containing fused ring containing a benzene ring.

[0460] Wherein the ring connecting to the parent structure is an aryl ring, non-limiting examples of which include: wait.

[0461] The aryl group may be substituted or unsubstituted. When substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0462] The term "heteroaryl" refers to a heteroaromatic system containing 1 to 4 heteroatoms and 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur and nitrogen. The heteroaryl group is preferably 5 to 12-membered, more preferably 5-membered or 6-membered, such as imidazolyl, furyl, thienyl, thiazolyl, pyrazolyl, oxazolyl, pyrrolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, thiadiazole, pyrazinyl, etc., preferably triazolyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, pyrimidinyl or thiazolyl; more preferably pyrazolyl, pyrrolyl and oxazolyl. The heteroaryl ring can be fused to an aryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is a heteroaryl ring, non-limiting examples of which include: wait.

[0463] The heteroaryl group may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0464] The term "alkoxy" refers to-O-(alkyl) and-O-(unsubstituted cycloalkyl), wherein the definition of alkyl is as described above. The limiting examples of alkoxy include: methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy. Alkoxy can be optionally substituted or unsubstituted, and when substituted, substituents are preferably one or more following groups, which are independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0465] "Haloalkyl" refers to an alkyl group substituted with one or more halogens, wherein alkyl is as defined above.

[0466] "Haloalkoxy" refers to an alkoxy group substituted with one or more halogens, wherein alkoxy is as defined above.

[0467] "Hydroxyalkyl" refers to an alkyl group substituted with a hydroxy group, wherein alkyl is as defined above.

[0468] "Alkenyl" refers to an alkenyl group, also known as an alkene group, which refers to a straight-chain or branched unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon double bond and the carbon-carbon double bond can be located at any position within the alkenyl group. The alkenyl group is a group having 2 to 20 (C 2-20 ), 2 to 15 (C 2- 15 ), 2 to 12 (C 2-12 ), 2 to 10 (C2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ), 2 to 4 (C 2-4 ) or 2 to 3 (C 2-3 ) carbon atoms. Non-limiting examples of alkenyl groups include: The alkenyl group can be further substituted by other related groups, for example, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0469] "Alkynyl" refers to (CH≡C-), which contains at least one carbon-carbon triple bond and the carbon-carbon triple bond can be located at any position within the alkynyl group, which contains at least one carbon-carbon double bond and the carbon-carbon double bond can be located at any position within the alkenyl group, and the alkynyl group is a 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 ), 2 to 4 (C 2-4 ) or 2 to 3 (C 2-3 ) carbon atoms. Non-limiting examples of alkynyl groups include: The alkynyl group can be further substituted by other related groups, for example, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0470] The term "alkenylcarbonyl" refers to -C(O)-(alkenyl), wherein the definition of alkenyl is as described above. Non-limiting examples of alkenylcarbonyl include: vinylcarbonyl, propenylcarbonyl, butenylcarbonyl. Alkenylcarbonyl can be optionally substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0471] "Hydroxy" refers to an -OH group.

[0472] "Halogen" refers to fluorine, chlorine, bromine or iodine.

[0473] "Amino" refers to -NH2.

[0474] "Cyano" refers to -CN.

[0475] "Nitro" refers to -NO2.

[0476] "Carbonyl" refers to -C(O)-.

[0477] "Carboxyl" refers to -C(O)OH.

[0478] "THF" refers to tetrahydrofuran.

[0479] "DMF" refers to N,N-dimethylformamide.

[0480] 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.

[0481] The hydrogen atoms described in the present invention can all be replaced by their isotope deuterium, and any hydrogen atom in the example compounds of the present invention can also be replaced by a deuterium atom.

[0482] The compounds of the present invention include all pharmaceutically acceptable isotopically labeled compounds, wherein one or more atoms of the compounds disclosed herein are replaced by an atom having the same atomic number but an atomic mass or mass number different from the atomic mass or mass number commonly found. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine. Examples of isotopes include deuterium, tritium, and the like.

[0483] "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.

[0484] "Substituted" means that one or more hydrogen atoms, preferably up to 5, more preferably 1 to 3 hydrogen atoms, in a group are replaced independently of one another by a corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and a person skilled in the art can determine (by experiment or theory) which substitutions are possible or impossible without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (e.g., olefinic) bond.

[0485] 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.

[0486] "Pharmaceutically acceptable salt" and "pharmaceutically usable salt" 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.

[0487] The compounds of the present invention, such as Formula (II-A1) to (II-19b) or specific compounds, are intended to include one or more of the following: a free base of the compound or a pharmaceutically acceptable salt thereof, a stereoisomer, or a mixture of two or more stereoisomers. Stereoisomers refer to compounds that differ only in their spatial arrangement. Stereoisomers include all diastereomeric and enantiomeric forms of a compound. Enantiomers are stereoisomers that are mirror images of each other. Diastereoisomers are stereoisomers with two or more chiral centers that are not identical and are not mirror images of each other. DETAILED DESCRIPTION

[0488] Example

[0489] The structures of the compounds were 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.

[0490] MS was measured using a FINNIGAN LCQAd (ESI) mass spectrometer (manufacturer: Thermo, model: Finnigan LCQ advantage MAX).

[0491] HPLC analysis was performed using an Agilent 1200DAD high pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high pressure liquid chromatograph (Gimini C18 150×4.6 mm column).

[0492] Average kinase inhibition rate and IC 50 The values ​​were determined using a NovoStar microplate reader (BMG, Germany).

[0493] 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.

[0494] Column chromatography generally uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier.

[0495] 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, Accela ChemBio Inc, Darui Chemicals, and other companies.

[0496] Unless otherwise specified in the examples, all reactions can be carried out under an argon atmosphere or a nitrogen atmosphere.

[0497] 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.

[0498] Hydrogen atmosphere means that the reaction bottle is connected to a hydrogen balloon with a capacity of about 1L.

[0499] The pressurized hydrogenation reaction uses a Parr 3916EKX hydrogenator and a Qinglan QL-500 hydrogen generator or an HC2-SS hydrogenator.

[0500] The hydrogenation reaction is usually carried out by evacuating the chamber and filling it with hydrogen, and the operation is repeated three times.

[0501] A CEM Discover-S 908860 microwave reactor was used for the microwave reaction.

[0502] Unless otherwise specified in the examples, the solution refers to an aqueous solution.

[0503] Unless otherwise specified in the examples, the reaction temperature is room temperature, 20°C to 30°C.

[0504] 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.

[0505] The eluent system for column chromatography and the developing solvent system for thin-layer chromatography used to purify the compound include: A: dichloromethane and methanol system, B: n-hexane and ethyl acetate system, C: dichloromethane and acetone 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.

[0506] Reference Example 1

[0507] 1-(2-Chloro-4-methyl-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0508] 1-(2-Chloro-4-methyl-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0509] 2-Chloro-4-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine 1a (50 mg, 0.29 mmol) was dissolved in 2.0 mL of N,N-dimethylformamide. 2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)acetic acid (77 mg, 0.29 mmol, prepared using the known method of Patent WO2018002760), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (168 mg, 0.44 mmol), and diisopropylethylamine (114 mg, 0.88 mmol) were added to the reaction system in sequence. The reaction was incubated at 25°C for 2 hours. 10 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative HPLC to obtain 35 mg of the title product 1 in a yield of 28.9%. MS m / z (ESI): 412.2 [M+1]

[0510] Reference Example 2

[0511] (3-Chloro-2,4-dimethyl-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)(3-chloro-4-fluorophenyl)methanone

[0512] 5-Chloro-3-cyano-4,6-dimethylpicolinate

[0513] 2a (50 g, 0.2487 mol) was dissolved in methanol (1000 mL). DPPF (13.78 g, 0.02486 mol), Et3N (49.32 g, 0.0.4874 mol), and Pd(OAc)2 (2.8 g, 0.01247 mol) were added. CO2 was replaced three times. The pressure was maintained at 0.25 MPa and the mixture was heated and stirred at 70°C for 16 h. LC / MS confirmed the reaction was complete. The reaction solution was then dried and purified by column chromatography using EA:PE = 1:5 to afford product 2b (40 g, 71.6% yield). MS m / z (ESI): 225.6.

[0514] 2b (15 g, 0.07 mol) was dissolved in methanol (150 mL), and NiCl2.6H2O (25.45 g, 0.7 mol) was added. The mixture was stirred for 5 min and replaced with a N2 balloon. NaBH4 (31.8 g, 0.1 mol) was added portionwise in an ice bath and stirred at room temperature for 1 h. The reaction solution was spin-dried and quenched with 2M HCl solution in an ice bath. 2N NaOH solution was then added dropwise to adjust the pH to 9-10. Boc anhydride (21.92 g, 0.1004 mol) was added and stirred at room temperature for 2 h. The mixture was extracted three times with 200 ml of EA. The organic phases were combined and dried over anhydrous sodium sulfate to afford crude product 2c (20 g), which was used directly in the next step. MS m / z (ESI): 297.8.

[0515] 2c (20 g, 0.07 mol) was dissolved in THF (200 mL). 1 M BH₃-THF (169 mL, 0.1 mol) was added dropwise in an ice-water bath. The mixture was stirred at room temperature for 10 min and then heated to reflux for 16 h. After the reaction mixture cooled to room temperature, 50 mL of methanol was added to quench the BH₃-THF. Initially, the methanol was added slowly to prevent sludging. After complete addition, the mixture was heated to reflux for 3-4 h and then cooled to room temperature. The reaction mixture was spun down to dryness and column chromatography with EA:PE = 1:5 to obtain 3 g of the product. The product with Boc residue was dissolved in 15 mL of EA, and 15 mL of 4 M EA / HCl solution was added. The mixture was stirred for 16 h. LCMS confirmed the reaction was complete, and the reaction mixture was spun down to dryness to obtain crude product 2d (2.6 g, yield: 21.1%). MS m / z (ESI): 183.7.

[0516] Reference Example 2 was obtained by referring to the synthesis method of Reference Example 1. MS m / z (ESI): 340.2.

[0517] Example 20

[0518] 1-(5,6-Dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0519] tert-Butyl 6,7-dimethyl-4-oxo-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate

[0520] To a mixture of 20a (5 g, 23.8 mmol) and 2-butanone (20 mL) was added polyphosphoric acid (100 g) at 100°C, followed by stirring at 120°C for 4 hours. After the reaction mixture was cooled to 15°C, it was quenched by the addition of water (1.5 L), and the pH of the mixture was adjusted to 10-11 by the addition of solid sodium hydroxide. Di-tert-butyl dicarbonate (10 g, 45.8 mmol) was added, and the reaction mixture was stirred at 15°C overnight and filtered after the reaction was complete. The collected solid was washed with water (7 x 50 mL) and a mixture of tert-butyl methyl ether and petroleum ether (1:1, 7 x 40 mL) to obtain crude Example 20b. MS m / z (ESI): 265.3 [M+1].

[0521] tert-Butyl 6,7-dimethyl-4-((trifluoromethyl)sulfonyl)oxy-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate

[0522] Triethylamine (25 g, 25 mmol) and trifluoromethanesulfonic anhydride (5.9 g, 21 mmol) were added separately to a solution of 20b (5 g, 19 mmol) in dichloromethane (200 mL) at 0°C. The reaction mixture was stirred at 0°C for 2 hours, then quenched with water (5 mL) and extracted with dichloromethane (3 x 40 mL). The combined organic layers were washed with saturated aqueous sodium chloride (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (eluent: petroleum ether / ethyl acetate = 5:1) provided the product 20c (4 g, yield: 58%). MS m / z (ESI): 397.4.

[0523] tert-Butyl 4-(diphenylmethylene)amino)-6,7-dimethyl-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate

[0524] To a solution of 20c (9.2 g, 23.2 mmol) in toluene (100 mL) were added 1,1-diphenylformimine (6.31 g, 34.8 mmol), palladium acetate (521 mg, 2.32 mmol), 1,1'-binaphthyl-2,2'-diylbis(diphenylphosphine) (BINAP; 1.45 g, 2.33 mmol), and cesium carbonate (11.3 g, 34.7 mmol). The mixture was heated at 100°C for 16 hours, then filtered and the filtrate concentrated in vacuo to afford crude product 20d, which was used directly in the next step. MS m / z (ESI): 428.6.

[0525] tert-Butyl 4-amino-6,7-dimethyl-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate

[0526] To a solution of crude product 20d in methanol (100 mL) were added sodium acetate (4.0 g, 48.8 mmol) and hydroxylamine hydrochloride (3.39 g, 48.8 mmol). The reaction mixture was stirred at room temperature for 72 hours. It was then filtered, and the filtrate was concentrated under reduced pressure. Recrystallization from ethyl acetate afforded 20e (5 g, yield: 82%).

[0527] MS m / z(ESI):264.3.

[0528] (E)-tert-Butyl 4-(((dimethylamino)methylene)amino)-6,7-dimethyl-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate

[0529] To a solution of 20e in toluene (10 mL) at room temperature was added 1,1-dimethoxy-N,N-dimethylimine (1.63 g, 13.68 mmol). The reaction mixture was heated at reflux for 2 h and then cooled to room temperature. Concentration afforded the crude product 20f, which was used directly in the next step. MS m / z (ESI): 319.4.

[0530] tert-Butyl (E)-4-(N'-hydroxycarboxamido)-6,7-dimethyl-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate

[0531] At room temperature, hydroxylamine hydrochloride (6.6 g, 94.3 mmol) was added to a solution of 20f in methanol (20 mL), and the reaction mixture was refluxed for 1 h and then cooled to room temperature. Water (15 mL) was added to the reaction mixture to quench the mixture, which was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and then directly concentrated to give a crude product 20 g, which was used directly in the next step. MS m / z (ESI): 307.4.

[0532] tert-Butyl 5,6-dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridine-8-carboxylate

[0533] To a solution of 20 g in THF (20 mL) at 0° C. was added trifluoroacetic anhydride (0.83 g, 3.93 mmol). The reaction mixture was stirred at room temperature overnight and then concentrated. Purification by silica gel chromatography (gradient: 33% to 100% ethyl acetate / petroleum ether) afforded the product 20h (450 mg, 42% yield), MS m / z (ESI): 289.

[0534] 5,6-Dimethyl-8,9-dihydro-7H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridine

[0535] To a solution of 20h (450 mg, 1.56 mmol) in ethyl acetate (10 mL) was added a solution of hydrogen chloride in ethyl acetate (4 M, 10 mL) at 0°C, and the reaction mixture was stirred at room temperature for 5 hours. The solvent was removed under reduced pressure to afford product 20i (300 mg, 85% yield), MS m / z (ESI): 189.2.

[0536] 1-(5,6-Dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0537] Example 20 was obtained by referring to the synthesis method of Reference Example 1. MS m / z (ESI): 431.4.

[0538] Example 32

[0539] 1-(2-(Trifluoromethyl)pyridin-4-yl)azetidin-3-yl 5,6-dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridine-8-carboxylic acid

[0540] 32a (500 mg, 2.21 mmol) was dissolved in a mixture of dioxane (5 mL) and water (1 mL). 32b (270 mg, 2.43 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (128 mg, 0.22 mmol), palladium acetate (49.67 mg, 0.2212 mmol), and cesium carbonate (2.16 g, 6.6372 mmol) were added. The atmosphere was purged with nitrogen three times and the mixture was heated at 100°C under reflux and stirred for 16 h. After the reaction was complete, the reaction solution was dried to give the product 32c (300 mg). MS m / z (ESI): 219.2 [M+1]

[0541] 32c (100 mg, 0.46 mmol) was dissolved in dry dichloromethane (1 mL). Dimethylaminopyridine (112 mg, 0.92 mmol) and BTC (112 mg, 0.38 mmol) were added and stirred for 2 h. Then, 20i (257 mg, 1.15 mmol) and triethylamine (464 mg, 4.5871 mmol) were added and stirred at room temperature for 16 h. The reaction mixture was spin-dried to give product 32 (32.6 mg, yield: 16.3%). MS m / z (ESI): 433.4 [M+1].

[0542] Example 39

[0543] 1-(6-methyl-2,3,7,9-tetrahydro-[1,4]oxazino[3,2-e]isoindol-8(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0544] 1-(4-amino-5-bromo-7-methylisoindol-2-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0545] The title product 39b was obtained by referring to the synthesis method of Reference Example 1. MS m / z (ESI): 471.2 [M+1]

[0546] 1-(5-Bromo-4-((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)-7-methylisoindolin-2-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0547] 39b (200 mg, 0.43 mmol) was dissolved in 5.0 mL of anhydrous tetrahydrofuran, and sodium hydride (34 mg, 0.85 mmol, 60%) was added to the reaction system. After stirring for 1 hour, (2-bromoethoxy)(tert-butyl)dimethylsilane (154 mg, 0.65 mmol) was added to the reaction system. The reaction was heated at 60°C for 15 hours. After cooling to room temperature, 20 mL of saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL × 3). The organic phases were combined, washed with saturated sodium chloride solution (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent system B to obtain the title product 39c (185 mg, yield: 69.3%). MS m / z (ESI): 629.2 [M+1]

[0548] 1-(5-Bromo-4-((2-hydroxyethyl)amino)-7-methylisoindolin-2-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0549] Under ice, 39c (185 mg, 0.29 mmol) was dissolved in 2 mL of dioxane. A 2 mL mixture of hydrogen chloride and 1,4-dioxane (4 M, V / V = 1:1) was added and allowed to react at 25°C for 2 hours. Saturated sodium bicarbonate solution was added to the reaction solution to adjust the pH to above 7. The mixture was extracted with dichloromethane (10 mL x 3). The combined organic phases were washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography using eluent System A to afford the title product 39d (128 mg, 84.8% yield). MS m / z (ESI): 513.2 [M+1].

[0550] 1-(6-methyl-2,3,7,9-tetrahydro-[1,4]oxazino[3,2-e]isoindol-8(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0551] 39d (100 mg, 0.19 mmol) was dissolved in 2.0 mL of toluene. Palladium acetate (4.4 mg, 0.02 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethoxyanthracene (23 mg, 0.04 mmol), and cesium carbonate (191 mg, 0.58 mmol) were added to the reaction system in sequence. The reaction was heated at 100°C for 15 hours. After cooling to room temperature, 10 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL × 3). The organic phases were combined, washed with saturated sodium chloride solution (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to give the title product 39 (25 mg, yield: 29.8%). MS m / z (ESI): 433.2 [M+1]

[0552] Example 42

[0553] 1-(5-methyl-6,8-dihydro-[1,2,3]triazolo[4,5-e]isoindol-7(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0554] 1-(4-azido-5-bromo-7-methylisoindol-2-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0555] Under ice-cooling, 39b (200 mg, 0.43 mmol) was dissolved in 5.0 mL of concentrated hydrochloric acid (6.0 M). 30% aqueous sodium nitrite solution (35 mg, 0.51 mmol) was added and the mixture was reacted at 0°C for 0.5 h. Sodium azide (84 mg, 1.29 mmol) was added to the reaction mixture and the mixture was reacted at 25°C for 1 h. The reaction mixture was adjusted to pH >7 by adding saturated sodium bicarbonate solution, and extracted with dichloromethane (10 mL x 3). The combined organic phases were washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography using eluent System A to afford the title product, 1-(4-azido-5-bromo-7-methylisoindol-2-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one 42a (174 mg, 82.5% yield). MS m / z (ESI): 497.2 [M+1].

[0556] 1-(5-methyl-6,8-dihydro-[1,2,3]triazolo[4,5-e]isoindol-7(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0557] 42a (100 mg, 0.20 mmol) was dissolved in 2.0 mL of anhydrous tetrahydrofuran at -78°C, and n-butyllithium (0.12 mL, 0.30 mmol, 2.5 M) was added to the reaction system. The reaction was allowed to react at 25°C for 2 hours. 10 mL of saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL x 3). The combined organic phases were washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to afford the title product 42 (33 mg, yield: 39.3%). MS m / z (ESI): 417.2 [M+1]

[0558] Example 43

[0559] 1-(5-methyl-6,8-dihydroimidazo[4,5-e]isoindol-7(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0560] 1-(5-methyl-6,8-dihydroimidazo[4,5-e]isoindol-7(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0561] 39b (200 mg, 0.21 mmol) was dissolved in 2.0 mL of 30% aqueous ammonia. Paraformaldehyde (32 mg, 1.1 mmol), cuprous iodide (4 mg, 0.02 mmol), 1,10-phenanthroline (7.3 mg, 0.04 mmol), and sodium carbonate (67 mg, 0.63 mmol) were added sequentially to the reaction system. The reaction was heated at 100°C for 10 hours. 10 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL x 2). The combined organic phases were washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to afford the title product 43 (27 mg, 30.7% yield). MS m / z (ESI): 416.2 [M+1].

[0562] Example 60

[0563] tert-Butyl 5,6-dimethyl-7,9-dihydro-8H-imidazo[1,2-a]pyrrolo[3,4-c]pyridine-8-carboxylate

[0564] At room temperature, sodium bicarbonate (3.2 g, 38 mmol, 2 eq) and 20e (5 g, 19 mmol, 1 eq) were added to a reaction flask. Ethanol (30 mL) was then added, and chloroacetaldehyde (4.5 g, 22.8 mmol, 1.2 eq) (40% aqueous solution) was added dropwise with stirring. The reaction mixture was stirred at 80°C overnight and then cooled to room temperature. The mixture was extracted with dichloromethane (50 mL × 3), washed with brine (20 mL × 3), and then dried and concentrated by column chromatography (eluent: dichloromethane / methanol = 5%-10%) to afford 60a (3 g, yield: 55%). MS m / z (ESI): 288.4.

[0565] 5,6-Dimethyl-8,9-dihydro-7H-imidazo[1,2-a]pyrrolo[3,4-c]pyridine

[0566] A solution of hydrogen chloride in ethyl acetate (4 M, 10 mL) was added to a solution of 60a (450 mg, 1.56 mmol) in ethyl acetate (10 mL) at 0°C, and the reaction mixture was stirred at room temperature for 5 hours. The solvent was removed under reduced pressure to give 60b (297 mg, yield: 85%), MS m / z (ESI): 188.2.

[0567] 1-(5,6-dimethyl-7,9-dihydro-8H-imidazo[1,2-a]pyrrolo[3,4-c]pyridin-8-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0568] Example 60 (60 mg, yield: 21.5%) was obtained by referring to the synthesis method of Reference Example 1. MS m / z (ESI): 430.4.

[0569] Example 76

[0570] 1-(4,5-dimethyl-2,3-dihydro-1H-pyrrolo[4,3-c]pyrazolo[1,5-a]pyridin-2-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one

[0571] 2-Methylprop-2-yl 6,7-dimethyl-4-[(trimethylsilyl)ethynyl]-2,3-dihydro-1H-pyrrolo[4,3-c]pyridine-2-carboxylate

[0572] Compound 76-1 (1 g, 2.52 mmol) was dissolved in triethylamine (10 mL), and bis(triphenylphosphine)palladium dichloride (89 mg, 126.14 μmol), cuprous iodide (96 mg, 504.56 μmol), and trimethylsilylacetylene (496 mg, 5.05 mmol, 713 μL) were added sequentially. The atmosphere was replaced with nitrogen three times, and then stirred at 50°C under nitrogen for 12 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (2 mL), and the organic phase was washed sequentially with saturated aqueous ammonium chloride (10 mL x 2) and saturated aqueous sodium chloride (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the title product 76-2 (1 g, crude product).

[0573] MS m / z(ESI):345.2[M+1]

[0574] 4-Ethynyl-6,7-dimethyl-2,3-dihydro-1H-pyrrolo[4,3-c]pyridine-2-carboxylic acid 2-methylprop-2-yl ester

[0575] Compound 76-2 (1 g, 2.52 mmol) was dissolved in methanol (20 mL), potassium hydroxide (89 mg, 126.14 μmol) was added, and the mixture was stirred at 20°C for 1 hour. The reaction mixture was diluted with water (40 mL) and extracted with ethyl acetate (20 mL x 2). The combined organic phases were washed with saturated sodium chloride (20 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent system A) to obtain the title product 76-3 (400 mg, yield: 50.6%). MS m / z (ESI): 273.2 [M+1]

[0576] 5-Amino-4-ethynyl-6,7-dimethyl-2-{[(2-methylprop-2-yl)oxy]carbonyl}-2,3-dihydro-1H-pyrrolo[4,3-c]pyridin-5-ol

[0577] Compound 76-3 (100 mg, 367.19 μmol) was dissolved in dichloromethane (5 mL), and compound 76-4 (87 mg, 403.90 μmol) was added. The mixture was stirred at 20°C for 12 hours. The reaction solution was directly concentrated under reduced pressure to obtain the title product 76-5 (200 mg, crude product). MS m / z (ESI): 288.2 [M]

[0578] 2-Methylpropane-2-yl 4,5-dimethyl-2,3-dihydro-1H-pyrrolo[4,3-c]pyrazolo[1,5-a]pyridine-2-carboxylate

[0579] Compound 76-5 (200 mg) was dissolved in anhydrous N,N-dimethylformamide (4 mL), and cesium carbonate (678 mg, 2.08 mmol) was added, followed by stirring at 20°C for 12 hours. The reaction solution was diluted with water (20 mL) and extracted with ethyl acetate (10 mL x 2). The combined organic phases were washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent system A) to obtain the title product 76-6 (20 mg, yield: 10.0%).

[0580] MS m / z(ESI):288.2[M+1]

[0581] 4,5-Dimethyl-2,3-dihydro-1H-pyrrolo[4,3-c]pyrazolo[1,5-a]pyridine

[0582] Compound 76-6 (20 mg) was dissolved in dichloromethane (2 mL), and a hydrochloric acid-dioxane solution (2 mL, 4 M) was added, followed by stirring at 20°C for 2 hours. The reaction solution was directly concentrated under reduced pressure to obtain the title product 76-7 (20 mg, crude, hydrochloride).

[0583] MS m / z(ESI):188.1[M+1]

[0584] 1-(4,5-dimethyl-2,3-dihydro-1H-pyrrolo[4,3-c]pyrazolo[1,5-a]pyridin-2-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one

[0585] Compound 76-7 (20 mg) and compound 76-8 (25 mg) were dissolved in anhydrous N,N-dimethylformamide (2 mL), and triethylamine (67 uL) and O-(7-azabenzotriazole-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (40 mg) were added in sequence, and then stirred at 20°C for 1 hour. The reaction solution was diluted with water (20 mL), extracted with ethyl acetate (10 mL × 2), and the organic phases were combined, washed with saturated aqueous sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by high performance liquid chromatography (0.1% formic acid / acetonitrile / water) to give the title product 1-(4,5-dimethyl-2,3-dihydro-1H-pyrrolo[4,3-c]pyrazolo[1,5-a]pyridin-2-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one 76 (10 mg).

[0586] MS m / z(ESI):430.2[M+1]

[0587] Example 77

[0588] 1-(1,5-dimethyl-6,8-dihydroimidazo[4,5-e]isoindol-7(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0589] 1-(1,5-dimethyl-6,8-dihydroimidazo[4,5-e]isoindol-7(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0590] 1-(5-Methyl-6,8-dihydroimidazo[4,5-e]isoindol-7(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one (50 mg, 0.12 mmol) was dissolved in 2.0 mL of N,N-dimethylformamide. Potassium carbonate (50 mg, 0.36 mmol) and iodomethane (26 mg, 0.18 mmol) were added to the reaction system in sequence. The reaction was heated at 50°C for 2 hours. 10 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to give the title product 77 (18 mg, yield: 34.8%). MS m / z (ESI): 430.2 [M+1]

[0591] Example 78

[0592] 1-(1,6-Dimethyl-2,3,7,9-tetrahydro-[1,4]oxazino[3,2-e]isoindol-8(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0593] Referring to the synthetic method of Example 77, the title product 78 was obtained using 78a as the starting material.

[0594] MS m / z(ESI):447.2[M+1]

[0595] Example 103

[0596] 1-(5,6-dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-((1S,2R)-2-(6-fluoropyridin-3-yl)cyclopropyl)ethan-1-one

[0597] Under nitrogen, diiodomethane (5.7 g, 21 mmol, 6.1 eq.) was added dropwise to a solution of diethylzinc (1 M, 10.5 mL, 3 eq.) in dichloromethane (25 mL) at -40°C. After the mixture was stirred for two hours, a solution of trichloroacetic acid (1.7 g, 10.5 mmol, 3 eq.) in dichloromethane (3 mL) was added dropwise. The reaction mixture was warmed to -10°C and stirred for two hours. A solution of 103a (1 g, 3.5 mmol, 1 eq.) in dichloromethane (3 mL) was slowly added. The reaction mixture was stirred at room temperature overnight and then quenched with aqueous citric acid (10%, 25 mL). The organic phase was washed with saturated aqueous sodium chloride solution and concentrated in vacuo. Silica gel chromatography (eluent: petroleum ether / ethyl acetate = 0%-7%) afforded the product 103b (340 mg, yield: 65%).

[0598] Bis(1-adamantyl)-butylphosphine (cataCXium A; 36 mg, 0.1 mmol, 0.1 eq.) was added to palladium acetate (22.5 mg, 0.1 mmol, 0.1 eq.). Degassed 2-methylbutan-2-ol (6 mL) was then added, and the reactor was purged of nitrogen. The catalyst and ligand were stirred under nitrogen for one hour. Degassed water (1 mL), cesium carbonate (1.63 g, 5 mmol, 5 eq.), and 5-bromo-2-fluoropyridine (176 mg, 1.1 mmol, 1.1 eq.) were then added to the mixture. Finally, a solution of 103b (340 mg, 1 mmol, 1 eq.) in 2-methylbutan-2-ol (1 mL) was added via syringe, and the mixture was repeatedly evacuated and refilled with nitrogen. The reaction mixture was heated at 75°C for 16 hours, then diluted with water (2 mL), and the diluted mixture was extracted with EA (3 x 20 mL). The combined organic phases were washed with saturated aqueous sodium chloride solution (10 mL), dried, concentrated, and chromatographed on silica gel (eluent: petroleum ether / ethyl acetate = 2%-10%) to give product 103c (291 mg, yield: 92%). MS m / z (ESI): 296.5

[0599] At room temperature, ruthenium chloride (21 mg, 0.1 mmol, 0.1 eq.) was added to a solution of 103c (291 mg, 0.98 mmol, 1 eq.) in acetonitrile (5 mL). A solution of sodium periodate (650 mg, 3 mmol, 3 eq.) in water (1 mL) was then added during stirring, and the reaction mixture was stirred at room temperature overnight. Hydrochloric acid (1 M, 1 mL) was then added, and the solution was removed in vacuo. The residual mixture was dissolved in acetonitrile (5 mL), then filtered through celite and washed with acetonitrile (5 mL). The product was concentrated to give 103d (180 mg, yield: 92%). MS m / z (ESI): 196.2

[0600] At room temperature, 103d (100 mg, 0.51 mmol), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (319 mg, 0.84 mmol, 1.8 eq.) and 20i (104 mg, 0.47 mmol) were dissolved in DMF (5 mL). The mixture was stirred for 5 min, and then N,N-diisopropylethylamine (210.8 mg, 1.63 mmol) was added dropwise at 0°C. The mixture was stirred at room temperature for half an hour and concentrated to give 103 (93 mg, yield: 49.7%). MS m / z (ESI): 366.4

[0601] Example 144

[0602] 1-(5,6-dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0603] Methyl 2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)acetate

[0604] Compound 2-chloro-5-(trifluoromethyl)pyrimidine 144a (2.0 g, 11.0 mmol) and methyl 2-(azetidin-3-yl)acetate (1.42 g, 11.0 mmol) were dissolved in 30 mL of acetonitrile. Cesium carbonate (8.93 g, 27.4 mmol) was added. After the addition was complete, the reaction was heated at 55°C for 1 hour. 50 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (30 mL x 2). The combined organic phases were washed with saturated sodium chloride solution (20 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was chromatographed on a silica gel column using eluent System B to afford the title product 144b (3.0 g, 99.5% yield). MS m / z (ESI): 276.2 [M+1]

[0605] 2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)acetic acid

[0606] 144b (800 mg, 2.9 mmol) was dissolved in 15 mL of a mixed solvent of methanol and water (V / V = 4:1). Anhydrous lithium hydroxide (278 mg, 11.6 mmol) was added. After the addition was complete, the reaction was stirred at 25°C for 1 hour. The methanol solvent was removed by vortexing, 1 M hydrochloric acid (10 mL) was added, and the mixture was extracted with dichloromethane (20 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the title product 2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)acetic acid 144c (759 mg) was obtained and used directly in the next step. MS m / z (ESI): 262.2 [M+1]

[0607] 1-(5,6-dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0608] 144c (759 mg, 2.9 mmol) was dissolved in 15 mL of N,N-dimethylformamide. 5,6-Dimethyl-8,9-dihydro-7H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridine (750 mg, 2.9 mmol), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.6 g, 4.3 mmol), and diisopropylethylamine (1.1 g, 8.7 mmol) were added to the reaction system in sequence. The mixture was reacted at 25°C for 1 hour. 30 mL of water was added to the reaction solution, and the mixture was extracted with dichloromethane (20 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (20 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to obtain the title product 144 (1.05 g, yield: 84.1%). MS m / z (ESI): 432.2 [M+1]

[0609] 1 H NMR (400MHz, DMSO) δ8.66(t,J=1.4Hz,2H),8.46(d,J=2.1Hz,1H),5.12(s,1H),4.98(s,1H),4.87(s,1H),4. 77(s,1H),4.37-4.23(m,2H),3.90-3.80(m,2H),3.11(s,2H),3.01-2.88(m,1H),2.73(s,3H),2.29(s,3H).

[0610] Example 284

[0611] (5,6-Dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)(3-((2-(trifluoromethyl)pyridin-4-yl)amino)cyclobutyl)methanone

[0612] Methyl 3-((5-(trifluoromethyl)pyrimidin-2-yl)amino)cyclobutane-1-carboxylate

[0613] Compound 284a (313 mg, 1.1 eq) and compound 284b (500 mg, 1.0 eq) were added to N-methylpyrrolidone (10 mL) and reacted at 120°C for 12 h. After completion of the reaction, the mixture was cooled to room temperature, and water (50 mL) was added. The mixture was extracted twice with ethyl acetate (100 mL). The combined organic phases were washed with saturated brine, dried, filtered, concentrated, and purified by silica gel chromatography (eluent: dichloromethane ether / methanol = 100% to 5%) to give product 284c (420 mg, 69.4% yield). MS m / z (ESI): 276.1.

[0614] 3-((5-(Trifluoromethyl)pyrimidin-2-yl)amino)cyclobutane-1-carboxylic acid

[0615] Compound 284c (420 mg, 1.0 eq) and lithium hydroxide (183 mg, 5 eq) were dissolved in methanol (10 mL) and reacted at 50°C for 4 h. After the reaction was complete, the mixture was cooled to 0°C and slowly added dropwise with 2M dilute hydrochloric acid to adjust the pH to 3-4. The mixture was concentrated to dryness to obtain the crude product, which was used in the next step according to the theoretical yield without purification. MS m / z (ESI): 262.2.

[0616] In the third step, Example 284 (220 mg, yield 34.6%) was obtained by referring to the synthesis method of the ninth step of Example 20.

[0617] MS m / z(ESI):431.4.

[0618] Compound Example 284 was separated by chiral column (chromatographic column: CHIRALCEL AS, 4.6*150 mm, 5 μm; detection wavelength (nm): 214; temperature (°C): 35; flow rate (mL / min): 10; mobile phase: Hexane:IPA:DEA=70:30:0.1%; running time (min): 12; linear mode: isocratic) to obtain the title product 284-P1 (7.8 mg, RT (retention time) = 6.667 min, yield: 7.2%); the title product 284-P2 (65.0 mg, RT (retention time) = 9.327 min, yield: 60.2%).

[0619] Example 292

[0620] 1-(4-methoxy-5-methyl-7,8-dihydro-6H-[1,2,4]triazacyclopenta[5,1-f]pyrrolo[4,3-b]pyridin-7-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one

[0621] 1-(4-methoxy-5-methyl-7,8-dihydro-6H-[1,2,4]triazacyclopenta[5,1-f]pyrrolo[4,3-b]pyridin-7-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one

[0622] Compound 293 (10 mg) was dissolved in anhydrous methanol (1 mL), and a solution of sodium methoxide (10 mg) in anhydrous methanol (1 mL) was added. The mixture was stirred at 70°C under nitrogen for 12 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure. The residue was purified by HPLC (0.1% formic acid / acetonitrile / water) to give the title product 292 (1.3 mg, yield: 12.1%). MS m / z (ESI): 447.2 [M+1]

[0623] Example 293

[0624] 1-(4-chloro-5-methyl-7,8-dihydro-6H-[1,2,4]triazacyclopenta[5,1-f]pyrrolo[4,3-b]pyridin-7-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one

[0625] Methyl 6-chloro-2-cyano-4-methylpyridine-3-carboxylate

[0626] Compound 293a (2.5 g, 11.36 mmol) was transferred to a 20 mL microwave tube. N-methylpyrrolidone (10 mL) was added, followed by cuprous cyanide (89 mg, 126.14 μmol). Nitrogen was bubbled through the tube for 30 seconds, and the mixture was stirred in a microwave oven at 180°C for 2 hours. Two parallel reactions were run and combined for post-processing. The reaction mixture was cooled to room temperature, poured into 5% aqueous ammonia (100 mL), extracted with ethyl acetate (100 mL), and filtered through Celite to remove the black insoluble matter. The organic phase was separated, washed with saturated sodium chloride solution (20 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to obtain the title product 293b (1.7 g, 35.5% yield). MS m / z (ESI): 211.0 [M+1].

[0627] 2-Cyano-6-{[(2,4-dimethoxyphenyl)methyl]amino}-4-methylpyridine-3-carboxylic acid methyl ester

[0628] Compound 293b (1.7 g, 8.07 mmol) was dissolved in acetonitrile (34 mL). 2,4-Dimethoxybenzylamine (1.62 g, 9.69 mmol, 1.46 mL) and triethylamine (1.23 g, 12.11 mmol, 1.69 mL) were added sequentially, and the mixture was stirred at 80°C for 16 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to obtain the title product 293c (1.2 g, 43.6% yield). MS m / z (ESI): 310.2 [M+1]

[0629] 2-{[(2,4-dimethoxyphenyl)methyl]amino}-4-methyl-6,7-dihydro-5H-pyrrolo[4,3-b]pyridin-5-one

[0630] Compound 293c (1.2 g, 3.52 mmol) was dissolved in methanol (24 mL). Nickel dichloride hexahydrate (1.67 g, 7.03 mmol) and sodium borohydride (1.33 g, 35.15 mmol) were added portionwise at 0°C. The mixture was stirred at 20°C for 1 hour. Triethylamine (1.07 g, 10.55 mmol, 1.47 mL) was added, and the temperature was raised to 50°C and stirred for 12 hours. The reaction solution was cooled to room temperature, and saturated ammonium chloride solution (100 mL) and ethyl acetate (40 mL) were added. The insoluble material was removed by filtration through celite. The organic phase was separated, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to obtain the title product 293d (600 mg, 54.5% yield).

[0631] MS m / z(ESI):282.2[M+1]

[0632] 2-Amino-4-methyl-6,7-dihydro-5H-pyrrolo[4,3-b]pyridine-6-carboxylic acid 2-methylprop-2-yl ester

[0633] Compound 293d (600 mg, 1.91 mmol) was dissolved in anhydrous tetrahydrofuran (6 mL). Borane in dimethyl sulfide (2 M, 6 mL) was added under nitrogen protection, and the mixture was stirred at 70°C for 12 hours. The reaction solution was cooled to 0°C, and anhydrous methanol (3 mL) was added dropwise to quench the reaction. Concentrated hydrochloric acid (12 M, 3 mL) was then added, and the temperature was raised to 70°C and stirred for 12 hours. The reaction solution was cooled again to 20°C, and sodium hydroxide solution (2 M, 18 mL) was slowly added to adjust the pH of the system to >8. Finally, di-tert-butyl dicarbonate (836 mg, 3.83 mmol) was added, and the mixture was stirred at 20°C for 2 hours. The reaction solution was diluted with water (20 mL) and extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with eluent System B to give the title product 293e (200 mg, yield: 41.9%).

[0634] MS m / z(ESI):250.2[M+1]

[0635] 2-{[(Z)-(Dimethylamino)methylidene]amino}-4-methyl-6,7-dihydro-5H-pyrrolo[4,3-b]pyridine-6-carboxylic acid 2-methylpropan-2-yl ester

[0636] Compound 293e (180 mg, 722 μmol) was dissolved in anhydrous toluene (5 mL). N,N-dimethylformamide dimethyl acetal (172 mg, 1.44 mmol) was added under nitrogen, and the mixture was stirred at 110°C for 2 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain the title product, 2-{[(Z)-(dimethylamino)methylidene]amino}-4-methyl-6,7-dihydro-5H-pyrrolo[4,3-b]pyridine-6-carboxylic acid-2-methylprop-2-yl ester 293f (240 mg, crude). MS m / z (ESI): 305.2 [M+1].

[0637] 5-Methyl-7,8-dihydro-6H-[1,2,4]triazacyclopenta[5,1-f]pyrrolo[4,3-b]pyridine-7-carboxylic acid-2-methylpropane-

[0638] 2-amino ester

[0639] Compound 293f (230 mg, 756 μmol) was dissolved in anhydrous methanol (10 mL). Anhydrous pyridine (179 mg, 2.27 mmol) and hydroxylaminesulfonic acid (171 mg, 1.51 mmol) were added sequentially under nitrogen, and the mixture was stirred at 60°C for 12 hours. The reaction solution was cooled to room temperature, and saturated ammonium chloride solution (20 mL) was added. The mixture was extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to obtain the title product 293 g (100 mg, 48.2% yield).

[0640] MS m / z(ESI):275.1[M+1]

[0641] 2-Methylpropane-2-yl 4-chloro-5-methyl-7,8-dihydro-6H-[1,2,4]triazacyclopenta[5,1-f]pyrrolo[4,3-b]pyridine-7-carboxylate

[0642] Compound 293g (40 mg, 146 μmol) was dissolved in anhydrous N,N-dimethylformamide (4 mL), and N-chlorosuccinimide (39 mg, 292 μmol) was added. The mixture was stirred at 60°C for 2 hours. The reaction solution was cooled to room temperature and diluted with water (40 mL). The mixture was extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to obtain the title product 293h (40 mg, yield: 88.8%). MS m / z (ESI): 309.1 [M+1]

[0643] 4-Chloro-5-methyl-7,8-dihydro-6H-[1,2,4]triazacyclopenta[5,1-f]pyrrolo[4,3-b]pyridine

[0644] Compound 293h (40 mg, 130 μmol) was dissolved in anhydrous dichloromethane (1 mL), and a 4 M solution of hydrogen chloride in 1,4-dioxane (1 mL) was added. The mixture was stirred at 25°C for 12 hours. The reaction solution was directly concentrated under reduced pressure to obtain the title product 293i (40 mg, crude dihydrochloride salt). MS m / z (ESI): 209.1 [M+1]

[0645] 1-(4-chloro-5-methyl-7,8-dihydro-6H-[1,2,4]triazacyclopenta[5,1-f]pyrrolo[4,3-b]pyridin-7-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one

[0646] Compound 293i (100 mg) and compound {1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}acetic acid (37 mg) were dissolved in anhydrous N,N-dimethylformamide (2 mL). Triethylamine (100 μL) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (59 mg) were added sequentially at 0°C, and the mixture was stirred at 20°C for 1 hour. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by HPLC (0.1% formic acid / acetonitrile / water) to obtain the title product 293 (22.1 mg, yield: 32.9%). MS m / z (ESI): 451.1 [M+1].

[0647] 1H NMR (400MHz, DMSO) δ8.59(s,1H),8.23(d,1H),6.81(s,1H),6.59(d,1H),5.27(s,1H),5. 00(d,2H),4.79(s,1H),4.25(t,2H),3.79(d,2H),3.16(s,1H),2.96(d,2H),2.45(d,3H).

[0648] Example 296

[0649] (5,6-Dimethyl-8,9-dihydro-7H-[1,2,4]triazacyclopenta[1,5-a]pyrrolo[4,3-c]pyridin-8-yl){1-[2-(trifluoromethyl)pyridin-4-yl]spiro[2.3]hexan-5-yl}methanone

[0650] Methyl 3-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylidene]cyclobutane-1-carboxylate

[0651] 2,2,6,6-Tetramethylpiperidine (1.32 g, 9.37 mmol, 1.58 mL) was dissolved in anhydrous tetrahydrofuran (15 mL). Under nitrogen, n-butyllithium (2.5 M, 3.75 mL) was added dropwise at -30°C and stirred for 0.5 h. The reaction solution was then cooled to -78°C and a solution of bis[(pinacolato)boryl]methane (2.09 g, 7.80 mmol) in anhydrous tetrahydrofuran (15 mL) was added dropwise. The mixture was stirred at -78°C for 0.5 h. Finally, a solution of methyl 3-carbonylcyclobutanecarboxylate 296a (2.09 g, 7.80 mmol) in anhydrous tetrahydrofuran (15 mL) was added dropwise. The temperature was naturally raised to 20°C and the reaction was stirred for 1 h. The reaction solution was cooled to 0°C and saturated ammonium chloride solution (100 mL) was added dropwise to quench and dilute the reaction. The product was extracted with ethyl acetate (30 mL × 2). The combined organic phases were washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography with eluent System B to give the title product 296b (1.2 g, yield: 61.0%), which was used directly in the next reaction.

[0652] Methyl 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[2.3]hexane-5-carboxylate

[0653] Under nitrogen, diethylzinc (1 M, 1.19 mL) was added to anhydrous dichloromethane (1 mL) at 0°C. A solution of diiodomethane (319 mg, 1.19 mmol) in anhydrous dichloromethane (0.5 mL) was added and stirred at 0°C for 0.5 h. Compound 296b (100 mg, 397 μmol) in anhydrous dichloromethane (0.5 mL) was then added dropwise. The mixture was naturally warmed to 20°C and stirred for 12 h. The reaction solution was cooled to 0°C and quenched and diluted by the dropwise addition of saturated ammonium chloride solution (20 mL). The mixture was extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford the title product 296c (115 mg, crude product), which was used directly in the next step.

[0654] 1 H NMR (400MHz, CDCl3) δ3.70(d,3H),3.34–3.17(m,1H),2.60–2.45(m,2H),2.37–2.19(m,2H),1.22(dd,12H),0.84–0.71(m,2H),-0.02–-0.12(m,1H).

[0655] Methyl 1-[2-(trifluoromethyl)pyridin-4-yl]spiro[2.3]hexane-5-carboxylate

[0656] Compound 296c (99 mg, 372 μmol) and 4-bromo-2-trifluoromethylpyridine (70 mg, 310 μmol) were dissolved in 3.6 mL of a mixture of 1,4-dioxane and water (V / V = 5:1). Potassium carbonate (86 mg, 619 μmol) and 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (23 mg, 31 μmol) were added sequentially. Nitrogen was bubbled through for 30 seconds, and the mixture was stirred in a microwave oven at 90°C for 2 hours. The reaction mixture was cooled to room temperature, diluted with water (20 mL), and extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to obtain the title product 296d (40 mg, 45.3% yield). MS m / z (ESI): 286.1 [M+1].

[0657] 1-[2-(Trifluoromethyl)pyridin-4-yl]spiro[2.3]hexane-5-carboxylic acid

[0658] Compound 296d (40 mg, 140 μmol) was dissolved in anhydrous tetrahydrofuran (3 mL). Potassium trimethylsilanol (54 mg, 421 μmol) was quickly added under nitrogen, and the mixture was stirred at 20°C for 1 hour. Dilute hydrochloric acid (2 M) was added dropwise to the reaction solution until it became weakly acidic. The solution was concentrated under reduced pressure and the water was removed by spun-coating with toluene to obtain the title product 296e (38 mg, crude), which was used directly in the next reaction.

[0659] MS m / z(ESI):272.1[M+1]

[0660] (5,6-Dimethyl-8,9-dihydro-7H-[1,2,4]triazacyclopenta[1,5-a]pyrrolo[4,3-c]pyridin-8-yl){1-[2-(trifluoromethyl)pyridin-4-yl]spiro[2.3]hexan-5-yl}methanone

[0661] Compound 296e (36 mg) and compound 5,6-dimethyl-8,9-dihydro-7H-[1,2,4]triazacyclopenta[1,5-a]pyrrolo[4,3-c]pyridine (30 mg) were dissolved in anhydrous N,N-dimethylformamide (2 mL). Triethylamine (48 uL) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (48 mg) were added sequentially at 0°C, and the mixture was stirred at 20°C for 1 hour. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by HPLC (0.1% formic acid / acetonitrile / water) to give the title product 296 (28.4 mg, yield: 54.0%). MS m / z (ESI): 442.2 [M+1]

[0662] 1H NMR(400MHz, CDCl3)δ8.57(dd,1H),8.42–8.32(m,1H),7.34–7.27(m,1H),7.02(td,1H),5.23–4.98(m,2H),4.88(d,2H),3.5 9–3.29(m,1H),2.81(s,3H),2.66(dd,1H),2.59–2.42(m,2H),2.35(d,3H),2.20–1.98(m,2H),1.40(ddd,1H),1.15(dt,1H).

[0663] Example 297

[0664] 1-(5,6-Dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(2-(2-(trifluoromethyl)pyridin-4-yl)cyclopropyl)ethan-1-one

[0665] Example 297 was obtained by referring to the synthesis method of Example 103. MS m / z (ESI): 416.4.

[0666] Example 298

[0667] 1-(5,6-dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(2-(5-(trifluoromethyl)pyrimidin-2-yl)cyclopropyl)ethan-1-one

[0668] Example 298 was obtained by referring to the synthesis method of Example 103. MS m / z (ESI): 417.4.

[0669] Example 299

[0670] (5,6-Dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)(3-((5-(trifluoromethyl)pyrimidin-2-yl)amino)cyclobutyl)methanone

[0671] Example 299 was obtained by referring to the synthesis method of Example 284. MS m / z (ESI): 432.4.

[0672] Example 304

[0673] 1-(5,6-dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(1-(6-ethoxypyridin-3-yl)azetidin-3-yl)ethan-1-one

[0674] Methyl 2-(1-(6-ethoxypyridin-3-yl)azetidin-3-yl)acetate

[0675] Under nitrogen, methyl 2-(azetidin-3-yl)acetate (3.84 g, 29.70 mmol), 5-bromo-2-ethoxypyridine (3 g, 14.85 mmol), 304a, cesium carbonate (14.61 g, 44.54 mmol), and Brettsphos-G4 (714.19 mg, 742.40 μmol) were added to 1,4-dioxane (60 mL). The reaction solution was stirred at 120°C for 5 hours, 60 mL of water was added, and the mixture was extracted with 80 mL of ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to afford the title product 304b (1.6 g, 43% yield). MS m / z (ESI): 251.2 [M+1].

[0676] 2-(1-(6-ethoxypyridin-3-yl)azetidin-3-yl)acetic acid

[0677] 304b (1.6 g, 6.39 mmol) and lithium hydroxide monohydrate (1 M, 19.18 mL) were added to methanol (30 mL). The reaction solution was stirred at 25°C for 1 hour and then dried to afford 304c (1.5 g, 99% yield). MS m / z (ESI): 237.2 [M+1]

[0678] 1-(5,6-dimethyl-7,9-dihydro-8H-pyrrolo[3,4-c][1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(1-(6-ethoxypyridin-3-yl)azetidin-3-yl)ethan-1-one

[0679] 20i (1.55 g, 8.25 mmol), 304c (1.5 g, 6.35 mmol), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (3.60 g, 9.52 mmol), and N,N-diisopropylethylamine (2.46 g, 19.05 mmol, 3.32 mL) were added to N,N-dimethylformamide (30 mL). The reaction solution was stirred at 25°C for 1 hour, 20 mL of water was added, and the product was extracted with 30 mL of ethyl acetate. The organic phase was concentrated under reduced pressure, and the resulting residue was purified by preparative HPLC to give the title product 304 (1.25 g, 48.6% yield). MS m / z (ESI): 407.2 [M+1]

[0680] 1 H NMR (400MHz, DMSO) δ8.46 (s, 1H), 7.37–7.30 (m, 1H), 6.92 (dd, J = 8.9, 3.2Hz, 1H ),6.63(d,J=8.7Hz,1H),5.11(s,1H),4.98(s,1H),4.86(s,1H),4.75(s,1H),4. 16(q,J=7.0Hz,2H),3.97(t,J=7.5Hz,2H),3.47(d,J=6.6Hz,2H),3.06(s,1H),2 .87(t,J=6.9Hz,2H),2.72(s,3H),2.29(d,J=2.7Hz,3H),1.27(d,J=7.0Hz,3H).

[0681] Example 317

[0682] 1-(4-chloro-5-methyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0683] 293i was obtained by following the preparation method of steps 1 to 8 of Example 293, and then reacted with 144c according to the preparation method of step 9 to obtain Example 317. MS m / z (ESI): 452.8;

[0684] 1H NMR (400MHz, DMSO) δ8.67 (s, 2H), 8.58 (d, J = 2.0Hz, 1H), 4.99 (d, J = 10.3Hz, 2H), 4.29 (t, J = 9.3Hz, 2H), 3.90-3.80 (m, 2H), 3.00-2.88 (m, 2H), 2.66 (s, 1H), 2.44 (d, J = 5.5Hz, 3H), 2.06-1.93 (m, 2H).

[0685] Example 326

[0686] 1-(5-methyl-1,2,3,6,7,8-hexahydrocyclopenta[1,2-d]pyrrolo[4,3-b]pyridin-2-yl)-2-{1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}ethan-1-one

[0687] 2-Hydroxy-4-methyl-6,7-dihydro-5H-cyclopenta[1,2-b]pyridine-3-carbonitrile

[0688] Compound 326a (5 g, 39.63 mmol) was dissolved in 100 mL of ethanol, and cyanoacetamide (3.33 g, 39.63 mmol) and piperidine (3.37 g, 39.63 mmol) were added sequentially. The mixture was then stirred and refluxed at 80°C for 12 hours. The reaction solution was cooled to room temperature, and a large amount of solid precipitated. The solid was filtered under reduced pressure, and the filter cake was rinsed with ice-cold ethanol (10 mL x 3). The filter cake was collected and dried under reduced pressure to give the title product, 2-hydroxy-4-methyl-6,7-dihydro-5H-cyclopenta[1,2-b]pyridine-3-carbonitrile 326b (3.4 g, yield: 49.2%).

[0689] MS m / z(ESI):175.1[M+1]

[0690] 2-Bromo-4-methyl-6,7-dihydro-5H-cyclopenta[1,2-b]pyridine-3-carbonitrile

[0691] Compound 326b (1 g, 5.74 mmol) was dissolved in anhydrous 1,4-dioxane (10 mL). Phosphorus oxybromide (1.62 g, 9.69 mmol, 1.46 mL) was added under nitrogen, and the mixture was heated to 90°C with stirring for 2 hours. The reaction mixture was cooled to room temperature, diluted with saturated sodium bicarbonate solution (100 mL), and extracted with ethyl acetate (20 mL x 2). The combined organic phases were washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to afford the title product, 2-bromo-4-methyl-6,7-dihydro-5H-cyclopenta[1,2-b]pyridine-3-carbonitrile 326c (700 mg, 51.4% yield).

[0692] MS m / z(ESI):237.0[M+1]

[0693] 3-Cyano-4-methyl-6,7-dihydro-5H-cyclopenta[1,2-b]pyridine-2-carboxylic acid methyl ester

[0694] Compound 326c (700 mg, 2.95 mmol) was dissolved in a mixed solvent of methanol (7 mL) and N,N-dimethylformamide (7 mL). [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane complex (241 mg, 0.30 mmol) and triethylamine (596 mg, 5.90 mmol) were added sequentially. The atmosphere was replaced with carbon monoxide three times, and the reaction was stirred at 100°C under a carbon monoxide balloon atmosphere (~15 psi) for 12 hours. The reaction solution was cooled to room temperature, and saturated ammonium chloride solution (70 mL) and ethyl acetate (40 mL) were added to the reaction solution. The insoluble material was removed by filtration with celite. The layers were separated, and the organic phase was washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with eluent System B to give the title product, 3-cyano-4-methyl-6,7-dihydro-5H-cyclopenta[1,2-b]pyridine-2-carboxylic acid methyl ester 326d (400 mg, yield: 62.7%).

[0695] MS m / z(ESI):217.1[M+1]

[0696] 5-Methyl-1,6,7,8-tetrahydrocyclopenta[d]pyrrolo[3,4-b]pyridin-3(2H)-one

[0697] Compound 326d (400 mg, 2.95 mmol) was dissolved in anhydrous methanol (8 mL). Nickel dichloride hexahydrate (1.40 g, 5.90 mmol) and sodium borohydride (1.12 g, 29.50 mmol) were added sequentially under ice-cooling. The mixture was stirred at 25°C for 1 hour. Triethylamine (894 mg, 8.85 mmol, 1.23 mL) was added, and the temperature was raised to 50°C and stirred for 12 hours. The reaction solution was cooled to room temperature, and saturated ammonium chloride solution (80 mL) and ethyl acetate (40 mL) were added. The insoluble material was removed by filtration through celite. The organic phase was separated, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to obtain the title product 326e (200 mg, 57.5% yield).

[0698] MS m / z(ESI):189.1[M+1]

[0699] 5-Methyl-1,2,3,6,7,8-hexahydrocyclopenta[d]pyrrolo[3,4-b]pyridine

[0700] Compound 326e (200 mg, 1.91 mmol) was dissolved in anhydrous tetrahydrofuran (4 mL). Borane in dimethyl sulfide (2 M, 4 mL) was added under nitrogen and stirred at 70°C for 12 h. The reaction mixture was cooled to 0°C and quenched by the dropwise addition of anhydrous methanol (4 mL). Concentrated hydrochloric acid (12 M, 2 mL) was then added, and the temperature was raised to 70°C and stirred for 12 h. The reaction mixture was cooled again to 20°C and the pH was adjusted to >8 by the slow addition of sodium hydroxide solution (2 M, 12 mL). The reaction mixture was diluted with water (40 mL) and extracted with ethyl acetate (20 mL × 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System B to afford the title product 326f (100 mg, 54.1% yield).

[0701] MS m / z(ESI):175.1[M+1]

[0702] 1-(5-methyl-3,6,7,8-tetrahydrocyclopenta[d]pyrrolo[3,4-b]pyridin-2(1H)-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0703] Compound 326f (100 mg) and compound {1-[2-(trifluoromethyl)pyridin-4-yl]azetidin-3-yl}acetic acid (100 mg) were dissolved in anhydrous N,N-dimethylformamide (2 mL). Triethylamine (100 μL) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (100 mg) were added sequentially at 0°C, and the mixture was stirred at 25°C for 1 hour. The reaction solution was diluted with water (20 mL) and extracted with ethyl acetate (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by high-performance liquid chromatography (0.1% formic acid / acetonitrile / water) to obtain the title product 326 (20 mg).

[0704] 1 H NMR (400MHz, CDCl3) δ8.27(d,1H),6.58(d,1H),6.34(s,1H),4.86(d,2H),4.74(s,2H),4.28(t, 2H),3.83–3.73(m,2H),3.31(s,1H),2.99–2.86(m,4H),2.82(d,2H),2.56(d,3H),2.23(p,2H).

[0705] MS m / z(ESI):417.2[M+1]

[0706] Example 327

[0707] 1-(5-methyl-3,6,7,8-tetrahydrocyclopenta[d]pyrrolo[3,4-b]pyridin-2(1H)-yl)-2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0708] Example 327 was obtained by referring to the synthesis method of Example 326. MS m / z (ESI): 418.4.

[0709] Example 328

[0710] 2-(1-(6-ethoxypyridin-3-yl)azetidin-3-yl)-1-(5-methyl-3,6,7,8-tetrahydrocyclopenta[d]pyrrolo[3,4-b]pyridin-2(1H)-yl)ethan-1-one

[0711] Example 328 was obtained by referring to the synthesis method of Example 326. MS m / z (ESI): 393.5.

[0712] Example 330

[0713] 1-(5,6-dimethyl-8,9-dihydro-7H-pyrrolo[4,3-f]quinoxalin-8-yl)-2-{1-[5-(trifluoromethyl)pyrimidin-2-yl]azetidin-3-yl}ethan-1-one

[0714] 4-Amino-1-oxyylidene-2,3-dihydro-1H-isoindole-2-carboxylic acid 2-methylprop-2-yl ester

[0715] Sodium hydroxide (1.4 g, 34 mmol, 60% purity) was added portionwise to a solution of 4-aminoisoindolin-1-one (5 g, 34 mmol) in tetrahydrofuran (50 mL) at 0°C. After stirring at 0°C for 30 minutes, di-tert-butyl dicarbonate (7.4 g, 34 mmol) was added to the reaction mixture, and the reaction mixture was stirred at room temperature for 1 hour. After completion, saturated aqueous ammonium chloride (30 mL) and water (20 mL) were slowly added dropwise to the reaction mixture to quench the reaction. The mixture was then extracted with ethyl acetate (100 mL x 2). The combined organic phases were washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a residue, which was purified by silica gel column chromatography using eluent System C to afford the title product 330b (4.6 g, 54.9% yield). MS m / z (ESI): 249.1 [M+1].

[0716] 4-Amino-7-bromo-1-oxyylidene-2,3-dihydro-1H-isoindole-2-carboxylic acid 2-methylprop-2-yl ester

[0717] N-Bromosuccinimide (3.3 g, 19 mmol) was added portionwise to a solution of 330b (4.6 g, 19 mmol) in acetonitrile (60 mL) at 0°C. The reaction mixture was allowed to warm to room temperature and allowed to react for 1 hour. After completion, the reaction mixture was quenched with water (100 mL) and extracted with ethyl acetate (100 mL x 2). The combined organic phases were washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System C to afford the title product 330c (5.2 g, 85.8% yield). MS m / z (ESI): 327.1 [M+1].

[0718] 4-Amino-7-methyl-1-oxyylidene-2,3-dihydro-1H-isoindole-2-carboxylic acid 2-methylprop-2-yl ester

[0719] [1,1'-Bis(di-tert-butylphosphino)ferrocene]palladium dichloride (296 mg, 458 μmol) was added to a solution of 330c (3 g, 9 mmol), trimethylboroxine (2.3 g, 18 mmol), and potassium carbonate (2.53 g, 18 mmol) in dioxane (30 mL) and water (3 mL). The atmosphere was purged with nitrogen three times and the mixture was allowed to react at 100°C for 2 hours. After completion, the reaction was quenched with water (100 mL) and extracted with ethyl acetate (100 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a residue, which was purified by silica gel column chromatography using eluent System C to afford the title product 330d (2.1 g, 87.3% yield).

[0720] MS m / z(ESI):263.1[M+1].

[0721] 4-Amino-5-bromo-7-methyl-1-oxo-2,3-dihydro-1H-isoindole-2-carboxylic acid 2-methylprop-2-yl ester

[0722] N-Bromosuccinimide (1.1 g, 6.1 mmol) was added portionwise to a solution of 330d (1.6 g, 6.1 mmol) in acetonitrile (30 mL) at 0°C. The reaction mixture was allowed to warm to room temperature and allowed to react for 1 hour. After completion, the reaction mixture was quenched with water (100 mL) and extracted with ethyl acetate (100 mL x 2). The combined organic phases were washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a residue, which was purified by silica gel column chromatography using eluent System C to afford the title product 330e (1.6 g, 76.9% yield). MS m / z (ESI): 341.0 [M+1].

[0723] 4-Amino-5-bromo-7-methyl-2,3-dihydro-1H-isoindole-2-carboxylic acid 2-methylprop-2-yl ester

[0724] Borane (1 M, 25 mL) was added to a solution of 330e (1.7 g, 5 mmol) in tetrahydrofuran (2 mL). The reaction mixture was heated at 70°C under nitrogen for 12 hours. After completion, methanol was added dropwise until no bubbles formed. The mixture was then heated at 70°C with stirring for 30 minutes. The reaction mixture was then filtered through celite, and the filter cake was rinsed with dichloromethane (100 mL). The filtrate was then dried and the resulting residue was purified by silica gel column chromatography using eluent System C to yield the title product 330f (1.1 g, 67.5% yield). MS m / z (ESI): 326.1 [M+1].

[0725] 4,5-Diamino-7-methyl-2,3-dihydro-1H-isoindole-2-carboxylic acid 2-methylprop-2-yl ester

[0726] Aqueous ammonia (2.2 g, 13 mmol) was added to a mixture of 330f (1.1 g, 3 mmol), cuprous iodide (64 mg, 336 μmol), tripotassium phosphate (1.4 g, 7 mmol), and N1,N2-bis(5-methyl-[1,1'-biphenyl]-2-yl)oxamide (283 mg, 672 μmol) in dimethyl sulfoxide (2 mL). The atmosphere was purged with nitrogen three times and microwaved at 100°C for 3 hours. After completion of the reaction, the reaction mixture was filtered through celite, the filter cake rinsed with dichloromethane (50 mL), and the filtrate was dried to dryness. The resulting residue was purified by silica gel column chromatography using eluent System C to give the title product 330 g (750 mg, 84.7% yield). MS m / z (ESI): 264.2 [M+1].

[0727] 2-Methylprop-2-yl-4,5-diamino-6-bromo-7-methyl-2,3-dihydro-1H-isoindole-2-carboxylate

[0728] N-Bromosuccinimide (152 mg, 854 μmol) was added portionwise to a solution of 330 g (150 mg, 569 μmol) in acetonitrile (4 mL) at room temperature. The reaction mixture was allowed to react at room temperature for 10 minutes. After completion, saturated sodium bicarbonate solution (20 mL) was added to the reaction mixture, which was then extracted with ethyl acetate (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford the crude title product 330h (120 mg, 61.6% yield). MS m / z (ESI): 342.1 [M+1].

[0729] 2-Methylprop-2-yl 5-bromo-6-methyl-8,9-dihydro-7H-pyrrolo[4,3-f]quinoxaline-8-carboxylate

[0730] A 40% aqueous solution of glyoxal (229 mg, 1.6 mmol) was added to a solution of 330h (180 mg, 526 μmol) in ethanol (5 mL). The reaction mixture was stirred at 50°C for 3 hours. After completion of the reaction, the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using eluent System C to afford the title product 330i (45 mg, 23.5% yield). MS m / z (ESI): 364.1 [M+1].

[0731] 2-Methylprop-2-yl 5,6-dimethyl-8,9-dihydro-7H-pyrrolo[4,3-f]quinoxaline-8-carboxylate

[0732] [1,1'-Bis(di-tert-butylphosphino)ferrocene]palladium dichloride (2 mg, 3 μmol) was added to a solution of 330i (20 mg, 55 μmol), trimethylboroxine (14 mg, 110 μmol), and potassium carbonate (15 mg, 110 μmol) in dioxane (0.8 mL) and water (0.1 mL). The atmosphere was purged with nitrogen three times and the mixture was allowed to react at 100°C for 2 hours. After completion, the reaction was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a residue, which was purified by silica gel column chromatography using eluent System C to afford the title product 330j (15 mg, 91.3% yield). MS m / z (ESI): 300.2 [M+1].

[0733] 5,6-Dimethyl-8,9-dihydro-7H-pyrrolo[4,3-f]quinoxaline

[0734] A 4 M solution of hydrogen chloride in 1,4-dioxane (1 mL) was added to a solution of 330j (20 mg, 67 μmol) in dioxane (0.2 mL). The reaction was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to afford the title product 330k (15 mg, 95% yield). MS m / z (ESI): 200.1 [M+1].

[0735] 1-(5,6-dimethyl-8,9-dihydro-7H-pyrrolo[4,3-f]quinoxalin-8-yl)-2-{1-[5-(trifluoromethyl)pyrimidin-2-yl]azetidin-3-yl}ethan-1-one

[0736] 330k (15 mg, 64 μmol) was added to a solution of {1-[5-(trifluoromethyl)pyrimidin-2-yl]azetidin-3-yl}acetic acid (17 mg, 64 μmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (29 mg, 76 μmol), and N,N-diisopropylethylamine (16 mg, 127 μmol) in N,N-dimethylformamide (0.6 mL). The reaction was stirred at room temperature for 1 hour. After completion, the reaction was quenched with water (2 mL) and extracted with ethyl acetate (3 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a residue that was purified by preparative HPLC to afford the title product 330 (20 mg, 70% yield). MS m / z (ESI): 443.2 [M+1].

[0737] Example 331

[0738] (4-Chloro-5-methyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)(1-(trifluoromethyl)-1H-pyrazol-4-yl)methanone

[0739] Refer to the preparation method of step 1 to step 6 of Example 293 to obtain 293g. After de-Boc protection according to the preparation method of step 8, refer to the preparation method of step 9 and react with 144c to prepare Example 331.

[0740] 1 H NMR (400MHz, DMSO) δ8.66(t,J=1.0Hz,2H),8.48(d,J=2.0Hz,1H),7.66(d,J=4.5Hz,1H),5.25(s,1H),4.96(d,J=2.7Hz,2 H),4.74(s,1H),4.29(t,J=8.7Hz,2H),3.90-3.82(m,2H),3.19-3.04(m,1H),2.99-2.88(m,2H),2.40(d,J=5.7Hz,3H).MS m / z(ESI):418.2.

[0741] Example 333

[0742] 1-(5-methyl-4-vinyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0743] tert-Butyl 5-methyl-4-vinyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridine-7-carboxylate

[0744] 4-Chloro-5-methyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridine-7-carboxylic acid tert-butyl ester 293h (500 mg, 1.62 mmol) was dissolved in 5.0 mL of a mixed solvent of 1,4-dioxane and water (V / V=4:1). Potassium vinyl fluoroborate (325 mg, 2.43 mmol), 1,1 ’bis(diphenylphosphinoferrocenepalladium dichloride) (136 mg, 0.16 mmol) and cesium carbonate (1.58 g, 4.86 mmol) were heated at 110°C for 5 hours. 20 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL x 2). The combined organic phases were washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography using eluent System B to obtain the title product 333a (410 mg, yield: 84.4%). MS m / z (ESI): 301.2 [M+1]

[0745] 5-Methyl-4-vinyl-7,8-dihydro-6H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridine

[0746] Compound 333a (100 mg, 0.33 mmol) was dissolved in 2.0 mL of 4.0 M hydrochloric acid / methanol and stirred at 25°C for 1 hour. The methanol solvent was removed to obtain the title product 333b (67 mg), which was used directly in the next step. MS m / z (ESI): 200.1 [M+1]

[0747] 1-(5-methyl-4-vinyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0748] Compound 5-methyl-4-vinyl-7,8-dihydro-6H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridine 333b (67 mg, 0.33 mmol) was dissolved in 2.0 mL of N,N-dimethylformamide. 2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)acetic acid (87 mg, 0.33 mmol), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (188 mg, 0.5 mmol), and diisopropylethylamine (129 mg, 1.0 mmol) were added to the reaction system in sequence. The reaction was incubated at 25°C for 1 hour. 10 mL of water was added to the reaction solution, and the mixture was extracted with dichloromethane (10 mL x 2). The organic phases were combined, washed with saturated sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to obtain the title product 333 (95 mg, yield: 64.2%). MS m / z (ESI): 444.2 [M+1]

[0749] Example 334

[0750] 1-(4-ethyl-5-methyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0751] 1-(4-ethyl-5-methyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-(1-(5-(trifluoromethyl)pyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0752] Compound 333 (50 mg, 0.11 mmol) was dissolved in 2.0 mL of methanol, and palladium / carbon (20 mg, 10%) was added. The atmosphere was replaced with hydrogen three times and the reaction was stirred for 1 hour. The filtrate was filtered, concentrated under reduced pressure, and the resulting residue was purified by preparative HPLC to obtain the title product 334 (35 mg, yield: 69.7%). MS m / z (ESI): 446.2 [M+1]

[0753] Example 346

[0754] 1-(4-chloro-5-methyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-(1-(5-fluoropyrimidin-2-yl)azetidin-3-yl)ethan-1-one

[0755] Refer to the preparation method of step 1 to step 8 of Example 293 to obtain 293i, and then refer to the preparation method of step 9 thereof to obtain 293i. Example 346 was prepared by reaction.

[0756] 1 H NMR (400MHz, DMSO-d6) δ8.59-8.58(m,1H), 8.44-8.42(m,2H), 5.26(s,1H), 5.01-4.97(m,2H), 4.78(s, 1H), 4.21-4.16(m,2H), 3.77-3.74(m,2H), 3.06(brs,1H), 2.94-2.89(m,2H), 2.44(d,J=8.0Hz,3H).MS m / z(ESI):402.2[M+1]

[0757] Example 348

[0758] (4-Ethyl-5-methyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)(1-(2-(trifluoromethyl)pyridin-4-yl)pyrrolidin-3-yl)methanone

[0759] Example 348 was obtained by referring to the synthesis method of Example 334. MS m / z (ESI): 445.2.

[0760] Example 349

[0761] 1-(4-ethyl-5-methyl-6,8-dihydro-7H-pyrrolo[3,4-e][1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-(1-(5-fluoro-2-methoxypyridin-4-yl)azetidin-3-yl)ethan-1-one

[0762] Example 349 was obtained by referring to the synthetic method of Example 334.

[0763] 1 H NMR (400MHz, DMSO-d6) δ8.46-8.45(m,1H), 7.74-7.73(m,1H), 5.78-5.75(m,1H), 5.22(s,1H), 4.97-4.95(m,2H), 4.74(s,1H), 4.23-4.19(m,2H) ), 3.79-3.75(m,2H), 3.73(s,3H), 3.11-3.08(m,1H), 3.05-2.99(m,2H) , 2.93-2.89(m,2H), 2.34(d,J=4.0Hz,3H), 1.20-1.16(t,J=8.0Hz,3H),

[0764] MS m / z(ESI):425.2[M+1]

[0765] Example 351

[0766] 1-(5-ethyl-6-methyl-7,9-dihydro-8H-pyrrolo[3,4-f]quinoxalin-8-yl)-2-(1-(2-(trifluoromethyl)pyridin-4-yl)azetidin-3-yl)ethan-1-one

[0767] Example 351 was obtained by referring to the synthesis method of Example 330. MS m / z (ESI): 456.2.

[0768] 1H NMR (400MHz, DMSO) δ1H NMR (400MHz, DMSO) δ9.53 (s, 1H), 8.51 (dd, J = 10.9, 1.7 Hz, 1H), 8.18 (dd, J = 8.5, 4.5 Hz, 1H), 7.79 (ddd, J = 8.4, 3.8, 1.7 Hz,1H),4.91–4.75(m,4H),2.85(ddt,J=20.5,14.2,7.6 Hz,4H),2.22(s,1H),2.11–2.00(m,4H).

[0769] MS m / z(ESI):336.1.

[0770] Biological test evaluation

[0771] 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.

[0772] 1. Cell Function Experiment

[0773] Test Example 1: Determination of the Effect of the Compounds of the Invention on Calcium Flux in Cells Stably Expressing M1-M5 Receptors

[0774] 1. Experimental purpose:

[0775] The compounds were tested for their effects on enhancing calcium flux in CHO-K1 / human M1 / 3 / 5 and CHO-K1 / Gα15M2 / 4 cells.

[0776] 2. Experimental instruments and reagents:

[0777] 2.1 Instruments:

[0778] 384-well test plate, 384-well plate, FLIPR Tip, FLIPR Penta plate reader, Dispendix non-contact nanoliter dispensing system, liquid pipette

[0779] 2.2 Reagents:

[0780] Ham's F-12 Nutrient Mix, fetal bovine serum, P / S (Gibco: 15140122), HBSS (Gibco: 14025076), HEPES (Gibco: 15630080), FLIPR calcium 6 assay kit (Molecular Devices: R8190), Probenecid (PBA) (Invitrogen: P36400), Acetylcholine chloride (Sigma: A6625-25G)

[0781] Complete culture medium: DMEM + 10% FBS + 1X P / S; cell seeding medium: DMEM + 10% FBS + 1X PS; experimental buffer 1: 1X HBSS + 20mM HEPES + 2.5mM Probenecid; experimental buffer 2: 1X HBSS + 20mM HEPES; cell lines: CHO-K1 / M1; CHO-K1 / M2 / Gα15; CHO-K1 / M3; CHO-K1 / M4 / Gα15; CHO-K1 / M5.

[0782] FLIPR calcium 6 assay kit: Dissolve Component A in assay buffer 1, shake for 1-2 minutes, and store in aliquots at -20°C.

[0783] 3. Experimental methods:

[0784] 1) CHO-K1 / M1; CHO-K1 / M2 / Gα15; CHO-K1 / M3; CHO-K1 / M4 / Gα15; and CHO-K1 / M5 cell lines were cultured separately in complete medium at 37°C, 5% CO2 until they reached 70%-90% confluency.

[0785] 2) The digested cells were resuspended in cell seeding medium, and 5,000 cells / well / 20 μL were seeded into a 384-well cell culture plate. The plates were cultured at 37° C. and 5% CO 2 for 24 hours.

[0786] 3) Take the cell culture plate out of the CO2 incubator and equilibrate at room temperature for 10 minutes.

[0787] 4) Remove Component A solution and equilibrate to room temperature. Add 20 μL of Component A solution to each well of the cell culture plate and incubate at room temperature in the dark for 1 hour.

[0788] 5) Prepare the muscarinic receptor agonist Acetylcholine chloride (ACh) (concentration: EC) using assay buffer 2.20 / EC 100 ), 30 μL of the prepared muscarinic receptor agonist was added to a 384-well agonist plate (PE: 6008590) using a Multidrop Combi; the positive control compound and the test compound working solution were diluted in a 3.16-fold gradient using a Dispendix pipetting workstation, and 450 nL was pipetted to a 384-well compound plate (PE: 6008590); 30 μL of assay buffer 2 was added to a 384-well compound plate (PE: 6008590) using a Multidrop Combi, the positive control compound and the test compound were diluted to 6X, the mixture was shaken and incubated at room temperature for use.

[0789] 6) Add 10 μL of the diluted 6X compound to the experimental wells of the corresponding 384-well cell plate using the FLIPR Penta and incubate for two minutes.

[0790] 7) Add 10 μL of the prepared muscarinic receptor agonist to the experimental wells of the corresponding 384-well cell plate using the FLIPR Penta and read and collect data simultaneously.

[0791] 4. Experimental data processing method:

[0792] FLIPR Penta reads and collects the fluorescence signal value (RFU), takes the maximum RFU value, and calculates the fluorescence intensity of the sample according to the low control (DMSO control group) and the high control (ACh EC 100 ) experimental group readings, calculate the percentage activation data {% activation rate = (RFUsample-RFUlow control) / (RFUhigh control-RFUlow control) × 100}, the concentration of the test compound after the reaction system was diluted 3.16 times to 11 concentrations ranging from 30 μM to 0.095 nM, use XLFit to fit the percentage activation rate and 11 point concentration data to the parametric nonlinear logic formula to calculate the compound EC 50 value

[0793] 5. Experimental results:

[0794] The results showed that the compound of the present invention showed good synergistic effect in the calcium flux effect experiment in cells stably expressing M4 receptors, and had no activity on the target M2. 50 Reaching above 30uM, it has better selectivity for M4.

[0795] Pharmacokinetics in Balb / c mice

[0796] 1. Research objectives:

[0797] Balb / c mice were used as test animals to study the pharmacokinetic behavior of the example compounds in plasma and brain of mice after oral administration at a dose of 5 mg / kg.

[0798] 2. Experimental Plan

[0799] 2.1 Test drugs: Compounds of the present invention, homemade.

[0800] 2.2 Experimental animals: Balb / c mouse, male.

[0801] 2.3 Administration:

[0802] Twenty-four male Balb / c mice were fasted overnight and administered orally at a dose of 5 mg / kg in a volume of 10 mL / kg.

[0803] 2.4 Drug preparation:

[0804] Oral administration drug preparation: 0.5% CMC-Na (1% Tween 80)

[0805] Weigh 0.50 g of sodium carboxymethyl cellulose (CMC-Na, viscosity: 800-1200 cps), dissolve it in 99 mL of purified water, add 1 ml of Tween 80, and mix and stir to form a clear solution.

[0806] The example compound was weighed and added to a 4-mL glass bottle, 2.4 mL of the solution was added, and ultrasonication was performed for 10 minutes to obtain a uniform suspension solution with a concentration of 0.5 mg / mL.

[0807] 2.5 Sample collection:

[0808] After the experimental animals were euthanized with CO2, blood and brain tissue were collected from the heart at 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h after administration. The blood was placed in EDTA-2K tubes and centrifuged at 6000 rpm at 4°C for 6 min to separate the plasma. The brain tissue was rinsed with pre-cooled PBS, wiped dry, weighed, and stored at -80°C. Food was consumed 4 h after administration.

[0809] 2.6 Sample processing:

[0810] 1) 40 μL of plasma sample was added to 160 μL of acetonitrile for precipitation. After mixing, the mixture was centrifuged at 3500×g for 5-20 minutes. The brain tissue was diluted and homogenized by centrifugation.

[0811] 2) Take 100 μL of the supernatant solution after treatment and perform LC / MS / MS analysis to determine the concentration of the test compound.

[0812] 2.7 Liquid phase analysis

[0813] Liquid phase conditions: Shimadzu LC-20AD pump

[0814] ●Mass spectrometry conditions: AB Sciex API 4000 mass spectrometer

[0815] ●Chromatographic column: phenomenex Gemiu 5um C18 50×4.6mm

[0816] ●Mobile phase: Liquid A is 0.1% formic acid aqueous solution, Liquid B is acetonitrile

[0817] Flow rate: 0.8 mL / min

[0818] Elution time: 0-4.0 minutes, eluent is as follows:

[0819] 3. Test results and analysis

[0820] The main pharmacokinetic parameters were calculated using WinNonlin 8.1. The results of the mouse pharmacokinetic experiment are shown in the following table.

[0821] 4. Experimental conclusions:

[0822] The data in the table show that in the mouse pharmacokinetic evaluation experiment, the example compounds of the present invention showed a higher exposure after oral administration.

[0823] 3. Pharmacokinetics in SD rats

[0824] 1. Research objectives:

[0825] SD rats were used as test animals to study the pharmacokinetic behavior of compound examples in plasma and brain in rats after oral administration at a dose of 5 mg / kg.

[0826] 2. Experimental Plan

[0827] 2.1 Test drug: Example of the present invention, homemade.

[0828] 2.2 Experimental animals: SD rats, male.

[0829] 2.3 Administration:

[0830] 24 male SD rats were fasted overnight and administered orally at a dose of 5 mg / kg in a volume of 10 mL / kg.

[0831] 2.4 Drug preparation:

[0832] Oral administration drug preparation: 0.5% CMC-Na (1% Tween 80)

[0833] Weigh 0.50 g of sodium carboxymethyl cellulose (CMC-Na, viscosity: 800-1200 cps), dissolve it in 99 mL of purified water, add 1 ml of Tween 80, and mix and stir to form a clear solution.

[0834] The example was weighed and added to a 100 mL glass bottle, 80 mL of the solution was added, and ultrasonication was performed for 10 minutes to obtain a uniform suspension solution with a concentration of 0.5 mg / mL.

[0835] 2.5 Sample collection:

[0836] After the experimental animals were euthanized with CO2, blood and brain tissue were collected from the heart at 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h after administration. The blood was placed in EDTA-2K tubes and centrifuged at 6000 rpm at 4°C for 6 min to separate the plasma. The brain tissue was rinsed with pre-cooled PBS, wiped dry, weighed, and stored at -80°C. Food was consumed 4 h after administration.

[0837] 2.6 Sample processing:

[0838] 3) 40 μL of plasma sample was added to 160 μL of acetonitrile for precipitation, and the mixture was centrifuged at 3500 × g for 5-20 minutes. The brain tissue was diluted and homogenized by centrifugation.

[0839] 4) Take 100 μL of the supernatant solution after treatment and perform LC / MS / MS analysis to determine the concentration of the test compound.

[0840] 2.7 Liquid phase analysis

[0841] Liquid phase conditions: Shimadzu LC-20AD pump

[0842] ●Mass spectrometry conditions: AB Sciex API 4000 mass spectrometer

[0843] ●Chromatographic column: phenomenex Gemiu 5um C18 50×4.6mm

[0844] ●Mobile phase: Liquid A is 0.1% formic acid aqueous solution, Liquid B is acetonitrile

[0845] Flow rate: 0.8 mL / min

[0846] Elution time: 0-4.0 minutes, eluent is as follows:

[0847] 3. Test results and analysis

[0848] The main pharmacokinetic parameters were calculated using WinNonlin 8.1. The results of the rat pharmacokinetic experiment are shown in the following table:

[0849] 4. Experimental conclusions:

[0850] The above results show that in the pharmacokinetic evaluation experiment in rats, the example compounds of the present invention showed higher exposure after oral administration, and the drug plasma protein free rate and brain exposure were higher. The drug plasma protein free rate can reach more than 8 times, or even more than 20 times, and the ratio of total compound concentration in the brain to total compound concentration in plasma can reach more than 0.2, or even more than 0.3.

Claims

1. A compound represented by general formula (II-B), (II-C), (II-D) or (II-E), a stereoisomer thereof or a pharmaceutically acceptable salt thereof: in: is a single bond or a double bond; X1 is independently selected from a bond, C, CR 11 , CR 11 R 22 or N; X2 is each independently selected from a bond, C, CR 22 , CR 11 R 22 or N; X3 is each independently selected from a bond, C, CR 33 , CR 11 R 22 or N; X4 is independently selected from a bond, C, CR 44 , CR 11 R 22 or N; L4 or L5 are each independently selected from a bond, C(R5R6), N(R5), O or S; X5 are each independently selected from CR 55 or N; M1, M2, M3 or M4 are each independently selected from C or N; When M1, M2, M3 or M4 is N, R7, R8, R9 or R 10 does not exist; R 11 , R 22 , R 33 or R 44 each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents of deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; Ring B or Ring C is present or absent, and when present, each is independently selected from cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; At least one of ring B and ring C exists; Ring F or ring G is independently selected from cycloalkyl, heterocyclic group, aryl or heteroaryl, and the cycloalkyl, heterocyclic group, aryl or heteroaryl may be further R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents; R1, R2, R3, R4, R5 or R6 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents of deuterium, oxo, thioxo, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl or cyano-substituted alkyl; Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form a cycloalkyl or heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally substituted with one or more substituents selected from deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl; R 55 , R7, R8, R9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, deuterated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 , -OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32 -、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; R 31 , R 32 , R 33 , R aa , R bb or R cc each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents of deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; m1 is each independently 0, 1 or 2; n1 is each independently 0, 1 or 2.

2. The compound according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is further represented by the general formula (II-A-1), (II-A-2), (II-A-3), (II) or (II-1): in: is a single bond or a double bond; X1 is independently selected from a bond, C, CR 11 , CR 11 R 22 or N; X2 is each independently selected from a bond, C, CR 22 , CR 11 R 22 or N; X3 is each independently selected from a bond, C, CR 33 , CR 11 R 22 or N; X4 is independently selected from a bond, C, CR 44 , CR 11 R 22 or N; X5 are each independently selected from CR 55 or N; M1, M2, M3 or M4 are each independently selected from C or N; When M1, M2, M3 or M4 is N, R7, R8, R9 or R 10 does not exist; X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 , (CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 , (CR 66 ) n2 , N or O; L4 or L5 are each independently selected from a bond, C(R5R6), N(R5), O or S; R 11 , R 22 , R 33 , R 44 , R 66 , R 77 , R 88 R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 is substituted with one or more substituents of a deuterated alkyl group; Ring F is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; Ring G is independently selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-14-membered heteroaryl, optionally further R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents; Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form a C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, the C 3-12 Cycloalkyl or 3-12 membered heterocyclic group, optionally substituted by deuterium, oxo, thio, 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 Haloalkyl, C 1- 6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 aryl or 5-12 membered heteroaryl is substituted with one or more substituents; R 55 , R7, R8, R9, R 10 or R 12 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 membered heteroaryl, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 , -OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally substituted by 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 aryl or 5-12 membered heteroaryl is substituted with one or more substituents; R 31 , R 32 , R 33 , R aa , R bb or R cc 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, halogenated, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1- 6-Hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 aryl or 5-12 membered heteroaryl is substituted with one or more substituents; m1 is each independently 0, 1 or 2; n1 is each independently 0, 1 or 2; and n2 is each independently 1 or 2.

3. The compound according to claim 1 or 2, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is not of the following structure:

4. The compound according to claim 2, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is further represented by general formula (II-B-1), (II-B-2) or (II-B-5): X1 is independently selected from a bond, C, CR 11 or N; X2 is each independently selected from a bond, C, CR 22 or N; X3 is each independently selected from a bond, C, CR 33 or N; X4 is each independently selected from a bond, C, CR 44 or N.

5. The compound according to claim 4, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is further represented by the general formula (II-A-a2), (II-A-a3), (II-A-a4), (II-A-a5), (II-A-a6), (II-A-a7), (II-A-a8) or (II-A-a9):

6. The compound according to claim 4, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is further represented by the general formula (II-A-a1), (II-B-a1), (II-B-a2), (II-B-a3), (II-B-a4), (II-B-a5), (II-B-a6), (II-B-a7), (II-B-a8), (II-B-a9) or (II-B-a10): Ring F is independently selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; Ring G is independently selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally further substituted by R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents.

7. The compound according to claim 6, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is further represented by the general formula (II-B-3), (II-B-4), (II-6), (II-7), (II-8), (II-9), (II-10), (II-11), (II-12), (II-13), (II-14), (II-15), (II-16), (II-17) or (II-18): in: X1 is independently selected from C, CR 11 or N; X2 is independently selected from C, CR 22 or N; X3 are each independently selected from CR 33 or N; X4 is each independently selected from CR 44 or N; X5 is each independently selected from CR 55 or N; X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 , (CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 , (CR 66 ) n2 , N or O; L4 is each independently selected from a bond, C(R5R6), N(R5), O or S; R 11 , R 22 , R 33 , R 44 , R 66 , R 77 , R 88 R1, R2, R3, R4, R5 or R6 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 is substituted with one or more substituents of a deuterated alkyl group; Alternatively, R1 and R2, R3 and R4, or R5 and R6 are linked to the connected carbon atoms to form a C 3-10 Cycloalkyl or 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl or 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S; R 55 , R7, R8, R9 or R 10 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 , -OCR 31 R 32 R 33 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 R 32 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S; R 31 , R 32 , R 33 , R aa , R bb or R cc 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S; m1 are each independently selected from 0, 1 or 2; and n1 is independently selected from 0, 1 or 2.

8. The compound according to claim 7, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is further represented by the general formula (II-1b), (II-2b), (II-3b), (II-4b), (II-5b), (II-6b), (II-7b), (II-8b), (II-9b), (II-10b), (II-11b), (II-12b), (II-13b), (II-14b), (II-15b), (II-16b), (II-17b), (II-18b) or (II-19b):

9. The compound according to any one of claims 1 to 7, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 11 , R 22 , R 33 or R 44 are each independently 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1- 3-Hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 is substituted with one or more substituents of a deuterated alkyl group; Preferably, R 11 , R 22 , R 33 or R 44 Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl is optionally deuterated by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 The deuterated alkyl group is substituted with one or more substituents.

10. The compound according to any one of claims 1 to 8, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 55 or R8 are each independently 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl, 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, -O(CR aa R bb ) n1 R 31 、-N(CR aa R bb ) n1 R 31 、-S(CR aa R bb ) n1 R 31 、-(CR aa R bb ) n1 C(O)R 31 、N=S=OR 31 R 32 、-(CH2) n1 C(O)NR 31 R 32 、-(CH2) n1 P(O)R 31 R 32 、-(CH2) n1 P(O)2R 31 、-(CR aa R bb ) n1 (NR 31 )C(O)R 32 、-(CR aa R bb ) n1 C(O)NR 31 R 32 、-(CR aa R bb ) n1 (NR 31 )S(O) m1 R 32 、-(CR aa R bb ) n1 S(O) m1 NR 31 R 32 、-(CR aa R bb ) n1 S(O)(=NR cc )R 32 or -(CR aa R bb ) n1 S(O) m1 R 32 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S; R 31 , R 32 or R 33 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 is substituted with one or more substituents of a deuterated alkyl group; Preferably, R 31 , R 32 or R 33 each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy, the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy or propoxy, optionally deuterated, hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 is substituted with one or more substituents of a deuterated alkyl group; R aa , R bb or R cc are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, the amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 Alkyl, optionally deuterated, hydroxy, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 is substituted with one or more substituents of a deuterated alkyl group; Preferably, R aa , R bb or R cc Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

11. The compound according to any one of claims 1 to 8, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R1, R2, R3, R4, R5 or R6 are each independently 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 is substituted with one or more substituents of a deuterated alkyl group; Preferably, R1, R2, R3, R4, R5 or R6 are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy; Alternatively, R1 and R2, R3 and R4, R5 and R6 are linked to the connected carbon atoms to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S; Preferably, R1 and R2, R3 and R4, R5 and R6 are linked to the connected carbon atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, oxo, thio, 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, R1 and R2, R3 and R4, R5 and R6 are linked to the connected carbon atoms to form a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group.

12. The compound according to any one of claims 1 to 8, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R7, R9 or R 10 are each independently 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S; Preferably, R7, R9 or R 10 are each independently 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, R7, R9 or R 10 Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, vinyl, allyl, propenyl, ethynyl, propynyl, propargyl, deuterated methyl, deuterated ethyl, deuterated propyl, fluoromethyl, fluoroethyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, propoxy, fluorine-substituted methoxy, fluorine-substituted ethoxy, trifluoromethoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, 2-hydroxypropyl, cyano-substituted methyl, cyano-substituted ethyl, cyano-substituted propyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

13. The compound according to any one of claims 3 to 8, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 12 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S; Preferably, R 12 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or 5-8 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, R 12 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, vinyl, allyl, propenyl, ethynyl, propynyl, propargyl, deuterated methyl, deuterated ethyl, deuterated propyl, fluoromethyl, fluoroethyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, propoxy, fluorinated methoxy, fluorinated ethoxy, trifluoromethoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, 2-hydroxypropyl, cyano-substituted methyl, cyano-substituted ethyl, cyano-substituted propyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

14. The compound according to any one of claims 1 to 3, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; Preferably, ring B is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or phenyl, optionally substituted with one or more of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl; More preferably, ring B is selected from optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl; Indicates the site of attachment to the fused ring.

15. The compound according to any one of claims 1 to 3, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Ring C is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; Preferably, ring C is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring C is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl.

16. The compound according to any one of claims 2 to 7, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 66 , R 77 or R 88 are each independently 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 is substituted with one or more substituents of a deuterated alkyl group; Preferably, R 66 , R 77 or R 88 Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl is optionally deuterated by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 The deuterated alkyl group is substituted with one or more substituents.

17. The compound according to any one of claims 1 to 4 or 6, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Ring F is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; Preferably, ring F is selected from C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Cycloalkyl, 5-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by deuterium, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl or cyano substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring F is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl; Further preferably, ring F is selected from optionally substituted with one or more substituents of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl or trifluoroethyl; It indicates the site connected to L4 or L5. When L4 or L5 is a bond, it indicates the site connected to the carbonyl group or ring G.

18. The compound according to any one of claims 1 to 4 or 6, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Ring G is selected from C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally substituted by R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents; Preferably, ring G is selected from C 3-8 Cycloalkyl, 5-6 membered monocyclic heterocyclic group containing 1-3 N, O or S atoms, 6-10 membered fused ring heterocyclic group containing 1-3 N, O or S atoms, 5-10 membered spirocyclic heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl, 5-6 membered monocyclic heteroaryl containing 1-3 N, O or S atoms, or 8-10 membered fused ring heteroaryl containing 1-3 N, O or S atoms, optionally substituted by R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents; More preferably, ring G is selected from benzene ring, naphthalene ring, pyridine, Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents; More preferably, ring G is selected from Optionally R 55 , R7, R8, R9 or R 10 is substituted with one or more substituents; It indicates the site connected to L5. When L5 is a bond, it indicates the site connected to ring F. When ring F does not exist, it indicates the site connected to L4. When L4 is a bond, it indicates the site connected to C(O).

19. The compound according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, wherein: The compound structure is as follows:

20. A method for preparing the compound represented by general formula (II-A-a4) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, comprising the following steps: The compound of general formula (III), its stereoisomer or a pharmaceutically acceptable salt thereof, reacts with the compound of general formula (III-A) to obtain the compound of general formula (II-A-a4); Preferably, the reaction is carried out in a condensation reagent, and the condensation reagent is preferably 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate, 1-propylphosphoric anhydride, O-(benzotriazole-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, N,N'-carbonyldiimidazole, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1H-benzotriazole-1-yloxytripyrrolidino hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, (2-oximino-ethyl cyanoacetate)-N,N-dimethyl 2-(4-(6-dimethoxy-1-yl)-4-methylmorpholine)-1,2-dihydroquinoline, 2-(4,6-dimethoxy-1-yl)-4-methylmorpholine hydrochloride, 2-(4,6-dimethoxy-1-yl)-4-methyl-1,2-dihydroquinoline, 2-(4,6-dimethoxy-1,3,5-triazine, 2-oxime ethyl cyanoacetate, 2-(2-(4-(6-dimethoxy-1-yl)-4-methyl-1,2-dihydroquinoline)-1,2-dihydroquinoline, 2-(4,6-dimethoxy-1,3,5-triazine ... More preferably, the reaction is carried out in a base, and the base is preferably diisopropylethylamine, N-methylmorpholine, N-methylimidazole, 4-dimethylaminopyridine, 2,6-lutidine, potassium carbonate, potassium tert-butoxide, sodium tert-butoxide, 1,8-diazabicyclo[5.4.0]undec-7-ene, trimethylamine, triethylamine, pyridine, piperidine, morpholine, diisopropyllithium amide, diethyllithium amide, bis(trimethylsilyl)amide, isopropylcyclohexyllithium amide, LiHMDS, potassium phosphate, potassium phosphate trihydrate, potassium phosphate dihydrate, potassium phosphate monohydrate, potassium acetate, sodium acetate, sodium bicarbonate, potassium bicarbonate, sodium carbonate, cesium carbonate, potassium hydroxide, sodium hydroxide, potassium hydride, sodium hydride, lithium hydroxide or 2-tert-butyl-1,1,3,3-tetramethylguanidine and mixtures thereof.

21. A compound represented by general formula (III), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, in, is a single bond or a double bond; X1 is independently selected from a bond, C, CR 11 or N; X2 is each independently selected from a bond, C, CR 22 or N; X3 is each independently selected from a bond, C, CR 33 or N; X4 is each independently selected from a bond, C, CR 44 or N; X6, X7 or X8 are each independently selected from (CR 66 R 77 ) n2 NR 88 , (CR 66 R 77 ) n2 NR 88 NR 88 (CR 66 R 77 ) n2 , (CR 66 ) n2 , N or O; R L1 is selected from hydrogen, deuterium or an amino protecting group; R 11 , R 22 , R 33 , R 44 , R 66 , R 77 , R 88 R1, R2, R3 or R4 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl are optionally substituted with one or more substituents of deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; n2 is 1 or 2.

22. The compound according to claim 21, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is further represented by general formula (III-1), (III-2), (III-3), (III-4) or (III-5): R L1 is selected from hydrogen, deuterium or an amino protecting group, wherein the amino protecting group is selected from a benzyl protecting group, a carboxylate protecting group, an acyl protecting group or a silyl protecting group; Preferably, the benzyl protecting group is selected from benzyl, 4-methoxybenzyl, 2,4-dimethoxybenzyl, 3,4-dimethoxybenzyl, 3-methoxybenzyl, 3,5-dimethoxybenzyl or 2,4,6-trimethoxybenzyl; the carboxylate protecting group is selected from allyloxycarbonyl, tert-butyloxycarbonyl, benzyloxycarbonyl, trimethylsilylethoxycarbonyl, trichloroethoxycarbonyl, 9-fluorenylmethoxycarbonyl, methoxycarbonyl or ethoxycarbonyl; the acyl protecting group is selected from acetyl, benzoyl, p-methoxybenzylcarbonyl, acetyl, toluenesulfonyl, p-nitrobenzenesulfonyl, phthaloyl, p-toluenesulfonyl or trifluoroacetyl; the silyl protecting group is selected from tert-butyldimethylsilyl or (trimethylsilyl)ethoxymethyl; R 11 , R 22 , R 33 , R 44 , R 66 , R 77 , R 88 R1, R2, R3 or R4 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 is substituted with one or more substituents of a deuterated alkyl group; Preferably, R 11 , R 22 , R 33 , R 44 , R 66 , R 77 , R 88 R1, R2, R3 or R4 are each independently 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 haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 is substituted with one or more substituents of a deuterated alkyl group; More preferably, R 11 , R 22 , R 33 , R 44 , R 66 , R 77 or R 88 Each of the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, oxirane, epoxypropyl or epoxybutyl is optionally deuterated by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 is substituted with one or more substituents of a deuterated alkyl group; R1, R2, R3 or R4 are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy or propoxy.

23. A method for preparing the compound of formula (III-1) according to claim 22, its stereoisomer or a pharmaceutically acceptable salt thereof, comprising the following steps: The compound of general formula (III-B), its stereoisomer or a pharmaceutically acceptable salt thereof is prepared by cyclization to obtain the compound of general formula (III-1); Preferably, the reaction is carried out in a cyclization reagent, and the cyclization reagent is preferably trifluoroacetic anhydride, p-toluenesulfonyl chloride, methanesulfonyl chloride, p-trifluoromethylbenzenesulfonyl chloride, 1-propylphosphoric anhydride, acetic anhydride, polyphosphoric acid, Eaton's reagent or boron trifluoride ether complex; Alternatively, a method for preparing the compound of formula (III-3), its stereoisomer or a pharmaceutically acceptable salt thereof comprises the following steps: The compound of general formula (III-D), its stereoisomer or a pharmaceutically acceptable salt thereof is reacted to obtain the compound of general formula (III-3); Optionally, the preparation method of the compound of formula (III-B), its stereoisomer or its pharmaceutically acceptable salt is as follows: The compound of general formula (III-C), its stereoisomer or a pharmaceutically acceptable salt thereof is reacted to obtain the compound of general formula (III-B); R L2 or R L3 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 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, cyano substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally deuterated, hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 is substituted with one or more substituents of a deuterated alkyl group; Preferably, R L2 or R L3 are each independently 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 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 aryl or a 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, cyano substituted C 1-3 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 atoms selected from N, O or S, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S, optionally substituted by deuterium, hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 The deuterated alkyl group is substituted with one or more substituents.

24. The compound according to claim 21 or 22, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound structure is as follows:

25. A pharmaceutical composition comprising a therapeutically effective dose of a compound according to any one of claims 1 to 19, a stereoisomer thereof or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.

26. Use of a compound according to any one of claims 1 to 19, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 25 in the preparation of a medicament for treating an M4-related disease, wherein the M4-related disease is preferably selected from Alzheimer's disease, schizophrenia or psychosis, pain, addiction, sleep disorders, cognitive disorders, Parkinson's disease or conditions, Parkinson's disease-levodopa-induced movement disorders, Huntington's disease, dry mouth, pulmonary hypertension, chronic obstructive pulmonary disease, asthma, urinary incontinence, glaucoma, Down syndrome, cerebral amyloid angiopathy, dementia, hereditary Dutch amyloidosis cerebral hemorrhage, Creutzfeldt-Jakob disease, prion disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, head trauma, stroke, pancreatitis, inclusion body myositis, other peripheral amyloidosis, diabetes, autism and atherosclerosis, more preferably Alzheimer's disease, schizophrenia, pain, addiction and sleep disorders.

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