Nitrogen-containing heterocyclic derivative modulator, preparation method therefor and use thereof

Abstract

The present invention relates to a nitrogen-containing heterocyclic derivative modulator, a preparation method therefor and the use thereof. The present invention specifically relates to a nitrogen-containing heterocyclic compound, a preparation method therefor, a pharmaceutical composition containing the compound, and the use thereof in the treatment of central nervous system diseases.

Description

Nitrogen heterocyclic derivative modifiers, their preparation methods and applications Technical Field

[0001] This invention belongs to the field of drug synthesis, specifically relating to a nitrogen heterocyclic derivative modifier, its preparation method, and its application. Background Technology

[0002] Dopamine (DA) is one of the major neurotransmitters in the nervous system. It exerts numerous important physiological functions by binding to dopamine receptors, including regulating learning, memory, and cognition, modulating mood, and controlling movement. Dopamine receptors belong to the G protein-coupled receptor (GPCR) superfamily, which includes D1-like receptors (D1Rs) and D2-like receptors (D2Rs). D1-like receptors consist of D1 and D5 receptors, which are co-expressed in the striatum, cortex, hippocampus, thalamus, and hindbrain. Specifically, D1 receptors are mainly distributed in the striatum, while D5 receptors are mainly distributed in the cortex / hippocampus. Pharmacological studies have reported that D1-like receptors couple with activating G proteins (Gs) to stimulate cAMP production. D2-like receptors, including D2, D3, and D4 receptors, exert their biological functions by activating inhibitory G proteins (Gi).

[0003] Dopamine D1 receptors are involved in many neuropharmacological and neurobiological functions. For example, D1 receptors are involved in synaptic plasticity, basal ganglia-mediated motor control, motor formation, top-down executive control, learning, and memory. D1 receptors are associated with a wide range of mental, neurological, neurodevelopmental, neurodegenerative, emotional, motivational, metabolic, cardiovascular, renal, ophthalmic, and endocrine disorders, including schizophrenia, cognitive impairment, ADHD, autism spectrum disorder, mild cognitive impairment, age-related cognitive decline, Alzheimer's disease, Parkinson's disease (PD), Huntington's disease, depression, anxiety, treatment-resistant depression, bipolar disorder, chronic apathy, anhedonia, chronic fatigue, post-traumatic stress disorder, seasonal affective disorder, social anxiety disorder, postpartum depression, serotonin syndrome, substance abuse and dependence, Tourette syndrome, tardive dyskinesia, somnolence, sexual dysfunction, migraine, systemic lupus erythematosus, hyperglycemia, hyperlipidemia in mammals, obesity, diabetes, sepsis, ischemic tubular necrosis, renal failure, refractory edema, somnolence, hypertension, congestive heart failure, postoperative hypotonia, sleep disorders, pain, and other conditions.

[0004] There are five dopamine pathways in the brain: (1) substantia nigra-striatal dopamine pathway; (2) mesolimbic dopamine pathway; (3) mesocortical dopamine pathway; (4) tuberoinfundibular dopamine pathway; and (5) thalamic dopamine pathway. The substantia nigra-striatal dopamine pathway is divided into the direct (go) dopamine pathway and the indirect (stop) dopamine pathway. Activation of D1 receptors stimulates the go pathway, while activation of D2-like receptors inhibits the stop pathway; both pathways work together to promote motor function. Parkinson's disease (PD) can be attributed to the selective loss of dopamine neurons in the substantia nigra. Clinical symptoms include motor disorders (including bradykinesia, rigidity, tremor, freezing, muscle spasms, and dystonia) and non-motor symptoms such as depression, cognitive impairment, and psychosis. As the disease progresses, motor function gradually deteriorates, leading to disability and a decline in quality of life. The prevalence of PD in people over 60 years of age in China is 1.37% (1.02%–1.73%). It is estimated that there are approximately 3.62 million PD patients in China. By 2030, the number of Parkinson's disease (PD) patients in China is projected to reach 4.94 million, accounting for half of the global PD population. Currently, the main clinical strategy for treating motor dysfunction in PD patients is the use of dopaminergic drugs, especially levodopa (a precursor to dopamine DA). These drugs can initially control motor symptoms, but long-term use leads to decreased efficacy and an increase in motor and non-motor complications. D2-like receptor agonists cause adverse reactions such as sleep disturbances, limiting their widespread use. In China, 83% of PD patients desire new treatment options, representing a significant market demand. Therefore, there is a need to develop drugs that modulate D1-like receptors to treat related diseases.

[0005] Currently, there are no marketed drugs that directly activate D1-like receptors. Full activation of D1-like receptors has been explored in small, early-stage clinical studies, validating the link between this target and Parkinson's disease (PD). However, cardiovascular side effects led to the termination of these studies, and the drugs exhibited dyskinesia symptoms similar to those experienced with levodopa. This may be related to striatal dysfunction and sensitization caused by repeated dopamine stimulation. Therefore, the main challenge in current research and development is controlling the degree of D1-like receptor activation. Clinical trials have demonstrated the efficacy of developing partial D1 agonists for the treatment of PD and other indications; for example, Tavapadon is currently in Phase III clinical trials. This patent aims to develop partial D1 and D5 agonists primarily for the treatment of movement disorders in PD patients. Summary of the Invention

[0006] The object of this invention is to provide a compound represented by general formula (IA) or (IE), its stereoisomers, or a pharmaceutically acceptable salt thereof, wherein the compound represented by general formula (IA) or (IE) has the following structure:

[0007] in:

[0008] M1 is selected from CR 1d R 1eor NR 1e ;

[0009] M2 is selected from O, S, NR 3a NOR 3b NC(O)R 3c NC(O)OR 3b NS(O)R 3c NS(O)2R 3c or NP(O)R 3b R 3c Preferred from O, S, NR 3a NOR 3b or NC(O)R 3c ;

[0010] M3 is selected from O, S, NR 3a NOR 3b NC(O)R 3c NC(O)OR 3b NS(O)R 3c NS(O)2R 3c or NP(O)R 3b R 3c Preferred from O, S, NR 3a NOR 3b or NC(O)R 3c ;

[0011] M 10 Selected from O or S;

[0012] L1 is selected from the bond, -(CH2). n1 O(CH2) n2 -、-(CH2) n1 C(O)(CH2) n2 -、-(CH2) n1 C(S)(CH2) n2 -、-(CH2) n1 NR N (CH2) n2 -、-(CH2) n1 S(CH2) n2 -、-(CH2) n1 S(O)(CH2) n2 -、-(CH2) n1 S(O)2(CH2) n2 -、-(CH2) n1 CONR N (CH2) n2 -、-(CH2) n1 S(O)2NR N (CH2) n2-、C 1-6 Alkylene, C 1-6 imidene group, C 1-6 Ethyne group, C 3-12 Cycloalkylene or 3-12 membered heterocyclic alkylene groups, wherein the -(CH2) group... n1 O(CH2) n2 -、-(CH2) n1 C(O)(CH2) n2 -、-(CH2) n1 C(S)(CH2) n2 -、-(CH2) n1 NR N (CH2) n2 -、-(CH2) n1 S(CH2) n2 -、-(CH2) n1 S(O)(CH2) n2 -、-(CH2) n1 S(O)2(CH2) n2 -、-(CH2) n1 CONR N (CH2) n2 -、-(CH2) n1 S(O)2NR N (CH2) n2 -、C 1-6 Alkylene, C 1-6 imidene group, C 1-6 Ethyne group, C 3-12 Cycloalkylene and 3-12 membered heterocyclic groups, optionally further modified by hydrogen, deuterium, halogen, substituted or unsubstituted amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0013] Ring A is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C6-14 Aryl or 5-14 heteroaryl groups;

[0014] R 1a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NRaa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0015] R 1b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0016] Or, R 1b With R a It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0017] R1d Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NRbb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0018] R 1e It is absent or selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1- 6-Deuterated Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0019] Or, R 1d With R 1e It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0020] R2 is selected from C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc=N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3- 12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 heteroaryl groups, optionally further divided by 1, 2, 3, 4, 5 or 6 R groups. b Substituents;

[0021] R 3a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0022] R 3b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0023] R 3c Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0024] R a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2)n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 Rff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0025] Or, any two R a It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0026] R b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2)n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee-(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m2 R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0027] R N Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0028] R aa Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0029] R bb Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0030] R cc Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0031] Or, R aa R bb With R cc Any two atoms in a given matrix can form a carbon atom with their adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1- 6-Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0032] R dd Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0033] R ee Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0034] R ff Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C.1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0035] Or, R dd R ee With R ff Any two atoms in a given matrix can form a carbon atom with their adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1- 6-Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0036] The substituents in the general formula (IA) can also be -SF5; the preferred substituents are R. 1b R 1c R 1d R 1e R a or R b ;

[0037] x is an integer of 0, 1, 2, 3, 4, 5 or 6; m1 is 0, 1 or 2; m2 is 0, 1 or 2; n1 is 0, 1, 2 or 3; n2 is 0, 1, 2 or 3; n3 is 0, 1, 2 or 3; and n4 is 0, 1, 2 or 3.

[0038] Another object of the present invention is to provide a compound of general formula (A), (A-1) or (A-2), its stereoisomer or a pharmaceutically acceptable salt thereof, wherein the compound of general formula (A), (A-1) or (A-2) has the following structure:

[0039] M5 is selected from CR 4b Or N;

[0040] L1 is selected from the bond, -(CH2). n1 O(CH2) n2 -、-(CH2) n1 C(O)(CH2) n2 -、-(CH2) n1 C(S)(CH2) n2 -、-(CH2) n1 NR N (CH2) n2 -、-(CH2) n1 S(CH2) n2 -、-(CH2) n1 S(O)(CH2) n2 -、-(CH2) n1 S(O)2(CH2) n2 -、-(CH2) n1 CONR N (CH2) n2 -、-(CH2) n1 S(O)2NR N (CH2) n2 -、C 1-6 Alkylene, C 1-6 imidene group, C 1-6 Ethyne group, C 3-12 Cycloalkylene or 3-12 membered heterocyclic alkylene groups, wherein the -(CH2) group... n1 O(CH2) n2 -、-(CH2) n1 C(O)(CH2) n2 -、-(CH2) n1 C(S)(CH2) n2 -、-(CH2) n1 NR N (CH2) n2 -、-(CH2) n1 S(CH2)n2 -、-(CH2) n1 S(O)(CH2) n2 -、-(CH2) n1 S(O)2(CH2) n2 -、-(CH2) n1 CONR N (CH2) n2 -、-(CH2) n1 S(O)2NR N (CH2) n2 -、C 1-6 Alkylene, C 1-6 imidene group, C 1-6 Ethyne group, C 3-12 Cycloalkylene and 3-12 membered heterocyclic groups, optionally further modified by hydrogen, deuterium, halogen, substituted or unsubstituted amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0041] Ring A is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl groups;

[0042] Ring B is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl groups;

[0043] R 4a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0044] R 4b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0045] R 4c Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 Rcc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0046] R 4dSelected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bbC(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0047] Or, R 4a R 4b R 4c With R 4d Any substituent in the middle is linked with L1 to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0048] R 4f R 4g and R 4h Each is independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bbS(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0049] Ra Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NRee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0050] Or, any two R a It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0051] R c Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 C(O)NR dd OR ee -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR ee C(O)R ff-(CH2) n4 NR ee S(O) m2 R ff -(CH2) n4 N=S(O)R dd R ee -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m2 R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd-CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3- 12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0052] Or, any two R c It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0053] Or, R a With R c Forming C with adjacent atoms 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0054] R N Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0055] R aa Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0056] R bb Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0057] R cc Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0058] Or, R aa R bb With R cc Any two atoms in a given matrix can form a carbon atom with their adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1- 6-Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0059] R dd Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0060] R ee Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0061] R ff Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0062] Or, R dd R ee With R ff Any two atoms in a given matrix can form a carbon atom with their adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1- 6-Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0063] The substituents in general formulas (A), (A-1), and (A-2) can also be -SF5; the preferred substituent is R. 4a ~R 4h R a or R c ;

[0064] x is an integer of 0, 1, 2, 3, 4, 5 or 6; y is an integer of 0, 1, 2, 3, 4, 5 or 6; m1 is 0, 1 or 2; m2 is 0, 1 or 2; n1 is 0, 1, 2 or 3; n2 is 0, 1, 2 or 3.

[0065] In some embodiments of the present invention Central B is selected from C 5-8 Saturated or unsaturated monocyclic cycloalkyl groups, C 7-12 Polycyclic alkyl, C 7-12 Spirocycloalkyl, 5-8 member saturated or unsaturated monocyclic heterocyclic groups, 7-12 member fused heterocyclic groups, 7-12 member spirocyclic groups, C 6-10 Aryl or 5-10 heteroaryl groups;

[0066] Preferably, Selected from

[0067] M2 is selected from O, S, NR 3a NOR 3b or NC(O)R 3c ;

[0068] M3 is selected from O, S, NR 3a NOR 3b or NC(O)R 3c ;

[0069] M6 is selected from CR 5d R 5e or NR 5e ;

[0070] M7 is selected from CR 5f R 5g or NR 5g ;

[0071] R 3a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0072] R 3b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0073] R 3c Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0074] R 5a R 5b R 5c R 5d R 5e R 5f R 5g R 5h R 5i R 5j and R 5kEach is independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, and C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 C(O)NR dd OR ee -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m2 R ff -(CH2) n4 N=S(O)R dd R ee -OC(R) dd R ee ) m2 (CH2) n4 R dd -NRee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of aryl and substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m2 R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-ORee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0075] Or, R 5d and R 5e or R 5f and R 5g It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1- 6-Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0076] Or, R 5b and R a R 5c and R a R 5d and R a or R 5f and R a It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 It is substituted by one or more substituents in the aryl group and substituted or unsubstituted 5-14 heteroaryl groups.

[0077] In certain embodiments of the invention, the compound represented by the general formula, its stereoisomers, or its pharmaceutically acceptable salts are further represented as shown in general formula (AI) or (A-II):

[0078] Y1 is selected from NH, N, CH2, CH, C, C(O), O or S; preferably N, C or C(O);

[0079] Y2 is selected from NH, N, CH2, CH, C, C(O), O or S; preferably N, C or C(O);

[0080] Y3 is selected from NH, N, CH2, CH, C, C(O), O or S; preferably N, C or C(O);

[0081] Alternatively, Y1 and Y2 or Y2 and Y3 can form C with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0082] Ring E does not exist or is selected from C. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 In aryl or 5-14 heteroaryl groups;

[0083] R4 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, and C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa-(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bbC(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0084] Alternatively, any two R4 atoms can form C with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0085] p is selected from 0, 1, 2, 3, 4, 5 or 6.

[0086] In some embodiments of the present invention Central A is selected from C 5-8 Saturated or unsaturated monocyclic cycloalkyl groups, C 7-12 Polycyclic alkyl, C 7-12 Spirocycloalkyl, C 7-12 Bridged cycloalkyl groups, 5-8 membered saturated or unsaturated monocyclic heterocyclic groups, 7-12 membered fused heterocyclic groups, 7-12 membered spirocyclic groups, 7-12 membered bridged heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl groups;

[0087] Preferably, Selected from

[0088] More preferably, Selected from

[0089] X1 is selected from CR 6a R 6b or NR 6b X2 is selected from CR 6c R 6dor NR 6d X3 is selected from CR 6e R 6f or NR 6f X4 is selected from CR 6g R 6h or NR 6h X5 is selected from CR 7a Or N;

[0090] Ring C is selected from C 3-6 Cycloalkyl or 3-6 membered heterocyclic groups;

[0091] Ring D is selected from C 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl, or 5-6 membered heteroaryl; preferably C 3-6 Cycloalkyl or 3-6 membered heterocyclic groups;

[0092] R 6a R 6c R 6e or R 6g Each is independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, and C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2- 6-alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1- 6-Deuterated Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0093] R 6b R 6d R 6f or R 6hNot present or independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0094] Or, R 6a R 6b R 6c R 6d R 6e R 6f R 6g or R 6h Any two atoms in a given matrix can form a carbon atom with their adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0095] R 7a It is absent or selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1- 6-Deuterated Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 It is substituted by one or more substituents in the aryl group and substituted or unsubstituted 5-14 heteroaryl groups.

[0096] In certain embodiments of the invention, the compounds represented by the general formula, their stereoisomers, or pharmaceutically acceptable salts thereof are further represented as shown in general formulas (I-11), (I-12), (I-16), or (I-17):

[0097] In some embodiments of the present invention, R2 is selected from -C(O)R cc -C(O)OR cc -NR aa R bb -C(O)NR aa R bb C 3-8 Monocyclic cycloalkyl, C 7-12 Polycyclic alkyl, C 7-12 Spirocycloalkyl, C 7-12 Bridged cycloalkyl, 3-8 membered monocyclic heterocyclic group, 7-12 membered fused heterocyclic group, 7-12 membered spirocyclic group, 7-12 membered bridged heterocyclic group, C 6-10 Aryl or 5-10 quinone heteroaryl; C is preferred 3-8 Monocyclic cycloalkyl, C 7-12 Polycyclic alkyl, C 7-12 Spirocycloalkyl, C 7-12 Bridged cycloalkyl, 3-8 membered monocyclic heterocyclic group, 7-12 membered fused heterocyclic group, 7-12 membered spirocyclic group, 7-12 membered bridged heterocyclic group, C 6-10 Aryl or 5-10 heteroaryl groups;

[0098] More

[0099] Further optimization

[0100] Optimal Selection

[0101] M4 is selected from O, S, CH2, or NH; M5 is selected from CR. 4b Or N;

[0102] Ring G is selected from C 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl or 5-6 membered heteroaryl; preferably phenyl, pyridyl, furanyl, pyrroleyl, thiophenyl, pyrazolyl, imidazoleyl, oxazolyl, isoxazolyl, thiazolyl or isothiazolyl;

[0103] The ring H is selected from 3-12 membered heterocyclic groups or 5-14 membered heteroaryl groups;

[0104] R 4a R 4b R 4c R 4d R4e R 4f R 4g R 4h R 4i R 4j R 4k or R 4l Each is independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, and C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NRee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m2 R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3- 12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0105] Or, any two R 4a R 4b R 4c R 4d R 4e R 4f R 4g R 4h R 4i R 4j R 4k or R 4l It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0106] n5 is selected from 0, 1, or 2; y is selected from 0, 1, 2, 3, or 4; q is selected from 0, 1, 2, 3, or 4.

[0107] In certain embodiments of the invention, the compounds represented by the general formula, their stereoisomers, or pharmaceutically acceptable salts thereof are further represented as those of general formulas (A-II-1), (A-II-2), (A-II-3), (A-II-4), (A-II-5), (A-II-6), (A-II-7), (A-II-8), (A-II-9), (A-II-10), (A-II-11), (A-II-12), (A-II-13), (A-II-14), (A-II-15), (A-II-16), (A-II-17), (A-II-18), (A-II-21), or (A-II-22):

[0108] Preferably, as shown in general formulas (A-II-19), (A-II-20), (A-II-23), or (A-II-24):

[0109] More preferably, as shown in general formulas (A-II-19-A), (A-II-19-B), (A-II-20-A), or (A-II-20-B):

[0110] X6 is selected from N or CR 6c Y4 is selected from N, O, S, NR 4i or CR 4i Y5 is selected from N, O, S, NR 4j or CR 4j Y6 is selected from N, O, S, NR 4k or CR 4k Y7 is selected from N, O, S or CR 4l M8 is selected from CR 8a R 8b O, NR 8c S, C(O), CR8a =CR 8b or C(O)NR 8c ;

[0111] R 4i R 4j R 4k and R 4l Each is independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, and C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 Raa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0112] R8 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, and C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0113] R 8a R 8b or R 8c Each is independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, and C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0114] n8 is selected from 0, 1, or 2; n9 is selected from 0, 1, or 2.

[0115] In some embodiments of the present invention, L1 is selected from bond, -O-, -NR. N -, -S-, -S(O)-, -S(O)2-, -C(O), -CONR N –、-S(O)2NR N –、C 1-6 Alkylene, C 3-6 Cycloalkylene or 3-6 membered heterocyclic alkylene, wherein the C 1-6 Alkylene, C 3-6 Cycloalkylene and 3-6-membered heterocyclic groups may be further modified by hydrogen, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 It is substituted by one or more substituents in the aryl group and the 5-14 heteroaryl group.

[0116] In some embodiments of the present invention, R a R 6a R 6c R 6e or R 6g Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, -SF5, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy or C 3-8 cycloalkyl, the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups and C 3-8 Cycloalkyl groups, optionally further modified by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C2O groups. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 The aryl group is substituted with one or more substituents selected from aryl and 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, -SF5, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy or C 3-8 cycloalkyl;

[0117] More preferably, R a R 6a R 6c R 6e or R 6g Each is independently selected from hydrogen, deuterium, fluorine, chlorine, -SF5, methyl, deuterated methyl, difluoromethyl, trifluoromethyl, methoxy, or deuterated methoxy; further preferably from hydrogen, deuterium, fluorine, chlorine, -SF5, methyl, deuterated methyl, difluoromethyl, or trifluoromethyl;

[0118] R 6b R 6d R 6f or R 6h It does not exist or is selected independently from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, -SF5, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy or C 3-8 cycloalkyl;

[0119] Preferably, R 6b R 6d R 6f or R 6h It is either absent or independently selected from hydrogen, deuterium, fluorine, chlorine, -SF5, methyl, deuterated methyl, difluoromethyl or trifluoromethyl.

[0120] In some embodiments of the present invention, R 5a R 5b R 5c R 5d R 5e R 5f R 5g R 5h R 5i R 5j and R 5kEach is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, -SF5, oxo group, thio group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1- 3-hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups or -C(O)R ff The amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups and C 3-8 Cycloalkyl groups, optionally further modified by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C2O groups. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 The aryl group is substituted by one or more substituents in the 5-14 membered heteroaryl group;

[0121] Preferably, R 5a R 5b R 5c R 5d R 5e R 5f R 5g R 5h R 5i R 5j and R 5k Each is independently selected from hydrogen, deuterium, fluorine, chlorine, -SF5, methyl, deuterated methyl, difluoromethyl, trifluoromethyl, methoxy, deuterated methoxy, or -C(O)R. ff .

[0122] The present invention further relates to a method for preparing compounds of general formula (A-II-9) or (A-II-10), their stereoisomers, or pharmaceutically acceptable salts thereof:

[0123] The compound of general formula (A-III-1), its stereoisomer or pharmaceutically acceptable salt thereof, and the compound of general formula (A-III-2), its stereoisomer or pharmaceutically acceptable salt thereof, are coupled together to give the compound of general formula (A-II-9), its stereoisomer or pharmaceutically acceptable salt thereof.

[0124] The compound of general formula (A-III-3), its stereoisomer or pharmaceutically acceptable salt thereof, and the compound of general formula (A-III-2), its stereoisomer or pharmaceutically acceptable salt thereof, are coupled together to give the compound of general formula (A-II-10), its stereoisomer or pharmaceutically acceptable salt thereof.

[0125] R L1 Selected from halogens, hydroxyl groups, and -OS(O) m3 -C 1-3 Alkyl group, -S(O) m3 -C 1-3 Alkyl, borate, boronic acid, chain boronic acid ester, or cyclic boronic acid ester, wherein C 1-3 The alkyl group may optionally be further substituted with one or more substituents selected from deuterium, halogen, amino, nitro, hydroxyl, and cyano; preferably chlorine, bromine, hydroxyl, -OS(O)2-CF3, -S(O)-CH3, -S(O)2-CH3, B(OH)2, or...

[0126] R L2 Selected from halogens, hydroxyl groups, and -OS(O) m3 -C 1-3 Alkyl group, -S(O) m3 -C 1-3 Alkyl, borate, boronic acid, chain boronic acid ester, or cyclic boronic acid ester, wherein C 1-3 The alkyl group may optionally be further substituted with one or more substituents selected from deuterium, halogen, amino, nitro, hydroxyl, and cyano; preferably chlorine, bromine, hydroxyl, -OS(O)2-CF3, -S(O)-CH3, -S(O)2-CH3, B(OH)2, or...

[0127] m3 is selected from 0, 1, or 2;

[0128] L1, X1, X2, R 6a R 6c R 6e R 6g Ring G, M5, R 4a R 4c R 4d , q, R 5a R 5c R 5hand as defined in any of the above implementation schemes.

[0129] In some embodiments of the present invention, the preparation method is further described as a method for preparing compounds of general formula (A-II-19) or (A-II-20), their stereoisomers, or pharmaceutically acceptable salts thereof:

[0130] The compound of general formula (A-III-3), its stereoisomer or pharmaceutically acceptable salt thereof, and the compound of general formula (A-III-4), its stereoisomer or pharmaceutically acceptable salt thereof, are coupled together to give the compound of general formula (A-II-19), its stereoisomer or pharmaceutically acceptable salt thereof.

[0131] The compound of general formula (A-III-3), its stereoisomer or pharmaceutically acceptable salt thereof, and the compound of general formula (A-III-5), its stereoisomer or pharmaceutically acceptable salt thereof, are coupled together to give the compound of general formula (A-II-20), its stereoisomer or pharmaceutically acceptable salt thereof.

[0132] Y4, Y5, Y6, and Y7 are defined as in any of the above implementation schemes.

[0133] In some embodiments of the present invention, the coupling reaction in the preparation method is carried out in the presence of a palladium catalyst.

[0134] In some embodiments of the present invention, the palladium catalyst is selected from palladium on carbon, palladium acetate, palladium diphenylphosphine ferrocene dichloride, tetratriphenylphosphine palladium, bis(triphenylphosphine) dichloride palladium, [1,1'-bis(diphenylphosphine)ferrocene] dichloride palladium, [(bis(1-adamantyl)butylphosphine)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate, methanesulfonate (dimethyl-n-butylphosphine)-2'-amino-1,1'-biphenyl-2-yl)palladium(II) dichloromethane adduct, or methanesulfonate [n-butylbis(1-adamantyl)phosphine](2-amino-1,1'-biphenyl-2-yl)palladium(II).

[0135] In some embodiments of the present invention, the substitution reaction in the preparation method is carried out in the presence of a base.

[0136] In some embodiments of the present invention, the alkali is selected from lithium hydroxide, sodium hydride, potassium carbonate, sodium carbonate, sodium n-propoxide, sodium tert-butoxide, N,N,N',N'-tetramethylethylenediamine, N,N diisopropylethylamine, or triethylamine.

[0137] The present invention further relates to a pharmaceutical composition comprising a therapeutically effective dose of any of the shown general formula compounds, their stereoisomers or pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0138] The present invention further relates to any of the compounds of the general formula shown, their stereoisomers or pharmaceutically acceptable salts thereof, or the use of the pharmaceutical compositions thereof in the preparation of dopamine receptor agonist drugs; wherein the dopamine receptor agonist is selected from full agonists or partial agonists; and wherein the dopamine receptor is selected from D1 receptors and / or D5 receptors.

[0139] The present invention further relates to the use of any compound represented by the general formula, its stereoisomers or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof in the preparation of medicaments for treating diseases or conditions associated with dysregulation of dopamine D1 receptor activation.

[0140] The present invention further relates to any compound of any general formula, its stereoisomers or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the preparation of a method for treating a disease or condition associated with dysregulation of dopamine D1 receptor activation.

[0141] The present invention also relates to a method for treating, preventing and / or treating a pre-prepared treatment of a disease or condition associated with dysregulation of dopamine D1 receptor activation, comprising administering to a patient a therapeutically effective dose of any compound of the general formula, its stereoisomer or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0142] In some embodiments of the invention, the pharmaceutical composition comprises the general formulas described herein and their compounds, stereoisomers thereof, or pharmaceutically acceptable salts thereof as active ingredients, wherein the weight percentage of the active ingredient is 1% to 95%, preferably 1% to 90%, 5% to 85%, 5% to 80%, 5% to 75%, 10% to 70%, 10% to 60%, or 10% to 50%.

[0143] In some embodiments of the invention, the pharmaceutical composition is selected from tablets, capsules, liquid formulations or injections, preferably also containing a filler, optionally a disintegrant, or further containing one or more of a flow aid or lubricant.

[0144] The present invention also provides methods for treating disease conditions using the compounds of the present invention, their stereoisomers, or pharmaceutical compositions thereof, including but not limited to conditions related to dysregulation of dopamine D1 receptor activation.

[0145] The present invention also relates to a method for treating diseases or conditions in mammals associated with dysregulation of dopamine D1 receptor activation, comprising administering to said mammal a therapeutically effective amount of the compound of the present invention, its stereoisomer, or a pharmaceutically acceptable salt, ester, prodrug, solvate, hydrate, or derivative thereof.

[0146] In some embodiments, the diseases or conditions described in this invention are selected from schizophrenia, cognitive impairment, dementia, Parkinson's disease, mild cognitive impairment, age-related cognitive decline, major depressive disorder, treatment-resistant depression, postpartum depression, Alzheimer's disease, ADHD, autism spectrum disorder, post-traumatic stress disorder, Tourette syndrome, tardive dyskinesia, sleep disorders, or pain.

[0147] Detailed description of the invention

[0148] Unless otherwise stated, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art, and in particular, the terms used in the specification and claims have the following meanings.

[0149] The term "alkyl" refers to a straight-chain or branched saturated aliphatic hydrocarbon group, which may optionally be substituted with one or more substituents. In certain embodiments, alkyl refers to a group having a carbon density of 1 to 20 (C). 1-20 ), 1 to 15 (C 1-15 ), 1 to 12 (C 1-12 ), 1 to 10 (C 1-10 ), 1 to 8 (C 1- 8) 1 to 6 (C) 1-6 ) or 1 to 3 (C 1-3 A straight-chain saturated hydrocarbon group with 3 to 20 carbon atoms, or a group with 3 to 20 carbon atoms. 3-20 ), 3 to 15 (C 3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 A branched saturated hydrocarbon group with 1 carbon atom. The straight-chain C group used here... 1-6 Alkyl and branched C 3-6 Alkyl groups are also called "lower alkyl groups". For example, C 1-6 Alkyl groups refer to linear saturated monovalent hydrocarbon groups having 1 to 6 carbon atoms or branched saturated monovalent hydrocarbon groups having 3 to 6 carbon atoms. In one embodiment, the C... 1-6The alkyl group contains 1 to 6 (e.g., 1, 2, 3, 4, 5, 6) carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2, 3-Dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched isomers thereof. In one embodiment, the alkyl group is an optionally substituted alkyl group as described elsewhere herein.

[0150] The term "alkylene" refers to an alkyl group in which one hydrogen atom is further substituted, wherein "alkyl" is defined as described above. Non-limiting examples of "alkylene" include methylene (-CH2-), ethylene (-(CH2)2-), propylene (-(CH2)3-), or butylene (-(CH2)4-). In one embodiment, the alkylene is an optionally substituted alkyl group as described elsewhere herein.

[0151] The term "alkenyl" refers to a straight-chain or branched unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon double bond, which can be located at any position within the alkenyl group, and the alkenyl group may optionally be substituted by one or more substituents. In a particular embodiment, the alkenyl group has a carbon content of 2 to 20 (C₂O₃). 2-20 ), 2 to 15 (C 2-15 ), 2 to 12 (C 2-12 ), 2 to 10 (C 2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ) or 2 to 4 (C 2-4 A straight-chain unsaturated hydrocarbon group with 3 to 20 carbon atoms, or a hydrocarbon group with 3 to 20 carbon atoms. 3-20 ), 3 to 15 (C3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3- 8) or 3 to 6 (C) 3-6 A branched unsaturated hydrocarbon group with 16 carbon atoms. Unless otherwise specified, the term "alkenyl" as used herein includes both straight-chain and branched alkenyl groups. For example, C 2-6 Alkenyl refers to a straight-chain unsaturated hydrocarbon group having 2 to 6 carbon atoms or a branched unsaturated hydrocarbon group having 3 to 6 carbon atoms. In one embodiment, the C 2-6 Alkenyl groups contain 2 to 6 (e.g., 2, 3, 4, 5, or 6) carbon atoms. Non-limiting examples of alkenyl groups include: Those skilled in the art will understand that the term "alkenyl" may also include groups having "cis" and "trans" configurations, or alternatively, "E" and "Z" configurations. In one embodiment, the alkenyl is an optionally substituted alkenyl as described elsewhere herein.

[0152] The term "alkynyl" refers to a straight-chain or branched unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon triple bond, which can be located at any position within the alkynyl group. The alkynyl group may optionally be substituted by one or more substituents. In a particular embodiment, the alkynyl group has a carbon content of 2 to 20 (C₂O₃). 2-20 ), 2 to 15 (C 2-15 ), 2 to 12 (C 2-12 ), 2 to 10 (C 2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ) or 2 to 4 (C 2-4 A straight-chain unsaturated hydrocarbon group with 3 to 20 carbon atoms, or a hydrocarbon group with 3 to 20 carbon atoms. 3-20 ), 3 to 15 (C 3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 A branched unsaturated hydrocarbon group with 12 carbon atoms. Unless otherwise specified, the term "alkynyl" as used herein includes both straight-chain and branched alkynyl groups. For example, C 2-6 Alkyne refers to a straight-chain unsaturated hydrocarbon group having 2 to 6 carbon atoms or a branched unsaturated hydrocarbon group having 3 to 6 carbon atoms. In one embodiment, the C 2-6 The alkynyl group contains 2 to 6 (e.g., 2, 3, 4, 5, 6) carbon atoms. Non-limiting examples of the alkynyl group include: In one embodiment, the alkynyl group is an optionally substituted alkynyl group as described elsewhere herein.

[0153] The term "cycloalkyl" refers to a monocyclic or polycyclic (two or more) cyclic group of a saturated or partially unsaturated aliphatic hydrocarbon, which may optionally be substituted with one or more substituents. In certain embodiments, the cycloalkyl ring comprises 3 to 20 (C 3-20 ), 3 to 12 (C 3-12 ), 3 to 8 (C 3-8 ), 3 to 6 (C 3-6 ) or 5 to 8 (C 5-8 ) carbon atoms; in one embodiment, the cycloalkyl ring comprises 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 It has 10 carbon atoms; it may contain one or more double bonds, but does not have a fully conjugated π-electron system. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenedyl, cyclohexadienyl, cycloheptyl, cyclohepttrienyl, or cyclooctyl, etc.; polycyclic cycloalkyl groups include spirocyclic alkyl, fused cycloalkyl, and bridged cycloalkyl. In one embodiment, the cycloalkyl group is an optionally substituted cycloalkyl group or an optionally fused cycloalkyl group with a heterocyclic group, aryl group, or heteroaryl group, as described elsewhere herein, and non-limiting examples include indanyl, tetrahydronaphthyl, benzocycloheptyl, etc.

[0154] The term "heterocyclic group" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon group, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus, or sulfur, wherein the nitrogen, phosphorus, or sulfur atom may optionally be oxidized, the nitrogen atom may optionally be quaternized, the ring carbon atom may optionally be substituted with oxygen, but excluding the -OO- or -OS- ring moieties, and the remaining ring atoms are carbon, which may contain one or more double bonds but does not have a fully conjugated π-electron system. In a particular embodiment, the heterocyclic group comprises 3 to 20, 3 to 12, 3 to 8, 3 to 6, or 5 to 8 ring atoms, wherein 1 to 4 are heteroatoms; in one embodiment, the heterocyclic group comprises 3 to 6, 4 to 6, 3 to 8, 3 to 10, 6 to 10, or 7 to 11 ring atoms; in one embodiment, the heterocyclic group comprises 3 to 8 (e.g., 3, 4, 5, 6, 7, 8) ring atoms; in a preferred embodiment, the heterocyclic group comprises 5 to 8 (e.g., 5, 6, 7, 8) ring atoms. Non-limiting examples of monocyclic heterocyclic groups include tetrahydropyrrole, azahexacyclic butyl, oxacyclobutyl, oxacyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrole, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, and pyranyl. Polycyclic heterocyclic groups include spiroheterocyclic, fused heterocyclic, and bridged heterocyclic groups. In one embodiment, the heterocyclic group is optionally substituted as described elsewhere herein, or is a heterocyclic group further cyclically linked to other cycloalkyl, heterocyclic, aryl, and heteroaryl groups by any two or more atoms on the ring.

[0155] The term "aryl" refers to an all-carbon monocyclic or fused polycyclic (i.e., a ring sharing adjacent carbon atom pairs) group containing at least one conjugated π-electron system, which may optionally be substituted by one or more substituents. In certain embodiments, the aryl group comprises 6 to 20, 6 to 14, or 6 to 10 ring atoms; in one embodiment, the aryl group may further refer to a bicyclic, tricyclic, or tetracyclic ring system, wherein at least one ring is an aromatic ring, and the other rings may be saturated, partially unsaturated carbon rings, or rings containing one or more heteroatoms independently selected from O, S, and N; in one embodiment, the aryl group is selected from benzo5-10-membered heteroaryl, benzo3-10-membered cycloalkyl, or benzo3-10-membered heterocyclic groups. In one embodiment, the aryl group is selected from benzo5-6-membered heteroaryl, benzo3-6-membered cycloalkyl, or benzo3-6-membered heterocyclic groups, wherein the heterocyclic group is a heterocyclic group containing 1 to 3 nitrogen, oxygen, or sulfur atoms. Non-limiting examples include phenyl, naphthyl, fluorenyl, chamomilecycloyl, anthraceneyl, phenanthryl, pyrene, biphenyl, terphenyl, dihydronaphthyl, indene, tetrahydronaphthyl (naphthyl),

[0156] The term "arylene" refers to a divalent aryl group formed by further substitution of one hydrogen atom of an aryl group, wherein the arylene group may be optionally substituted or unsubstituted, as defined above for aryl groups.

[0157] The term "heteroaryl" refers to an optionally substituted monocyclic, polycyclic group or ring system comprising at least one aromatic ring having one or more heteroatoms independently selected from O, S, and N. In certain embodiments, a heteroaryl comprises 5 to 20, 5 to 14, 5 to 10, or 5 to 8 ring atoms, of which 1 to 4 are heteroatoms; in one embodiment, a heteroaryl comprises 5 or 6 ring atoms; in certain embodiments, a heteroaryl may further refer to a bicyclic, tricyclic, or tetracyclic ring, wherein at least one ring is an aromatic ring having one or more heteroatoms independently selected from O, S, and N, and the other rings may be saturated, partially unsaturated carbocyclic rings, or rings comprising one or more heteroatoms independently selected from O, S, and N. In one embodiment, the heteroaryl group is selected from heteroaryl-6-10 aryl, heteroaryl-3-10 cycloalkyl, or heteroaryl-3-10 heterocyclic group; in a further embodiment, the heteroaryl group is selected from 5- or 6-membered heteroaryl-6-10 aryl, 5- or 6-membered heteroaryl-3-6 cycloalkyl, or 5- or 6-membered heteroaryl-3-6 heterocyclic group, wherein the heterocyclic group is a heterocyclic group containing 1-3 nitrogen atoms, oxygen atoms, or sulfur atoms. Non-limiting examples include: furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrroloyl, thiadiazolyl, thiazolyl, thiophene, tetrazolyl, triazinyl, triazolyl, benzofuranyl, benzimidazolyl, benziisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiaphenyl, benzobenzenethio, benzothiaphenyl, benzotriazolyl, imidazopyridyl, imidazothiazolyl Indazinyl, indolyl, inzolyl, isobenzofuranyl, isobenzothiophenyl, isoindolyl, isoquinolinyl, naphridinyl, oxazolopyridyl, phthalazinyl, pteridinyl, purine, pyridopyridyl, pyrrolopyridyl, quinolinyl, quinoxolinyl, quinazolinyl, thiadiazopyrimidinyl, thienenopyridyl, acridineyl, benzoindolyl, carbazole, biphenylfuranyl, phenanthrololinyl, phenanthidyl, phenpyrazinyl, phenazinyl, phenthiazinyl, phenoxazinyl, xanthonyl,

[0158] The term "heteroaryl" refers to a divalent heteroaryl group formed by further substitution of one hydrogen atom of a cycloalkyl group, wherein the heteroaryl group may be optionally substituted or unsubstituted, as defined above.

[0159] The term "alkoxy" refers to -O- (alkyl) and -O- (unsubstituted cycloalkyl), wherein the definition of alkyl or cycloalkyl is as described above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentoxy, or cyclohexyloxy. In one embodiment, the alkoxy group is an optionally substituted alkoxy group as described elsewhere herein.

[0160] The term "alkylacyl" refers to -C(O)-alkyl, where the definition of alkyl is as described above.

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

[0162] The term “haloalkoxy” refers to an alkoxy group that has been substituted with one or more halogens, where the definition of an alkoxy group is as described above.

[0163] The term "hydroxyalkyl" refers to an alkyl group that has been substituted with a hydroxyl group, where the definition of alkyl is as described above.

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

[0165] The term "alkenyl carbonyl" refers to -C(O)-(alkenyl), where alkenyl is defined as previously stated. Non-limiting examples of alkenyl carbonyl include vinyl carbonyl, propenyl carbonyl, or butenyl carbonyl. In one embodiment, the alkenyl carbonyl is an optionally substituted alkenyl carbonyl as described elsewhere herein.

[0166] The term "aminocarbonyl" refers to NH2-C(O)-.

[0167] The term "alkylaminocarbonyl" refers to an aminocarbonyl group (NH2-C(O)-) in which one or both hydrogen atoms are replaced by an alkyl group, wherein the definition of alkyl is as described above.

[0168] The term "alkylamino" refers to an amino group in which one or both of the two hydrogen atoms are replaced by an alkyl group, as defined above.

[0169] The term "carbonyl" refers to the -C(O)-, -(CO)-, or -C(=O)- group. All designations are interchangeable in the specification.

[0170] The term "hydrogen" includes protons ( 1 H), deuterium (2 H), tritium ( 3 H) and / or mixtures thereof. In certain embodiments, one or more hydrogen-occupied sites in the compound may be enriched with deuterium and / or tritium. Such isotope-enriched analogs may be prepared from suitable isotopically labeled starting materials available from commercial sources or by known literature procedures, wherein the hydrogen or hydrogen atom described in this patent includes its isotopes (H) and / or mixtures thereof. 1 H), deuterium ( 2 H), tritium ( 3 H) and / or mixtures thereof.

[0171] The alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, arylene, heteroaryl, heteroarylene, heteroalkyl, alkoxy, alkylthio, hydroxyalkyl, alkenylcarbonyl, aminocarbonyl, alkylaminocarbonyl, alkylamino, and alkylacyl groups may be substituted or unsubstituted. In one embodiment, the substituent is selected from one or more of the following groups: alkyl, deuterated alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, alkylacyl, halogen, mercapto, hydroxyl, nitro, cyano, azide, oxime, phosphate ester, oxo, thio, carboxyl, carboxylic acid ester, cycloalkyl, heterocyclic, aryl, heteroaryl, heterocycloalkoxy, cycloalkylthio, or heterocycloalkylthio.

[0172] The term "substituted or unsubstituted" indicates that the modified substituent may optionally be further substituted by one or more of the following substituents, selected from alkyl, deuteralkyl, haloalkyl, alkenyl, alkoxy, alkylthio, alkylamino, alkylacyl, halogen, mercapto, hydroxyl, nitro, cyano, azide, oxime, phosphate ester, oxo, thio, carboxyl, carboxylic acid ester, cycloalkyl, heterocyclic, aryl, heteroaryl, heterocyclic alkoxy, cycloalkylthio, heterocyclic alkoxy, -(CH2) n -、-(CH2) n R, -(CH2) n OR, -O(CH2) n R, -(CH2) n SR, -(CH2) n C(O)R、-(CH2) n C(O)OR, -(CH2) n S(O) m R, -(CH2) n NRR'、-(CH2) n C(O)NRR'、-(CH2) n NRC(O)R'、-(CH2) n NRS(O) m R'、-OC(RR') n (CH2)m R”, ​​-NR(CH2) n R'、-CH=CH(CH2) n R'、-CH=CH(CH2) n NRR'、-CH=CH(CH2) n NRC(O)R'、-CH=CH(CH2) n NRC(O)NR'R", =N-OR or =CRR';

[0173] R, R', or R” are each independently selected from alkyl, deuterated alkyl, haloalkyl, alkenyl, alkoxy, alkylthio, alkylamino, alkylacyl, halogen, mercapto, hydroxyl, nitro, cyano, azide, oxime, phosphate ester, oxo, thio, carboxyl, carboxylic acid ester, cycloalkyl, heterocyclic, aryl, heteroaryl, heterocyclic alkoxy, cycloalkylthio, or heterocyclic alkoxy.

[0174] n is selected from 0, 1, 2, 3 or 4; m is selected from 0, 1 or 2.

[0175] The different terms such as "X is selected from A, B, or C", "X is selected from A, B, and C", "X is A, B, or C", and "X is A, B, and C" all express the same meaning, that is, X can be any one or more of A, B, and C.

[0176] "Optional" or "optionally" means that the event or environment described below may but does not have to occur, and the description includes the possibility or absence of such event or environment. For example, "optionally alkyl-substituted heterocyclic group" means that the alkyl group may but does not have to be present, and the description includes cases where the heterocyclic group is substituted with an alkyl group and cases where the heterocyclic group is not substituted with an alkyl group.

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

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

[0179] Unless otherwise stated, the indefinite articles “a” and “an” and the definite article “the” in this specification and claims include both plural and singular forms.

[0180] "Pharmaceutical composition" means a mixture containing one or more of the compounds described herein or their physiologically / pharmacologically acceptable salts or prodrugs, along with other chemical components, such as physiologically / pharmacologically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to a living organism, thereby promoting the absorption of the active ingredient and the exertion of its biological activity.

[0181] "Medicinal salts" refer to the salts of the compounds of this invention, which are safe and effective when used in mammals and have the appropriate biological activity.

[0182] "Stereoisomers" encompass all enantiomers / non-corresponding isomers / transisomers / stereoisomers of the present invention and enantiomers / non-corresponding isomers / stereoisomers enriched thereon.

[0183] "Restricted rotation isomers" refer to stereoisomers with axial or planar chirality resulting from restricted intramolecular rotation (as shown in the example below).

[0184] "Stereoisopure" refers to a composition containing one stereoisomer of a compound but substantially lacking another stereoisomer of that compound. For example, a stereoisopure composition of a compound having one chiral center will substantially lack the opposing enantiomer of that compound. A stereoisopure composition of a compound having two chiral centers will substantially lack other diastereomers of that compound. A typical stereoisomeric pure compound comprises, by mass, more than about 80% of one stereoisomer of the compound and less than about 20% of another stereoisomer of the compound; more than about 90% of one stereoisomer of the compound and less than about 10% of another stereoisomer of the compound; more than about 95% of one stereoisomer of the compound and less than about 5% of another stereoisomer of the compound; more than about 97% of one stereoisomer of the compound and less than about 3% of another stereoisomer of the compound; or more than about 99% of one stereoisomer of the compound and less than about 1% of another stereoisomer of the compound.

[0185] "Stereoisomeric enrichment" refers to a composition containing a stereoisomer of a compound at a mass content greater than about 55%, about 60%, about 70%, or about 80%.

[0186] "Enantiomerically pure" refers to a stereoisomerically pure composition of a compound having a single chiral center. Similarly, the term "enantiomerically enriched" refers to a stereoisomerically enriched composition of a compound having a single chiral center.

[0187] "Optical activity" and "enantiomeric activity" refer to a molecular combination having an enantiomer excess of not less than about 50%, not less than about 70%, not less than about 80%, not less than about 90%, not less than about 91%, not less than about 92%, not less than about 93%, not less than about 94%, not less than about 95%, not less than about 96%, not less than about 97%, not less than about 98%, not less than about 99%, not less than about 99.5%, or not less than about 99.8%. In a particular embodiment, the compound comprises about 95% or more of the desired enantiomer or diastereomer by weight of the racemic compound and about 5% or less of the subpreferred enantiomer or diastereomer.

[0188] In describing optically active compounds, the prefixes R and S are used to indicate the absolute configuration of the molecule relative to its chiral center. (+) and (-) are used to indicate the optical rotation of the compound, i.e., the direction of the plane of polarized light rotated by the optically active compound. The prefix (-) indicates that the compound is levorotatory, i.e., the compound rotates the plane of polarized light to the left or counterclockwise. The prefix (+) indicates that the compound is dextrorotatory, i.e., the compound rotates the plane of polarized light to the right or clockwise. However, the signs (+) and (-) for optical rotation are independent of the absolute configuration R and S of the molecule.

[0189] The compounds of this invention include all of their "stereoisomers", "stereoisomeric purity", "stereoisomeric enrichment", "enantiomeric purity", "optical activity", "enantiomeric activity" and "optical isomers". Detailed Implementation

[0190] The present invention is further described below with reference to embodiments, but these embodiments are not intended to limit the scope of the present invention.

[0191] Example

[0192] The structures of the compounds of this invention were determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer with deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), and deuterated chloroform (CDCl3) as solvents, and tetramethylsilane (TMS) as the internal standard.

[0193] The determinations were performed using LC-MS with an Agilent 1200 Infinity Series mass spectrometer. The determinations were performed using an Agilent 1200DAD high-performance liquid chromatograph (Sunfire C). 18 150×4.6mm chromatographic column) and Waters 2695-2996 high-performance liquid chromatograph (Gimini C) 18 (150×4.6mm chromatographic column).

[0194] Thin-layer chromatography (TLC) uses Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The standard size for TLC is 0.15mm to 0.20mm, while the standard size for separating and purifying products using TLC is 0.4mm to 0.5mm. Column chromatography generally uses Yantai Huanghai 200-300 mesh silica gel as the carrier.

[0195] The starting materials used in the embodiments of the present invention are known and commercially available, or can be synthesized using or in accordance with methods known in the art.

[0196] Unless otherwise specified, all reactions in this invention are carried out under continuous magnetic stirring, in a dry nitrogen or argon atmosphere, using a dry solvent, and the reaction temperature is expressed in degrees Celsius.

[0197] Example 1

[0198] Preparation of 4-(4-hydroxy-2-methyl-phenyl)-3-methyl-5-thiazolyl-4-yl-1H-imidazol-2-one

[0199] Step 1: Preparation of Compounds 1-2

[0200] 1-Iodo-4-methoxy-2-methylbenzene (10 g, 40.31 mmol) was dissolved in dimethyl sulfoxide (100 mL), and 1-methyl-1H-imidazolium-2(3H)-one (2.64 g, 26.88 mmol), sodium acetate trihydrate (10.97 g, 80.63 mmol), and palladium acetate (603.37 mg, 2.69 mmol) were added sequentially. The reaction was carried out at 80 °C for 3 hours under nitrogen protection. After the reaction was complete, the reaction solution was cooled to room temperature, poured into water, extracted with ethyl acetate, washed with water, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain 1.2 g of 4-(4-methoxy-2-methyl-phenyl)-3-methyl-1H-imidazol-2-one and 2.65 g of 4-(4-methoxy-2-methyl-phenyl)-3-methyl-1H-imidazol-2-one / 4-(4-methoxy-2-methyl-phenyl)-1-methyl-1,3-dihydro-2H-imidazol-2-one = 2 / 1. MS m / z (ESI): 219 [M+H] + .

[0201] Step 2: Preparation of compounds 1-3

[0202] Dissolve 1-2 (1.2 g, 5.50 mmol) in N,N-dimethylformamide (5 mL), add N-bromosuccinimide (978 mg, 5.50 mmol), and react at room temperature for 1 hour. Pour the reaction solution into water, extract with ethyl acetate, wash the organic phase with water, then with saturated brine, dry to anhydrous sodium sulfate, filter, concentrate, and purify by silica gel column chromatography to give 5-bromo-4-(4-methoxy-2-methyl-phenyl)-3-methyl-1H-imidazol-2-one (1.2 g, yield 73.5%). MS m / z (ESI): 297 [M+H] + .

[0203] Step 3: Preparation of compounds 1-4

[0204] 1-3 (200 mg, 673.07 μmol) was dissolved in 1,4-dioxane (3 mL), followed by the sequential addition of 4-(tri-n-butyltin)thiazole (378 mg, 1.01 mmol) and bis(triphenylphosphine)palladium dichloride (47 mg, 67.31 μmol). The reaction was carried out at 90 °C for 17 hours under nitrogen protection. After the reaction was completed, the reaction solution was cooled to room temperature, and saturated potassium fluoride solution was added and stirred for 2 hours. The mixture was filtered, and the filtrate was extracted with ethyl acetate. The organic phase was washed once with water, then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain 4-(4-methoxy-2-methyl-phenyl)-3-methyl-5-thiazolyl-4-yl-1H-imidazol-2-one (58 mg, yield 28.6%). MS m / z (ESI): 302 [M+H] + .

[0205] Step 4: Preparation of compounds 1-5

[0206] Dissolve 1-4 (50 mg, 165.91 μmol) in dichloromethane (4 mL), and add boron tribromide solution (2.0 M, 331.83 μL) dropwise under an ice-water bath. After the addition is complete, allow the mixture to return to room temperature and react for 1 hour. Upon completion of the reaction, quench with methanol under ice bath conditions. Concentrate the crude product under reduced pressure and purify by silica gel column chromatography to obtain 4-(4-hydroxy-2-methyl-phenyl)-3-methyl-5-thiazolyl-4-yl-1H-imidazol-2-one (13 mg, yield 27.3%). MS m / z (ESI): 288 [M+H] + .

[0207] Step 5: Preparation of Example 1

[0208] Dissolve 1-5 (13 mg, 45.24 μmol) in N,N-dimethylformamide (1 mL), add potassium carbonate (19 mg, 135.73 μmol) and 2-fluoro-3-(trifluoromethyl)pyridine (15 mg, 90.49 μmol), and react at 100 °C for 1 hour under nitrogen protection. Filter the reaction solution, concentrate, and directly prepare 4-(4-hydroxy-2-methyl-phenyl)-3-methyl-5-thiazolyl-4-yl-1H-imidazol-2-one (4 mg, yield 30.8%) by HPLC purification. MS m / z (ESI): 433 [M+H] + .

[0209] Example 2

[0210] Preparation of 5-acetyl-3-methyl-4-[2-methyl-4-[[3-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-1H-imidazol-2-one

[0211] Step 1: Preparation of Compound 2-2

[0212] 5-Bromo-4-(4-methoxy-2-methyl-phenyl)-3-methyl-1H-imidazol-2-one (600 mg, 2.02 mmol) was dissolved in 1,4-dioxane (10 mL), followed by the addition of tributyl(1-ethoxyethylene)tin (1.09 g, 3.03 mmol) and bis(triphenylphosphine)phosphine dichloride palladium (142 mg, 201.92 μmol). The reaction was carried out at 90 °C for 17 hours under nitrogen protection. After the reaction was completed, the reaction solution was cooled to room temperature, and a saturated potassium fluoride solution was added and stirred for 2 hours. The mixture was filtered, and the filtrate was extracted with ethyl acetate. The organic phase was washed once with water, then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain 5-acetyl-4-(4-methoxy-2-methyl-phenyl)-3-methyl-1H-imidazol-2-one (200 mg, yield 38.1%). MS m / z (ESI): 261 [M+H].

[0213] Step 2: Preparation of compounds 2-3

[0214] 2-2 (80 mg, 307.35 μmol) was dissolved in dichloromethane (4 mL), and boron tribromide solution (2.0 M, 614.70 μL) was added dropwise under an ice-water bath. After the addition was complete, the reaction was allowed to return to room temperature for 1 hour. Upon completion of the reaction, methanol was added under ice bath conditions to quench the reaction. The crude product was concentrated under reduced pressure and purified by silica gel column chromatography to give 5-acetyl-4-(4-hydroxy-2-methyl-phenyl)-3-methyl-1H-imidazol-2-one (30 mg, yield 39.6%). MS m / z (ESI): 247 [M+H].

[0215] Step 3: Preparation of Example 2

[0216] 2-3 (30 mg, 121.82 μmol) was dissolved in N,N-dimethylformamide (1 mL), and potassium carbonate (51 mg, 365.47 μmol) and 2-fluoro-3-(trifluoromethyl)pyridine (30 mg, 182.73 μmol) were added. The mixture was reacted at 100 °C for 1 hour under nitrogen protection. The reaction solution was filtered, concentrated, and purified by HPLC to obtain 5-acetyl-3-methyl-4-[2-methyl-4-[[3-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-1H-imidazol-2-one (20 mg, yield 42.0%). Separation by chiral column (model: CHIRALCEL AS-H; mobile phase: CO2 / Methanol = 80% / 20%) yielded isomers 1 and 2 of Example 2. MS m / z (ESI): 392 [M+H].

[0217] The preparation of the following examples follows the synthesis method of Example 1 or Example 2:

[0218] Alternatively, Example 83 can be synthesized using the following method:

[0219] Example 83

[0220] Preparation of 5-acetyl-4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-3-methyl-1H-imidazol-2-one

[0221] Step 1: Preparation of Compound 83-2

[0222] 5-Bromo-2-iodotoluene (23.5 g, 79.14 mmol) was dissolved in dimethyl sulfoxide (250 mL), followed by the sequential addition of 1-methyl-1H-imidazol-2(3H)-one (5.18 g, 52.76 mmol), sodium acetate (12.98 g, 158.29 mmol), and palladium acetate (1.18 g, 5.28 mmol). The reaction was carried out at 80 °C for 3 hours under nitrogen protection. After the reaction was completed, the reaction solution was cooled to room temperature, poured into saturated ammonium chloride water, extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain 4-(4-bromo-2-methyl-phenyl)-3-methyl-1H-imidazol-2-one (5.3 g, yield 37.6%). MS m / z (ESI): 267, 269 [M+H, M+2+H].

[0223] Step 2: Preparation of compound 83-3

[0224] 83-2 (1.0 g, 3.74 mmol), (5-fluoro-8-quinolinyl)boric acid (595.75 mg, 3.12 mmol), tetrakis(triphenylphosphine)palladium (721 mg, 623.94 μmol), and potassium carbonate were added sequentially to a mixture of water / ethanol / toluene (5 mL / 5 mL / 10 mL). The mixture was purged with nitrogen three times and reacted at 80 °C for 17 hours. After the reaction was completed, the reaction solution was cooled to room temperature, poured into water, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain 4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-3-methyl-1H-imidazol-2-one (1.0 g, yield 76.9%). MS m / z (ESI): 334 [M+H].

[0225] Step 3: Preparation of compound 83-4

[0226] 83-3 (1.0 g, 2.40 mmol) was dissolved in N,N-dimethylformamide (10 mL), and N-bromosuccinimide (448.5 mg, 2.52 mmol) was added. The reaction was carried out at room temperature for 1 hour. Upon cooling, the reaction solution was poured into water, resulting in the precipitation of a solid. The solid was filtered, washed with water, and dried to give 5-bromo-4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-3-methyl-1H-imidazol-2-one (680 mg, yield 68.73%). MS m / z (ESI): 412, 414 [M+H, M+2+H].

[0227] Step 4: Preparation of Example 83

[0228] 83-4 (600 mg, 2.02 mmol) was dissolved in 1,4-dioxane (10 mL), and tributyl(1-ethoxyethylene)tin (893.5 mg, 2.47 mmol) and bis(triphenylphosphine)palladium dichloride (115.8 mg, 164.95 μmol) were added sequentially. The reaction was carried out at 90 °C for 2 hours under nitrogen protection. The reaction solution was cooled to room temperature, and saturated potassium fluoride solution was added and stirred for 2 hours. The mixture was filtered, and the filtrate was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by preparative chromatography to obtain 5-acetyl-4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-3-methyl-1H-imidazol-2-one (126 mg, yield 16.6%). Isomers 1 and 2 of Example 83 were obtained by separation using a chiral column (model: CHIRALCEL AS-H; mobile phase: carbon dioxide / methanol = 80% / 20%). MS m / z (ESI): 376 [M+H].

[0229] The preparation methods of the following examples are the same as those in Examples 1, 2, or 83:

[0230] The preparation methods in the following examples are based on the synthesis method of Example 1:

[0231] Alternatively, the following embodiments are prepared using the following synthesis method:

[0232] Example 112

[0233] Preparation of 4-acetyl-5-(4-(5-chloro-8-quinolinyl)-2-methylphenyl)-1-methyl-1,3-dihydro-2H-imidazol-2-one

[0234] Step 1: Preparation of 112-2

[0235] 5-Acetyl-4-(4-hydroxy-2-methyl-phenyl)-3-methyl-1H-imidazol-2-one (800 mg, 3.25 mmol) was dissolved in N,N-dimethylformamide (15 mL), and triethylamine (660 mg, 6.50 mmol) and N-phenylbis(trifluoromethanesulfonylimide) (1.75 g, 4.88 mmol) were added. The mixture was reacted at room temperature for 2 hours. The reaction solution was extracted with water and ethyl acetate, washed three times with water and once with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain 4-(5-acetyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazol-4-yl)-3-methylphenyltrifluoromethanesulfonate (1.02 g, yield 82.9%).

[0236] Step 2: Preparation of (5-chloroquinoline-8-yl)boronic acid

[0237] At room temperature, 1,1-bis(diphenylphosphine)diberberine palladium dichloride (0.75 g, 1.03 mmol) was added to a mixture of 8-bromo-5-chloroquinoline (2.50 g, 10.31 mmol), KOAc (2.53 g, 25.77 mmol), bis(pinarate)diboron (3.93 g, 15.46 mmol), and 1,4-dioxane (50 mL). The mixture was heated to 90 °C and stirred for 4 hours under nitrogen protection. The reaction mixture was filtered, and the filtrate was used directly for the next reaction. MS m / z (ESI): 208 [M+H].

[0238] Step 3: Preparation of Example 112

[0239] 112-2 (0.97 g, 2.57 mmol), 1,1-bis(diphenylphosphine)diberberine palladium dichloride (0.19 g, 0.26 mmol), cesium carbonate (1.68 g, 5.15 mmol), and water (10 mL) were added sequentially to a solution of (5-chloroquinoline-8-yl)boric acid (0.54 g, 2.60 mmol) in dioxane (50 mL). The mixture was purged with nitrogen three times, and the temperature was raised to 90 °C for 16 hours. The reaction solution was cooled to room temperature, poured into water, extracted with ethyl acetate, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain approximately 800 mg of crude product. Further purification by high-performance liquid chromatography yielded a white solid product, 4-acetyl-5-(4-(5-chloro-8-quinolinyl)-2-methylphenyl)-1-methyl-1,3-dihydro-2H-imidazol-2-one (105 mg, yield 10.3%). MS m / z (ESI): 392 [M+H].

[0240] Example 131

[0241] 4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-3-methyl-5-(2,2,2-trideuterated acetyl)-1H-imidazol-2-one

[0242] Step 1: Preparation of 131-2

[0243] 4-Chloro-3-methyl-2-oxo-1H-imidazol-5-ylcarboxylate tert-butyl ester (232.0 mg, 997.15 μmol), 5-fluoro-8-[3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl]quinoline (434.6 mg, 1.20 mmol), cesium carbonate (649.78 mg, 1.99 mmol), and cataCXium A Pd G3 (108.93 mg, 149.57 μmol) were sequentially added to 1,4-dioxane (20 mL) and mixed. The mixture was stirred at 90 °C for 18 hours under nitrogen protection. The reaction solution was cooled, quenched with water, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to give tert-butyl 4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-3-methyl-2-oxo-1H-imidazol-5-ylcarboxylate (300 mg, yield 69%). MS m / z (ESI): 434 [M+H].

[0244] Step 2: Preparation of 131-3

[0245] 131-2 (300 mg, 692.08 μmol) and trifluoroacetic acid (157.8 mg, 1.38 mmol) were added sequentially to DCM (10 mL), and the mixture was stirred at 20 °C for 18 hours. The mixture was concentrated under reduced pressure and purified by preparative high-performance liquid chromatography (HPLC) to obtain 4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-3-methyl-2-oxo-1H-imidazol-5-ylcarboxylic acid (200 mg, yield 76.58%). MS m / z (ESI): 378 [M+H].

[0246] Step 3: Preparation of 131-4

[0247] 131-3 (200 mg, 529.99 μmol) and N-methoxymethylamine (48.6 mg, 794.98 μmol) were dissolved in THF (10 mL), and EDCI (203.2 mg, 1.06 mmol), HOBt (143.2 mg, 1.06 mmol), and DIEA (205.5 mg, 1.59 mmol, 276.94 μL) were added sequentially. The mixture was stirred at 25 °C for 15 hours. The mixture was quenched with water, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give 4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-N-methoxy-N,3-dimethyl-2-oxo-1H-imidazol-5-ylformamide (150 mg, yield 67.32%). MS m / z (ESI): 421 [M+H].

[0248] Step 4: Preparation of Example 131

[0249] 131-4 (150 mg, 356.77 μmol) was dissolved in THF (10 mL), and CD3MgI (301.9 mg, 1.78 mmol) was slowly added dropwise at -70 °C. The mixture was then stirred at room temperature for 15 hours. The solution was concentrated under reduced pressure and purified by high performance liquid chromatography (HPLC) to obtain 4-[4-(5-fluoro-8-quinolinyl)-2-methyl-phenyl]-3-methyl-5-(2,2,2-trideuteracetyl)-1H-imidazol-2-one (30 mg, yield 22.22%). MS m / z (ESI): 379 [M+H].

[0250] 1 H NMR(400MHz, CDCl3)δ9.03(dd,J=4.2,1.8Hz,1H),8.55(dd,J=8.5,1.8Hz,1H),8.39(s,1H),7.79–7.71(m,3H ),7.56(dd,J=8.5,4.2Hz,1H),7.40(d,J=7.8Hz,1H),7.35(dd,J=9.3,8.1Hz,1H),3.13(s,3H),2.34(s,3H).

[0251] Example 211

[0252] Preparation of 4-acetyl-5-(2-chloro-4-(5-chloro-1,7-naphthid-8-yl)phenyl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one

[0253] Step 1: Preparation of 211-2

[0254] 1,3-Dihydro-2H-imidazol-2-one (84 g, 1 mol) was dissolved in dichloromethane (1 L), and triethylamine (404 g, 4 mol) and 4-dimethylaminopyridine (12.2 g, 100 mmol) were added sequentially with stirring at 0 °C. Separately, di-tert-butyl dicarbonate (236 g, 2 mol) was dissolved in dichloromethane (0.5 L) and added dropwise rapidly, followed by stirring overnight. The reaction mixture was quenched to neutral with 0.5 M hydrochloric acid solution, and 10% citric acid was added with continued stirring. The mixture was extracted with dichloromethane, filtered, and concentrated under reduced pressure to give compound 2-oxo-1H-imidazol-1,3(2H)-dicarboxylic acid di-tert-butyl ester (208 g, yield 73%). MS m / z (ESI): 285 [M+H].

[0255] Step 2: Preparation of 211-3

[0256] Isopropylamine (148.06 g, 1.46 mol) was added to a solution of 211-2 (208 g, 731.6 mmol) in 1.5 L of tetrahydrofuran, and the mixture was stirred at room temperature for 10 hours. The reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography to give tert-butyl 2-oxo-2,3-dihydro-1H-imidazolium-1-carboxylate (90 g, yield 66.8%). MS m / z (ESI): 185 [M+H].

[0257] Step 3: Preparation of 211-4

[0258] 211-3 (42 g, 228 mmol) and potassium tert-butoxide (51.17 g, 456.05 mmol) were dissolved in tetrahydrofuran (1 L). Deuterated iodomethane (49.58 g, 342.03 mmol) was slowly added under ice bath conditions, and the mixture was stirred at room temperature for 2 hours. The solution was neutralized to pH 7 with 1 M dilute hydrochloric acid, extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give tert-butyl 3-(deuterated methyl)-2-oxo-2,3-dihydro-1H-imidazolium-1-carboxylate (25 g, 55% yield). MS m / z (ESI): 202 [M+H].

[0259] Step 4: Preparation of 211-5

[0260] A solution of 211-4 (30 g, 149.08 mmol) in 300 mL of dichloromethane was added to trifluoroacetic acid (84.99 g, 745.39 mmol), and the mixture was stirred at room temperature for 8 hours. The solution was neutralized to pH 7 with saturated sodium bicarbonate solution, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give compound 1-(deuterated methyl)-1,3-dihydro-2H-imidazol-2-one (10 g, 66% yield). MS m / z (ESI): 102 [M+H].

[0261] Step 5: Preparation of 211-6

[0262] 4-Bromo-2-chloro-1-iodobenzene (9.4 g, 29.67 mmol) was dissolved in dimethyl sulfoxide (100 mL), followed by the addition of 211-5 (2.0 g, 19.78 mmol), sodium acetate trihydrate (8.07 g, 59.34 mmol), and palladium acetate (450 mg, 1.48 mmol). The reaction mixture was then subjected to nitrogen at 80 °C for 6 hours. The reaction solution was cooled to room temperature, washed with saturated ammonium chloride solution, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 5-(4-bromo-2-chlorophenyl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (1.6 g, 28% yield). MS m / z (ESI): 292 [M+H].

[0263] Step 6: Preparation of 211-7

[0264] 211-6 (1.6 g, 5.51 mmol), pinacol diboronate (2.80 g, 11.01 mmol), 1,1-bis(diphenylphosphine)diberberine palladium dichloride (403 mg, 0.55 mmol), potassium acetate (1.08 g, 11.01 mmol), and dioxane (30 mL) were added to a reaction flask and reacted under nitrogen at 90 °C for 4 hours. The reaction solution was cooled to room temperature, quenched with water, extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 5-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)phenyl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (1.4 g, yield 75.3%). MS m / z (ESI): 338 [M+H].

[0265] Step 7: Preparation of 211-8

[0266] 211-7 (1.4 g, 4.15 mmol), 1,1-bis(diphenylphosphine)diphenylferric palladium dichloride (304 mg, 0.41 mmol), potassium carbonate (1.15 g, 8.31 mmol), and water (5 mL) were sequentially added to a solution of 5,8-dichloro-1,7-naphthidine (866 mg, 4.35 mmol) in dioxane (20 mL). The reaction was carried out under nitrogen at 85 °C for 3 hours. The reaction solution was cooled, quenched with water, extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 5-(2-chloro-4-(5-chloro-1,7-naphthidin-8-yl)phenyl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (920 mg, yield 59.3%). MS m / z (ESI): 374 [M+H].

[0267] Step 8: Preparation of 211-9

[0268] 211-8 (920 mg, 2.46 mmol) was dissolved in acetonitrile (25 mL), and N-bromosuccinimide (438 mg, 2.46 mmol) was slowly added under ice bath conditions. The reaction was carried out under nitrogen protection under ice bath conditions for 1 hour. The reaction solution was poured into ice water, and a large amount of solid precipitated. The solid was filtered and dried to give 4-bromo-5-(2-chloro-4-(5-chloro-1,7-naphthid-8-yl)phenyl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (800 mg, yield 71.8%). MS m / z (ESI): 454 [M+H].

[0269] Step 9: Preparation of Example 211

[0270] 211-9 (800 mg, 1.76 mmol) was dissolved in dioxane (20 mL), followed by the sequential addition of tributyl(1-ethoxyethylene)tin (1.27 g, 3.53 mmol) and bis(triphenylphosphine)palladium dichloride (124 mg, 0.18 mmol). The reaction was carried out at 95 °C for 3 hours under nitrogen protection. The reaction solution was cooled to room temperature, and saturated potassium fluoride solution (50 mL) was added and stirred for 2 hours. The mixture was filtered, and the filtrate was extracted with ethyl acetate, washed with water, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by liquid chromatography to give 4-acetyl-5-(2-chloro-4-(5-chloro-1,7-naphthid-8-yl)phenyl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (372 mg, yield 50.9%). MS m / z (ESI): 416 [M+H].

[0271] 1H NMR (400MHz, DMSO) δ11.03(s,1H),9.26(d,J=4.1Hz,1H),8.93(s,1H),8.71(d,J=8.6Hz,1H),8.4 3(s,1H),8.28(d,J=8.1Hz,1H),8.04(dd,J=8.6,4.2Hz,1H),7.81(d,J=8.0Hz,1H),1.88(s,3H).

[0272] Example 639 Restricted Transisomer Separation

[0273] SFC chiral separation yielded isomer 1 (peak time: 3.168 min) and isomer 2 (peak time: 3.577 min).

[0274] Chiral splitting conditions:

[0275] Example 725

[0276] Preparation of 5-acetyl-4-[2-fluoro-4-(5-fluoro-8-quinolinyl)-6-(trideuterium methoxy)phenyl]-3-(trideuterium methyl)-1H-imidazo[4,5-b]pyridine-2(3H)-one

[0277] Step 1: Preparation of 725-2

[0278] Under nitrogen protection, sodium deuteroxide (2.15 g, 37.63 mmol) was added to a solution of 5-bromo-1,3-difluoro-2-iodobenzene (10 g, 31.36 mmol) in deuterated methanol (50 mL), and the mixture was heated to 65 °C and stirred for 16 hours. The mixture was concentrated to give the crude product. It was diluted with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to give 5-bromo-1-fluoro-2-iodo-3-(trideuteroxy)benzene (7.8 g, yield 74.5%). MS m / z (ESI): 335 [M+H].

[0279] Step 2: Preparation of 725-3

[0280] 725-2 (3.22 g, 9.64 mmol) and 3-(trideutermethyl)-1H-imidazol-2-one (750 mg, 7.42 mmol) were dissolved in DMSO (3 mL). Sodium acetate trihydrate (3.03 g, 22.25 mmol) and palladium acetate (166.5 mg, 741.68 μmol) were added at 20 °C. Under nitrogen protection, the mixture was heated to 80 °C and reacted for 3 hours. After cooling to room temperature, the mixture was quenched with saturated NH4Cl solution, extracted with dichloromethane, washed twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by silica gel column chromatography yielded 0.5 g of 4-[4-bromo-2-fluoro-6-(trideuteroxymethoxy)phenyl]-3-(trideutermethyl)-1H-imidazol-2-one (22% yield). MS m / z (ESI): 308 [M+H].

[0281] Step 3: Preparation of 725-4

[0282] 725-3 (500 mg, 1.63 mmol) and (5-fluoro-8-quinolinyl)boric acid (342.0 mg, 1.79 mmol) were dissolved in 1,4-dioxane (15 mL) and water (4 mL). Cesium carbonate (1.06 g, 3.26 mmol) and Pd(dppf)Cl2 (119.0 mg, 162.79 μmol) were added. The mixture was heated to 90 °C for 2 hours under nitrogen protection. The reaction solution was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. After filtration and concentration, the solution was purified by silica gel column chromatography to give 4-[2-fluoro-4-(5-fluoro-8-quinolinyl)-6-(trideuteriummethoxy)phenyl]-3-(trideuteriummethyl)-1H-imidazol-2-one (0.6 g, yield 98.7%). MS m / z (ESI): 374 [M+H].

[0283] Step 4: Preparation of 725-5

[0284] Under nitrogen protection, NBS (367.0 mg, 2.06 mmol) was added to 10 mL of DMF (725-4, 700.0 mg, 1.87 mmol), and the mixture was stirred at 25 °C for 2 minutes. The mixture was quenched with 30 mL of saturated sodium bicarbonate solution, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to give 5-bromo-4-[2-fluoro-4-(5-fluoro-8-quinolinyl)-6-(trideuterium methoxy)phenyl]-3-(trideuterium methyl)-1H-imidazol-2-one (0.8 g, 94.3% yield). MS m / z (ESI): 452, 454 [M+H, M+2+H].

[0285] Step 5: Preparation of Example 725

[0286] Under nitrogen protection, 725-5 (700 mg, 1.55 mmol) was dissolved in 1,4-dioxane (10 mL), followed by the sequential addition of tributyl(1-ethoxyethylene)tin (838.4 mg, 2.32 mmol) and Pd(dppf)Cl2 (113.14 mg, 154.77 μmol). The mixture was heated to 90 °C and reacted for 2 hours. The reaction solution was cooled, and saturated potassium fluoride solution was added and stirred for 1 hour. The mixture was filtered, and the filtrate was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain 5-acetyl-4-[2-fluoro-4-(5-fluoro-8-quinolinyl)-6-(trideuterium methoxy)phenyl]-3-(trideuterium methyl)-1H-imidazol-2-one (300 mg, yield 46.7%). MS m / z (ESI): 416 [M+H].

[0287] 1 H NMR(400MHz,MeOD)δ8.99(dd,J=4.1,2.0Hz,1H),8.64(d,J=8.3Hz,1H),7.90(t,J=7.1Hz ,1H),7.69(dd,J=8.7,4.2Hz,2H),7.47(t,J=8.9Hz,2H),7.33–7.21(m,1H),2.06(s,3H).

[0288] Example 1017

[0289] Preparation of 5-acetyl-4-(3-methyl-5-thieno[2,3-c]pyridin-7-yloxy-2-pyridyl)-3-(trideutermethyl)-1H-imidazol-2-one

[0290] Step 1: Preparation of 1017-2

[0291] 2-Chloro-5-hydroxy-3-methylpyridine (50 g, 348.26 mmol), potassium carbonate (120.33 g, 870.66 mmol), and benzyl bromide (71.48 g, 417.91 mmol) were added to N,N-dimethylformamide (500 mL), and the reaction was carried out at 85 °C for 17 hours. The mixture was cooled and filtered. The filter cake was washed with ethyl acetate, the filtrate was washed with water, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography to obtain the target compound 5-(benzyloxy)-2-bromo-3-methylpyridine (69.5 g, yield 71.7%). MS m / z (ESI): 278 [M+H].

[0292] Step 2: Preparation of 1017-3

[0293] 1017-2 (69.5 g, 249.87 mmol), (E)-1-ethoxyvinyl-2-boronate pinacol ester (59.39 g, 299.84 mmol), sodium carbonate (52.97 g, 499.73 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (18.28 g, 24.99 mmol) were added to dioxane / water (900 mL / 100 mL), purged with nitrogen, and reacted at 100 °C for 17 hours. After cooling, the mixture was diluted with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain (E)-5-(benzyloxy)-2-(2-ethoxyvinyl)-3-methylpyridine (62.5 g, 95.9% yield). MS m / z (ESI): 270 [M+H].

[0294] Step 3: Preparation of 1017-4

[0295] 1017-3 (62.5 g, 23.05 mmol) and N-bromosuccinimide (43.37 g, 243.65 mmol) were added to tetrahydrofuran (100 mL) and ethanol (500 mL), and reacted at room temperature for 2 hours. The mixture was concentrated under reduced pressure, slurried in diethyl ether, filtered, and concentrated again under reduced pressure to give 5-(benzyloxy)-2-(1-bromo-2,2-diethoxyethyl)-3-methylpyridine (91.5 g, 100% yield). MS m / z (ESI): 394 [M+H].

[0296] Step 4: Preparation of 1017-5

[0297] 1017-4 (91.5 g, 232.05 mmol), potassium iodide (38.52 g, 232.05 mmol), potassium carbonate (192.42 g, 1.39 mol), and deuterated methylamine hydrochloride (49.00 g, 696.15 mmol) were added to acetonitrile (1 L). The mixture was reacted in a sealed container at 85 °C for 17 hours. After cooling and filtration, the filter cake was washed with ethyl acetate, concentrated under reduced pressure, and purified by silica gel column chromatography to give 1-(5-(benzyloxy)-3-methylpyridin-2-yl)-2,2-diethoxy-N-deuterated methylethyl-1-amine (44.5 g, yield 55.7%). MS m / z (ESI): 348 [M+H].

[0298] Step 5: Preparation of 1017-6

[0299] 1017-5 (39.5 g, 114.67 mmol) and trimethylsilyl isocyanate (26.42 g, 229.35 mmol) were added to ultra-dry tetrahydrofuran (400 mL) and reacted in a sealed container at 50 °C for 17 hours. The mixture was concentrated under reduced pressure to give 1-(1-(5-(benzyloxy)-3-methylpyridin-2-yl)-2,2-diethoxyethyl)-1-methylurea (44.4 g, 100% yield). MS m / z (ESI): 391 [M+H].

[0300] Step 6: Preparation of 1017-7

[0301] 1017-6 (44.5 g, 114.67 mmol) and trifluoroacetic acid (40 mL) were added to ultra-dry toluene (400 mL), mixed thoroughly, and reacted at 105 °C for 3 hours. The mixture was then cooled to room temperature, concentrated under reduced pressure, and the pH was adjusted to neutral with saturated sodium bicarbonate. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to give 5-(5-(benzyloxy)-3-methylpyridin-2-yl)-1-deuterated methyl-1,3-dihydro-2H-imidazol-2-one (18 g, yield 53.1%). MS m / z (ESI): 299 [M+H].

[0302] Step 7: Preparation of 1017-8

[0303] 1017-7 (18 g, 60.37 mmol) was dissolved in methanol, and 5% palladium on carbon solid (1 g) was added. The mixture was then purged with nitrogen and hydrogen, and reacted at room temperature for 16 hours. The solution was filtered, concentrated, and purified by silica gel column chromatography to give 5-(5-hydroxy-3-methylpyridin-2-yl)-1-(methyl-d3)-1,3-dihydro-2H-imidazo[2,1-b]thiazol-2-one (9.0 g, yield 72.0%). MS m / z (ESI): 209 [M+H].

[0304] Step 8: Preparation of 1017-9

[0305] To a solution of 1017-8 (100 mg, 0.48 mmol) and 7-chlorothieno[2,3-c]pyridine (81.46 mg, 0.48 mmol) in dimethyl sulfoxide (5 mL), N,N,N',N'-tetramethylethylenediamine (22.32 mg, 0.19 mmol), cuprous iodide (36.58 mg, 0.19 mmol), and cesium carbonate (390.19 mg, 1.2 mmol) were added, and the mixture was microwaved at 120 °C for 1.5 h. After cooling, the mixture was washed with saturated ammonium chloride solution, extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to give 4-(3-methyl-5-thieno[2,3-c]pyridin-7-yloxy-2-pyridyl)-3-(trideuterylmethyl)-1H-imidazol-2-one (50 mg, yield 30.5%). MS m / z(ESI): 342 [M+H].

[0306] Step 9: Preparation of 1017-10

[0307] Tetrabutylammonium tribromide (62.14 mg, 0.13 mmol) was added to a 20 mL solution of dichloromethane containing 1017-9 (40 mg, 0.12 mmol) under ice bath conditions, and the reaction was carried out for 2 minutes on ice. The reaction was quenched with sodium thiosulfate solution, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to give 5-bromo-4-(3-methyl-5-thieno[2,3-c]pyridin-7-yloxy-2-pyridyl)-3-(trideutermethyl)-1H-imidazol-2-one (40 mg, yield 62.6%). MS m / z (ESI): 420 [M+H].

[0308] Step 10: Preparation of 1017-11

[0309] To a solution of 1017-10 (40 mg, 0.05 mmol) and tributyl(1-ethoxyvinyl)stanane (34.8 mg, 0.10 mmol) in dioxane (5 mL), bis(triphenylphosphine)palladium dichloride (5.08 mg, 0.01 mmol) was added, purged with nitrogen, and reacted at 90 °C for 6 hours. The mixture was stirred in potassium fluoride solution for 1 hour, extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate solution, filtered, and concentrated. The crude product was used directly in the next reaction to give 5-(1-ethoxyvinyl)-3-deuterated methyl-4-(3-methyl-5-thieno[2,3-c]pyridin-7-yloxy-2-pyridyl)-1H-imidazol-2-one (33 mg, crude product). MS m / z (ESI): 412 [M+H].

[0310] Step 11: Preparation of Example 1017

[0311] Formic acid (1 mL) was added to a 5 mL solution of acetonitrile (33 mg, 0.08 mmol) and reacted at room temperature for 1 hour. The reaction solution was concentrated and purified by high performance liquid chromatography to give 5-acetyl-4-(3-methyl-5-thieno[2,3-c]pyridin-7-yloxy-2-pyridyl)-3-(trideutermethyl)-1H-imidazol-2-one (5.4 mg, yield 14.9%). MS m / z (ESI): 384 [M+H].

[0312] 1 H NMR (400MHz, MeOD) δ8.63 (d, J=2.5Hz, 1H), 8.04 (dd, J=8.5, 5.4Hz, 2H), 7.91 (d, J= 2.6Hz,1H),7.67(d,J=5.6Hz,1H),7.59(d,J=5.3Hz,1H),2.36(s,3H),1.92(s,3H).

[0313] The preparation of the following examples follows the synthesis method of Example 211 or Example 1017:

[0314] Alternatively, the following embodiments are prepared using the following synthesis method:

[0315] Example 1091

[0316] Synthesis of 5-acetyl-4-[3-methyl-5-(5-methylthieno[2,3-c]pyridin-7-yl)oxy-2-pyridyl]-3-(trideutermethyl)-1H-imidazo[4,5-b]pyridin-2(1H)-one

[0317] Step 1: Preparation of Compound 1091-2

[0318] 7-Chlorothiophene[2,3-c]pyridine 1091-1 (5 g, 29.48 mmol) was dissolved in DCM (50 mL), and m-chloroperoxybenzoic acid (10.2 g, 58.95 mmol) was added. The mixture was purged with nitrogen, and the reaction solution was stirred at 20 °C for 12 hours. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography to give 7-chlororothiophene[2,3-c]pyridine 6-oxide (3.88 g, yield 70.9%). MS m / z (ESI): 186 [M+H].

[0319] Step 2: Preparation of compound 1091-3

[0320] Compound 1091-2 (3.88 g, 20.90 mmol) was suspended in phosphorus oxychloride (25 mL, 268.21 mmol) and stirred at 110 °C for 12 hours. The reaction mixture was poured into ice water (100 mL), the pH was adjusted to 8 with saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to give 5,7-dichlorothieno[2,3-c]pyridine (2.57 g, yield 60.3%). MS m / z (ESI): 204 [M+H].

[0321] Step 3: Preparation of compound 1091-4

[0322] 5-Acetyl-4-(5-hydroxy-3-methyl-2-pyridyl)-3-(trideutermethyl)-1H-imidazol-2-one (180 mg, 719.23 μmol), 1091-3 (176.1 mg, 863.07 μmol) and potassium carbonate (198.8 mg, 1.44 mmol) were suspended in DMSO (7 mL), and cuprous iodide (68.5 mg, 359.61 μmol) was added. The mixture was stirred at 100 °C for 16 hours. After cooling to room temperature, the reaction solution was quenched with water, extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography to give 4-acetyl-5-(5-((5-chloro-thieno[2,3-c]pyridin-7-yl)oxy)-3-methylpyridin-2-yl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (300 mg, yield 99.8%). MS m / z (ESI): 418 [M+H].

[0323] Step 4: Preparation of Example 1091

[0324] 1091-4 (100 mg, 239.30 μmol), trimethylcycloboroxane (3.5 M tetrahydrofuran solution, 205 μL), and potassium carbonate (99.2 mg, 717.90 μmol) were dissolved in a mixed solvent of 1,4-dioxane (2 mL) and water (0.4 mL). [1,1'-bis(di-tert-butylphosphine)ferrocene]palladium dichloride (7.7 mg, 11.97 μmol) was added, and the mixture was purged with nitrogen. The reaction solution was stirred at 110 °C for 10 hours. After cooling to room temperature, the reaction solution was quenched with water, extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by reversed-phase preparative high-performance liquid chromatography to give 5-acetyl-4-[3-methyl-5-(5-methylthieno[2,3-c]pyridin-7-yl)oxy-2-pyridyl]-3-(trideuterylmethyl)-1H-imidazo[4,5-b]pyridin-2(1H)-one (34.0 mg, yield 35.2%). MS m / z (ESI): 398 [M+H].

[0325] 1 H NMR (400MHz, CDCl3) δ = 8.93 (br s, 1H), 8.67 (d, J = 2.5Hz, 1H), 7.75-7.67 (m, 2H), 7.39-7.31 (m, 2H), 2.50 (s, 3H), 2.30 (s, 3H), 1.88 (s, 3H).

[0326] Example 1097

[0327] Preparation of 5-(5-((1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylpyridin-2-yl)-4-acetyl-1-(methyl-d3)-1,3-dihydro-2H-imidazo[1,2-a]pyridin-2-one

[0328] Step 1: Preparation of 1097-2

[0329] Under ice bath conditions, tetrabutylammonium tribromide (19.97 g, 41.4 mmol) was added dropwise to a 200 mL solution of acetonitrile (1097-1, 12.48 g, 42.26 mmol). After the addition, the reaction solution changed from clear to turbid. The mixture was stirred under ice bath conditions for 3 minutes. The solution was quenched with sodium thiosulfate solution, extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, purified by silica gel column chromatography, concentrated, dissolved in dichloromethane, and then petroleum ether was added. A large amount of solid precipitated out. Filtration yielded 5-(5-(benzyloxy)-3-methylpyridin-2-yl)-4-bromo-1-(methyl-d3)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (10 g, yield 63.3%). MS m / z (ESI): 377 [M+H].

[0330] Step 2: Preparation of 1097-3

[0331] 1097-2 (5 g, 13.25 mmol), 1-ethoxybutane (6.64 g, 66.3 mmol), palladium acetate (595 mg, 2.65 mmol), DPEPos (2.86 g, 5.30 mmol), and DIEA (5.14 g, 39.76 mmol, 6.93 mL) were stirred at 100 °C for 15 hours in n-butanol (50 mL). The reaction mixture was evaporated to dryness and purified by silica gel column chromatography to give 4-acetyl-5-(5-(benzyloxy)-3-methylpyridin-2-yl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (3 g, yield 66.5%). MS m / z (ESI): 341 [M+H].

[0332] Step 3: Preparation of 1097-4

[0333] Under nitrogen protection, 10% wet Pd / C (535 mg, 0.44 mmol) was added to a methanol (30 mL) solution at 1097-3 (3 g, 8.81 mmol) at room temperature, and the mixture was stirred at room temperature for 13 hours under a hydrogen atmosphere. The reaction solution was filtered through diatomaceous earth, the solid was washed with methanol, and the filtrate was evaporated to dryness to give 5-acetyl-4-(5-hydroxy-3-methyl-2-pyridyl)-3-(trideuterylmethyl)-1H-imidazol-2-one (2 g, yield 90.7%). MS m / z (ESI): 251 [M+H].

[0334] Step 4: Preparation of 1097-6

[0335] Sodium hydride (393 mg, 9.83 mmol, 60% purity) was added to a tetrahydrofuran (30 mL) solution of 4-chloro-1H-pyrrolo[3,2-c]pyridine (1 g, 6.55 mmol) at 0 °C. The mixture was stirred at 0 °C for 30 minutes, and then 2-(chloromethoxy)ethyltrimethylsilane (1.64 g, 9.83 mmol) was added dropwise. The mixture was stirred at 0 °C for 1 hour. The reaction solution was quenched with ammonium chloride aqueous solution, extracted with ethyl acetate, and the organic phase was washed with brine. After rotary evaporation, the solution was purified by silica gel column chromatography to obtain 2-[(4-chloropyrrolo[3,2-c]pyridin-1-yl)methoxy]ethyltrimethylsilane (500 mg, yield 27.0%). MS m / z (ESI): 283 [M+H].

[0336] Step 5: Preparation of 1097-7

[0337] 1097-4 (100 mg, 0.4 mmol), 1097-6 (226 mg, 0.8 mmol), palladium acetate (18 mg, 0.08 mmol), cesium carbonate (390 mg, 1.2 mmol), and Me4t-butylXPhos (76.84 mg, 0.16 mmol) were stirred at 120 °C for 2 hours in dimethyl sulfoxide (5 mL). Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and brine, evaporated to dryness, and purified by silica gel column chromatography to give 5-acetyl-4-[3-methyl-5-[1-(2-trimethylsilylethoxymethyl)pyrrolo[3,2-c]pyridin-4-yl]oxy-2-pyridyl]-3-(trideuterylmethyl)-1H-imidazol-2-one (100 mg, yield 50.4%). MS m / z (ESI): 497 [M+H].

[0338] Step 6: Preparation of 1097-8

[0339] Trifluoroacetic acid (3 mL) was added to a solution of 1097-7 (100 mg, 0.2 mmol) and L-cysteine ​​(73.2 mg, 0.6 mmol) in dichloromethane (3 mL) at room temperature, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was evaporated to dryness to give 5-acetyl-4-[5-[1-(hydroxymethyl)pyrrolo[3,2-c]pyridin-4-yl]oxy-3-methyl-2-pyridyl]-3-(trideuterylmethyl)-1H-imidazol-2-one (150 mg, crude). MS m / z (ESI): 397 [M+H].

[0340] Step 7: Preparation of Example 1097

[0341] Potassium carbonate (166 mg, 1.2 mmol) was added to a methanol (6 mL) solution of 1097-8 (150 mg, 0.2 mmol, crude product) at room temperature, and the mixture was stirred at 50 °C for 1 hour. The reaction mixture was evaporated to dryness, water was added, and the solution was extracted with ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate, concentrated, and purified by high performance liquid chromatography to give 5-acetyl-4-[3-methyl-5-(1H-pyrrolo[3,2-c]pyridin-4-yloxy)-2-pyridyl]-3-(trideutermethyl)-1H-imidazol-2-one (18.7 mg, yield 21.5%). MS m / z (ESI): 367 [M+H].

[0342] 1 H NMR (400MHz, DMSO) δ11.78(s,1H),10.95(s,1H),8.54(d,J=2.5Hz,1H),7.79(d,J=2.4Hz,1H),7.74 (d,J=5.8Hz,1H),7.56–7.38(m,1H),7.25(d,J=5.8Hz,1H),6.62(s,1H),2.23(s,3H),1.81(s,3H).

[0343] Example 1251

[0344] Step 1: Preparation of Compound 1251-2

[0345] The compound N-(2H3)methyl-1-amino-N-{1-[5-(benzyloxy)-3-(trifluoromethyl)pyridin-2-yl]-2,2-diethoxyethyl}methaneamide (360 mg, 809.97 μmol, referencing the synthesis of intermediate 1017-6) was dissolved in a mixture of methanol (3.6 mL) and water (3.6 mL), and dilute hydrochloric acid (2 M, 1.21 mL) was added. The mixture was heated to 100 °C and stirred for 16 hours. The solution was directly concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to give 3-(2H3)methyl-4-[5-(benzyloxy)-3-(trifluoromethyl)pyridin-2-yl]-2,3-dihydro-1H-imidazol-2-one (260 mg, yield 91.1%). MS m / z (ESI): 353 [M+H].

[0346] Step 2: Preparation of compound 1251-3

[0347] Anhydrous acetonitrile (5 mL) was added to 1251-2 (250 mg, 709.57 μmol), followed by the addition of tetra-n-butylammonium tribromide (513 mg, 1.06 mmol) in portions at 0 °C. The mixture was then stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium sulfite solution, extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 3-(2H3)methyl-4-[5-(benzyloxy)-3-(trifluoromethyl)pyridin-2-yl]-5-bromo-2,3-dihydro-1H-imidazol-2-one (220 mg, yield 71.9%). MS m / z (ESI): 431 [M+H].

[0348] Step 3: Preparation of compound 1251-4

[0349] 1251-3 (200 mg, 463.80 μmol) and n-butyl vinyl ether (139 mg, 1.39 mmol) were dissolved in n-butanol (4 mL). Palladium acetate (10 mg, 46.38 μmol), DPEphos (37 mg, 69.57 μmol), and N,N-diisopropylethylamine (180 mg, 1.39 mmol) were added sequentially. The mixture was purged with nitrogen and stirred at 110 °C for 2 hours. The reaction mixture was cooled to room temperature, dilute hydrochloric acid was added, and the mixture was stirred for 10 minutes. The mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography to obtain 3-(2H3)methyl-5-acetyl-4-[5-(benzyloxy)-3-(trifluoromethyl)pyridin-2-yl]-2,3-dihydro-1H-imidazol-2-one (300 mg, crude product). MS m / z (ESI): 395 [M+H].

[0350] Step 4: Preparation of compound 1251-5

[0351] 1251-4 (300 mg, crude product) was dissolved in anhydrous methanol (10 mL), and wet palladium on carbon (60 mg) was added under nitrogen protection. The mixture was then purged with hydrogen and stirred at room temperature for 12 hours under a hydrogen balloon atmosphere. The solution was filtered with diatomaceous earth as an aid, washed with a small amount of methanol, and the filtrate was collected, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 3-(2H3)methyl-5-acetyl-4-[5-hydroxy-3-(trifluoromethyl)pyridin-2-yl]-2,3-dihydro-1H-imidazol-2-one (300 mg, containing ~45% residual n-butanol). MS m / z (ESI): 305 [M+H].

[0352] Step 5: Preparation of Example 1251

[0353] Dissolve 1251-5 (50 mg, 164.34 μmol) and 1-chloropyrrolo[1,2-a]pyrazine (30 mg, 197.21 μmol) in anhydrous dimethyl sulfoxide (1 mL), then add cuprous iodide (3 mg, 16.43 μmol), 2,2,6,6-tetramethyl-3,5-heptadione (5 mg, 24.65 μmol) and cesium carbonate (80 mg, 246.52 μmol) in sequence. Bubble with nitrogen for 30 seconds, seal the tube and stir for 16 hours at 120 °C. The reaction mixture was cooled to room temperature and filtered. The filtrate was directly purified by high-performance liquid chromatography to obtain 3-(2H3)methyl-5-acetyl-4-[5-(pyrrolo[1,2-a]pyrazin-1-yloxy)-3-(trifluoromethyl)pyridin-2-yl]-2,3-dihydro-1H-imidazol-2-one (20.6 mg, yield 29.7%). MS m / z (ESI): 421 [M+H].

[0354] 1 H NMR (400MHz, DMSO) δ11.19(s,1H),9.14(d,J=2.5Hz,1H),8.58(d,J=2.6Hz,1H),8.17(dd,J=4.8,1.0Hz,1H),7.88( dd,J=2.6,1.4Hz,1H),7.12(d,J=4.8Hz,1H),7.02(dt,J=4.1,1.2Hz,1H),6.95(dd,J=4.1,2.5Hz,1H),1.86(s,3H).

[0355] Example 1388

[0356] Step 1: Preparation of 1388-2

[0357] Compound 1388-1 (500 mg, 1.33 mmol, referring to the synthesis of intermediate 1017-10) was dissolved in anhydrous N,N-dimethylformamide (10 mL), and sodium hydride (80 mg, 1.99 mmol) was added in portions at 0 °C under nitrogen protection, with stirring for 0.5 h. SEM-Cl (265 mg, 1.59 mmol) was added dropwise, and the reaction was allowed to proceed to room temperature for 12 h. The reaction was quenched dropwise by adding saturated ammonium chloride solution under ice bath conditions. The mixture was diluted with water, extracted with ethyl acetate, and the organic phases were combined. The mixture was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3-(2H3)methyl-4-[5-(benzyloxy)-3-methylpyridin-2-yl]-5-bromo-1-(5,5-dimethyl-2-oxa-5-silazhex-1-yl)-2,3-dihydro-1H-imidazol-2-one (280 mg, yield 41.6%). MS m / z (ESI): 507 [M+H].

[0358] Step 2: Preparation of compound 1388-3

[0359] 1388-2 (260 mg, 512.31 μmol) was dissolved in anhydrous N,N-dimethylformamide (5 mL), followed by the addition of zinc cyanide (180 mg, 1.54 mmol) and Pd(dppf)Cl2 (37 mg, 51.23 μmol). The mixture was bubbled under nitrogen for 30 seconds and then microwaved at 150 °C for 2 hours. The reaction mixture was cooled to room temperature, diluted with water, extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3-(2H3)methyl-4-[5-(benzyloxy)-3-methylpyridin-2-yl]-1-(5,5-dimethyl-2-oxa-5-silazhex-1-yl)-2-oxoylideimidazol-5-carboxynitrile (180 mg, yield 77.4%). MS m / z (ESI): 454 [M+H].

[0360] Step 3: Preparation of compound 1388-4

[0361] 1388-3 (140 mg, 308.63 μmol) was dissolved in anhydrous tetrahydrofuran (5 mL). Ethyl magnesium bromide (3 M, 1.03 mL) was added under nitrogen protection in an ice bath, and the mixture was stirred at 20 °C for 2 hours. The reaction mixture was cooled to 0 °C, and the reaction was quenched with dilute hydrochloric acid (1 M, 2.5 mL). The mixture was diluted with water, extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography to give 3-(2H3)methyl-4-[5-(benzyloxy)-3-methylpyridin-2-yl]-1-(5,5-dimethyl-2-oxa-5-silazhex-1-yl)-5-propionyl-2,3-dihydro-1H-imidazol-2-one (100 mg, yield 42.0%). MS m / z (ESI): 485 [M+H].

[0362] Step 4: Preparation of compound 1388-5

[0363] 100 mg of 1388-4 was dissolved in 5 mL of anhydrous methanol. Under nitrogen protection, 20 mg of wet palladium on carbon was added, followed by hydrogen purging. The mixture was stirred at room temperature for 16 hours under a hydrogen balloon atmosphere. The solution was filtered with diatomaceous earth as an aid, washed with a small amount of methanol, and the filtrate was collected and concentrated under reduced pressure. The residue was purified by thin-layer chromatography to give 3-(2H3)methyl-1-(5,5-dimethyl-2-oxa-5-silazhex-1-yl)-4-(5-hydroxy-3-methylpyridin-2-yl)-5-propionyl-2,3-dihydro-1H-imidazol-2-one (40 mg, yield 78.2%). MS m / z (ESI): 395 [M+H].

[0364] Step 5: Preparation of compound 1388-6

[0365] Dissolve 1388-5 (5 mg, 12.67 μmol) and 1-chloropyrrolo[1,2-a]pyrazine (3.87 mg, 25.35 μmol) in anhydrous dimethyl sulfoxide (0.1 mL), then add cuprous iodide (2 mg, 12.67 μmol), 2,2,6,6-tetramethyl-3,5-heptadione (5 mg, 25.35 μmol) and cesium carbonate (6 mg, 19.01 μmol) in sequence. Bubble under nitrogen for 30 seconds, seal the tube and stir for 12 hours at 120 °C. The reaction mixture was cooled to room temperature, diluted with water, extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain 3-(2H3)methyl-1-(5,5-dimethyl-2-oxa-5-silazhex-1-yl)-4-[3-methyl-5-(pyrrolo[1,2-a]pyrazin-1-yloxy)pyridin-2-yl]-5-propionyl-2,3-dihydro-1H-imidazol-2-one (6 mg, yield 92.7%). MS m / z (ESI): 511.2 [M+H].

[0366] Step 6: Preparation of Example 1388

[0367] 1388-6 (6 mg) was dissolved in trifluoroacetic acid (0.5 mL), and cysteine ​​(6 mg) was added. The mixture was then stirred at 15 °C for 16 hours. The solution was directly concentrated under reduced pressure and purified by high-performance liquid chromatography to give 3-(2H3)methyl-4-[3-methyl-5-(pyrrolo[1,2-a]pyrazin-1-yloxy)pyridin-2-yl]-5-propionyl-2,3-dihydro-1H-imidazol-2-one (1.0 mg, yield 21.5%). MS m / z (ESI): 381 [M+H].

[0368] 1 H NMR (400MHz, DMSO) δ10.96(s,1H),8.59(d,J=2.6Hz,1H),8.12(d,J=4.9Hz,1H),7.87(dd,J=21.4,2.6Hz,2H ),7.09(d,J=4.7Hz,1H),6.99–6.85(m,2H),2.23(s,3H),2.13(dt,J=7.5,3.9Hz,2H),0.85(t,J=7.2Hz,3H).

[0369] Example 1518

[0370] Preparation of 4-acetyl-5-(5-((8-fluoropyrrolo[1,2-a]pyrazin-1-yl)oxy)-3-methylpyridin-2-yl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one

[0371] Step 1: Preparation of Compound 1518-2

[0372] Cs₂CO₃ (13.6 g, 41.78 mmol) was added to a mixed solution of 1518-1 (4.6 g, 32.14 mmol), 2-bromo-1,1-diethoxyethane (7.6 g, 38.56 mmol), and DMF (46 mL). The mixture was heated to 100 °C and stirred for 16 hours under nitrogen protection. The reaction solution was cooled, quenched with water, and extracted with petroleum ether. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The filtrate was purified by silica gel column chromatography to give methyl 1-(2,2-diethoxyethyl)-3-fluoro-1H-pyrrole-2-carboxylate (7.2 g, yield 86.4%). MS m / z (ESI): 260 [M+H].

[0373] Step 2: Preparation of compound 1518-3

[0374] Lithium hydroxide (3.3 g, 139.0 mmol) was added to a mixed solution of 1518-2 (7.2 g, 27.8 mmol), water (58 mL), and ethanol (58 mL). The mixture was heated to 50 °C and stirred for 16 hours under nitrogen protection. The ethanol was removed by concentration under reduced pressure. The pH was adjusted to 1-2 with 6N hydrochloric acid solution. The mixture was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated and purified by silica gel column chromatography to give 1-(2,2-diethoxyethyl)-3-fluoro-1H-pyrrole-2-carboxylic acid (5.7 g, yield 83.7%). MS m / z (ESI): 246 [M+H].

[0375] Step 3: Preparation of compound 1518-4

[0376] Under ice bath conditions, EDCI (4.1 g, 21.2 mmol), HOBT (2.9 g, 21.2 mmol), and triethylamine (5 g, 48.99 mmol) were added sequentially to a mixture of 1518-3 (4 g, 16.3 mmol) and ammonium chloride (4.4 g, 81.6 mmol) in DMF (65 mL). After 5 minutes, the mixture was moved to room temperature and reacted for 4 hours. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to give 1-(2,2-diethoxyethyl)-3-fluoro-1H-pyrrole-2-carboxamide (3.5 g, 87.4% yield). MS m / z (ESI): 245 [M+H].

[0377] Step 4: Preparation of compound 1518-5

[0378] Under nitrogen protection and at room temperature, 1518-4 (3.5 g, 25.55 μmol) was added to acetic acid (20 mL), and the mixture was heated to 105 °C and stirred for 3 hours. The solution was concentrated under reduced pressure, diluted with dichloromethane, and concentrated again under reduced pressure. The concentrate was added to petroleum ether, stirred for ten minutes, and filtered to give 8-fluoropyrrolo[1,2-a]pyrazin-1-ol (2.0 g, yield 91.8%). MS m / z (ESI): 153 [M+H].

[0379] Step 5: Preparation of compound 1518-6

[0380] 1518-5 (1 g) was added to POCl3 (10 mL) and heated to 80 °C with stirring for 2 hours. After the reaction was complete, the mixture was concentrated under reduced pressure, diluted and quenched with saturated sodium bicarbonate aqueous solution, extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated and purified by silica gel column chromatography to give 1-chloro-8-fluoropyrrolo[1,2-a]pyrazine (1.0 g, yield 89.2%). MS m / z (ESI): 171 [M+H] + .

[0381] Step 6: Preparation of Example 1518

[0382] 5-Acetyl-4-(5-hydroxy-3-methyl-2-pyridyl)-3-(trideutermethyl)-1H-imidazol-2-one (45 mg, 0.18 mmol), 1-chloro-8-fluoropyrrolo[1,2-a]pyrazine (61.34 mg, 0.36 mmol), 2,2,6,6-tetramethyl-3,5-heptadecane (13 mg, 0.072 mmol), CuI (6.85 mg, 0.036 mmol) and cesium carbonate (176 mg, 0.54 mmol) were stirred at 120 °C for 1.5 hours in dimethyl sulfoxide (2.5 mL). The reaction solution was filtered and purified by high-performance liquid chromatography (HPLC) to give 4-acetyl-5-(5-((8-fluoropyrrolo[1,2-a]pyrazin-1-yl)oxy)-3-methylpyridin-2-yl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (41.4 mg, yield 50.8%). MS m / z (ESI): 385 [M+H].

[0383] 1H NMR (400MHz, DMSO) δ10.97(s,1H),8.62(d,J=2.4Hz,1H),7.98–7.94(m,1H),7.92(d,J=2.1Hz, 1H),7.73–7.64(m,1H),6.98(d,J=4.9Hz,1H),6.81(d,J=3.0Hz,1H),2.25(s,3H),1.82(s,3H).

[0384] Example 1519

[0385] Synthesis of 4-acetyl-1-(methyl-d3)-5-(3-methyl-5-((7-methylpyrrolo[1,2-a]pyrazin-1-yl)oxy)pyridin-2-yl)-1,3-dihydro-2H-imidazol-2-one

[0386] Step 1: Preparation of Compound 1519-2

[0387] 7-Bromo-1-chloropyrrolo[1,2-a]pyrazine (400 mg, 1.73 mmol), trimethylcycloboroxane (3.5 M tetrahydrofuran solution, 987 μL), and potassium carbonate (716.5 mg, 5.18 mmol) were dissolved in a mixed solvent of 1,4-dioxane (15 mL) and water (3 mL). 1,1-bis(diphenylphosphine)dimerferropalladium dichloride (125.7 mg, 172.80 μmol) was added. The reaction system was purged with nitrogen three times, and the reaction mixture was stirred at 95 °C for 10 hours. 20 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (10 mL × 3). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to give 1-chloro-7-methylpyrrolo[1,2-a]pyrazine (74.5 mg, yield 25.9%). MS m / z (ESI): 167 [M+H].

[0388] Step 2: Preparation of Example 1519

[0389] 5-Acetyl-4-(5-hydroxy-3-methyl-2-pyridyl)-3-(trideutermethyl)-1H-imidazol-2-one (75 mg, 299.68 μmol), compound 1519-2 (74.5 mg, 447.16 μmol), 2,2,6,6-tetramethyl-3,5-heptadecyl dione (22.1 mg, 119.87 μmol) and cesium carbonate (292.9 mg, 899.04 μmol) were suspended in dimethyl sulfoxide (2 mL), and cuprous iodide (11.4 mg, 59.94 μmol) was added. The mixture was purged with nitrogen, and the reaction solution was stirred at 110 °C for 12 hours. The reaction solution was cooled, quenched with water, extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by reversed-phase preparative high-performance liquid chromatography to obtain 4-acetyl-1-(methyl-d3)-5-(3-methyl-5-((7-methylpyrrolo[1,2-a]pyrazin-1-yl)oxy)pyridin-2-yl)-1,3-dihydro-2H-imidazol-2-one (20.1 mg, yield 17.3%). MS m / z (ESI): 381 [M+H].

[0390] 1 H NMR (400MHz, CDCl3) δ = 8.83-8.69 (m, 1H), 8.63 (br s,1H),7.73(d,J=1.9Hz,1H),7.57(d,J=4.8Hz,1H),7.30(s,1H),7.01(d,J=4.8Hz,1H),6.78(s,1H),2.37(s,3H),2.31(s,3H),1.87(s,3H).

[0391] Example 1520

[0392] Synthesis of 4-acetyl-5-(5-((7-fluoropyrrolo[1,2-a]pyrazin-1-yl)oxy)-3-methylpyridin-2-yl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one

[0393] Step 1: Preparation of Compound 1520-2

[0394] Cesium carbonate (10.47 g, 32.14 mmol) was added to a 50 mL solution of DMF containing 1520-1 (2.3 g, 16.07 mmol). After stirring at room temperature for 0.5 hours, bromoacetaldehyde diethanolamide (4.75 g, 24.11 mmol) was added, and the reaction was continued at 100 °C with stirring for 10 hours. The reaction solution was quenched with water, extracted with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give a colorless liquid, methyl 1-(2,2-diethoxyethyl)-4-fluoro-1H-pyrrole-2-carboxylate (4.17 g, 100% yield). MS m / z (ESI): 260 [M+H].

[0395] Step 2: Preparation of compound 1520-3

[0396] Compound 1520-2 (4.17 g, 16.08 mmol) was dissolved in ethanol (30 mL), and a solution of lithium hydroxide (1.16 g, 48.25 mmol) in water (15 mL) was added. The reaction mixture was stirred at 50 °C for 12 hours. The reaction mixture was concentrated under reduced pressure, and the residue was adjusted to pH 4 with 10% citric acid aqueous solution. Extraction was performed with ethyl acetate, and the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give a white solid 1-(2,2-diethoxyethyl)-4-fluoro-1H-pyrrole-2-carboxylic acid (3.8 g, yield 96.3%). MS m / z (ESI): 246 [M+H].

[0397] Step 3: Preparation of compound 1520-4

[0398] To a DMF (16 mL) solution of compound 1520-3 (1.2 g, 4.89 mmol), ammonium chloride (1.31 g, 24.47 mmol), and 1-hydroxybenzotriazole (991.7 mg, 7.34 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.41 g, 7.34 mmol) and triethylamine (2.05 mL, 14.68 mmol) were added sequentially. The reaction mixture was stirred at 20 °C for 12 h. The reaction mixture was quenched with water, extracted with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 1-(2,2-diethoxyethyl)-4-fluoro-1H-pyrrole-2-carboxamide (1.18 g, 98.7% yield). MS m / z (ESI): 245 [M+H].

[0399] Step 4: Preparation of compound 1520-5

[0400] Compound 1520-4 (1.18 g, 4.83 mmol) was dissolved in acetic acid (30 mL) and stirred at 105 °C for 4 hours. The reaction solution was concentrated under reduced pressure to obtain a crude product, which was then slurried with n-hexane to give 7-fluoropyrrolo[1,2-a]pyrazin-1(2H)-one (570 mg, yield 77.6%). MS m / z (ESI): 153 [M+H].

[0401] Step 5: Preparation of compound 1520-6

[0402] Compound 1520-5 (570 mg, 3.75 mmol) was dissolved in acetonitrile (5 mL), and phosphorus oxychloride (5 mL, 53.64 mmol) was added. The mixture was stirred at 80 °C for 2 hours. The reaction solution was poured into ice water, the pH was adjusted to 8 with saturated sodium bicarbonate solution, and the solution was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography to give 1-chloro-7-fluoropyrrolo[1,2-a]pyrazine (530 mg, yield 82.9%). MS m / z (ESI): 171 [M+H].

[0403] Step 6: Preparation of Example 1520

[0404] 5-Acetyl-4-(5-hydroxy-3-methyl-2-pyridyl)-3-(trideutermethyl)-1H-imidazol-2-one (75 mg, 299.68 μmol), compound 1520-6 (61.3 mg, 359.61 μmol), 2,2,6,6-tetramethyl-3,5-heptadecyl dione (22.1 mg, 119.87 μmol) and cesium carbonate (292.9 mg, 899.04 μmol) were suspended in dimethyl sulfoxide (2 mL), and cuprous iodide (11.4 mg, 59.94 μmol) was added. The reaction system was purged with nitrogen three times, and the reaction solution was stirred at 110 °C for 12 hours. After cooling to room temperature, the reaction solution was quenched with water, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by reversed-phase preparative high-performance liquid chromatography to obtain 4-acetyl-5-(5-(((7-fluoropyrrolo[1,2-a]pyrazin-1-yl)oxy)-3-methylpyridin-2-yl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (47.6 mg, yield 39.8%). MS m / z (ESI): 385 [M+H].

[0405] 1H NMR (400MHz, CDCl3) δ=8.86(br s,1H),8.64(br s,1H),7.73(s,1H),7.58(br d,J=4.4Hz,1H),7.33(br s,1H),7.14(br d,J=4.1Hz,1H),6.69(s,1H),2.32(s,3H),1.88(s,3H).

[0406] Example 1521

[0407] Step 1: Preparation of Compound 1521-2

[0408] 5-Bromo-2-chloropyridin-3-ol (22 g, 105.55 mmol) was dissolved in acetone (250 mL), and potassium carbonate (29.17 g, 211.09 mmol) was added. After stirring at room temperature for 0.5 hours, deuterated iodomethane (18.36 g, 126.65 mmol) was added, and the reaction was stirred at 20 °C for 12 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 5-bromo-2-chloro-3-(trideuteriummethoxy)pyridine (20.9 g, yield 87.8%). MS m / z (ESI): 225, 227 [M+H].

[0409] Step 2: Preparation of compound 1521-3

[0410] 1521-2 (2.2 g, 9.76 mmol), cesium carbonate (9.54 g, 29.76 mmol), benzyl alcohol (5.28 g, 48.8 mmol), and 3,4,7,8-tetramethyl-1,10-phenanthroline (461 mg, 1.95 mmol) were added to toluene (70 mL), and the mixture was heated to 110 °C and reacted for 17 hours. After cooling to room temperature, the reaction mixture was filtered, the filter cake was washed with ethyl acetate, the filtrate was poured into water, extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 5-benzyloxy-2-chloro-3-(trideuteroxy)pyridine (2.1 g, yield 85.2%). MS m / z (ESI): 253 [M+H].

[0411] Step 3: Preparation of compound 1521-4

[0412] 1521-3 (2.1 g, 8.31 mmol), (E)-1-ethoxyvinyl-2-boronic acid pinacol ester (1.98 g, 9.97 mmol), potassium carbonate (2.87 g, 20.77 mmol), and Pd(dppf)Cl2 (607 mg, 0.83 mmol) were added to dioxane / water (25 mL / 5 mL), purged with nitrogen, and reacted at 100 °C for 17 hours. After cooling, concentration, washing with water, extraction with ethyl acetate, concentration under reduced pressure, and purification by silica gel column chromatography yielded 5-benzyloxy-2-[(E)-2-ethoxyvinyl]-3-(trideuterylmethoxy)pyridine (1.9 g, yield 79.3%). MS m / z (ESI): 289 [M+H].

[0413] Step 4: Preparation of compound 1521-5

[0414] 1521-4 (1.9 g, 6.59 mmol) and NBS (1.23 g, 6.92 mmol) were added to tetrahydrofuran (20 mL) and ethanol (76 mL), and the reaction was carried out at room temperature for 2 hours. The reaction solution was quenched with water, extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 5-(benzyloxy)-2-(1-bromo-2,2-diethoxyethyl)-3-methylpyridine (0.28 g, yield 10.3%).

[0415] Step 5: Preparation of compound 1521-6

[0416] 1521-5 (12.0 g, 29.03 mmol), potassium hydroxide (32.58 g, 580.66 mmol), and deuterated methylamine hydrochloride (20.48 g, 290.33 mmol) were added to dioxane / water (250 mL / 25 mL). The mixture was reacted in a sealed container at 100 °C for 3.5 hours. After cooling, the reaction solution was filtered, the filter cake was washed with ethyl acetate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain 1-[5-benzyloxy-3-(trideuteroxymethoxy)-2-pyridyl]-2,2-diethoxy-N-(trideutermethyl)ethylamine (3.8 g, yield 35.7%). MS m / z (ESI): 367 [M+H].

[0417] Step 6: Preparation of compound 1521-7

[0418] 1521-6 (8.7 g, 23.74 mmol), trimethylsilyl isocyanate (5.47 g, 47.48 mmol), and potassium carbonate (6.56 g, 47.48 mmol) were added to dichloromethane (180 mL), reacted at room temperature for 3 hours, concentrated under reduced pressure, and purified by silica gel column chromatography to give 1-[1-[5-benzyloxy-3-(trideuteroxymethoxy)-2-pyridyl]-2,2-diethoxyethyl]-1-(trideutermethyl)urea (8.0 g, yield 82.3%). MS m / z (ESI): 410 [M+H].

[0419] Step 7: Preparation of compound 1521-8

[0420] 1521-7 (8 g, 19.51 mmol) and p-toluenesulfonic acid (9.97 g, 57.89 mmol) were added to ultra-dry toluene (120 mL), and the reaction was carried out at 105 °C for 2 h. After cooling, the mixture was concentrated under reduced pressure, adjusted to neutral with saturated sodium bicarbonate, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 4-[5-benzyloxy-3-(trideuteroxymethoxy)-2-pyridyl]-3-(trideutermethyl)-1H-imidazol-2-one (2.6 g, yield 42.5%). MS m / z (ESI): 318 [M+H].

[0421] Step 8: Preparation of compound 1521-9

[0422] 0.8 g (2.52 mmol) of 1521-8 was added to ultra-dry acetonitrile (45 mL) and cooled to 0 °C. Tetrabutylammonium tribromide (0.97 g, 2.02 mmol) was dissolved in ultra-dry acetonitrile (1 mL) and added dropwise. The reaction was carried out in an ice bath for 3 minutes. The reaction was quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give 4-[5-benzyloxy-3-(trideuteriummethoxy)-2-pyridyl]-5-bromo-3-(trideuteriummethyl)-1H-imidazol-2-one (0.3 g, yield 30.0%). MS m / z (ESI): 396, 398 [M+H].

[0423] Step 9: Preparation of compound 1521-10

[0424] Under nitrogen purging, 1521-9 (70 mg, 0.18 mmol), vinyl n-butyl ether (88 mg, 0.88 mmol), DIPEA (68 mg, 0.53 mmol), palladium acetate (8 mg, 0.04 mmol), and DPEphos (38.05 mg, 70.66 μmol) were added to n-butanol (2 mL), and the mixture was sealed and reacted at 100 °C for 17 hours. After cooling to room temperature, the n-butanol was removed by concentration with water, and the product was separated by reverse-phase preparative column chromatography to obtain 5-acetyl-4-[5-benzyloxy-3-(trideuteriummethoxy)-2-pyridyl]-3-(trideuteriummethyl)-1H-imidazol-2-one (25 mg, yield 39.4%). MS m / z (ESI): 360 [M+H].

[0425] Step 10: Preparation of compound 1521-11

[0426] 1521-10 (25 mg, 69.56 μmol) was dissolved in methanol (2 mL), and Pd / C (4.22 mg, 34.78 μmol) was added. The mixture was then purged with hydrogen and reacted at room temperature under a hydrogen balloon for 3 hours. The mixture was filtered, and the filtrate was concentrated to give 5-acetyl-4-[5-hydroxy-3-(trideuteriummethoxy)-2-pyridyl]-3-(trideuteriummethyl)-1H-imidazol-2-one (16 mg, yield 85.4%). MS m / z (ESI): 270 [M+H].

[0427] Step 11: Preparation of Example 1521

[0428] 1521-11 (25 mg, 92.84 μmol) was dissolved in dimethyl sulfoxide (1 mL), and cesium carbonate (61 mg, 185.67 μmol) and 1-chloro-H-pyrrolo[1,2-A]pyrazine (16 mg, 102.12 μmol) were added. The reaction was carried out at 90 °C for 4 hours. After filtration, 4-acetyl-5-(3-(methoxy-d3)-5-(pyrrolo[1,2-a]pyrazin-1-yloxy)pyridin-2-yl)-1-(methyl-d3)-1,3-dihydro-2H-imidazol-2-one (3 mg, yield 5.60%) was prepared from the filtrate. MS m / z (ESI): 386 [M+H].

[0429] 1 H NMR (400MHz, DMSO) δ10.91(s,1H),8.38(d,J=2.2Hz,1H),8.13(d,J=4.8Hz,1H),7.88–7.83(m,1H),7.80 (d,J=2.2Hz,1H),7.10(d,J=4.8Hz,1H),6.98(d,J=4.0Hz,1H),6.92(dd,J=4.1,2.5Hz,1H),1.83(s,3H)

[0430] The preparation of the following examples follows the synthesis method of Example 1518 or Example 1521:

[0431] The NMR characterization data of the relevant embodiments are shown in the table below:

[0432] Biological testing evaluation

[0433] The present invention will be further described and explained below with reference to test examples, but these embodiments are not intended to limit the scope of the present invention.

[0434] Test Example 1: Determination of the binding effect of the compound of the present invention on dopamine D1 receptors

[0435] 1. Experimental Objective: To determine the IC50 of the test compound's binding to dopamine D1 receptors using a radioisotope ligand binding assay. 50 .

[0436] 2. Experimental instruments and reagents:

[0437] 2.1 Instrument: Envision (PE-Cisbio: 2105-0020), Unifilter-96GF / C filter plates (PE: 6005174), ECHO (Labcyte: ECHO 555), Bravo (Agilent: Bravo V11), MicroBeta2 (PE: CNLL0153).

[0438] 2.2 Reagents: DMSO (Sigma: D4540); Poly ethyleneimine, PEI (Sigma: P3143); MicroScint-O cocktail (PE: 6013611); [ 3 H]SCH 23390 (PE: NET930250UC); HEK293 D1 stable transgenic cells.

[0439] 3. Experimental methods:

[0440] 1) Preparation of cell membrane proteins: Dilute cell membrane proteins to the specified concentration using experimental buffer;

[0441] 2) Preparation of radioactive isotope ligands: Dilute the radioactive isotope ligands to the specified concentration using experimental buffer solution;

[0442] 3) Dilution of positive and test compounds: Positive compounds were serially diluted 4-fold at 8 sites. Test compounds were initially diluted to a final concentration of 10 μM, and were also serially diluted 4-fold at 8 sites. 1 μL of the diluted compound was transferred to the reaction plate according to the compound arrangement diagram. 1 μL of the prepared nonspecific binding compound and DMSO were transferred to the reaction plate, serving as the nonspecific binding well (low signal control: LC) and the total binding well (high signal control: HC), respectively.

[0443] 4) Add 100 μL of the specified concentration of cell membrane protein according to the arrangement of the reaction plate;

[0444] 5) Add 100 μL of a radioactive isotope of the specified concentration;

[0445] 6) After sealing, incubate on a shaker at a specified temperature for a specified time;

[0446] 7) Immerse the GF / C plate in 50 μL of 0.3% PEI solution at room temperature for at least half an hour;

[0447] 8) After the reaction is complete, collect the cell membrane onto a GF / C filter plate using cell harvesting and wash it four times with cold wash buffer.

[0448] 9) Place the GF / C board in a 50℃ oven and dry for 1 hour;

[0449] 10) Seal the bottom of the dried GF / C filter plate with a membrane, add 50 μL of scintillation solution to each well, and seal it.

[0450] 11) Read the values ​​using MicroBeta2.

[0451] 4. Experimental data processing methods:

[0452] Calculation formula: % Inhibition rate = 100 × [1 - (sample well reading - non-specific binding well reading) / (total binding well reading - non-specific binding well reading)].

[0453] The data was analyzed using the model "log(inhibitor) vs. response--Variable slope" in GraphPad Prism 5.0.

[0454] 5. Experimental Results and Conclusions:

[0455] The above methods demonstrate that the compounds of this invention exhibit good binding activity to both dopamine D1 and D5 receptors. In tests measuring the binding activity to the dopamine D1 receptor, the compounds showed binding efflux rates of approximately 0.1 nM to 100 nM (Ki or IC50). 50The bioactivity of the dopamine D5 receptor was measured in assays showing a range of approximately 0.1 nM to 100 nM (Ki or IC50). 50 (value) biological activity.

[0456] In some embodiments, the compounds of the present invention bind to the Ki or IC of dopamine D1 receptors. 50 The value is less than about 100 nM, preferably less than about 50 nM, more preferably less than about 20 nM, and even more preferably less than about 10 nM;

[0457] In some embodiments, the compounds of the present invention bind to the dopamine D5 receptor at a Ki or IC level. 50 The value is less than about 100 nM, preferably less than about 50 nM, more preferably less than about 20 nM, and even more preferably less than about 10 nM;

[0458] Test Example 2: Determination of the agonistic effects of the compounds of the present invention on dopamine D1 and D5 receptors.

[0459] 1. Experimental objective: To detect the agonistic effect of the compound on dopamine D1 and D5 receptors.

[0460] 2. Experimental instruments and reagents:

[0461] 2.1 Instruments: Microplate reader (PE: Envision), 96-well plate (ThermoFisher: 249944), 384-well plate (PE: 6007680), pipettes (Eppendorf, 100-1000uL), 12-channel electric pipette (METTLER TOLEDO: 2-20uL), 12-channel electric pipette (Eppendorf: 15-300uL), refrigerated centrifuge (Eppendorf: 5810R).

[0462] 2.2 Reagents: cAMP Kit (PE: TRF0263); IBMX (Sigma: I5879); FBS (AUS GeneX: FBS500-S); Ham's F-12K (Kaighn's) Medium (Hyclone: ​​SH30526.01); Flpin-CHO-D1 cells; Flpin-CHO-D5 cells

[0463] 3. Experimental methods:

[0464] 1) Cell treatment: Digest the cells, resuspend them in experimental buffer, and seed them into 384 cell culture plates at a seeding density of 8000 cells per well and a seeding volume of 15 μl per well.

[0465] 2) Compound preparation: Dilute the compound with experimental buffer solution;

[0466] 3) Add 4 μl of the compound to each well and incubate at 37°C for 30 minutes;

[0467] 4) Freeze-thaw Eu-cAMP tracer and Ulight-anti-cAMP, then dilute them with lysis buffer;

[0468] 5) Add 5 μl of Eu-cAMP tracer to the well, and then add 5 μl of Ulight-anti-cAMP to the well;

[0469] 6) Centrifuge the reaction plate at 200g for 30 seconds at room temperature, let it stand at room temperature for 1 hour, and then collect data using Envision.

[0470] 4. Experimental data processing methods:

[0471] Calculate the inhibition rate using the following formula: %Activity = 100 - (Signal) cmpd -Signal Ave_PC ) / (Signal Ave_VC -Signal Ave_PC )×100

[0472] The data was analyzed using the model "log(agonist) vs. response - Variable slope" in GraphPad Prism 5.0, and the nonlinear fitting conformed to the following formula:

[0473] Y=Bottom+(Top-Bottom) / (1+10(LogEC50-X)×Hillslope)

[0474] Where X: compound concentration log value; Y: %Activity.

[0475] 5. Experimental Results:

[0476] Table 1: Agonistaltic activity of compounds on dopamine D1 and D5 receptors

[0477] 6. Experimental conclusions: The compounds shown in this invention exhibit good partial agonistic effects on both dopamine D1 and D5 receptors.

[0478] Test Example 3: Determination of the effect of the compound of the present invention in promoting the recruitment of β-arrestin by dopamine D1 receptor.

[0479] 1. Experimental objective: To investigate the effect of the compound on promoting the recruitment of β-arrestin by dopamine D1R.

[0480] 2. Main experimental instruments and reagents:

[0481] 2.1 Reagents: Nano-Glo Live Cell Assay System (Promega: N2012); FuGENE HD Transfection Reagent (Promega: E-2311); FBS (Gibco: 10099141C); DMEM (Gibco: 10565018); Opti-MEM (Gibco: 11058-021).

[0482] 2.2 Cells: HEK-293 cells.

[0483] 3. Experimental Methods: HEK-293 cells were seeded at a density of 4e6 cells into T75 culture dishes (12 mL of DMEM containing 10% FBS), and transfected with equal proportions of D1R-LgBiT and SmBiT-β-arrestin2 using FUGENE reagent. After 24 h, the cells were resuspended in Opti-MEM and seeded at a density of 3e5 cells / mL into 96-well plates, 100 μL per well. Preparation Add 25 μL of Live Cell Reagent to each well and incubate for 30 min in an incubator. Add the compound to induce β-arrestin2 recruitment, and read the plate using Envision.

[0484] 4. Experimental data processing methods:

[0485] Use the following formula to calculate recruitment activity: %Activity = (Signal cmpd -Signal Ave_VC ) / (Signal Ave_PC -Signal Ave_VC )×100

[0486] The data was analyzed using the model "log(agonist) vs. response -- variable slope" in GraphPad Prism, and the nonlinear fitting conformed to the following formula:

[0487] Y=Bottom+(Top-Bottom) / (1+10(LogEC50-X)×Hillslope)

[0488] Where X: compound concentration log value; Y: %Activity.

[0489] 5. Experimental Results:

[0490] Table 2: Agonist Activity of Compounds on Dopamine D1 Receptor Recruiting β-arrestin

[0491] 6. Experimental Conclusion: The compounds of the present invention have a low Emax value, indicating that the ability of the compounds to recruit β-arrestin2 after stimulating D1R is weak.

[0492] Test Example 4 Rat PK Experiment

[0493] 1. Research Objective: Using SD rats as test animals, study the pharmacokinetic behavior of the compounds in the examples after oral administration in rats (plasma).

[0494] 2. Test Scheme

[0495] 2.1 Test Drugs: The compounds of the present invention, self-made.

[0496] 2.2 Test Animals: 3 male SD rats in each group. Shanghai Jiesijie Laboratory Animal Co., Ltd., Animal Production License Number (SCXK (Shanghai) 2013-0006 N0.311620400001794).

[0497] 2.3 Drug Preparation:

[0498] Oral Administration Drug Preparation: 10% Captisol in 50 mM citrate buffer pH 5.0

[0499] Preparation of 50 mM Citric Acid: Weigh 4.8 g of citric acid into a 1000 ml glass bottle, add ultrapure water to 300 ml, stir magnetically to completely dissolve it, and supplement ultrapure water to 500 ml to prepare 50 mM citric acid.

[0500] Preparation of 50 mM Citric Acid (10% Captisol, PH = 5): Weigh 50 g of Captisol powder, add it to a 1000 ml glass bottle, add 300 ml of 50 mM citric acid, stir magnetically to completely dissolve it, supplement citric acid to 500 ml, and adjust the PH = 5 with 10 M NaOH.

[0501] Weigh the compound in the example and dissolve it in this solution, shake well, and ultrasonicate for 15 minutes to obtain a colorless and clear solution with a concentration of 3 mg / mL.

[0502] 2.4 Administration: 3 male SD rats in each group; after fasting overnight, they are administered PO respectively, with a dose of 5 - 30 mg / kg and an administration volume of 10 mL / kg.

[0503] 2.5 Sample collection: 0.2 mL of blood was collected from the jugular vein before administration and at 0.25 h, 0.5 h, 1.0 h, 2.0 h, 4.0 h, 6.0 h, 8.0 h, and 24.0 h after administration. The blood was placed in EDTA-2K tubes and centrifuged at 6000 rpm for 6 min at 4 °C to separate the plasma. The plasma was stored at -20 °C. Food was consumed 4 h after administration.

[0504] 3. Experimental Results: The final measurement results were obtained using the LCMS / MS method:

[0505] Table 3: Pharmacokinetic parameters of the compounds administered orally in rats

[0506] 4. Experimental conclusion: The results show that the compounds in the examples have high oral exposure levels.

Claims

1. A compound of general formula (IA) or (IE), its stereoisomer, or a pharmaceutically acceptable salt thereof: in: M3 is selected from O, S, NR 3a NOR 3b NC(O)R 3c NC(O)OR 3b NS(O)R 3c NS(O)2R 3c or NP(O)R 3b R 3c Preferred from O, S, NR 3a NOR 3b or NC(O)R 3c ; M 10 selected from O or S; L1 is selected from the bond, -(CH2). n1 O(CH2) n2 -、-(CH2) n1 C(O)(CH2) n2 -、-(CH2) n1 C(S)(CH2) n2 -、-(CH2) n1 NR N (CH2) n2 -、-(CH2) n1 S(CH2) n2 -、-(CH2) n1 S(O)(CH2) n2 -、-(CH2) n1 S(O)2(CH2) n2 -、-(CH2) n1 CONR N (CH2) n2 -、-(CH2) n1 S(O)2NR N (CH2) n2 -、C 1-6 Alkylene, C 1-6 imidene group, C 1-6 Ethyne group, C 3-12 Cycloalkylene or 3-12 membered heterocyclic alkylene groups, wherein the -(CH2) group... n1 O(CH2) n2 -、-(CH2) n1 C(O)(CH2) n2 -、-(CH2) n1 C(S)(CH2) n2 -、-(CH2) n1 NR N (CH2) n2 -、-(CH2) n1 S(CH2) n2 -、-(CH2) n1 S(O)(CH2) n2 -、-(CH2) n1 S(O)2(CH2) n2 -、-(CH2) n1 CONR N (CH2) n2 -、-(CH2) n1 S(O)2NR N (CH2) n2 -、C 1-6 Alkylene, C 1-6 imidene group, C 1-6 Ethyne group, C 3-12 Cycloalkylene and 3-12 membered heterocyclic groups, optionally further modified by hydrogen, deuterium, halogen, substituted or unsubstituted amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2- 6-Alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; Ring A is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl groups; R 1a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R 1b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; Or, R 1b With R a It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R 1d Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R 1e It is absent or selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R2 is selected from C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2- 6-olefin, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1- 6-alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 heteroaryl groups, optionally further divided by 1, 2, 3, 4, 5 or 6 R groups. b Substituents; R 3a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R 3b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R 3c Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; Or, any two R a It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of aryl and substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m2 R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R N Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R aa Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R bb Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R cc Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; Or, R aa R bb With R cc Any two atoms in a given matrix can form a carbon atom with their adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R dd Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R ee Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R ff Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; Or, R dd R ee With R ff Any two atoms in a given matrix can form a carbon atom with their adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; The substituents in the general formula (IA) can also be -SF5; the preferred substituents are R. 1b R 1d R 1e R a or R b ; x is an integer of 0, 1, 2, 3, 4, 5 or 6; m1 is 0, 1 or 2; m2 is 0, 1 or 2; n1 is 0, 1, 2 or 3; n2 is 0, 1, 2 or 3; n3 is 0, 1, 2 or 3; and n4 is 0, 1, 2 or 3.

2. A compound of Formula (A-I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: ###00001### (A-I) M5 is selected from CR 4b Or N; Y1 is selected from NH, N, CH2, CH, C, C(O), O or S; preferably N, C or C(O); Y2 is selected from NH, N, CH2, CH, C, C(O), O or S; preferably N, C or C(O); Y3 is selected from NH, N, CH2, CH, C, C(O), O or S; preferably N, C or C(O); Alternatively, Y1 and Y2 or Y2 and Y3 can form C with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; L1 is selected from the bond, -(CH2). n1 O(CH2) n2 -、-(CH2) n1 C(O)(CH2) n2 -、-(CH2) n1 C(S)(CH2) n2 -、-(CH2) n1 NR N (CH2) n2 -、-(CH2) n1 S(CH2) n2 -、-(CH2) n1 S(O)(CH2) n2 -、-(CH2) n1 S(O)2(CH2) n2 -、-(CH2) n1 CONR N (CH2) n2 -、-(CH2) n1 S(O)2NR N (CH2) n2 -、C 1-6 Alkylene, C 1-6 imidene group, C 1-6 Ethyne group, C 3-12 Cycloalkylene or 3-12 membered heterocyclic alkylene groups, wherein the -(CH2) group... n1 O(CH2) n2 -、-(CH2) n1 C(O)(CH2) n2 -、-(CH2) n1 C(S)(CH2) n2 -、-(CH2) n1 NR N (CH2) n2 -、-(CH2) n1 S(CH2) n2 -、-(CH2) n1 S(O)(CH2) n2 -、-(CH2) n1 S(O)2(CH2) n2 -、-(CH2) n1 CONR N (CH2) n2 -、-(CH2) n1 S(O)2NR N (CH2) n2 -、C 1-6 Alkylene, C 1-6 imidene group, C 1-6 Ethyne group, C 3-12 Cycloalkylene and 3-12 membered heterocyclic groups, optionally further modified by hydrogen, deuterium, halogen, substituted or unsubstituted amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2- 6-Alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; Ring A is selected from C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl or 5-14 membered heteroaryl; Ring E is absent or selected from C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl or 5-14 membered heteroaryl; R4 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, and C. 1-6 Alkyl, C 1- 6-Deuterated Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; Alternatively, any two R4 atoms can form C with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R 4b Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc =N-OR bb or = CR aa R cc The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R a Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; Or, any two R a It can form carbon with adjacent atoms. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl, wherein C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl and 5-14 quinone heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R c Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 C(O)NR dd OR ee -(CH2) n4 P(O)R dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m2 R ff -(CH2) n4 N=S(O)R dd R ee -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n4 -、-(CH2) n4 R dd -(CH2) n4 OR ee -O(CH2) n4 R dd -(CH2) n4 SR ee -(CH2) n4 C(O)R ff -(CH2) n4 C(O)OR ff -(CH2) n4 S(O) m2 R ff -(CH2) n4 NR dd R ee -(CH2) n4 C(O)NR dd R ee -(CH2) n4 NR ee C(O)R ff -(CH2) n4 NR ee S(O) m2 R ff -OC(R) dd R ee ) m2 (CH2) n4 R dd -NR ee (CH2) n4 R dd -CH=CH(CH2) n4 R dd -CH=CH(CH2) n4 NR dd R ee -CH=CH(CH2) n4 NR ee C(O)R ff -CH=CH(CH2) n4 NR ee C(O)NR dd R ff =N-OR ee or = CR dd R ff The C mentioned therein 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; or, any two R c may form, with the adjacent atoms, a C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl or 5-14 membered heteroaryl, said C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5-14 membered heteroaryl; or R a with R c form a C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl or 5-14 membered heteroaryl, said C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C R N Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R aa Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R bb one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, substituted or unsubstituted 3- to 12-membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1- hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, substituted or unsubstituted 3- to 12-membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, substituted or unsubstituted 3- to 12-membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thioxo, substituted or unsubstituted R cc one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, substituted or unsubstituted 3- to 12-membered heterocyclyl, substituted or unsubstituted 6-14 aryl and substituted or unsubstituted 5- to 14-membered heteroaryl; and 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1- hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, substituted or unsubstituted 3- to 12-membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, substituted or unsubstituted 3- to 12-membered heterocyclyl, substituted or unsubstituted 6-14 aryl and substituted or unsubstituted 5- to 14-membered heteroaryl; and or R aa , R bb , and R cc any two of which, together with the adjacent atoms, can form a C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, or 5-14 membered heteroaryl, said C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, optionally further substituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, substituted with one or more substituents; R dd one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, 3-12 membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1- hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, 3-12 membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, 3-12 membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted R ee Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; R ff Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; or R dd , R ee , and R ff any two of which, together with the adjacent atoms, can form a C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, or 5-14 membered heteroaryl, said C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, optionally further substituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl, and substituted or unsubstituted 5-14 membered heteroaryl; x is an integer of 0, 1, 2, 3, 4, 5 or 6; y is an integer of 0, 1, 2, 3, 4, 5 or 6; m1 is 0, 1 or 2; m2 is 0, 1 or 2; n1 is 0, 1, 2 or 3; n2 is 0, 1, 2 or 3; n3 is 0, 1, 2 or 3; n4 is 0, 1, 2 or 3; and p is selected from 0, 1, 2, 3, 4, 5 or 6.

3. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that, C 5-8 saturated or unsaturated monocyclic cycloalkyl, C 7-12 fused cycloalkyl, C 7-12 spiro cycloalkyl, C 7-12 bridged cycloalkyl, 5-8 membered saturated or unsaturated monocyclic heterocyclyl, 7-12 membered fused heterocyclyl, 7-12 membered spiro heterocyclyl, 7-12 membered bridged heterocyclyl, C 6- 10 aryl or 5-10 membered heteroaryl; Preferably, selected from the group consisting of More preferably, selected from the group consisting of X1is selected from CR 6a R 6b or NR 6b ; X2is selected from CR 6c R 6d or NR 6d ; X3is selected from CR 6e R 6f or NR 6f ; X4is selected from CR 6g R 6h or NR 6h ; X5is selected from CR 7a or N; Ring C is selected from C 3-6 Cycloalkyl or 3-6 membered heterocyclic groups; Cycloalkyl, 3-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; preferably C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; preferably C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; preferably C R 6a , R 6c , R 6e or R 6g are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, -SF5, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, wherein said C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5-14 membered heteroaryl; R 6b R 6d R 6f or R 6h Not present or independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, -SF5, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents from a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 aryl and 5-14 heteroaryl groups, optionally further substituted or unsubstituted with hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, or C. 1-6 Alkyl, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Hydroxyalkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups; or, R 6a or, R 6b or, R 6c or, R 6d or, R 6e or, R 6f or, R 6g or, R 6h any two of which, together with the adjacent atoms to which they are attached, can form a C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, or 5-14 membered heteroaryl, said C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, optionally further substituted with one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl, and substituted or unsubstituted 5-14 membered heteroaryl; R 7a none or one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, 3-12 membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, 3-12 membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 1-6 alkyl, substituted or unsubstituted 1-6 deuteroalkyl, substituted or unsubstituted 1-6 haloalkyl, substituted or unsubstituted 1-6 hydroxyalkyl, substituted or unsubstituted 1-6 alkoxy, substituted or unsubstituted 1-6 haloalkoxy, substituted or unsubstituted 2-6 alkenyl, substituted or unsubstituted 2-6 alkynyl, substituted or unsubstituted 3-12 cycloalkyl, 3-12 membered heterocyclyl, substituted or unsubstituted 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted 4. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to claim 1 or 3, characterized in that, The compounds shown, or a pharmaceutically acceptable salt thereof, are further illustrated by the general formulas (I-11), (I-12), (I-16), or (I-17): R 1c It is absent or selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, -(CH2) n3 -、-(CH2) n3 R aa -(CH2) n3 OR bb -O(CH2) n3 R aa -(CH2) n3 SR bb -(CH2) n3 C(O)R cc -(CH2) n3 C(O)OR cc -(CH2) n3 S(O) m1 R cc -(CH2) n3 NR aa R bb -(CH2) n3 C(O)NR aa R bb -(CH2) n3 NR bb C(O)R cc -(CH2) n3 NR bb S(O) m1 R cc -OC(R) aa R bb ) m1 (CH2) n3 R aa -NR bb (CH2) n3 R aa -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc , -CH=CH(CH2) n3 NR bb C(O)NR aa R cc , =N-OR bb or =CR aa R cc wherein the C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5-14 membered heteroaryl.

5. The compound, stereoisomer, or pharmaceutically acceptable salt thereof of any one of claims 1, 3, or 4, wherein, R2is selected from -C(O)R cc , -C(O)OR cc , -NR aa R bb , -C(O)NR aa R bb , C 3-8 monocyclic cycloalkyl, C 7-12 fused cycloalkyl, C 7-12 spiro cycloalkyl, C 7-12 bridged cycloalkyl, 3-8 membered monocyclic heterocyclyl, 7-12 membered fused heterocyclyl, 7-12 membered spiro heterocyclyl, 7-12 membered bridged heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl; preferably C 3-8 monocyclic cycloalkyl, C 7-12 fused cycloalkyl, C 7-12 spiro cycloalkyl, C 7-12 bridged cycloalkyl, 3-8 membered monocyclic heterocyclyl, 7-12 membered fused heterocyclyl, 7-12 membered spiro heterocyclyl, 7-12 membered bridged heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl; more preferably Further preferred M4 is selected from O, S, CH2, or NH; M5is selected from CR 4b or N; Ring G is selected from C 3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; preferably phenyl, pyridyl, furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl or isothiazolyl; The ring H is selected from 3-12 membered heterocyclic groups or 5-14 membered heteroaryl groups; R 4a , R 4b , R 4c , R 4d , R 4e , R 4f , R 4g , R 4h , R 4i , R 4j , R 4k or R 4l is each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, -SF5, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1- 6hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, 5-14 membered heteroaryl, -(CH2) n4 -, -(CH2) n4 R dd , -(CH2) n4 OR ee , -O(CH2) n4 R dd , -(CH2) n4 SR ee , -(CH2) n4 C(O)R ff , -(CH2) n4 C(O)OR ff , -(CH2) n4 S(O) m2 R ff , -(CH2) n4 P(O)R dd R ee , -(CH2) n4 NR dd R ee , -(CH2) n4 C(O)NR dd R ee , -(CH2) n4 NR ee C(O)R ff , -(CH2) n4 NR ee S(O) m R ff , -OC(R dd R ee ) m2 (CH2) n4 R dd , -NR ee (CH2) n4 R dd , -CH=CH(CH2) n4 R dd , -CH=CH(CH2) n4 NR dd R ee , -CH=CH(CH2) n4 NR ee C(O)R ff , -CH=CH(CH2) n4 NR ee C(O)NR dd R ff , =N-OR ee or =CR dd R ff wherein the C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl are optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5-14 membered heteroaryl; preferably selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, 5-14 membered heteroaryl, -(CH2) n4 , n4 R dd , n4 OR ee , n4 R dd , n4 SR ee , n4 C(O)R ff , n4 C(O)OR ff , n4 S(O) m2 R ff , n4 NR dd R ee , n4 C(O)NR dd R ee , n4 NR ee C(O)R ff , n4 NR ee S(O) m2 R ff , -OC(R dd R ee ) m2 (CH2) n4 R dd , -NR ee (CH2) n4 R dd , -CH=CH(CH2) n4 R dd , -CH=CH(CH2) n4 NR dd R ee , -CH=CH(CH2) n4 NR ee C(O)R ff , -CH=CH(CH2) n4 NR ee C(O)NR dd R ff = N-OR ee or = CR dd R ff wherein the C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5-14 membered heteroaryl; or, any two R 4a , R 4b , R 4c , R 4d , R 4e , R 4f , R 4g , R 4h , R 4i , R 4j , R 4k or R 4l may form, with the atom to which they are attached, a C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, or 5-14 membered heteroaryl, said C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6- 14 aryl, and 5-14 membered heteroaryl, optionally further substituted by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl, and substituted or unsubstituted 5-14 membered heteroaryl; n5 is selected from 0, 1, or 2; y is selected from 0, 1, 2, 3, or 4; q is selected from 0, 1, 2, 3, or 4.

6. The compound according to any one of claims 1 to 5, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, The compounds shown, or a pharmaceutically acceptable salt thereof, are further illustrated by the general formulas (A-II-1), (A-II-3), (A-II-7), (A-II-8), (A-II-9), (A-II-10), (A-II-21), or (A-II-22): Preferably, as indicated by general formula (A-II-19), (A-II-20), (A-II-23) or (A-II-24): More preferably, as indicated by general formula (A-II-19-A), (A-II-19-B), (A-II-20-A) or (A-II-20-B): X6is selected from N or CR 6c ; Y4is selected from N, O, S, NR 4i or CR 4i ; Y5is selected from N, O, S, NR 4j or CR 4j ; Y6is selected from N, O, S, NR 4k or CR 4k ; Y7is selected from N, O, S or CR 4l ; Y8is selected from N or CR 4m ; Y9is selected from N or CR 4n ; M8is selected from CR 8a R 8b , O, NR 8c , S, C(O), CR 8a =CR 8b or C(O)NR 8c ; R 4i , R 4j , R 4k , R 4l , R 4m , and R 4n are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, 5-14 membered heteroaryl, -(CH2) n3 -, -(CH2) n3 R aa , -(CH2) n3 OR bb , -O(CH2) n3 R aa , -(CH2) n3 SR bb , -(CH2) n3 C(O)R cc , -(CH2) n3 C(O)OR cc , -(CH2) n3 S(O) m1 R cc , -(CH2) n3 NR aa R bb , -(CH2) n3 C(O)NR aa R bb , -(CH2) n3 NR bb C(O)R cc , -(CH2) n3 NR bb S(O) m1 R cc , -OC(R aa R bb ) m1 (CH2) n3 R aa , -NR bb (CH2) n3 R aa , -CH=CH(CH2) n3 R aa -CH=CH(CH2) n3 NR aa R bb -CH=CH(CH2) n3 NR bb C(O)R cc -CH=CH(CH2) n3 NR bb C(O)NR aa R cc = N-OR bb or = CR aa R cc wherein the C 1- 6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5-14 membered heteroaryl; R 5a , R 5b , R 5c , R 5d , R 5e , R 5f , R 5g , R 5h , R 5i , R 5j , and R 5k are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, -SF5, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, 5-14 membered heteroaryl, -(CH2) n4 -, -(CH2) n4 R dd , -(CH2) n4 OR ee , -O(CH2) n4 R dd , -(CH2) n4 SR ee , -(CH2) n4 C(O)R ff , -(CH2) n4 C(O)OR ff , -(CH2) n4 S(O) m2 R ff , -(CH2) n4 NR dd R ee , -(CH2) n4 C(O)NR dd R ee , -(CH2) n4 C(O)NR dd OR ee , -(CH2) n4 P(O)R dd R ee , -(CH2) n4 NR ee C(O)R ff , -(CH2) n4 NR ee S(O) m2 R ff , -(CH2) n4 N=S(O)R dd R ee , -OC(R dd R ee ) m2 (CH2) n4 R dd , -NR ee (CH2) n4 R dd , -CH=CH(CH2) n4 R dd , -CH=CH(CH2) n4 NR dd R ee , -CH=CH(CH2) n4 NR ee C(O)R ff , -CH=CH(CH2) n4 NR ee C(O)NR dd R ff , =N-OR ee or =CR dd R ff wherein the C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl are optionally further substituted by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 one or more substituents of the aryl and substituted or unsubstituted 5-14 membered heteroaryl; preferably selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, C 1-6 alkyl, C 1- 6deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, 5-14 membered heteroaryl, -(CH2) n4 -, -(CH2) n4 R dd -, -(CH2) n4 OR ee -, -O(CH2) n4 R dd -, -(CH2) n4 SR ee -, -(CH2) n4 C(O)R ff -, -(CH2) n4 C(O)OR ff -, -(CH2) n4 S(O) m2 R ff -, -(CH2) n4 NR dd R ee -, -(CH2) n4 C(O)NR dd R ee -, -(CH2) n4 P(O)R dd R ee -, -(CH2) n4 NR ee C(O)R ff -, -(CH2) n4 NR ee S(O) m2 R ff -, -OC(R dd R ee ) m2 (CH2) n4 R dd -, -NR ee (CH2) n4 R dd -, -CH=CH(CH2) n4 R dd -, -CH=CH(CH2) n4 NR dd R ee , -CH=CH(CH2) n4 NR ee C(O)R ff , -CH=CH(CH2) n4 NR ee C(O)NR dd R ff , =N-OR ee or =CR dd R ff wherein said C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl and 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3- to 12-membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5- to 14-membered heteroaryl; or R 5d and R 5e or R 5f and R 5g may form, with the atom to which they are attached, a C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, or 5-14 membered heteroaryl, said C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, optionally further substituted by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, substituted with one or more substituents; or R 5b and R a , R 5c and R a , R 5d and R a or R 5f and R a may form, with the atom to which they are attached, a C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, or 5-14 membered heteroaryl, said C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl, and substituted or unsubstituted 5-14 membered heteroaryl; R8is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, -SF5, oxo, thioxo, C 1-6 alkyl, C 1- 6deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl and 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl and 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl and 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocycyl, C 6-14 aryl, 5-14 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5-14 membered heteroaryl; R 8a , R 8b , or R 8c are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, -SF5, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, wherein said C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl; and wherein said C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, 5-14 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl and 5-14 membered heteroaryl, optionally further substituted by hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 deuteroalkyl, substituted or unsubstituted C 1-6 haloalkyl, substituted or unsubstituted C 1-6 hydroxyalkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 1-6 haloalkoxy, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-12 cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclyl, substituted or unsubstituted C 6-14 aryl and substituted or unsubstituted 5-14 membered heteroaryl; n8 is selected from 0, 1, or 2; n9 is selected from 0, 1, or 2.

7. The compound, its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, characterized in that, L1is selected from the group consisting of a bond, -O-, -NR N -, -S-, -S(O)-, -S(O)2-, -C(O), -CONR N -, -S(O)2NR N -, C 1-6 alkylene, C 3-6 cycloalkylene, or 3-6 membered heterocyclyl, wherein said C 1-6 alkylene, C 3-6 cycloalkylene, and 3-6 membered heterocyclyl is optionally further substituted with one or more substituents selected from the group consisting of hydrogen, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1- 6alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl.

8. The compound, its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, characterized in that, R a , R 6a , R 6c , R 6e or R 6g are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, -SF5, C 1-3 alkyl, C 1- deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy or C 3-8 cycloalkyl, said amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy and C 3-8 cycloalkyl, optionally further substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, mercapto, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl and 5- to 14-membered heteroaryl; preferably hydrogen, deuterium, halogen, amino, hydroxyl, cyano, -SF5, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy or C 3-8 cycloalkyl; More preferably, R a , R 6a , R 6c , R 6e or R 6g is each independently selected from hydrogen, deuterium, fluorine, chlorine, -SF5, methyl, deuterated methyl, difluoromethyl, trifluoromethyl, methoxy or deuterated methoxy; further preferably from hydrogen, deuterium, fluorine, chlorine, -SF5, methyl, deuterated methyl, difluoromethyl or trifluoromethyl; R 6b , R 6d , R 6f or R 6h is absent or each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, -SF5, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy or C 3-8 cycloalkyl; R 6b , R 6d , R 6f or R 6h are each independently selected from hydrogen, deuterium, fluorine, chlorine, -SF5, methyl, deuterated methyl, difluoromethyl or trifluoromethyl.

9. The compound according to any one of claims 1 to 8, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, characterized in that, R 5a , R 5b , R 5c , R 5d , R 5e , R 5f , R 5g , R 5h , R 5i , R 5j , and R 5k are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, -SF5, oxo, thioxo, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heterocyclyl, or -C(O)R ff , said amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, and C 3-8 cycloalkyl, are optionally further substituted with one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, thiol, oxo, thioxo, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl; R 5a , R 5b , R 5c , R 5d , R 5e , R 5f , R 5g , R 5h , R 5i , R 5j and R 5k are each independently selected from hydrogen, deuterium, fluorine, chlorine, -SF5, methyl, deuterated methyl, difluoromethyl, trifluoromethyl, methoxy, deuterated methoxy, or -C(O)R ff .

10. The compound according to any one of claims 1 to 9, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, characterized in that, selected from the group consisting of:

11. A method of preparing a compound represented by General Formula (A-II-9) or (A-II-10), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, characterized by comprising: The compound of general formula (A-III-1), its stereoisomer or its pharmaceutically acceptable salt, and the compound of general formula (A-III-2), its stereoisomer or its pharmaceutically acceptable salt, are coupled or substituted to give the compound of general formula (A-II-9), its stereoisomer or its pharmaceutically acceptable salt. The compound of general formula (A-III-3), its stereoisomer or its pharmaceutically acceptable salt, is obtained by coupling or substitution reaction with the compound of general formula (A-III-2), its stereoisomer or its pharmaceutically acceptable salt. R L1 selected from halogen, hydroxyl, -OS(O) m3 -C 1-3 alkyl, -S(O) m3 -C 1-3 alkyl, boronic acid group, boronate group, chain boronate group or cyclic boronate group, said C 1-3 alkyl is optionally further substituted with one or more substituents of deuterium, halogen, amino, nitro, hydroxyl and cyano; preferably chloro, bromo, hydroxyl, -OS(O)2-CF3, -S(O)-CH3, -S(O)2-CH3, B(OH)2or R L2 selected from halogen, hydroxyl, -OS(O) m3 -C 1-3 alkyl, -S(O) m3 -C 1-3 alkyl, boronic acid group, boronate group, chain boronate group or cyclic boronate group, said C 1-3 alkyl is optionally further substituted with one or more substituents of deuterium, halogen, amino, nitro, hydroxyl and cyano; preferably chloro, bromo, hydroxyl, -OS(O)2-CF3, -S(O)-CH3, -S(O)2-CH3, B(OH)2or m3 is selected from 0, 1, or 2; L1is defined in claim 1 or 2; X1, X2, R 6a , R 6c , R 6e , R 6g is defined in claim 3; ring G, M5, R 4a , R 4c , R 4d , q is defined in claim 5; R 5a , R 5c , R 5h and is defined in claim 6.

12. A pharmaceutical composition comprising a therapeutically effective dose of the compound shown in any one of claims 1 to 10, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, or excipients.

13. The use of the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, according to any one of claims 1 to 10, or the pharmaceutical composition of claim 12, in the preparation of a dopamine receptor agonist medicament; wherein the dopamine receptor agonist is selected from full agonists or partial agonists; and wherein the dopamine receptor is selected from D1 receptors and / or D5 receptors.

14. Use of a compound according to any one of claims 1 to 10, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 12, for the manufacture of a medicament for the treatment of a disease or disorder associated with dysregulation of dopamine D1 receptor activation; wherein the disease or disorder is selected from schizophrenia, cognitive impairment, dementia, Parkinson's disease, mild cognitive impairment, age-related cognitive decline, major depressive disorder, treatment-resistant depression, postpartum depression, Alzheimer's disease dementia, hyperactivity, autism spectrum disorder, post-traumatic stress disorder, Tourette's syndrome, tardive dyskinesia, a sleep disorder or pain.

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