Aza cyclic derivative inhibitors, methods of making and using same

Abstract

The present invention relates to azacyclic derivative inhibitors, methods of making and using the same. In particular, the present invention relates to compounds of the general formula, methods of making the same, pharmaceutical compositions containing the same, and uses of the same in the treatment of central nervous system disorders.

Description

Technical Field

[0001] This invention belongs to the field of drug synthesis, specifically relating to a nitrogen heterocyclic derivative inhibitor, 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 of general formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound of general formula (I) has the following structure:

[0007]

[0008] in:

[0009] M1 is selected from CR 1d R 1eor NR 1e ;

[0010] M2 is selected from O, S, NR 3a NOR 3b or NC(O)R 3c ;

[0011] M3 is selected from O, S, NR 3a NOR 3b or NC(O)R 3c ;

[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 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;

[0013] Ring A is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-14 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 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, 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 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;

[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 6-14 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 2-6Alkyne 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;

[0016] 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 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 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;

[0017] Or, R 1b With R 1c 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 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;

[0018] 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;

[0019] 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, 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 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 bbor = 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 in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0020] 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 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;

[0021] 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 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;

[0022] 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 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C6-14 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, 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 and 5-14 heteroaryl groups, optionally further divided by 1, 2, 3, 4, 5 or 6 R groups. b Substituents;

[0023] 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;

[0024] 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;

[0025] 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 2-6alkynyl 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;

[0026] 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 6-14aryl 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 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;

[0027] 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;

[0028] 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 1-6Alkoxy, 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 = CRdd 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;

[0029] 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 3-12Cycloalkyl, 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;

[0030] 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 1-6Alkoxy, 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;

[0031] 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 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;

[0032] 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;

[0033] 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 6-14Aryl 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 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;

[0034] 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 1-6Halogenated 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;

[0035] 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;

[0036] R ffSelected 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;

[0037] 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 6-14Aryl 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 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;

[0038] 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.

[0039] In some embodiments of the present invention Central A is selected from C 5-8 Saturated or unsaturated monocyclic cycloalkyl groups, C 7-12 fused cycloalkyl, 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;

[0040] Preferably, Selected from

[0041] More preferably, Selected from

[0042] X1 is selected from CR 6a R 6b or NR 6b X2 is selected from CR 6c R 6d or NR 6d X3 is selected from CR 6e R 6f or NR 6f X4 is selected from CR 6g R 6hor NR 6h X5 is selected from CR 7a Or N;

[0043] Ring C is selected from C 3-6 Cycloalkyl or 3-6 membered heterocyclic groups;

[0044] Ring D is selected from C 3-6 Cycloalkyl or 3-6 membered heterocyclic groups;

[0045] R 6a R 6c R 6e Or R 6g 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 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 6-14The aryl group is substituted with one or more substituents in a group consisting of substituted or unsubstituted 5-14 heteroaryl groups;

[0046] R 6b R 6d R 6f Or R 6h Not present or independently 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;

[0047] Or, R 6a R 6b R 6c R 6d R 6e R6f 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 1-6 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;

[0048] 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 6-14aryl 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 group, 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.

[0049] In certain embodiments of the invention, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof is further represented as shown in general formulas (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), or (I-7):

[0050]

[0051] X6 is selected from N or CR 6c ;

[0052] M8 is selected from CR 8a R 8b O, NR 8c S, C(O), CR 8a =CR 8b or C(O)NR 8c ;

[0053] R8 is 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 membered heteroaryl, wherein the 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 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;

[0054] Or, R8 and R 1c 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 R group is substituted by one or more substituents in the aryl group and substituted or unsubstituted 5-14 heteroaryl groups. 8a R 8b Or R8c 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 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;

[0055] n6 is selected from 0, 1, or 2; n7 is selected from 0, 1, or 2; n8 is selected from 0, 1, or 2; n9 is selected from 0, 1, or 2; z is selected from 0, 1, 2, 3, 4, 5, or 6.

[0056] In certain embodiments of the invention, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof is characterized in that R2 is selected from C 3-8 Monocyclic cycloalkyl, C 7-12 fused cycloalkyl, C 7-12 Spirocycloalkyl, C7-12 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;

[0057] Preferred

[0058] M4 is selected from O, S, CH2, or NH; M5 is selected from CR. 4b Or N;

[0059] 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 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) 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 ddR 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 3-12Cycloalkyl, 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;

[0060] n5 is selected from 0, 1, or 2; y is selected from 0, 1, 2, 3, or 4.

[0061] In certain embodiments of the invention, the compounds shown or their pharmaceutically acceptable salts are further shown as in general formulas (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), or (II-7):

[0062]

[0063]

[0064] X6 is selected from N or CR 6c M8 is selected from CR 8a R 8b O, NR 8c S, C(O), CR 8a =CR 8b or C(O)NR 8c ;

[0065] Or, R 4d C is formed by linking with L1. 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;

[0066] R8 is 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 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;

[0067] Or, R8 and R 1c 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 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 group, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-14 The R group is substituted by one or more substituents in the aryl group and substituted or unsubstituted 5-14 heteroaryl groups. 8a R 8b Or R 8c 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 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 3-12Cycloalkyl, 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;

[0068] n6 is selected from 0, 1, or 2; n7 is selected from 0, 1, or 2; n8 is selected from 0, 1, or 2; n9 is selected from 0, 1, or 2; z is selected from 0, 1, 2, 3, 4, 5, or 6.

[0069] 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.

[0070] The present invention further relates to a pharmaceutical composition comprising a therapeutically effective dose of any of the compounds of the general formula shown or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0071] The present invention further relates to the use of any of the compounds of the general formula shown or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition thereof, 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.

[0072] The present invention further relates to the use of compounds of the general formula 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.

[0073] The present invention further relates to a compound of the general formula or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in the preparation of a method for treating a disease or condition associated with dysregulation of dopamine D1 receptor activation.

[0074] The present invention also relates to a method for treating, preventing and / or treating a pre-prepared treatment for a disease or condition associated with dysregulation of dopamine D1 receptor activation, comprising administering to a patient a therapeutically effective dose of a compound of the general formula or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0075] In some embodiments of the invention, the pharmaceutical composition, based on free base, comprises 0.1% to 95% by weight of the compound, its stereoisomers, or a pharmaceutically acceptable salt thereof, preferably 90%, 85%, 80%, 75%, 70%, 60%, or 50%.

[0076] 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.

[0077] The present invention also provides a method for treating disease conditions using the compounds or pharmaceutical compositions of the present invention, including but not limited to conditions related to dysregulation of dopamine D1 receptor activation.

[0078] 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 or a pharmaceutically acceptable salt, ester, prodrug, solvate, hydrate or derivative thereof.

[0079] 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 dementia, ADHD, autism spectrum disorder, post-traumatic stress disorder, Tourette syndrome, tardive dyskinesia, sleep disorder, or pain.

[0080] Detailed description of the invention

[0081] 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.

[0082] 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... 1-6 The 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.

[0083] 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.

[0084] 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 (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 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.

[0085] 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.

[0086] 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.

[0087] The term "spirocycloalkyl" refers to an aliphatic hydrocarbon polycyclic group that shares a single carbon atom (called a spiro atom) between its monocyclic rings. It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. In certain embodiments, the spirocycloalkyl group comprises 5 to 20 carbon atoms. 5-20 ), 6 to 14 (C 6-14 ), 7 to 12 (C 7-12 ) or 7 to 10 (C 7-10 (e.g., 7, 8, 9, 10, 11, 12) carbon atoms. Spirocycloalkyl groups are classified as monospirocycloalkyl, bispirocycloalkyl, or polyspirocycloalkyl groups based on the number of shared spiro atoms between rings, with one embodiment being monospirocycloalkyl and bispirocycloalkyl. In one embodiment, it is a 4-membered / 4-membered, 3-membered / 5-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered, or 5-membered / 6-membered monospirocycloalkyl. In one embodiment, the spirocycloalkyl group is an optionally substituted spirocycloalkyl group described elsewhere herein. Non-limiting examples of spirocycloalkyl groups include:

[0088]

[0089] The term "fused-cycle alkyl" refers to a fully carbon polycyclic group in which each ring in a system shares an adjacent pair of carbon atoms with the other rings in the system, wherein one or more rings may contain one or more double bonds, but no ring has a fully conjugated π-electron system. In a particular embodiment, the fused-cycle alkyl comprises 5 to 20 (C 5-20 ), 6 to 14 (C 6-14 ), 7 to 12 (C 7-12 ) or 7 to 10 (C 7-10 (e.g., 7, 8, 9, 10, 11, 12) carbon atoms. Depending on the number of rings, they can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic fused-ring alkyl groups. In one embodiment, they are bicyclic or tricyclic, and in another embodiment, they are 3-membered / 5-membered, 4-membered / 5-membered, 5-membered / 5-membered, or 5-membered / 6-membered bicyclic alkyl groups. In one embodiment, the fused-ring alkyl group is an optionally substituted fused-ring alkyl group described elsewhere herein or an fused-ring alkyl group optionally fused with a heterocyclic group, aryl group, or heteroaryl group. Non-limiting examples of fused-ring alkyl groups include:

[0090]

[0091] The term "bridged cycloalkyl" refers to a fully carbon polycyclic group in which any two rings share two non-directly bonded carbon atoms. It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. In certain embodiments, the bridged cycloalkyl group comprises 5 to 20 (C...) 5-20 ), 6 to 14 (C 6-14 ), 7 to 12 (C 7-12 ) or 7 to 10 (C7-10 (e.g., 7, 8, 9, 10, 11, 12) carbon atoms. Depending on the number of rings, they can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic bridged alkyl groups, preferably bicyclic or tricyclic. In one embodiment, the bridged alkyl group is an optionally substituted bridged alkyl group described elsewhere herein. Non-limiting examples of bridged alkyl groups include:

[0092]

[0093] 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.

[0094] The term "spiroheterocyclic group" refers to a polycyclic heterocyclic group in which one or more ring atoms share a single atom (called a spiro atom), wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, and the remaining ring atoms are carbon. It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. In a particular embodiment, the spiroheterocyclic group comprises 5 to 20 or 6 to 14 ring atoms; in one embodiment, it comprises 7 to 12 (e.g., 7, 8, 9, 10, 11, 12) ring atoms; spiroheterocyclic groups are classified as monospirocyclic, bispirocyclic, or multispirocyclic groups according to the number of shared spiro atoms between rings; monospirocyclic and bispirocyclic groups are preferred; in one embodiment, the spiroheterocyclic group is a 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered, or 5-membered / 6-membered monospirocyclic group; in one embodiment, the spiroheterocyclic group is an optionally substituted spiroheterocyclic group described elsewhere herein; non-limiting examples of spiroheterocyclic groups include:

[0095]

[0096] The term "fused heterocyclic group" refers to a polycyclic heterocyclic group in which each ring in a system shares an adjacent pair of atoms with other rings in the system. One or more rings may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. One or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus, or sulfur, and the remaining ring atoms are carbon. In a particular embodiment, the fused heterocyclic group comprises 5 to 20 or 6 to 14 ring atoms, and in one embodiment comprises 7 to 12 (e.g., 7, 8, 9, 10, 11, 12) ring atoms; it can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic fused heterocyclic groups depending on the number of constituent rings; bicyclic or tricyclic is preferred; in one embodiment it is a 5-membered / 5-membered or 5-membered / 6-membered bicyclic fused heterocyclic group; in one embodiment, the fused heterocyclic group is optionally substituted as described elsewhere herein, or a fused heterocyclic group that can be fused with cycloalkyl, heterocyclic, aryl, or heteroaryl groups; non-limiting examples of fused heterocyclic groups include:

[0097]

[0098] The term "bridged heterocyclic group" refers to a polycyclic heterocyclic group in which any two rings share two non-directly bonded atoms. It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. One or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus, or sulfur, and the remaining ring atoms are carbon. In certain embodiments, the bridged heterocyclic group comprises 5 to 20 or 6 to 14 ring atoms; in one embodiment, it comprises 7 to 12 (e.g., 7, 8, 9, 10, 11, 12) ring atoms; depending on the number of constituent rings, it can be classified as a bicyclic, tricyclic, tetracyclic, or polycyclic bridged heterocyclic group; preferably bicyclic, tricyclic, or tetracyclic; in one embodiment, it is bicyclic or tricyclic; in one embodiment, the bridged heterocyclic group is an optionally substituted bridged heterocyclic group described elsewhere herein; non-limiting examples of bridged heterocyclic groups include:

[0099]

[0100] 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),

[0101] 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.

[0102] 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,

[0103] 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.

[0104] The term "heteroalkyl" refers to a stable straight-chain or branched, or cyclic, hydrocarbon group, or a combination thereof, consisting of the indicated number of carbon atoms and one or more (one to three in one embodiment) heteroatoms selected from O, N, Si, and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen heteroatom may optionally be quaternized. In one embodiment, the heteroatoms O, N, and S may be placed at any internal position within the heteroalkyl group. In one embodiment, the heteroatom Si may be placed at any position within the heteroalkyl group (e.g., internal or terminal positions), including positions where the alkyl group is attached to the remainder of the molecule. Non-limiting examples include: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2-S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, and -CH=CH-N(CH3)-CH3. At most two heteroatoms can be consecutive, for example, -CH2-NH-O-CH3 and -CH2-O-Si(CH3)3. In certain embodiments, the heteroalkyl group is an optionally substituted heteroalkyl group described elsewhere herein.

[0105] 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.

[0106] The term "alkylacyl" refers to -C(O)-alkyl, where the definition of alkyl is as described above.

[0107] 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,

[0108] 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.

[0109] 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.

[0110] 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.

[0111] The term "haloalkylthio" refers to an alkylthio group substituted with one or more halogens, wherein the definition of alkylthio is as described above.

[0112] 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.

[0113] The term "aminocarbonyl" refers to NH2-C(O)-.

[0114] 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.

[0115] 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.

[0116] The term "carbonyl" refers to the -C(O)-, -(CO)-, or -C(=O)- group. All designations are interchangeable in the specification.

[0117] 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 comprises its isotopes (H) and / or mixtures thereof. 1 H), deuterium ( 2 H), tritium ( 3 H) and / or mixtures thereof.

[0118] 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.

[0119] 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';

[0120] R, R', or R” are each independently 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, or heterocyclic alkoxy.

[0121] n is selected from 0, 1, 2, 3 or 4;

[0122] m is selected from 0, 1, or 2.

[0123] 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.

[0124] "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.

[0125] 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.

[0126] "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).

[0127] 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.

[0128] "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.

[0129] "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.

[0130] "Stereoisomers" encompass all enantiomers / non-corresponding isomers / stereoisomers of the present invention, as well as enantiomers / non-corresponding isomers / stereoisomers enriched in this invention.

[0131] "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.

[0132] "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%.

[0133] "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.

[0134] "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.

[0135] 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.

[0136] 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

[0137] 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.

[0138] Example

[0139] 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.

[0140] 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). 18150×4.6mm chromatographic column) and Waters 2695-2996 high-performance liquid chromatograph (Gimini C) 18 (150×4.6mm chromatographic column).

[0141] 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.

[0142] 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.

[0143] 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.

[0144] Example 1

[0145]

[0146] Step 1: Preparation of Compounds 1-2

[0147] Under nitrogen protection, PPh3 (201.02 mg, 766.41 μmol), 3-(trifluoromethyl)pyridin-2-ol (100 mg, 613.13 μmol), and tert-butyl 4-hydroxy-2-methylpiperidin-1-carboxylate (110 mg, 510.94 μmol) were dissolved in a dry tetrahydrofuran (2.0 mL) solution. DIAD (155 mg, 766.61 μmol) was added dropwise at room temperature, and the mixture was stirred at room temperature for 4 hours. The reaction solution was added dropwise to water and extracted with ethyl acetate. The organic phase was washed three times with water, dried over anhydrous sodium sulfate, filtered, and purified by silica gel column chromatography to obtain a colorless oily tert-butyl 2-methyl-4-[[3-(trifluoromethyl)-2-pyridinyl]oxy]piperidin-1-carboxylate (130 mg, yield 70.6%).

[0148] MS m / z(ESI): 361 [M+H].

[0149] Step 2: Preparation of compounds 1-3

[0150] At room temperature, tert-butyl 2-methyl-4-[[3-(trifluoromethyl)-2-pyridinyl]oxy]piperidine-1-carboxylate (1.1 g, 3.05 mmol) was dissolved in dichloromethane (8 mL), TFA (4 mL) was added, and the mixture was stirred for 2 hours. The solvent was then removed by concentration. The crude product was diluted with ethyl acetate, and the pH was adjusted to 8-10 with saturated sodium bicarbonate aqueous solution. The product was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the organic phase was concentrated to give 2-[(2-methyl-4-piperidine)oxy]-3-(trifluoromethyl)pyridine (600 mg, yield 75.5%).

[0151] MS m / z(ESI): 261 [M+H].

[0152] Step 3: Preparation of compounds 1-5

[0153] 6-Amino-1,5-dimethylpyrimidin-2,4-dione (1.0 g, 6.45 mmol), NaNO₂ (667 mg, 9.67 mmol), and CuCl₂ (1.73 g, 12.89 mmol) were added sequentially to a mixture of water (12 mL) and MeCN (12 mL). The mixture was stirred overnight at room temperature. An aqueous solution of sulfuric acid (1 N, 20 mL) and ethyl acetate (10 mL) were added, and the mixture was stirred for 20 minutes, resulting in a precipitate. The precipitate was filtered, and the filter cake was washed with water and ethyl acetate to give a white solid product. The organic layer of the filtrate was concentrated to a smaller volume, during which additional precipitate formed; the filtrate was filtered, and the filter cake was washed with ethyl acetate / petroleum ether at a ratio of 1:1. The filter cakes were combined, dried, and weighed to give 6-chloro-1,5-dimethylpyrimidin-2,4-dione (450 mg, yield 40.0%).

[0154] MS m / z(ESI): 175 [M+H].

[0155] Step 4: Preparation of Compound 1

[0156] Compounds 1-3 (100 mg, 0.38 mmol) and 1-5 (35 mg, 0.20 mmol) were dissolved in N,N-dimethylacetamide (20 mL). Tris(dibenzylacetone)dipalladium (90 mg, 0.10 mmol), 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (115 mg, 0.20 mmol), and potassium tert-butoxide (85 mg, 0.76 mmol) were added sequentially to the reaction system. The reaction mixture was purged with nitrogen three times and heated at 100 °C for 12 hours under nitrogen protection. Cool, add water, extract with ethyl acetate, combine organic phases, wash with saturated sodium chloride solution, dry with anhydrous sodium sulfate, filter, concentrate, and purify by high performance liquid chromatography to give the product 1,5-dimethyl-6-(2-methyl-4-((3-(trifluoromethyl)-2-pyridyl)oxy)-1-piperidinyl)pyrimidine-2,4(1H,3H)-dione (7.3 mg, yield 18.3%).

[0157] MS m / z(ESI): 399 [M+H].

[0158] The synthesis methods in the following embodiments are based on Embodiment 1:

[0159]

[0160]

[0161]

[0162]

[0163]

[0164]

[0165]

[0166]

[0167]

[0168]

[0169]

[0170]

[0171]

[0172]

[0173]

[0174]

[0175]

[0176]

[0177] Biological testing evaluation

[0178] 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.

[0179] Test Example 1: Determination of the binding effect of the compound of the present invention on dopamine D1 receptors

[0180] 1. Experimental objective:

[0181] The IC50 of the test compound's binding to dopamine D1 receptor was determined using a radioisotope ligand binding assay. 50 .

[0182] 2. Experimental instruments and reagents:

[0183] 2.1 Instruments:

[0184] Envision (PE-Cisbio: 2105-0020), Unifilter-96GF / C filter plates (PE: 6005174), ECHO (Labcyte: ECHO 555), Bravo (Agilent: Bravo V11), MicroBeta2 (PE: CNLL0153)

[0185] 2.2 Reagents:

[0186] DMSO (Sigma: D4540); Poly ethyleneimine, PEI (Sigma: P3143); MicroScint-Ococktail (PE: 6013611); [ 3 H]SCH 23390 (PE: NET930250UC); HEK293 D1 stable cells

[0187] 3. Experimental methods:

[0188] 1) Preparation of cell membrane proteins: Dilute cell membrane proteins to the specified concentration using experimental buffer;

[0189] 2) Preparation of radioactive isotope ligands: Dilute the radioactive isotope ligands to the specified concentration using experimental buffer solution;

[0190] 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.

[0191] 4) Add 100 μL of the specified concentration of cell membrane protein according to the arrangement of the reaction plate;

[0192] 5) Add 100 μL of a radioactive isotope of the specified concentration;

[0193] 6) After sealing, incubate on a shaker at a specified temperature for a specified time;

[0194] 7) Immerse the GF / C plate in 50 μL of 0.3% PEI solution at room temperature for at least half an hour;

[0195] 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.

[0196] 9) Place the GF / C board in a 50℃ oven and dry for 1 hour;

[0197] 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.

[0198] 11) Read the values ​​using MicroBeta2.

[0199] 4. Experimental data processing methods:

[0200] Calculation formula: % Inhibition rate = 100 × [1 - (sample well reading - non-specific binding well reading) / (total binding well reading - non-specific binding well reading)].

[0201] The data was analyzed using the model "log(inhibitor) vs. response--Variableslope" in GraphPad Prism 5.0.

[0202] 5. Experimental Results and Conclusions:

[0203] 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.

[0204] 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;

[0205] 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;

[0206] Test Example 2: Determination of the agonistic effects of the compounds of the present invention on dopamine D1 and D5 receptors.

[0207] 1. Experimental objective:

[0208] The agonistic effects of the compound on dopamine D1 and D5 receptors were investigated.

[0209] 2. Experimental instruments and reagents:

[0210] 2.1 Instruments:

[0211] Microplate reader (PE: Envision), 96-well plate (ThermoFisher: 249944), 384-well plate (PE: 6007680), pipettes (Eppendorf, 100-1000uL), 12-channel electric pipettes (METTLER TOLEDO: 2-20uL), 12-channel electric pipettes (Eppendorf: 15-300uL), refrigerated centrifuge (Eppendorf: 5810R).

[0212] 2.2 Reagents:

[0213] 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

[0214] 3. Experimental methods:

[0215] 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.

[0216] 2) Compound preparation: Dilute the compound with experimental buffer solution;

[0217] 3) Add 4 μl of the compound to each well and incubate at 37°C for 30 minutes;

[0218] 4) Freeze-thaw Eu-cAMP tracer and Ulight-anti-cAMP, then dilute them with lysis buffer;

[0219] 5) Add 5 μl of Eu-cAMP tracer to the well, and then add 5 μl of Ulight-anti-cAMP to the well;

[0220] 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.

[0221] 4. Experimental data processing methods:

[0222] Use this formula to calculate the inhibition rate:

[0223] %Activity=100-(Signal) cmpd -Signal Ave_PC ) / (Signal Ave_VC -Signal Ave_PC The 100×100 data points were analyzed using the "log(agonist) vs. response--Variable slope" model in GraphPad Prism 5.0. The nonlinear fitting conforms to the following formula:

[0224] Y = Bottom + (Top - Bottom) / (1 + 10) (LogEC50-X)×Hillslope )

[0225] Where X: compound concentration log value; Y: %Activity.

[0226] 5. Experimental Results and Conclusions:

[0227] The above methods demonstrate that the compounds of this invention exhibit good partial agonistic activity against both dopamine D1 and D5 receptors, with agonistic activity against dopamine D1 receptors ranging from approximately 0.1 nM to 100 nM (EC5). 50 The biological activity of ) showed agonistic activity against dopamine D5 receptors, ranging from approximately 0.1 nM to 100 nM (EC).50 ) biological activity.

[0228] In some embodiments, the compounds of the present invention exhibit EC50-60% agonistic activity against dopamine D1 receptors. 50 Less than about 100 nM, preferably less than about 50 nM, more preferably less than about 20 nM, and more preferably less than about 10 nM;

[0229] In some embodiments, the compounds of the present invention exhibit EC5-like agonistic activity against dopamine D5 receptors. 50 Less than about 100 nM, preferably less than about 50 nM, further preferably less than about 20 nM, and more preferably less than about 10 nM.

Claims

1. A compound of general formula (I) or a pharmaceutically acceptable salt thereof: in: M1 is selected from CR 1d R 1e or NR 1e ; M2 is selected from O, S, NR 3a NOR 3b or NC(O)R 3c ; M3 is selected from O, S, NR 3a NOR 3b or NC(O)R 3c ; 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; 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 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, R 1b With R 1c 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; 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; 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; 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; 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 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; 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, 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, 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 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 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 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; 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 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, 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, 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, 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, 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; 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. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, 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; Preferably, Selected from More preferably, Selected from X1 is selected from CR 6a R 6b or NR 6b X2 is selected from CR 6c R 6d or 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; Ring C is selected from C 3-6 Cycloalkyl or 3-6 membered heterocyclic groups; Ring D is selected from C 3-6 Cycloalkyl or 3-6 membered heterocyclic groups; R 6a R 6c R 6e Or R 6g 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 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 6b R 6d R 6f Or R 6h Not present or independently 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 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 1-6 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 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.

3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that, The compounds shown or their pharmaceutically acceptable salts are further shown as in general formulas (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), or (I-7): X6 is selected from N or CR 6c ; M8 is selected from CR 8a R 8b O, NR 8c S, C(O), CR 8a =CR 8b or C(O)NR 8c ; R8 is 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 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, R8 and R 1c 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 R group is substituted by one or more substituents in the aryl group and substituted or unsubstituted 5-14 heteroaryl groups. 8a R 8b Or R 8c 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 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; n6 is selected from 0, 1, or 2; n7 is selected from 0, 1, or 2; n8 is selected from 0, 1, or 2; n9 is selected from 0, 1, or 2; z can be selected from 0, 1, 2, 3, 4, 5 or 6.

4. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, characterized in that, R2 is selected from 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 heteroaryl groups; Preferred M4 is selected from O, S, CH2, or NH; M5 is selected from CR 4b Or N; 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 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) 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; n5 is selected from 0, 1, or 2; y is selected from 0, 1, 2, 3 or 4.

5. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that, The compounds shown or their pharmaceutically acceptable salts are further shown as in general formulas (II-1), (II-2), (II-3), (II-4), (II-5), (II-6) or (II-7): X6 is selected from N or CR 6c ; M8 is selected from CR 8a R 8b O, NR 8c S, C(O), CR 8a =CR 8b or C(O)NR 8c ; Or, R 4d C is formed by linking with L1. 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; R8 is 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 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, R8 and R 1c 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 R group is substituted by one or more substituents in the aryl group and substituted or unsubstituted 5-14 heteroaryl groups. 8a R 8b Or R 8c 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 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; n6 is selected from 0, 1, or 2; n7 is selected from 0, 1, or 2; n8 is selected from 0, 1, or 2; n9 is selected from 0, 1, or 2; z is selected from 0, 1, 2, 3, 4, 5, or 6.

6. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, characterized in that, L1 is selected from key, -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.

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

8. A pharmaceutical composition comprising a therapeutically effective dose of any of the compounds shown in claims 1 to 7 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, or excipients.

9. The use of the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, or the pharmaceutical composition of claim 8, 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.

10. The use of any compound shown in claims 1 to 7 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 8, in the preparation of a treatment for a disease or condition associated with dopamine D1 receptor dysregulation; wherein the disease or condition 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, ADHD, autism spectrum disorder, post-traumatic stress disorder, Tourette syndrome, tardive dyskinesia, sleep disorder, or pain.

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