Tri-fused ring derivative inhibitor as well as preparation method and application thereof

Abstract

The invention relates to a tricyclic derivative inhibitor as well as a preparation method and application thereof. In particular, the invention relates to a tricyclic derivative compound, a preparation method thereof, a pharmaceutical composition containing the compound, and an application of the compound in treating cancers.

Description

Technical Field

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

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

[0003] Methylthioadenosine phosphorylase (MTAP) catalyzes the conversion of methionine (MTA) to methionine, which is crucial for maintaining normal cellular function. Deletion mutations in the MTAP gene lead to intracellular MTA accumulation. MTA competes with SAM, the substrate of PRMT5, resulting in decreased PRMT5 activity and the production of large amounts of the PRMT5-MTA complex. MTAP gene deletion increases tumor dependence on PRMT5. Inhibition of PRMT5 in MTAP-deficient tumors can have a "synthetic lethal" effect. PARP inhibitors, based on the "synthetic lethal" theory, have achieved great success in precision oncology. The MTAP gene is adjacent to CDKN2A, the most common tumor suppressor gene in human cancers, and is often co-deleted with CDKN2A. This co-deletion accounts for 10%-15% of all cancers, mainly occurring in non-small cell lung cancer (12%-20%), glioma (53%), pancreatic cancer (30%), and DLBCL (20%), indicating a huge market potential.

[0004] Currently, there are no PRMT5 inhibitors on the market. Early PRMT5 inhibitors were all non-selective substrate SAM competitive inhibitors, which had serious hematologic toxicity and a small safety window in clinical practice. The clinical progress of first-generation PRMT5 inhibitors GSK-3326595, JNJ-64619178, and PF-06939999 has been unsatisfactory. Next-generation PRMT5 inhibitors targeting the PRMT5-MTA complex are effective only against tumors lacking MTAP and enriched by MTA, exhibiting high selectivity for MTAP wild-type tumors. Mechanistically, they reduce hematologic toxicity and have been validated in preclinical studies, potentially significantly improving the safety window.

[0005] This patent relates to a novel selective PRMT5-MTA inhibitor that is active only against MTAP-deficient cells and has weak inhibitory effects on MTAP wild-type cells. This avoids the hematologic toxicity and other side effects associated with the inhibition of MTAP wild-type cells by non-selective PRMT5 inhibitors used in clinical practice. This highly selective PRMT5-MTA inhibitor, as a novel PRMT5-MTA inhibitor, can be used to treat various tumors, cancers, and other diseases. Summary of the Invention

[0006] The object of this invention is to provide a compound of general formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein the compound of general formula (I) has the following structure: M1 is selected from -N- or -CR a -; M2 is selected from -N- or -CR b -; M3 is selected from N or C; N is preferred. Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 quinone heteroaryl; C is preferred 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl, or 5-6 membered heteroaryl; Ring B is selected from C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl or 5-14 quinone heteroaryl; C is preferred 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Fused cycloalkyl groups, 6-10 fused heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl groups; L1 is selected from the key, -CR aa R bb -、-C(O)-、-NR cc C(O), -S(O) m1 -or NR cc Preferred - CRaa R bb -、-C(O)-、-S(O) m1 -or NR cc ; L2 is selected from the bond, -CR aa R bb -、-C(O)-、-S(O) m1 -or NR cc Preferred - CR aa R bb -、-C(O)-、-S(O) m1 -or NR cc ; R1 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, -(CR cc R dd ) n1 -C 3-12 cycloalkyl, -(CR cc R dd ) n1 -3-12-membered heterocyclic group, -(CR cc R dd ) n1 -C 6-12 Aryl, -(CR cc R dd ) n1 -5-12-aryl heteroaryl, -SF5, -OR e -NR e R f -C(O)R e -C(O)OR e -C(O)NR e R f -N=S(O)R e R f -S(O)R e (=NR f ) or -P(O)R e R f The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl and =CR gg R hh One or more substituents are substituted in the group; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, -(CR cc R dd ) n1 -C 3-8 cycloalkyl, -(CR cc R dd ) n1 -3-8 membered heterocyclic group, -(CR cc R dd ) n1 -C 6-10 Aryl, -(CR cc R dd ) n1 -5-10% heteroaryl, -OR e -NR e R f -C(O)R e -C(O)NR e R f or -P(O)R e R f The amino group, C 1-3 Alkyl, C 2-6alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; Or R1 and R a R b Or R c Link formation C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents from 5-12 heteroaryl groups; preferably, a C13 group is formed. 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally further converted by deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R2 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic, C6-12 aryl, 5-12 membered heteroaryl, -(CH2) n2 OR ee -(CH2) n2 NR ee R ff -(CH2) n2 C(O)R ee -(CH2) n2 C(O)NR ee R ff -(CH2) n2 P(O)R ee R ff or =CR ee R ff The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -Y1-C 3-12 Cycloalkyl, -Y1-3-12-membered heterocyclic group, -Y1-C 6-12 Aryl, -Y1-5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h -C(=NR) i )NR g R h or =R g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12aryl, substituted or unsubstituted 5-12 heteroaryl and =CR e R f One or more substituents are substituted in the group; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl and =CR e R f One or more substituents in it are replaced; Or any two R3 atoms can link with their adjacent atoms to form C. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents from 5-12 heteroaryl groups; preferably, a C13 group is formed. 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally further converted by deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R a R b R c R e and R f Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic, C6-12 aryl, 5-12 membered heteroaryl, -(CH2) n2 OR ee -(CH2) n2 NR ee R ff -(CH2) n2 C(O)R ee -(CH2) n2 C(O)OR ee -(CH2)n2 C(O)NR ee R ff -(CH2) n2 N=S(O)R ee R ff -(CH2) n2 S(O)R ee (=NR ff ) or -(CH2) n2 P(O)R ee R ff The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl and =CR gg R hh One or more substituents are substituted in the group; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; Y1 is selected from key, -O-, -S-, -C(O), -NR j -、-C(O)NR j -、-NR j C(O)-、-S(O)2NR j -、-NR j S(O)2-, C 1-6 Alkylene, -OC 1-6 alkylene-, -C 1-6 Alkylene-O-, -NR j -C 1-6 alkylene-, -C 1-6 Alkylene-NR j -、C 2-6 imide or C 2-6 The acetylenic group, the C 1-6 Alkylene, C 2-6 imide and C 2-6 Alynyl group, optionally replaced by deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R g R h R i and R j Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; Or, R g With R h Link formation C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R aa R bb R cc and R dd Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R ee and R ff Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R gg and R hh Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; x is selected from 0, 1, 2, 3, 4, 5 or 6; y is selected from 0, 1, 2, 3, 4, 5 or 6; m1 is selected from 0, 1 or 2; m2 is selected from 0, 1 or 2; n1 is selected from 0, 1, 2, 3 or 4; and n2 is selected from 0, 1, 2, 3 or 4.

[0007] In a preferred embodiment of the invention, the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, is characterized in that... Selected from , , , or .

[0008] The present invention also provides a compound of formula (B) or (B-1), its stereoisomer or a pharmaceutically acceptable salt thereof: M a Selected from CR 2a NR 2a Or N; M b Selected from CR 2b NR 2b Or N; M c Selected from C or N; M d Selected from C or N; Or, R 2a With R 2b The link forms a ring A; Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, optionally surrounded by 0, 1, 2, 3, 4, 5 or 6 Rs. 2c Replaced; Ring B is selected from C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl groups; The ring C is selected from C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, 5-membered heterocyclic group, 6-membered heterocyclic group, 7-membered heterocyclic group, phenyl, 5-membered heteroaryl or 6-membered heteroaryl; Ring D is selected from C 3-8 Monocyclic cycloalkyl, C 6-12 Fused cycloalkyl groups, 3-8 membered monocyclic heterocyclic groups, or 6-12 membered fused heterocyclic groups; L2 is selected from the bond, -(CR aa R bb ) m2 -、-(CR aa R bb ) m2 C(O)-、-(CR aa R bb ) m2 NR cc C(O), -(CR) aa R bb ) m2 S(O) m1 -or-(CR) aa R bb ) m2 NRcc -; L5 is selected from the bond, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L6 is selected from the bond, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L7 is selected from the key, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L8 is selected from the key, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; Alternatively, L8 can be linked with any one of L5, L6, and L7 to form C. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 2a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 2b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 2c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic, C6-12 aryl, 5-12 membered heteroaryl, -(CH2) n2 OR ee -(CH2) n2 NR ee R ff -(CH2) n2 C(O)R ee -(CH2) n2 C(O)NR ee R ff -(CH2) n2 P(O)R ee R ff or =CR ee R ff The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or =R g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl and =CR e R f One or more substituents in it are replaced; Or any two R3 atoms can link with their adjacent atoms to form C. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents from 5-12 heteroaryl groups; preferably, a C13 group is formed. 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally further converted by deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R6 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 9a and R 9b Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -OR i -NR i R j -C(O)R i -C(O)OR i-C(O)NR i R j -N=S(O)R i R j -S(O)R i (=NR j ) or -P(O)R i R j The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, substituted or unsubstituted amino, hydroxyl, cyano, nitro, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, oxo, thio, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 The aryl group is substituted with one or more substituents selected from substituted or unsubstituted 5-12 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R e and R f Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R g and R h Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; Or, R g With R h Link formation C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R i and R j Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R N Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R aa R bb and R cc Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R ee and R ff Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; y is selected from 0, 1, 2, 3, 4, 5 or 6; z is selected from 0, 1, 2, 3, 5 or 6; m1 is selected from 0, 1 or 2; m2 is selected from 0, 1 or 2; n2 is selected from 0, 1, 2, 3 or 4; n7 is selected from 0, 1, 2, 3 or 4; n8 is selected from 0, 1, 2, 3 or 4; n9 is selected from 0, 1, 2, 3 or 4; n10 is selected from 0, 1, 2, 3 or 4.

[0009] In a preferred embodiment of the invention, the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof is characterized further as shown in general formula (A), (A-1), or (A-2): M1 is selected from -N- or -CR a -; M a Selected from CR 2a NR 2a Or N; M b Selected from CR 2b NR 2b Or N; Or, R 2a With R 2b The link forms a ring A; Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, optionally surrounded by 0, 1, 2, 3, 4, 5 or 6 Rs. 2c Replaced; Ring B is selected from C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl or 5-14 heteroaryl groups; L2 is selected from the bond, -(CR aa R bb ) m2 -、-(CR aa R bb ) m2 C(O)-、-(CR aa R bb ) m2 NR cc C(O), -(CR) aa R bb )m2 S(O) m1 -or-(CR) aa R bb ) m2 NR cc -; L5 is selected from the bond, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L6 is selected from the bond, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L7 is selected from the key, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 2a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 2b Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 2c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic, C6-12 aryl, 5-12 membered heteroaryl, -(CH2) n2 OR ee -(CH2) n2 NR ee R ff -(CH2) n2 C(O)R ee -(CH2) n2 C(O)NR ee R ff -(CH2) n2 P(O)R ee R ff or =CR ee R ff The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or =R g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl and =CR e R f One or more substituents in it are replaced; Or any two R3 atoms can link with their adjacent atoms to form C. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents from 5-12 heteroaryl groups; preferably, a C13 group is formed. 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally further converted by deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R4 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NRh ) or -P(O)R g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl and =CR e R f One or more substituents in it are replaced; R 9a and R 9b Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -OR i -NR i R j -C(O)R i -C(O)OR i -C(O)NRi R j -N=S(O)R i R j -S(O)R i (=NR j ) or -P(O)R i R j The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, substituted or unsubstituted amino, hydroxyl, cyano, nitro, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, oxo, thio, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 The aryl group is substituted with one or more substituents selected from substituted or unsubstituted 5-12 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic, C6-12 aryl, 5-12 membered heteroaryl, -(CH2) n2 OR ee -(CH2) n2 NR ee R ff -(CH2) n2 C(O)R ee -(CH2) n2 C(O)NR ee R ff Or -(CH2) n2 P(O)R ee R ff The amino group, C 1-6 Alkyl, C 2-6alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic, C6-12 aryl, 5-12 membered heteroaryl, -(CH2) n2 OR ee -(CH2) n2 NR ee R ff -(CH2) n2 C(O)R ee -(CH2) n2 C(O)NR ee R ff Or -(CH2) n2 P(O)R ee R ff The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R e and R f Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R g and R h Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; Or, R g With R h Link formation C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R i and R j Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R N Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R aa R bband R cc Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R ee and R ff Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; y is selected from 0, 1, 2, 3, 4, 5 or 6; m1 is selected from 0, 1 or 2; m2 is selected from 0, 1 or 2; n2 is selected from 0, 1, 2, 3 or 4; n8 is selected from 0, 1, 2, 3 or 4; n9 is selected from 0, 1, 2, 3 or 4; n10 is selected from 0, 1, 2, 3 or 4.

[0010] In a preferred embodiment of the invention, the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof is characterized in that it is further represented as shown in general formula (III-E), (III-E-1), or (III-E-2): L5 is selected from the bond, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C(=CR) 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from 5-12 heteroaryl groups; preferably self-bonded, -O-, -S-, -C(O), -NR. N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L6 is selected from the bond, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C(=CR) 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from 5-12 heteroaryl groups; preferably self-bonded, -O-, -S-, -C(O), -NR. N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L7 is selected from the key, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C(=CR) 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from 5-12 heteroaryl groups; preferably self-bonded, -O-, -S-, -C(O), -NR. N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 9a and R 9b Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -OR i -NR i R j -C(O)R i -C(O)OR i -C(O)NR i R j -N=S(O)R i R j -S(O)R i (=NR j ) or -P(O)R i R j The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, substituted or unsubstituted amino, hydroxyl, cyano, nitro, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 Alkyne, oxo, thio, substituted or unsubstituted C 1-6 Deuterated alkyl, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkoxy, substituted or unsubstituted C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 The aryl group is substituted with one or more substituents selected from substituted or unsubstituted 5-12 heteroaryl groups; preferably from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R N Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; n8 is selected from 0, 1, 2, 3, or 4; n9 is selected from 0, 1, 2, 3, or 4; n10 is selected from 0, 1, 2, 3, or 4; Ring A, Ring B, L2, M1, M3, R c R1, R2, R3, R4, x, and y are defined as in any of the above implementation schemes.

[0011] In a preferred embodiment of the invention, the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof is characterized in that it is further a compound, its stereoisomer, or a pharmaceutically acceptable salt thereof represented by general formula (IV-E): M5 is selected from N or CR. 3a M6 is selected from N or CR 3b ; R5 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 3a R 3b R 3d and R 3e Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or -C(=NR) i )NR g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl and =CR e R f One or more substituents in it are replaced; R 3c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or -C(=NR) i )NR g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl and =CR e R f One or more substituents in it are replaced; Ring A, M1, M3, R c The definitions of R2, x, L5, L6, L7, n8, and n9 are as defined in any of the above implementation schemes.

[0012] In a preferred embodiment of the invention, the compound, its stereoisomers, or pharmaceutically acceptable salts thereof are characterized in that ring A is selected from 3-12-membered heterocyclic groups or 5-12-membered heteroaryl groups; preferably 5-membered heterocyclic groups, 6-membered heterocyclic groups, 5-membered heteroaryl groups, or 6-membered heteroaryl groups; more preferably... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or More preferably , , or .

[0013] In a preferred embodiment of the invention, the compound, its stereoisomers, or pharmaceutically acceptable salts thereof are characterized in that ring B is selected from 3-6-membered heterocyclic benzophenyl or 3-6-membered heterocyclic benzo5-6-membered heteroaryl; preferably... , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0014] In a preferred embodiment of the invention, the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof is characterized further as shown in general formula (VI-A) or (VI-B): M5 is selected from N or CR. 3a M6 is selected from N or CR 3b ; R5 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 3a R 3b R 3d and R 3e Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or -C(=NR) i )NR g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl and =CR e R f One or more substituents in it are replaced; R 3c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or -C(=NR) i )NR g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl and =CR e R f One or more substituents in it are replaced; n11 is selected from 0, 1, or 2.

[0015] In a preferred embodiment of the present invention, L6 is selected from -O-, -S-, -C(O), and -NR. N -、C 1-3 Alkylene or C 2-4 alkenyl, the C 1-3 Alkylene and C 2-4 alkenyl group, optionally replaced by deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; In a preferred embodiment of the present invention, n8 is selected from 1, 2 or 3; n9 is selected from 0, 1 or 2.

[0016] In a preferred embodiment of the invention, R2 or R 2c Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, cyano-substituted C 1-3 Alkyl, C 3-8 cycloalkyl or -C(O)NR ee R ff The amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, cyano-substituted C 1-3 Alkyl and C 3-8 Cycloalkyl, optionally with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, cyano-substituted C 1-3 Alkyl and C3-8 One or more substituents in the cycloalkyl group are substituted; R ee and R ff Each is independently selected from hydrogen, deuterium, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 alkyl; Preferred elements include hydrogen, deuterium, fluorine, chlorine, methyl, deuterated methyl, difluoromethyl, and trifluoromethyl. , or .

[0017] In a preferred embodiment of the present invention, R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl or cyano-substituted C 1-3 Alkyl group; preferably hydrogen, deuterium, fluorine, chlorine, methyl, deuterated methyl, difluoromethyl or trifluoromethyl.

[0018] The present invention also provides a compound as shown in general formula (AI), its stereoisomer, or a pharmaceutically acceptable salt thereof: R' is selected from hydrogen, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or C 1-6 Hydroxyalkyl; R is selected from halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl or ; R'' is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; The preferred compounds are those represented by the following general formula (A-II): Preferably, the compound represented by formula (A-II) is further represented as shown by formula (IV-EI), formula (IV-AI), or formula (IV-BI): Pg1 is selected from hydrogen, allyloxycarbonyl, trifluoroacetyl, tert-butylsulfinyl, 2,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, nitrobenzenesulfonyl, triphenylmethyl, phosphoxycarbonyl, 9-fluorenmethoxycarbonyl, benzyl, p-toluenesulfonyl, p-methoxybenzyl, formate, acetyl, benzyloxycarbonyl, phthaloyl, tert-butyloxycarbonyl, or p-methoxyphenyl; preferably benzyl, p-methoxybenzyl, or tert-butyloxycarbonyl. Pg2 is selected from hydrogen, allyloxycarbonyl, trifluoroacetyl, tert-butylsulfinyl, 2,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, nitrobenzenesulfonyl, triphenylmethyl, phosphoxycarbonyl, 9-fluorenmethoxycarbonyl, benzyl, p-toluenesulfonyl, p-methoxybenzyl, formate, acetyl, benzyloxycarbonyl, phthaloyl, tert-butyloxycarbonyl, or p-methoxyphenyl; preferably hydrogen, benzyl, p-methoxybenzyl, or tert-butyloxycarbonyl. M1, M a M b Ring A, Ring B, L2, L5, L6, L7, R a R b R c R3, M5, M6, R 3a R 3b R 3c R 3d R 3e R5, n11, n8, n9, x, and y are as defined in any of the above implementation schemes.

[0019] The present invention also provides a method for preparing compounds of general formula (A), their stereoisomers or pharmaceutically acceptable salts thereof, characterized in that: The compound represented by general formula (AI) reacts with a condensing agent and a base to give the compound represented by general formula (A-II), and further removal of the protecting group gives the compound represented by general formula (A); Preferably, the method is a method for preparing compounds represented by general formula (IV-E), their stereoisomers, or pharmaceutically acceptable salts thereof: The compound represented by general formula (IV-EI) reacts with a condensing agent and a base to give the compound represented by general formula (IV-E-II), and further removal of the protecting group gives the compound represented by general formula (IV-E). Alternatively, the method may be a method for preparing compounds of general formula (VI-A), their stereoisomers, or pharmaceutically acceptable salts thereof: The compound represented by general formula (VI-AI) reacts with a condensing agent and a base to give the compound represented by general formula (VI-A-II), and further removal of the protecting group gives the compound represented by general formula (VI-A); Alternatively, the method may be a method for preparing compounds of general formula (VI-B), their stereoisomers, or pharmaceutically acceptable salts thereof: The compound represented by general formula (VI-BI) reacts with a condensing agent and a base to give the compound represented by general formula (VI-B-II), and further removal of the protecting group gives the compound represented by general formula (VI-B). Pg1 is selected from hydrogen, allyloxycarbonyl, trifluoroacetyl, tert-butylsulfinyl, 2,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, nitrobenzenesulfonyl, triphenylmethyl, phosphoxycarbonyl, 9-fluorenmethoxycarbonyl, benzyl, p-toluenesulfonyl, p-methoxybenzyl, formate, acetyl, benzyloxycarbonyl, phthaloyl, tert-butyloxycarbonyl, or p-methoxyphenyl; preferably benzyl, p-methoxybenzyl, or tert-butyloxycarbonyl. Pg2 is selected from hydrogen, allyloxycarbonyl, trifluoroacetyl, tert-butylsulfinyl, 2,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, nitrobenzenesulfonyl, triphenylmethyl, phosphoxycarbonyl, 9-fluorenmethoxycarbonyl, benzyl, p-toluenesulfonyl, p-methoxybenzyl, formate, acetyl, benzyloxycarbonyl, phthaloyl, tert-butyloxycarbonyl, or p-methoxyphenyl; preferably hydrogen, benzyl, p-methoxybenzyl, or tert-butyloxycarbonyl. M1, M a M b Ring A, Ring B, L2, L5, L6, L7, R a R b R c R3, M5, M6, R 3a R 3b R 3c R 3d R 3e R5, n11, n8, n9, x, and y are as described in any of the above embodiments.

[0020] In a preferred embodiment of the present invention, the condensing agent in the preparation method is selected from sulfoxide, phosphorus oxychloride, p-toluenesulfonyl chloride, methanesulfonyl chloride, dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, carbonyl diimidazole, ethyl chloroformate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, O-benzotriazole-tetramethylurea hexafluorophosphate, or tetramethylchlorourea hexafluorophosphonate; preferably phosphorus oxychloride, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, O-benzotriazole-tetramethylurea hexafluorophosphate, or tetramethylchlorourea hexafluorophosphonate. The base is selected from potassium carbonate, methylamine, triethylamine, diisopropylamine, pyridine, imidazole, N-methylimidazolium, or N-methylmorpholine.

[0021] The present invention further relates to a pharmaceutical composition comprising a compound shown in any embodiment of a therapeutically effective dose, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0022] The present invention further relates to the use of the compound shown in any embodiment, its stereoisomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition thereof in the preparation of a PRMT5 inhibitor medicament.

[0023] The present invention further relates to the use of the compounds shown in any embodiment, their stereoisomers or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof in the preparation of a medicament for treating cancer, wherein the cancer is selected from MTAP-associated cancers.

[0024] The present invention further relates to the compounds shown in any embodiment, their stereoisomers or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the preparation of a method for treating cancer, wherein the cancer is selected from MTAP-associated cancers.

[0025] In some implementations, the cancer is selected from lung cancer, hepatocellular carcinoma, breast cancer, skin cancer, bladder cancer, liver cancer, pancreatic cancer, head and neck cancer, glioma, glioblastoma, esophageal cancer, pancreatic cancer, mesothelioma, melanoma, astrocytoma, undifferentiated pleomorphic sarcoma, diffuse large B-cell lymphoma, leukemia, gastric adenocarcinoma, myxofibrosarcoma, cholangiosarcoma, brain cancer, gastric cancer, kidney cancer, endometrial cancer, ovarian tumor, prostate cancer, lymphoma, non-Hodgkin lymphoma, urinary tract cancer, soft tissue cancer, pleural cancer, colorectal cancer, colorectal cancer, or bile duct cancer; the lung cancer is selected from non-small cell lung cancer, squamous cell carcinoma of the lung, or adenocarcinoma of the lung; the esophageal cancer is selected from esophageal squamous cell carcinoma or esophageal adenocarcinoma.

[0026] The present invention also relates to a method of treating, preventing and / or treating cancer, comprising administering to a patient a therapeutically effective dose of a compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, as shown in any of the embodiments.

[0027] The present invention also relates to a method of treating cancer in mammals, comprising administering to the mammal a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt, ester, prodrug, solvate, hydrate or derivative thereof.

[0028] 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 its pharmaceutically acceptable salts, preferably 90%, 85%, 80%, 75%, 70%, 60%, or 50%.

[0029] 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.

[0030] In some embodiments of the present invention, the pharmaceutical composition is an immediate-release formulation or a sustained-release formulation.

[0031] In some embodiments of the invention, the unit dose of the pharmaceutical composition, calculated as free base, of the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof is 1-1000 mg, preferably 1-500 mg, or preferably 1 mg, 2 mg, 3 mg, 5 mg, 10 mg, 20 mg, 40 mg, 50 mg, 60 mg, 80 mg, 100 mg, 200 mg, 300 mg, 400 mg, or 500 mg.

[0032] In some embodiments of the invention, the compound, its stereoisomers, or pharmaceutically acceptable salts thereof may be administered by any convenient method, such as oral, parenteral, oral, sublingual, nasal, rectal, intrathecal, or transdermal administration, and accordingly modified pharmaceutical compositions.

[0033] In some embodiments of the invention, the compound, its stereoisomers, or pharmaceutically acceptable salts thereof may be formulated into liquid or solid dosage forms, such as syrups, suspensions, emulsions, tablets, capsules, powders, granules, or lozenges.

[0034] In some implementations, this method relates to the treatment of conditions such as lung cancer, hepatocellular carcinoma, breast cancer, skin cancer, bladder cancer, liver cancer, pancreatic cancer, head and neck cancer, glioma, glioblastoma, esophageal cancer, pancreatic cancer, mesothelioma, melanoma, astrocytoma, undifferentiated pleomorphic sarcoma, diffuse large B-cell lymphoma, leukemia, gastric adenocarcinoma, myxofibrosarcoma, cholangiosarcoma, brain cancer, gastric cancer, kidney cancer, endometrial cancer, ovarian tumor, prostate cancer, lymphoma, non-Hodgkin's lymphoma, urinary tract cancer, soft tissue cancer, pleural cancer, colorectal cancer, colorectal cancer, or bile duct cancer.

[0035] In some implementations, the lung cancer is selected from non-small cell lung cancer, squamous cell carcinoma of the lung, or adenocarcinoma of the lung; the esophageal cancer is selected from esophageal squamous cell carcinoma or esophageal adenocarcinoma.

[0036] Detailed description of the invention 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.

[0037] The term "alkyl" refers to a straight-chain or branched saturated aliphatic hydrocarbon group, which may optionally be substituted with one or more substituents. In certain embodiments, alkyl refers to a group having a carbon density of 1 to 20 (C). 1-20 ), 1 to 15 (C 1-15 ), 1 to 12 (C 1-12 ), 1 to 10 (C 1-10 ), 1 to 8 (C 1-8 ), 1 to 6 (C 1-6 ) or 1 to 3 (C 1-3 A straight-chain saturated hydrocarbon group with 3 to 20 carbon atoms, or a group with 3 to 20 carbon atoms. 3-20 ), 3 to 15 (C 3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 A branched saturated hydrocarbon group with 1 carbon atom. The straight-chain C group used here... 1-6 Alkyl and branched C 3-6 Alkyl groups are also called "lower alkyl groups". For example, C 1-6 Alkyl groups refer to linear saturated monovalent hydrocarbon groups having 1 to 6 carbon atoms or branched saturated monovalent hydrocarbon groups having 3 to 6 carbon atoms. In one embodiment, the C 1-6The alkyl group contains 1 to 6 carbon atoms (e.g., 1, 2, 3, 4, 5, 6). 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.

[0038] 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.

[0039] 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 having a carbon atom content of 3 to 20. 3-20 ), 3 to 15 (C3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 A branched unsaturated hydrocarbon group with 16 carbon atoms. Unless otherwise specified, the term "alkenyl" as used herein includes both straight-chain and branched alkenyl groups. For example, C 2-6 Alkenyl refers to a straight-chain unsaturated hydrocarbon group having 2 to 6 carbon atoms or a branched unsaturated hydrocarbon group having 3 to 6 carbon atoms. In one embodiment, the C 2-6 Alkenyl groups contain 2 to 6 (e.g., 2, 3, 4, 5, or 6) carbon atoms. Non-limiting examples of alkenyl groups include: , , , , or 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.

[0040] The term "alkenyl" refers to an alkenyl group in which one hydrogen atom is further substituted, wherein the definition of "alkenyl" is as previously stated. In one embodiment, the alkenyl group is an optionally substituted alkyl group as described elsewhere herein.

[0041] 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 having a carbon atom content of 3 to 20. 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 2-6Alkyne 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: , , or In one embodiment, the alkynyl group is an optionally substituted alkynyl group as described elsewhere herein.

[0042] The term "ynynyl" refers to an ynyl group in which one hydrogen atom is further substituted, wherein the definition of "ynyl" is as previously stated. In one embodiment, the ynynyl group is an optionally substituted alkyl group as described elsewhere herein.

[0043] 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 14 (C 3-14 ), 3 to 12 (C 3-12 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 ) carbon atoms; in one embodiment, the cycloalkyl ring 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.

[0044] The term "cycloalkylene" refers to a divalent cycloalkyl group formed by further substitution of one hydrogen atom of a cycloalkyl group, wherein the cycloalkylene is optionally substituted or unsubstituted, and the cycloalkyl group is defined as described above.

[0045] 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, 8 to 20, 10 to 20, 3 to 16, 8 to 16, 10 to 16, 3 to 14, 5 to 14, 8 to 14, 3 to 12, 5 to 12, 8 to 12, 3 to 8, or 3 to 6 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. 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.

[0046] The term "tricyclic heterocyclic group" refers to a heterocyclic group in a system that consists of three rings, wherein the three rings can be fused ring systems, spirocyclic systems, or bridged ring systems. In one embodiment, a tricyclic heterocyclic group is a system in which at least one of the three rings is a heterocyclic group, and the other two rings can be cycloalkyl, heterocyclic, aryl, or heteroaryl. The definitions of cycloalkyl, heterocyclic, aryl, or heteroaryl are as described above, and non-limiting examples of preferred tricyclic heterocyclic groups are as follows: , , , , , , , , , , , or wait.

[0047] The term "subheterocyclic group" refers to a divalent heterocyclic group formed by further substituting one hydrogen atom of a heterocyclic group, wherein the subheterocyclic group may be optionally substituted or unsubstituted, as defined above.

[0048] 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, 6 to 12, 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), , , , , , , , , , , , , and .

[0049] 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.

[0050] 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, the heteroaryl comprises 5 to 20, 5 to 14, 5 to 12, or 5 to 10 ring atoms, of which 1 to 4 are heteroatoms; in one embodiment, the heteroaryl comprises 5 or 6 ring atoms; in certain embodiments, the 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, , , , , , , , , and .

[0051] 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.

[0052] 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.

[0053] 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.

[0054] The term "alkylacyl" refers to -C(O)-alkyl, where the definition of alkyl is as described above.

[0055] 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, or .

[0056] 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.

[0057] 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.

[0058] 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.

[0059] The term "haloalkylthio" refers to an alkylthio group substituted with one or more halogens, wherein the definition of alkylthio is as described above.

[0060] 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.

[0061] The term "aminocarbonyl" refers to NH2-C(O)-.

[0062] 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.

[0063] 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.

[0064] The term "carbonyl" refers to the -C(O)-, -(CO)-, or -C(=O)- group. All designations are interchangeable in the specification.

[0065] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0066] The term "oxo" or "side oxygen" refers to =O.

[0067] The term "C(X)" or "C(=X)" refers to Group. When X is O, it represents a carbonyl group; when X is S, it represents a mercapto group; when X is NR, it represents a... When X is CRR, it means that the group is .

[0068] 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 isotopically enriched analogs can be prepared from suitable isotopically labeled starting materials available from commercial sources or by known literature procedures.

[0069] 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, 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.

[0070] 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.

[0071] "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.

[0072] 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.

[0073] "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 substituted 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). Substituents can be selected from deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, oxo, thio, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl.

[0074] "Substituted or unsubstituted" means that it may or may not be substituted. When it can be substituted, the substituent is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -SF5, -C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, C(O)R, C(O)OR, C(O)NRR', N=S(O)RR', S(O)R (=NR'), P(O)RR' or =RR'; R and R' are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, --C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups.

[0075] 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.

[0076] "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.

[0077] "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.

[0078] "Stereoisomers" encompass all enantiomers / non-corresponding isomers / stereoisomers of the present invention, as well as enantiomers / non-corresponding isomers / stereoisomers enriched in this invention.

[0079] "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.

[0080] "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%.

[0081] "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.

[0082] "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.

[0083] 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. Detailed Implementation

[0084] 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.

[0085] Example The structures of the compounds of this invention were determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). NMR shift ( ) with 10 -6 The unit (ppm) is given. NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer, with deuterated dimethyl sulfoxide (DMSO) as the solvent. d 6 ), deuterated chloroform (CDCl3), deuterated methanol (CD3OD), with tetramethylsilane (TMS) as the internal standard.

[0086] MS measurements were performed using a Finnigan LCQAd (ESI) mass spectrometer (manufacturer: Thermo, model: Finnigan LCQ advantage MAX).

[0087] The HPLC determination was performed using an Agilent 1200DAD high-performance liquid chromatograph (Sunfire C). 18 150×4.6mm chromatographic column) and Waters 2695-2996 high-performance liquid chromatograph (Gimini C) 18 (150×4.6mm chromatographic column).

[0088] Mean inhibition rate of kinases and IC 50 The values ​​were determined using a NovoStar microplate reader (BMG GmbH, Germany).

[0089] Thin-layer chromatography silica gel plates are Yantai Huanghai HSGF254 or Qingdao GF254. The silica gel plates used in thin-layer chromatography (TLC) have a size of 0.15 mm to 0.2 mm, and the size used for thin-layer chromatography separation and purification of products is 0.4 mm to 0.5 mm.

[0090] Column chromatography typically uses Yantai Huanghai silica gel with a mesh size of 200-300 as the carrier.

[0091] The known starting materials of this invention can be synthesized using or according to methods known in the art, or can be purchased from companies such as ABCR GmbH & Co. KG, Acros Organics, Aldrich Chemical Company, Accela ChemBio Inc, and Darui Chemicals.

[0092] Unless otherwise specified in the examples, the reactions can be carried out under an argon or nitrogen atmosphere.

[0093] Argon or nitrogen atmosphere refers to a reaction flask connected to an argon or nitrogen gas balloon with a volume of approximately 1L.

[0094] A hydrogen atmosphere refers to a reaction vessel connected to a hydrogen balloon with a volume of approximately 1L.

[0095] The pressurized hydrogenation reaction was performed using a Parr 3916EKX hydrogenator and a Qinglan QL-500 hydrogen generator or an HC2-SS hydrogenator.

[0096] The hydrogenation reaction is usually carried out under vacuum, filled with hydrogen gas, and repeated 3 times.

[0097] The microwave reaction was performed using a CEM Discover-S 908860 microwave reactor.

[0098] Unless otherwise specified in the examples, "solution" refers to an aqueous solution.

[0099] Unless otherwise specified in the examples, the reaction temperature is room temperature, which is 20 ℃ to 30 ℃.

[0100] The reaction process in the examples was monitored using thin-layer chromatography (TLC). The developing solvent systems used in the reactions were: A: dichloromethane and methanol system, B: n-hexane and ethyl acetate system, C: petroleum ether and ethyl acetate system, and D: acetone. The volume ratio of the solvents was adjusted according to the polarity of the compounds.

[0101] The eluent systems for column chromatography and the developing solvent systems for thin-layer chromatography used to purify the compounds include: A: n-hexane and ethyl acetate system, B: n-hexane and tetrahydrofuran system. The volume ratio of the solvents is adjusted according to the polarity of the compounds. Small amounts of basic or acidic reagents such as triethylamine and acetic acid can also be added for adjustment.

[0102] The chiral preparation HPLC conditions in the examples are as follows, t R Indicates the retention period: Chiral preparation conditions: Chiral analysis conditions: The compounds in the embodiments of the present invention are prepared according to the preparation steps of the following examples: Example 1 4-Amino-12-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-9,10,11,12-tetrahydroimidazo[1,5-a][1,5]oxazolino[8,7-g]quinoxalo-13(7H)-one Step 1: Dissolve 10 g (52.53 mmol) of 3-((tert-butyldimethylsilyl)oxo)propane-1-ol 1a in 100 mL of tetrahydrofuran, and add sodium hydride (2.73 g, 68.29 mmol, 60% purity) under ice bath conditions. After stirring for 15 minutes, add potassium (bromomethyl)trifluoroborate (10.02 g, 49.91 mmol) and allow the reaction to proceed at room temperature with stirring for approximately 16 hours. Add potassium hydrofluoric acid solution (4.5M) to the reaction solution, stir at room temperature for 30 minutes, evaporate the reaction solution to dryness, add 1000L of hot acetone, stir at 80°C for about 15 minutes, filter off impurities by hot filtration, distill the acetone under reduced pressure until solid precipitates, add twice the amount of diethyl ether, filter under ice bath, dry the residue to obtain 8,8,9,9-tetramethyl-3,7-dioxa-8-silza-1-boronadecan-1-trifluoroborate potassium 1b (4.3 g), yield: 26.4%.

[0103] Step 2: Methyl 7-bromo-4-((3,4-dimethoxybenzyl)amino)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester (5.2 g, 10.99 mmol), potassium 8,8,9,9-tetramethyl-3,7-dioxa-8-silaz-1-boronadecan-1-trifluoroborate 1b (4.3 g, 13.19 mmol), methanesulfonic acid [n-butyldi(1-adamantyl)phosphine](2-amino-1,1'-biphenyl-2-yl)palladium(II) (800 mg, 1.10 mmol), and cesium carbonate (5.37 g, 16.48 mmol) were dissolved in 60 mL of dioxane and 15 mL of water. The reaction was carried out in a nitrogen atmosphere and microwaved at 110 °C for 2 hours. Water (100 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL × 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give methyl 7-((3-((tert-butyldimethylsilyl)oxo)propoxy)methyl)-4-((3,4-dimethoxybenzyl)amino)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 1c (3.3 g), yield: 50.5%. MS m / z (ESI): 595 [M+1] Step 3: Dissolve 7-((3-((tert-butyldimethylsilyl)oxo)propoxy)methyl)-4-((3,4-dimethoxybenzyl)amino)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 1c (3.3 g, 5.56 mmol) in 60 mL of tetrahydrofuran, add tetrabutylammonium fluoride (2.90 g, 11.10 mmol, 2 M in THF), and stir the reaction at room temperature for 2 hours. The reaction was quenched by adding saturated ammonium chloride solution (100 mL), and extracted with ethyl acetate (100 mL x 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with eluent system C to give methyl 4-((3,4-dimethoxybenzyl)amino)-7-((3-hydroxypropoxy)methyl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 1d (1.5 g), yield: 56.3%. MS m / z (ESI): 481 [M+1] Step 4: Methyl 4-((3,4-dimethoxybenzyl)amino)-7-((3-hydroxypropoxy)methyl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 1d (1.5 g, 3.12 mmol) was dissolved in dichloromethane (120 mL), the mixture was purged with nitrogen three times, cooled to 0 °C, and then triphenylphosphine (1.64 g, 6.24 mmol) and carbon tetrabromide (2.07 g, 6.24 mmol) were added. The system was reacted at 25 °C for 2 hours. The reaction solution was distilled under reduced pressure, and the residue was purified by silica gel column chromatography with eluent system C to give methyl 7-((3-bromopropoxy)methyl)-4-((3,4-dimethoxybenzyl)amino)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 1e (630 mg), yield: 37.1%. MS m / z (ESI): 543 [M+1] Step 5: Dissolve 7-((3-bromopropoxy)methyl)-4-((3,4-dimethoxybenzyl)amino)imidazo[1,5-a]quinoxaline-8-carboxylic acid methyl ester 1e (560 mg, 1.03 mmol), 2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridine-5-amine 3c (270 mg, 1.24 mmol), sodium iodide (309 mg, 2.06 mmol), and potassium carbonate (427 mg, 3.09 mmol) in acetonitrile (60 mL), purge with nitrogen three times, and react the mixture at 80 °C for 15 hours. The reaction mixture was quenched with water, extracted with ethyl acetate (50 mL × 2), washed with saturated brine (50 mL x 2), dried over anhydrous sodium sulfate, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system C to give methyl 4-((3,4-dimethoxybenzyl)amino)-7-((3-((2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)amino)propoxy)methyl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 1f (360 mg), yield: 51.3%. MS m / z (ESI): 681 [M+1] Step 6: Dissolve methyl 4-((3,4-dimethoxybenzyl)amino)-7-((3-((2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)amino)propoxy)methyl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 1f (350 mg, 0.51 mmol) in tetrahydrofuran (5 mL), water (5 mL) and methanol (5 mL), add lithium hydroxide (62 mg, 2.57 mmol), purge with nitrogen three times, and react the system at 25 °C for 16 hours. Adjust the pH to 5-6 with 1 M dilute hydrochloric acid, extract with ethyl acetate (50 mL × 3), wash with saturated brine (50 mL x 2), dry the organic phase with anhydrous sodium sulfate, and concentrate the filtrate under reduced pressure to give 1f (125 mg) of 4-((3,4-dimethoxybenzyl)amino)-7-((3-((2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)amino)propoxy)methyl)imidazo[1,5-a]quinoxaline-8-carboxylic acid, yield: 36.5%. MS m / z (ESI): 667 [M+1] Step 7: Dissolve 4-((3,4-dimethoxybenzyl)amino)-7-((3-((2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)amino)propoxy)methyl)imidazo[1,5-a]quinoxaline-8-carboxylic acid 1f (125 mg, 0.18 μmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (68 mg, 0.54 mmol) in N,N-dimethylformamide (20 mL), add N,N-diisopropylethylamine (93 mg, 0.72 mmol, 72 μL), and react the mixture at 25 °C for 48 hours. Quench with water, extract with ethyl acetate (80 mL × 3), wash with saturated brine, dry to anhydrous sodium sulfate, and concentrate the filtrate under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give 1 g (63 mg) of 4-((3,4-dimethoxybenzyl)amino)-12-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-9,10,11,12-tetrahydroimidazo[1,5-a][1,5]oxazolino[8,7-g]quinoxalin-13(7H)-one, yield: 53.9%. MS m / z (ESI): 649 [M+1] Step 8: Dissolve 1 g (63 mg, 0.10 mmol) of 4-((3,4-dimethoxybenzyl)amino)-12-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-9,10,11,12-tetrahydroimidazo[1,5-a][1,5]oxazolino[8,7-g]quinoxaline-13(7H)-one in trifluoroacetic acid (2 mL), and react the mixture at 90 °C for 0.5 hours. The residue was concentrated and purified by silica gel column chromatography using eluent system A to give 4-amino-12-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-9,10,11,12-tetrahydroimidazo[1,5-a][1,5]oxazolino[8,7-g]quinoxalin-13(7H)-one 1 (9.7 mg), yield: 19.4%. MS m / z (ESI): 499 [M+1] 1 H NMR (400 MHz, DMSO) δ 9.23 (d, 1H), 8.33 (dd, 1H), 8.22 (s, 1H), 8.08 (s, 2H), 7.87 (dd, 1H), 7.44 (d, 1H), 5.63 – 5.36 (m, 1H), 4.89 – 4.70(m, 3H), 4.47 – 4.13 (m, 3H), 3.94 – 3.64 (m, 2H), 3.09 (dd, 2H), 2.18 – 1.91(m, 1H), 1.15 (d, 1H). Example 2 (Z)-4-((2,4-dimethoxybenzyl)amino)-13-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-10,11,12,13-tetrahydroacrylino[4,3-g]imidazo[1,5-a]quinoxaline-14(9H)-one Step 1: 2-(trifluoromethyl)-8H-pyrano[3,4-b]pyridin-5-one 2a (3 g, 13.82 mmol) and hydroxylamine hydrochloride (960 mg, 13.82 mmol) were dissolved in ethanol (30 mL) and sodium acetate (3.40 g, 41.45 mmol). The mixture was purged with nitrogen three times and reacted at 80 °C for 1 hour. After cooling to room temperature, the mixture was concentrated, quenched with water, extracted with ethyl acetate (100 mL x 3), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent system B to give 2-(trifluoromethyl)-6H-pyrano[3,4-b]pyridin-5(8H)-one oxime 2b (3.10 g), yield: 96.7%. MS m / z (ESI): 233 [M+1] Step 2: 2-(trifluoromethyl)-6H-pyrano[3,4-b]pyridine-5(8H)-ketooxime 2b (3.1 g, 13.35 mmol) and wet palladium on carbon (811 mg, 0.67 mmol, 10% purity) were dissolved in methanol (40 mL), and the reaction was carried out under hydrogen balloon at 25 °C for 4 hours with hydrogen purging three times. The mixture was filtered and concentrated to obtain 2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridine-5-amine 2c (2.80 g, crude product). MS m / z (ESI): 219 [M+1] Step 3: Methyl 7-bromo-4-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 2d (1 g, 2.12 mmol) and cuprous iodide (81 mg, 0.42 mmol) were dissolved in N,N-dimethylformamide (11 mL) and triethylamine (11 mL). The mixture was purged with nitrogen three times. Hex-5-yn-1-ol (1.04 g, 10.61 mmol) and bis(triphenylphosphine)palladium dichloride (149 mg, 0.21 mmol) were added. The mixture was purged with nitrogen three times. The system was reacted at 40 °C for 16 hours. Cool to room temperature, concentrate, quench with water, extract with ethyl acetate (60 mL x 3), wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate to give methyl 4-((2,4-dimethoxybenzyl)amino)-7-(6-hydroxyhex-1-yn-1-yl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 2e (0.95 g, crude). MS m / z (ESI): 489 [M+1] Step 4: Methyl 4-((2,4-dimethoxybenzyl)amino)-7-(6-hydroxyhex-1-en-1-yl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 2e (0.95 g, 1.94 mmol) and Raney nickel (100 mg) were dissolved in methanol (10 mL) and tetrahydrofuran. The reaction was carried out under hydrogen purging three times at 25 °C for 0.5 h under a hydrogen balloon. The mixture was filtered and concentrated to obtain methyl (Z)-4-((2,4-dimethoxybenzyl)amino)-7-(6-hydroxyhex-1-en-1-yl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 2f (0.90 g, crude product). MS m / z (ESI): 491 [M+1] Step 5: 2f of methyl(Z)-4-((2,4-dimethoxybenzyl)amino)-7-(6-hydroxyhex-1-en-1-yl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester (0.9 g, 1.83 mmol) was dissolved in dichloromethane (10 mL), the mixture was purged with nitrogen three times, cooled to 0 °C, and then triphenylphosphine (962 mg, 3.67 mmol) and carbon tetrabromide (1.22 g, 3.67 mmol) were added. The system was reacted at 25 °C for 2 hours. The mixture was then concentrated. The residue was purified by silica gel column chromatography using eluent system B to give 2g (560 mg) of methyl(Z)-7-(6-bromohex-1-en-1-yl)-4-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester, yield: 55.2%. MS m / z (ESI): 553 [M+1] Step 6: Dissolve 2 g (1 g, 1.81 mmol) of methyl(Z)-7-(6-bromohex-1-en-1-yl)-4-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester, 3 c (788 mg, 3.61 mmol) of 2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridine-5-amine, and 541.67 mg, 3.61 mmol of sodium iodide in acetonitrile (60 mL). Add N,N-diisopropylethylamine (1.40 g, 10.84 mmol, 1.89 mL), purge with nitrogen three times, and react the mixture at 80 °C for 15 hours. Quench with water, extract with ethyl acetate (80 mL x 3), wash with saturated brine, dry with anhydrous sodium sulfate, filter, and concentrate. The residue was purified by silica gel column chromatography using eluent system A to give methyl(Z)-4-((2,4-dimethoxybenzyl)amino)-7-(6-((2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)amino)hex-1-en-1-yl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester 2h (410 mg), yield: 32.9%. MS m / z (ESI): 691 [M+1] Step 7: Dissolve methyl(Z)-4-((2,4-dimethoxybenzyl)amino)-7-(6-((2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)amino)hex-1-en-1-yl)imidazo[1,5-a]quinoxaline-8-carboxylic acid ester (430 mg, 0.62 mmol) in tetrahydrofuran (5 mL), water (5 mL), and methanol (5 mL). Add lithium hydroxide (60 mg, 2.49 mmol), purge with nitrogen three times, and react the system at 25 °C for 16 hours. Adjust the pH to 5-6 with 1 M dilute hydrochloric acid, extract with ethyl acetate (50 mL x 3), wash with saturated brine (30 mL) and dry with anhydrous sodium sulfate, filter, and concentrate to obtain (Z)-4-((2,4-dimethoxybenzyl)amino)-7-(6-((2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)amino)hex-1-en-1-yl)imidazo[1,5-a]quinoxaloline-8-carboxylic acid 2i (410 mg, crude product). MS m / z (ESI): 677 [M+1] Step 8: Dissolve Z)-4-((2,4-dimethoxybenzyl)amino)-7-(6-((2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)amino)hex-1-en-1-yl)imidazo[1,5-a]quinoxaline-8-carboxylic acid 2i (56 mg, 83 μmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (62 mg, 0.17 mmol) in N,N-dimethylformamide (10 mL), add N,N-diisopropylethylamine (54 mg, 0.41 mmol, 72 μL), purge with nitrogen three times, and react the system at 25 °C for 48 hours. Quenching with water, extraction with ethyl acetate (80 mL x 3), washing with saturated brine, drying on anhydrous sodium sulfate, filtering, and concentrating. The residue was purified by silica gel column chromatography using eluent system A to give (Z)-4-((2,4-dimethoxybenzyl)amino)-13-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-10,11,12,13-tetrahydroacetanoin[4,3-g]imidazo[1,5-a]quinoxaline-14(9H)-one 2j (16 mg), yield: 29.4%. MS m / z (ESI): 659 [M+1] Step 9: Dissolve (Z)-4-((2,4-dimethoxybenzyl)amino)-13-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-10,11,12,13-tetrahydroacecenolide[4,3-g]imidazo[1,5-a]quinoxaline-14(9H)-one 2j (5 mg, 7.6 μmol) in trifluoroacetic acid (2 mL), purge with nitrogen three times, and react the system at 90 °C for 0.5 hours. The residue was concentrated and purified by silica gel column chromatography using eluent system A to give Z)-4-((2,4-dimethoxybenzyl)amino)-13-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-10,11,12,13-tetrahydroacetano[4,3-g]imidazo[1,5-a]quinoxaline-14(9H)-one 2 (0.55 mg), yield: 14.2%. MS m / z (ESI): 509 [M+1] 1H NMR (400 MHz, MeOD) δ 9.07 (d, 1H), 8.27 (d, 1H), 8.18–8.06 (m,1H), 7.99–7.92 (m, 1H), 7.79 (dd, 3.0 Hz, 1H), 7.25 (d, 1H), 6.65 (dd, 1H), 6.10–5.99 (m, 1H), 5.88–5.78 (m, 1H), 4.51 (dd, 1H), 4.34 (dd, 1H), 4.28–4.20 (m, 1H), 3.65–3.58 (m, 1H), 3.09–2.98 (m, 1H), 2.13 (s, 1H), 2.04–1.96 (m,1H), 1.56 (s, 3H), 1.29 (s, 2H). Examples 2A & 2B (R,Z)-4-amino-13-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-10,11,12,13-tetrahydroacrylino[4,3-g]imidazo[1,5-a]quinoxaline-14(9H)-one The product rel-(R,Z)-4-amino-13-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-10,11,12,13-tetrahydroacrylino[4,3-g]imidazo[1,5-a]quinoxaline-14(9H)-one 2 (55 mg, 4.24 mmol) was obtained by chiral preparative HPLC separation of (Z)-4-((2,4-dimethoxybenzyl)amino)-13-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-10,11,12,13-tetrahydroacrylino[4,3-g]imidazo[1,5-a]quinoxaline-14(9H)-one 2A (18) The yield of rel-(S,Z)-4-amino-13-(2-(trifluoromethyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-10,11,12,13-tetrahydroacecenobenz[4,3-g]imidazo[1,5-a]quinoxaline-14(9H)-one 2B (20 mg) was 36.4%. MS m / z (ESI): 509 [M+1] Example 2A: 1H NMR (400 MHz, MeOD) δ 9.06 (dd, 1H), 8.21 (dd, 1H), 8.08–7.91 (m, 2H), 7.78 (dd, 1H), 7.25 (dd, 1H), 6.65 (dd, 1H), 6.09–5.77 (m, 1H),5.52–5.26 (m, 1H), 4.60 (s, 1H), 4.51 (dd, 1H), 4.23 (ddd, 1H), 3.62 (t, 1H),3.04 (dt, 1H), 2.23–2.07 (m, 1H), 2.03–1.95 (m, 1H), 1.77 (q, 1H), 1.60 (dt,1H), 1.45–1.20 (m, 3H). Example 2B: 1 H NMR (400 MHz, MeOD) δ 8.97 (d, 1H), 8.12 (dd, 1H), 7.98–7.82 (m, 2H), 7.69 (dd, 1H), 7.15 (d, 1H), 6.55 (dd, 1H), 6.00–5.69 (m, 1H),5.42–5.16 (m, 1H), 4.42 (dd, 1H), 4.28–4.08 (m, 2H), 3.52 (t, 1H), 2.95 (dt,1H), 2.12–1.97 (m, 1H), 1.93–1.84 (m, 1H), 1.71–1.61 (m, 1H), 1.46 (d, 1H), 1.37–1.05 (m, 3H). Example 3 (Z)-4-amino-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,9,10,11,12-hexahydro-13H-azo[3,4-g]furan[3,4-c]quinoline-13-one Step 1: Dissolve methyl 7-[(Z)-5-bromopenta-1-enyl]-4-[(2,4-dimethoxyphenyl)methylamino]-1,3-dihydrofuran[3,4-c]quinoline-8-carboxylic acid ester 3a (0.7 g, 1.29 mmol) in acetonitrile (20 mL), add [5-(trifluoromethyl)-2-pyridyl]methylamine (273.27 mg, 1.55 mmol), potassium carbonate (536.06 mg, 3.88 mmol), and sodium iodide (387.58 mg, 2.59 mmol), purge three times with nitrogen, and react the mixture at 80 °C for 16 hours. Quench with water, extract with ethyl acetate (100 mL × 3), wash with saturated brine, dry with anhydrous sodium sulfate, filter, and concentrate. The residue was purified by silica gel column chromatography using eluent system A to give 3b (329 mg, 516.76 μmol), yield: 39.97%. MS m / z (ESI): 637 [M+1] + Step 2: Dissolve 3b (329 mg, 516.76 μmol) in tetrahydrofuran (5 mL), methanol (5 mL), and water (5 mL). Add lithium hydroxide monohydrate (65.05 mg, 1.55 mmol). React the mixture at 50 °C for 3 hours. Concentrate the reaction solution to remove the organic phase, adjust to neutral with 2N hydrochloric acid, extract with dichloromethane (with 10% methanol), wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate to obtain 3c (220 mg, 353.34 μmol), yield: 68.38%. MS m / z (ESI): 623 [M+1] + Step 3: Dissolve 3c (210 mg, 337.28 μmol) in N,N-dimethylformamide (20 mL), add N,N-diisopropylethylamine (65.38 mg, 505.92 μmol, 88.12 μL), and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)hexafluorophosphate urea (190.87 mg, 505.92 μmol). Stir the reaction mixture at room temperature for 30 minutes. Quench with water, extract with ethyl acetate (50 mL × 3), wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate. Purify the residue by silica gel column chromatography using eluent system A to obtain 3d (188 mg, 310.94 μmol), yield: 92.19%. MSm / z (ESI): 604 [M+1] + Step 4: 188 mg (310.94 μmol) of 3d solution was added to trifluoroacetic acid (10 mL), and the reaction mixture was reacted at 80 °C for 1 hour. The reaction solution was adjusted to pH 8-9 with sodium bicarbonate aqueous solution, extracted with dichloromethane (with 10% methanol), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was used to prepare Example 3 (13.4 mg, 29.49 μmol) in reverse process, yield: 9.48%. MS m / z (ESI): 454 [M+1] + 1 H NMR (400 MHz, DMSO) δ 8.59 (s, 1H), 8.59 (s, 2H), 8.24 (dd, J =8.4,2.1 Hz, 1H), 7.74 (s, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.52 (s, 1H), 6.62(d, J = 10.8 Hz, 1H), 6.07 (d, J = 6.8 Hz, 1H), 5.46 (dd, J = 6.3,3.4 Hz,2H), 5.13-4.99 (m, 3H), 4.53 (d, J = 15.9 Hz, 1H), 2.21-2.08 (m, 1H), 2.05-1.87 (m, 1H), 1.70 (d, J = 9.9 Hz, 2H), 1.40 (s, 1H), 1.27 (d, J = 5.8 Hz, 1H) The preparation of the following examples is based on Example 2: The preparation of the following examples is based on Example 1: Alternatively, the following examples use the following preparation method: Example 6 4-Amino-12-((2'-(trifluoromethyl)-[3,4'-dipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H )-ketone Following the preparation method of Example 1, 12-((5-bromopyridin-2-yl)methyl)-4-((3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4-] was obtained from 3-(benzyloxy)prop-1-ol 6a (10.0 g, 60.24 mmol). c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H )-Keto-6i (2.1 g), yield 9.9%. MS m / z (ESI): 619 [M+1] Step 8: Add 12-((5-bromopyridin-2-yl)methyl)-4-((3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H 1,1'-keto-6i (120 mg, 0.19 mmol), 2-(trifluoromethyl)-4-pyridineboronic acid (72 mg, 0.38 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane (15 mg, 0.02 mmol), and potassium carbonate (52 mg, 0.38 mmol) were dissolved in 5 mL of dioxane and 1 mL of water. The reaction was carried out at 100 °C for 2 hours under nitrogen atmosphere. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL × 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give the title product 4-((3,4-dimethoxybenzyl)amino)-12-((2'-(trifluoromethyl)-[3,4'-dipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenotin[7,8- g Quinoxaline-13(1) H )-Ketocone 6j (110 mg), yield 84.5%. MS m / z (ESI): 686 [M+1] Referring to the synthesis method in step 8 of Example 1, the method was synthesized via 4-((3,4-dimethoxybenzyl)amino)-12-((2'-(trifluoromethyl)-[3,4'-dipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazononanones[7,8- g Quinoxaline-13(1) H )-keto 6j (110 mg, 0.16 mmol) yields 4-amino-12-((2'-(trifluoromethyl)-[3,4'-dipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H )-Keto-6 (47 mg), yield 54.9%. MS m / z (ESI): 536 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.12 (d, 1H), 8.89 (d, 1H), 8.68 - 8.01(m, 5H), 7.68 (dd, 3H), 5.46 (d, 2H), 5.23 (d, 1H), 5.09 (d, 2H), 4.70 (dd,2H), 4.42 (d, 1H), 3.94 - 3.77 (m, 1H), 3.36 (ddd, 3H), 1.97 (d, 1H), 1.25(d, 1H). Example 8 4-Amino-12-((5-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuran[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: 5-Bromo-2-cyanopyridine 8a (3.85 g, 21.04 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentane (4.86 g, 23.14 mmol), sodium carbonate (3.34 g, 31.56 mmol), and bis(triphenylphosphine)palladium dichloride (1.48 mmol, 2.10 mmol) were dissolved in dioxane (50 mL) and water (10 mL), purged with nitrogen, and stirred at 90 °C for approximately 2 hours. The reaction mixture was filtered to remove solids, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography using eluent system B to obtain the title product 5-(3,6-dihydro-2H-pyran-4-yl)pyridinium 8b (3.10 g), in 79.2% yield. MS m / z (ESI): 187 [M+1] Step 2: 5-(3,6-dihydro-2H-pyran-4-yl)pyridinium 8b (4.12 g, 22.13 mmol) and Raney nickel (3.92 g) were dispersed in methanol (60 mL) and stirred at room temperature for 3 hours under hydrogen atmosphere. The reaction mixture was filtered to remove solids, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography with eluent system B to give the title product (5-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)methyl)tert-butyl carbamate 8c (2.30 g), yield 36.1%. MS m / z (ESI): 291 [M+1] Step 3: 8c (1.60 g, 5.51 mmol) of (5-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)methyl)carbamate tert-butyl ester (8d) was dissolved in dioxane hydrochloride solution (5 mL, 4 M) and methanol (20 mL), and stirred at room temperature for 3 hours. The reaction solution was concentrated to give the title product (5-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)methylamine hydrochloride 8d (1.10 g), yield 88.0%. MS m / z (ESI): 191 [M+1] Following the synthetic method described in steps six through nine of Example 2, 4-amino-12-((5-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuran[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 8 (52 mg) was obtained from methyl 7-((3-(3-bromopropoxy)methyl)-4-((3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 8 in 29.7% yield. MS m / z (ESI): 473 [M+1] 1 H NMR (400 MHz, CD3OD) δ 8.70 (s, 1H), 8.21 (dd, , 1H), 7.83 (d, 1H),7.77 (s, 1H), 7.70 (s, 1H), 6.47 (s, 1H), 5.52 (m, 2H), 5.20 (m, 3H), 4.97(d, 1H), 4.59 (m, 2H), 4.35 (m, 2H), 3.96 (m, 3H), 3.45 (m, 3H), 2.57 (s,2H), 2.08 (m, 1H), 1.31 (m, 1H). Example 9 4-Amino-12-[(5-cyanopyridin-2-yl)methyl]-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazinedecano[7,8-g]quinoline-13(1H)-one Following the synthetic method described in steps 5 through 8 of Example 1, 4-amino-12-[(5-cyanopyridin-2-yl)methylamine dihydrochloride 9a (222 mg, 1.00 mmol) and 7-((3-bromopropyl)methyl)-4-(2,4-dimethoxybenzylamino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester (272 mg, 0.50 mmol) were synthesized to yield 4-amino-12-[(5-cyanopyridin-2-yl)methyl]-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazacyclodecano[7,8-g]quinoline-13(1H)-one 9 (5.0 mg), in 2.4% yield, using (5-cyanopyridin-2-yl)methylamine dihydrochloride 9a (222 mg, 1.00 mmol) and 7-((3-bromopropyl)methyl)-4-(2,4-dimethoxybenzylamino)-1,3-dihydrofurano[3,4-c][1,5]oxazacyclodecano[7,8-g]quinoline-13(1H)-one 9. 1 H NMR (400 MHz, DMSO-d6) δ 9.02 (d, 1H), 8.34 (t, 1H), 7.74 (d, 1H), 7.50 (s, 1H), 7.31 (s, 1H), 5.40 (t, 2H), 5.15 (d, 1H), 5.05 (t, 2H), 4.73(d, 1H), 4.56 (d, 1H), 4.44 (d, 1H), 3.80 (d, 1H), 3.45 (q, 2H), 3.41 (d,1H), 1.91 (q, 1H), 1.22 (d, 1H). Example 10 4-Amino-12-((5-(methylsulfonyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Following the synthetic method described in steps six through nine of Example 2, methyl 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 10a (600 mg, 1.10 mmol) yielded 4-amino-12-((5-(methanesulfonyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 10 (132 mg), in 25.6% yield. MS m / z (ESI): 469 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.06 (d, 1H), 8.68 - 8.59 (m, 1H), 8.35 (dd, 1H), 7.87–7.68 (m, 2H), 7.57 (d, 2H), 5.43 (t, 2H), 5.21 (d, 1H), 5.06(t, 2H), 4.75 (d, 1H), 4.59 (d, 1H), 4.46 (d, 1H), 3.82 (dt, J 1H), 3.47 -3.42 (m, 1H), 3.25 (d, 1H), 1.94 (q, 1H), 1.74 (s, 4H), 1.24 (d, 1H). Example 11 12-((5-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methyl)-4-amino-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: 5-Fluoropyridine-2-onitrile 11a (4.5 g, 36.86 mmol) and 1,2,3-triazole 11b (5.09 g, 73.71 mmol) were dissolved in DMF (30 mL), and Cs₂CO₃ (36.02 g, 110.57 mmol) was added. The mixture was purged three times with nitrogen and kept under nitrogen protection. The reaction was stirred at 80°C for 16 hours. The reaction solution was filtered, and water (200 mL) was added to the filtrate. The solution was extracted with ethyl acetate (200 mL × 3), and the organic phases were combined. The mixture was washed with water (200 mL × 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was stirred with ethyl acetate:petroleum ether (50 mL:20 mL) for 15 minutes, filtered, and the filter cake was dried under reduced pressure. The filter cake was purified using Pre-HPLC to obtain 5-(triazol-2-yl)pyridine-2-onitrile 11c (3... g), Yield: 47.6%. MS m / z (ESI): 172 [M+1] Step 2: 5-(triazol-2-yl)pyridin-2-onitrile 11c (1.3 g, 7.60 mmol) was dissolved in HCl (6 mL) methanol solution, and Pd / C (260.00 mg, 2.45 mmol) was added. The mixture was purged with hydrogen three times under hydrogen protection. The reaction was carried out at 35 °C with stirring for 5 hours. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The concentrated residue was stirred with ethyl acetate (30 mL) for 15 minutes, filtered, and the filter cake was dried under reduced pressure to give [5-(triazol-2-yl)-2-pyridinyl]methylamine 11d (800 mg, hydrochloride), yield 60.1%. MS m / z (ESI): 176 [M+1] Step 3: 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 11e (500 mg, 917 μmol) and [5-(triazol-2-yl)-2-pyridyl]methylamine 11d (291.04 mg, 1.38 mmol, CL) were dissolved in acetonitrile (10 mL). Cs₂CO₃ (896.06 mg, 2.75 mmol) and NaI (274.82 mg, 1.83 mmol) were added sequentially. The mixture was purged with nitrogen three times, and nitrogen protection was maintained. The reaction was carried out at 80°C with stirring for 16 minutes. The reaction solution was concentrated under reduced pressure for hours; the concentrated residue was purified by Pre-HPLC to give 11 f (240 mg) of methyl 7-(3-((5-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methyl)amino)propoxy)methyl-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid, in a yield of 40.5%. MS m / z (ESI): 641 [M+1] Step 4: 11f (190 mg, 297 μmol) of compound 7-(3-((5-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methyl)amino)propoxy)methyl-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester was dissolved in THF (3 mL) / MeOH (1 mL) / Water (1 mL). LiOH (28.45 mg, 1.19 mmol) was added, the mixture was purged with nitrogen three times, and nitrogen protection was maintained. The reaction was carried out at 25 °C with stirring for 16 hours. The reaction solution was concentrated under reduced pressure, and water (10 mmol) was added to the concentrated residue. mL), adjusted pH to 4-5 with 2M dilute hydrochloric acid, concentrated under reduced pressure to give 11 g (240 mg, crude) of 7-((3-((5-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methyl)amino)propoxymethyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid. MS m / z (ESI): 627 [M+1] Step 5: 11 g (130 mg, 208 μmol) of compound 7-((3-((5-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methyl)amino)propoxymethyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid was dissolved in DMF (5 mL), and DIEA (26.85 mg, 208 μmol, 37 μL) and HATU (78.39 mg, 208 μmol) were added. The mixture was purged with nitrogen three times under nitrogen protection. The reaction was carried out at 25 °C. The mixture was stirred for 16 hours; the reaction solution was concentrated under reduced pressure to give 12-(5-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methyl)-4-(3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 11h (150 mg, crude product). MS m / z (ESI): 609 [M+1] Step 6: Compound 12-(5-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methyl)-4-(3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one (90 mg, 148 μmol) was dissolved in TFA (2 mL), purged three times with nitrogen, and protected with nitrogen. The reaction was carried out at 80 °C. The mixture was stirred for 0.5 hours. The reaction solution was concentrated under reduced pressure, and the concentrated residue was separated and purified by Pre-HPLC to give 12-((5-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methyl)-4-amino-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 11 (44 mg), yield 64.9%. MS m / z (ESI): 458 [M+1] 1H NMR (400 MHz, DMSO-d6) δ 9.22 (d, 1H), 8.43 (dd, 1H), 8.23 ​​(s, 2H), 7.74 (d, 1H), 7.64 (s, 1H), 7.57 (s, 1H), 5.44 (t, 2H), 5.22 (d, 1H), 5.07(t, 2H), 4.74 (d, 1H), 4.60 (d, 1H), 4.40 (d, 1H), 3.80 (d, 1H), 3.43 (d,1H), 3.30 (d, 2H), 2.03 - 1.86 (m, 1H), 1.28 - 1.18 (m, 1H). Example 12 4-Amino-12-(3-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Following steps one through six of the method in Example 11, the title compound 4-amino-12-(3-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 12 (31 mg) was obtained by reacting 3-chloro-4-fluorobenzonitrile 12a (150 mg, 963 µmol) with 3-chloro-4-fluorobenzonitrile 12a (31 mg) in a yield of 6.5%. MS m / z (ESI): 458 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.17 (s, 2H), 7.81 (d, 1H), 7.70 (d, 1H), 7.65 - 7.61 (m, 2H), 7.58 (s, 1H), 5.42 (d, 2H), 5.18 (d, 1H), 5.06 (t, 2H),4.76 (d, 1H), 4.59 (d, 1H), 4.35 (d, 1H), 3.85 - 3.75 (m, 1H), 3.41 (s, 1H),3.29 - 3.18 (m, 2H), 1.95 (q, 1H), 1.22 (d, 1H). Example 13 4-Amino-12-[(5-ethynylpyridin-2-yl)methyl]-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazinedecano[7,8-g]quinoline-13(1H)-one Step 1: Add N-[(5-bromo-2-pyridyl)methyl]tert-butyl carbamate 13a (5 g, 17.41 mmol), trimethylethynylsilane (2.57 g, 26.12 mmol, 3.69 mL), Pd(PPh3)2Cl2 (611 mg, 870.62 μmol), CuI (166 mg, 871 μmol), and TEA (50 mL) sequentially to a single-necked flask. Replace the flask with a nitrogen atmosphere and react at 50°C for 5 hours. Quench the reaction by cooling, and concentrate the system to dryness. Dissolve the EA, filter, and wash successively with saturated NH4Cl solution, saturated NaHCO3 solution, and saturated NaCl solution. Dry with anhydrous Na2SO4, filter, and concentrate the filtrate to dryness. The residue was purified by silica gel column chromatography using eluent system A to give the title product (5-(trimethylsilylethynyl)pyridin-2-yl)methylcarbamate tert-butyl 13b (4.84 g), in 91.3% yield. MS m / z (ESI): 305 [M+1] Step 2: To a single-necked flask, add (5-(trimethylsilylethynyl)pyridin-2-yl)methylcarbamate tert-butyl 13b (4.84 g, 15.90 mmol), THF (50 mL), and 1M TBAF solution (15.9 mL, 15.90 mmol) sequentially. Replace the atmosphere with nitrogen and react at 25°C for 1 hour. Concentrate the system to dryness, dissolve in EA, wash with saturated NaCl solution, dry with anhydrous Na₂SO₄, filter, and concentrate to dryness. Purify the residue by silica gel column chromatography using eluent system A to give the title product (5-(trimethylsilylethynyl)pyridin-2-yl)methylamine 13c (2.9 g), yield 78.5%. MS m / z (ESI): 205 [M+1] Following the synthetic method described in steps five through eight of Example 1, 4-amino-12-[(5-ethynylpyridin-2-yl)methyl]-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazhecyclodecano[7,8-g]quinoline-13(1H)-one 13 (14.0 mg) was obtained by reacting (5-(trimethylsilylethynyl)pyridin-2-yl)methylamine 13c (308 mg, 1.50 mmol) and 7-((3-bromopropyl)methyl)-4-(2,4-dimethoxybenzylamino)-1,3-dihydrofurano[3,4-c][1,5]oxazhecyclodecano[7,8-g]quinoline-13(1H)-one 13 (14.0 mg) with (5-(trimethylsilylethynyl)pyridin-2-yl)methylamine 13c (308 mg, 1.50 mmol) and 7-((3-bromopropyl)methyl)-4-(2,4-dimethoxybenzylamino)-1,3-dihydrofurano[3,4-c][1,5]oxazhecyclodecano[7,8-g]quinoline-13(1H)-one 13 (14.0 mg) in 6.7% yield. MS m / z (ESI): 415 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.67 (t, 1H), 7.94 (dd, 1H), 7.59 (s, 1H), 7.56 (dd, 1H), 7.49 (s, 1H), 5.41 (s, 2H), 5.15 (d, 1H), 5.05 (s, 2H), 4.72(d, 1H), 4.58 (d, 1H), 4.45 (s, 1H), 4.33 (d, 1H), 3.77 (d, 1H), 3.42 (q,1H), 3.23 (d, 2H), 1.91 (q, 1H), 1.20 (d, 1H). Example 15 4-Amino-12-((5-(2,2,2-trifluoroethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Referring to steps six through nine of Example 2, methyl 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 15a (600 mg, 1.10 mmol) and 5-methylsulfonyl-2-pyridyl)methylamine hydrochloride (410 mg, 2.20 mmol, synthesized using the known method “WO2009 / 117421, 2009, A2”) yielded 4-amino-12-((5-(2,2,2-trifluoroethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 15 (20 mg), in 3.8% yield. MS m / z (ESI): 473 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.54 (d, 1H), 7.88 - 7.80 (m, 1H), 7.56 -7.48 (m, 2H), 7.40 (s, 1H), 6.68 (s, 2H), 5.36 (t, 2H), 5.18 (d, 1H), 5.02(d, 2H), 4.70 (d, 1H), 4.54 (d, 1H), 4.28 (d, 1H), 3.76 (q, 3H), 3.45 (t,1H), 3.17 (d, 2H), 1.96 - 1.85 (m, 1H), 1.21 (d, 1H). Example 16 4-Amino-12-((2'-(trifluoromethyl)-[3,4'-dipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H )-ketone Referring to the synthesis methods of step 8 in Example 6 and step 8 in Example 1, the synthesis was carried out via 12-((5-bromopyridin-2-yl)methyl)-4-((3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H)-Keto 16a (120 mg, 0.19 mmol) yields 4-amino-12-((2'-(trifluoromethyl)-[3,4'-dipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H )-Keto-16 (36 mg), yield 44.1%. MS m / z (ESI): 431 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ8.38 (d, 1H), 7.82 - 7.29 (m, 6H), 5.41 (s,2H), 5.16 (d, 1H), 5.05 (s, 2H), 4.64 (dd, 2H), 4.21 (d, 1H), 3.75 (d, 1H), 3.30 (ddd, 3H), 2.07 - 1.80 (m, 2H), 1.20 (d, 1H), 1.07 - 0.96 (m, 2H), 0.76- 0.64 (m, 2H). Example 17 4-Amino-12-((5-cyclopropyl-3-fluoropyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: Dissolve 3,5-difluoropyridine-2-onitrile 17a (5 g, 35.69 mmol) in DMA (30 mL). Slowly add morpholine (3.26 g, 37.48 mmol) and TEA (7.22 g, 71.38 mmol, 9.96 mL) under ice bath conditions. Heat the reaction mixture to 100°C and react for 2 hours. Cool the reaction solution to room temperature and add water to precipitate a large amount of white solid. Filter the solid, wash the filter cake with water, and dry it. Purify the crude product by column chromatography to obtain 3-fluoro-5-morpholinopyridine-2-onitrile 17b (1.9 g, 9.17 mmol), yield 25.7%. MS m / z (ESI): 208 [M+1] Step 2: Dissolve 1.9 g (9.17 mmol) of 3-fluoro-5-morpholinopyridin-2-onitrile 17b in methanol (40 mL), add Pd / C (782.60 mg, 644.38 μmol, 10% purity) and concentrated hydrochloric acid (12 M, 978.28 μL). Replace the hydrogen gas three times with a hydrogen balloon and react at room temperature for 16 hours. Filter the reaction solution with diatomaceous earth, wash the filter cake twice with methanol (5 mL), concentrate the filtrate, and pass it through a column to obtain (3-fluoro-5-morpholino-2-pyridyl)methylamine 17c (560 mg, 2.65 mmol), yield 28.9%. MS m / z (ESI): 212 [M+1] Step 3: Dissolve 17c of 3-fluoro-5-morpholino-2-pyridyl)methylamine (500 mg, 2.37 mmol) in ACN (20 mL), add methyl 7-(3-bromopropoxymethyl)-4-[(2,4-dimethoxyphenyl)methylamino]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid (400 mg, 733.38 μmol), sodium iodide (219.85 mg, 1.47 mmol), and cesium carbonate (716.85 mg, 2.20 mmol), purge with nitrogen, and heat to 80°C for 16 hours. The reaction solution was extracted with water and ethyl acetate, the organic phase was dried and concentrated, and then filtered through a column to give methyl 4-[(2,4-dimethoxyphenyl)methylamino]-7-[3-[(3-fluoro-5-morpholino-2-pyridyl)methylamino]propoxymethyl]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 17d (190 mg, 281.17 μmol), yield 38.3%. MS m / z (ESI): 677 [M+1] Step 4: Dissolve methyl 4-[(2,4-dimethoxyphenyl)methylamino]-7-[3-[(3-fluoro-5-morpholino-2-pyridyl)methylamino]propoxymethyl]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 17d (190 mg, 281.17 μmol) in tetrahydrofuran (4 mL), add lithium hydroxide monohydrate (58.99 mg, 1.41 mmol), methanol (2 mL), and water (1 mL), and stir overnight at room temperature. Concentrate the reaction solution to remove methanol and tetrahydrofuran, and adjust the pH to 3-4 with dilute hydrochloric acid. Extracted with ethyl acetate, the organic phase was concentrated to give 4-[(2,4-dimethoxyphenyl)methylamino]-7-[3-[(3-fluoro-5-morpholino-2-pyridyl)methylamino]propoxymethyl]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 17e (155 mg, 234.24 μmol), yield 83.3%. MS m / z (ESI): 662 [M+1] Step 5: Dissolve 4-[(2,4-dimethoxyphenyl)methylamino]-7-[3-[(3-fluoro-5-morpholino-2-pyridyl)methylamino]propoxymethyl]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 17e (120 mg, 181.08 μmol) in DMF (2.00 mL), add DIEA (140.41 mg, 1.09 mmol, 189.24 μL) and HATU (136.63 mg, 362.15 μmol), and stir at room temperature for 2 hours. Extracted with water and ethyl acetate, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give 4-((3,4-dimethoxybenzyl)amino)-12-((3-fluoro-5-morpholinpyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 17f (190 mg, 177.10 μmol, 60% purity), yield 97.8%. MS m / z (ESI): 645 [M+1] Step 6: Take 4-((3,4-dimethoxybenzyl)amino)-12-((3-fluoro-5-morpholinpyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 17f (182.5 mg, 284 μmol), heat to 80°C and stir for half an hour. The reaction solution is directly concentrated to remove TFA, and the crude product is reverse-phase prepared by lyophilization to obtain 4-amino-12-((5-cyclopropyl-3-fluoropyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 17 (38 mg, 77 μmol), yield 27.2%. MS m / z (ESI): 494 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.49(s, 1H), 7.30 (dd, 1H), 7.18 (s, 1H), 6.62 (s, 2H), 5.41-5.34 (m, 1H), 5.32 (dt, 2H), 5.01 (d, 2H), 4.71 - 4.50 (m, 2H), 4.09 (d, 1H), 3.75 (t, 4H), 3.51 - 3.45 (m, 2H), 3.24(t, 6H), 1.25 - 1.14 (m, 2H). Example 18 4-Amino-12-((5-cyclopropyl-3-fluoropyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: 5-Bromo-3-fluoropyridine-2-onitrile 18a (5 g, 24.88 mmol), cyclopropylboronic acid (3.42 g, 39.80 mmol), Cs₂CO₃ (16.21 g, 49.75 mmol), and Pd(dppf)Cl₂ (910 mg, 1.24 mmol) were added to a single-necked flask, and then dissolved in dioxane (50 mL) and water (5 mL). The reaction mixture was stirred at 100°C for 16 hours. The reaction solution was evaporated to dryness and dissolved in 60 mL of EA. The solution was washed successively with water (50 mL) and saturated brine (50 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to obtain 5-cyclopropyl-3-fluoropyridine-2-onitrile 18b (3.6 g, 22.20 mmol), with a yield of 89.2%. MS m / z (ESI): 163 [M+1] Step 2: Dissolve 3.6 g (22.20 mmol) of 5-cyclopropyl-3-fluoropyridin-2-onitrile 18b in MeOH (40 mL), add Pd / C (1.89 g, 1.56 mmol, 10% purity) and HCl (12 M, 2.37 mL), and react three times with a hydrogen balloon, stirring overnight at room temperature. Filter the reaction solution, add triethylamine to the filtrate to adjust the pH to 8-9, stir, and pass through a column to obtain the product (5-cyclopropyl-3-fluoro-2-pyridinyl)methylamine 18c (700 mg, 4.21 mmol), yield 19.0%. MS m / z (ESI): 167 [M+1] Step 3: Dissolve methyl 7-(3-bromopropoxymethyl)-4-[(2,4-dimethoxyphenyl)methylamino]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 18c (550 mg, 1.01 mmol) and (5-cyclopropyl-3-fluoro-2-pyridyl)methylamine (503 mg, 3.03 mmol) in ACN (10 mL), add NaI (302 mg, 2.02 mmol) and Cs2CO3 (986 mg, 3.03 mmol), replace with nitrogen, and react at 80℃ for 16 hours. The reaction solution was diluted with ethyl acetate (20 mL) and filtered. The filtrate was concentrated, mixed, and passed through a column to give methyl 7-[3-[(5-cyclopropyl-3-fluoro-2-pyridyl)methylamino]propoxymethyl]-4-[(2,4-dimethoxyphenyl)methylamino]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 18d (400 mg, 634 μmol), yield 62.9%. MS m / z (ESI): 632 [M+1] Step 4: Dissolve 18d (190 mg, 281.17 μmol) of 7-[3-[(5-cyclopropyl-3-fluoro-2-pyridyl)methylamino]propoxymethyl]-4-[(2,4-dimethoxyphenyl)methylamino]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester in THF (4 mL), add LiOH·H2O (58.99 mg, 1.41 mmol), MeOH (2 mL) and Water (1 mL), and stir overnight at room temperature. The reaction mixture was concentrated to remove methanol and tetrahydrofuran. The pH was adjusted to 3-4 with dilute hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic phase was concentrated to give 4-[(2,4-dimethoxyphenyl)methylamino]-7-[3-[(3-fluoro-5-morpholino-2-pyridinyl)methylamino]propoxymethyl]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 18e (155 mg, 234.24 μmol), yield 83.3%. MS m / z (ESI): 618 [M+1] Step 5: Dissolve 4-[(2,4-dimethoxyphenyl)methylamino]-7-[3-[(3-fluoro-5-morpholino-2-pyridyl)methylamino]propoxymethyl]-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 18e (120 mg, 194.28 μmol) in DMF (3.00 mL), add DIEA (150.65 mg, 1.17 mmol, 203.04 μL) and HATU (146.59 mg, 388.56 μmol), and stir at room temperature for 2 hours. Extracted with water and ethyl acetate, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give 12-((5-cyclopropyl-3-fluoropyridin-2-yl)methyl)-4-(3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 18f (110 mg, 184 μmol), yield 94.8%. MS m / z (ESI): 600 [M+1] Step 6: Dissolve 12-((5-cyclopropyl-3-fluoropyridin-2-yl)methyl)-4-(3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 18f (110 mg, 184 μmol) in TFA (4 mL), heat to 80 °C and stir for half an hour. The reaction solution was directly concentrated to remove TFA, and the crude product was reverse-phase prepared by lyophilization to give 4-amino-12-((5-cyclopropyl-3-fluoropyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 18 (45 mg, 100 μmol), yield 54.3%. MS m / z (ESI): 449 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.53 (s, 1H), 7.38 (d, 1H), 7.25 (s, 1H), 7.04 (s, 2H), 5.34 (dd, 3H), 5.02 (s, 2H), 4.68 (d, 1H), 4.57(d, 1H), 4.17 (d, 1H), 3.79 (d, 1H), 3.51-3.44 (m, 1H) , 3.26-3.12 (m, 2H) ,2.08-1.88 (m, 2H) , 1.24 (s, 1H), , 1.10-1.00 (m, 2H) , 0.85-0.77 (m, 2H). Example 20 4-Amino-12-((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: Compound 5-(trifluoromethyl)pyridin-2-nitrile 20a (1 g, 5.81 mmol) was dissolved in HCl (6 mL, 4 M) methanol solution. Pd / C (100 mg, 94 μmol, 10% purity) was added, and the mixture was purged three times with hydrogen under hydrogen protection. The reaction was carried out at 35 °C with stirring for 16 hours. A layer of diatomaceous earth was spread in a vacuum funnel, and the reaction solution was filtered. The filter cake was washed with ethanol, and the filtrate was concentrated under reduced pressure. Petroleum ether (30 mL) was added to the concentrated residue, and the mixture was stirred for 15 minutes. The mixture was filtered, and the filter cake was dried under reduced pressure to obtain (3-fluoro-5-(trifluoromethyl)pyridin-2-yl)methylamine 20b (1.3 g, hydrochloride), with a yield of 97.0%. MSm / z (ESI): 195 [M+1] Referring to steps three through six of the method in Example 11, the title compound 4-amino-12-((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 20 (41 mg) was obtained by passing compounds 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 20 (41 mg) in 9.7% yield by passing compounds 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 20. MS m / z (ESI): 477 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.35 (dd, 1H), 7.65 (s, 1H), 7.42 (s, 1H), 5.51 - 5.32 (m, 3H), 5.07 (t, 2H), 4.67 (q, 2H), 4.41 (d, 1H), 3.87 (dt, 1H), 3.49 (td, 1H), 3.31 (dd, 2H), 2.00 (q, 1H), 1.27 (td, 1H). Example 25 4-Amino-12-((5-(dimethylphospho)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenotin[7,8-g]quinoline-13(1H)-one Step 1: 12-((5-bromopyridin-2-yl)methyl)-4-((2,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoinro[7,8-g]quinoline-13(1H)-one 25a (200 mg, 0.322 mmol, see synthesis steps in Example 1), dimethylphosphine (50 mg, 0.646 mmol), 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (24 mg, 0.0322 mmol), and potassium carbonate (89 mg, 0.646 mmol) were dissolved in dioxane (5 mL) and water (1 mL). The reaction mixture was purged with nitrogen three times and reacted at 100 °C for 3 hours. The residue was concentrated and purified by high-performance liquid chromatography (HPLC) using eluent system A to give 4-((2,4-dimethoxybenzyl)amino)-12-((5-(dimethylphospho)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconitano[7,8-g]quinoline-13(1H)-one 25b (85 mg), yield 42%. MS m / z (ESI): 617 [M+1] Step 2: Dissolve 85 mg (0.137 mmol) of 4-((2,4-dimethoxybenzyl)amino)-12-((5-(dimethylphospho)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxacono-[7,8-g]quinoline-13(1H)-one 25b in trifluoroacetic acid (4 mL), purge with nitrogen three times, and react the system at 60 °C for 1 hour. The residue was concentrated and purified by high-performance liquid chromatography (HPLC) using eluent system A to give 25 (24 mg) of 4-amino-12-((5-(dimethylphospho)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoinro[7,8-g]quinoline-13(1H)-one, in 37% yield. MS m / z (ESI): 467 [M+1] 1H NMR (400 MHz, DMSO-d6) δ 8.88 (m, 1H), 8.19 (m, 1H), 7.68-7.63 (m,1H), 7.57 (s, 1H), 7.47 (s, 1H), 7.19 (s, 1H), 5.39 (m, 2H), 5.20 (m, 1H),5.03 (m, 2H), 4.72 (m, 1H), 4.57 (m, 1H), 4.35 (m, 1H), 3.79 (m, 1H), 3.47-3.41 (m, 2H), 3.22 (m, 2H), 2.00-1.87 (m, 1H), 1.73 (m, 6H), 1.22 (m, 1H). Example 26 4-Amino-12-((5-(trifluoromethyl)benzothiazo-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuran[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: Dissolve 2-iodo-5-(trifluoromethyl)aniline 26a (5.00 g, 17.42 mmol), N-(2-amino-2-thioethyl)carbamate tert-butyl ester (3.98 g, 20.90 mmol), 1,1'-bis(diphenylphosphine)ferrocene (3.86 g, 6.97 mmol), calcium oxide (1.95 g, 34.84 mmol), and tris(dibenzylindenacetone)palladium (3.19 g, 3.48 mmol) in acetonitrile (150 mL), purge with nitrogen, and saturate at 60°C. o The mixture was stirred at C for approximately 16 hours. The reaction solution was filtered to remove solids, and the filtrate was concentrated under reduced pressure. Purification was performed by silica gel column chromatography using eluent system B to give the title product (5-(trifluoromethyl)benzo[d]thiazolyl)methyl)carbamate tert-butyl 26b (5.10 g), in 88.1% yield. MS m / z (ESI): 333 [M+1] Step 2: 5.80 g (17.45 mmol) of (5-(trifluoromethyl)benzo[d]thiazol-2-yl)methyl)carbamate tert-butyl ester 26b was dissolved in dioxane hydrochloride solution (50 mL, 4 M) and tetrahydrofuran (50 mL), and stirred at room temperature for 16 hours. The reaction solution was concentrated to give the title product (5-(trifluoromethyl)benzo[d]thiazol-2-yl)methylamine hydrochloride 26c (3.10 g), yield 66.1%. MS m / z (ESI): 233 [M+1] Following the synthetic method described in steps six through nine of Example 2, 4-amino-12-((5-(trifluoromethyl)benzothiazol-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuran[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 26 (50 mg) was obtained from methyl 7-((3-bromopropoxy)methyl)-4-((3,4-dimethoxybenzyl)amino)-1,3-dihydrofuran[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one in 5.0% yield. MS m / z (ESI): 515 [M+1] 1 H NMR (400 MHz, CD3OD) δ 8.30 (m, 1H), 8.24 (m, 1H), 7.74 (m, 1H), 7.70 (m, 2H), 5.49 (m, 3H), 5.19 (m, 2H), 4.90 (m, 2H), 4.61 (d, 1H), 3.92(m, 1H), 3.49 (m, 3H), 2.15 (m, 2H). Examples 36 & 66 4-Amino-8-(3-chlorobenzyl)-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,7,8,9,10,11,12-octahydro-13H-[1,5]diazo[7,8-g]furan[3,4-c]quinoline-13-one and 4-amino-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,7,8,9,10,11,12-octahydro-13H-[1,5]diazo[7,8-g]furan[3,4-c]quinoline-13-one Step 1: 3-Chlorobenzaldehyde 36a (5.00 g, 35.57 mmol) and 3-[tert-butyl(dimethyl)silyl)oxypropane-1-amine (7.07 g, 37.35 mmol) were dissolved in methanol (100 mL) and stirred at room temperature for 1 hour. The reaction mixture was cooled to 0 °C, and sodium borohydride (1.35 g, 35.57 mmol) was added and stirred for approximately 2 hours. The reaction mixture was quenched with water and extracted with dichloromethane. The extract was concentrated and purified by silica gel column chromatography using eluent system B to give the title product 3-((tert-butyldimethylsilyl)oxy)-N-(3-chlorobenzyl)propane-1-amine 36b (10.30 g), yield 92.2%. MS m / z (ESI): 314 [M+1] Step 2: Potassium bromomethyl(trifluoro)borate (4.12 g, 22.13 mmol), 3-((tert-butyldimethylsilyl)oxy)-N-(3-chlorobenzyl)propane-1-amine 36b (12.00 g, 38.22 mmol), and sodium iodide (3.82 g, 25.48 mmol) were dispersed in acetonitrile (200 mL) and heated at 80 °C. o Stirred at C for 16 hours. The reaction mixture was filtered to remove solids, the filtrate was concentrated, and the solution was slurried with diethyl ether and filtered to give the title product ((((3-((tert-butyldimethylsilyl)oxy)propyl)(3-chlorobenzyl)amino)methyl)potassium trifluoroborate)36c (5.00 g), yield 45.2%. MS m / z (ESI): 434 [M+1] Referring to the preparation method of Example 1, 4-amino-8-(3-chlorobenzyl)-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,7,8,9,10,11,12-octahydro-13H-[1,5]diazo[7,8-g]furan[3,4-c]quinoline-13-one 36 (30g) was obtained by reacting potassium trifluoroborate 36c (2.00 g, 4.62 mmol) with ((((3-(((tert-butyldimethylsilyl)oxy)propyl)(3-chlorobenzyl)amino)methyl)trifluoroborate potassium salt 36c (2.00 g, 4.62 mmol). The yield was 1.1%; simultaneously, 4-amino-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,7,8,9,10,11,12-octahydro-13H-[1,5]diazo[7,8-g]furan[3,4-c]quinoline-13-one 66 (36 mg) was obtained, with a yield of 1.7%. Example 36: MS m / z (ESI): 582 [M+1] 1 H NMR (400 MHz, MeOD) δ 8.90 (s, 1H), 8.18 (m, 1H), 7.77 (m, 1H), 7.68 (m, 2H), 7.51 (s, 1H), 7.37 (m, 3H), 5.56 (m, 3H), 5.17 (m, 2H), 4.31(m, 2H), 3.90 (m, 3H), 3.42 (m, 2H), 2.87 (m, 1H), 2.58 (m, 1H), 1.99 (m,2H). Example 66: MS m / z (ESI): 458 [M+1] 1H NMR (400 MHz, MeOD) δ8.94 (d, 1H), 8.20 (m, 1H), 8.08 (s, 1H), 7.95 (s, 1H), 7.66 (d, 1H), 5.55 (m, 2H), 5.20 (m, 2H), 4.76 (s, 2H), 4.53(s, 2H), 3.83 (m 2H), 3.22 (m, 2H), 2.20 (m, 2H). Example 42 6-((4-amino-13-oxo-1,3,7,10,11,13-hexahydrofurano[3,4-) c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-12(9) H )-yl)methyl)-[3,4'-dipyridine]-2'-carboxynitrile Referring to the synthesis methods of step 8 in Example 6 and step 8 in Example 1, the synthesis was carried out via 12-((5-bromopyridin-2-yl)methyl)-4-((3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H )-keto 42a (120 mg, 0.19 mmol) yielded 6-((4-amino-13-oxo-1,3,7,10,11,13-hexahydrofurano[3,4-) c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-12(9) H 42 (67 mg) of methyl(3,4'-dipyridine)-2'-carboxynitrile was obtained, with a yield of 71.2%. MS m / z (ESI): 493 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.12 (d, 1H), 8.89 (d, 1H), 8.28 (tt, 5H), 7.71 (d, 1H), 7.63 (d, 2H), 5.46 (s, 2H), 5.23 (d, 1H), 5.09 (t, 2H), 4.69(dd, 2H), 4.42 (d, 1H), 3.92 - 3.76 (m, 1H), 3.36 (ddd, 3H), 1.97 (d, 1H),1.25 (d, 1H). Example 43 4-Amino-12-((5-(trifluoromethyl)-[2,3'-bipyridin]-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: Compounds 5-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)pyridinecarboxynitrile 43a (9.5 g, 42.04 mmol) and 2-bromo-5-(trifluoromethyl)pyridine 43b (11.61 g, 50.44 mmol) were dissolved in 1',4-Dioxane (200 mL) / Water (20 mL). Pd(dppf)Cl2 (3.08 g, 4.20 mmol) and K2CO3 (17.43 g, 126.11 mmol) were added sequentially. The mixture was purged with nitrogen three times under nitrogen protection. The reaction was carried out at 100 °C with stirring for 16 hours. The reaction solution was filtered, and water (200 mL) was added to the filtrate. The mixture was extracted with ethyl acetate (200 mL × 3). The organic phases were combined and extracted with water (200 mL × 3). 3) Wash, dry with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and separate and purify the concentrated residue using purification system C to give 43c (8.2 g) of 5-[5-(trifluoromethyl)-2-pyridyl]pyridine-2-onitrile, yield 78.3%. MS m / z (ESI): 250 [M+1] Step 2: Compound 5-[5-(trifluoromethyl)-2-pyridyl]pyridine-2-nitrile 43c (1.5 g, 6.02 mmol) was dissolved in HCl (3 mL) methanol solution, and Pd / C (300.00 mg, 247 μmol, 10% purity) was added. The mixture was purged three times with hydrogen and kept under hydrogen protection. The reaction was carried out at 35 °C with stirring for 5 hours. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The concentrated residue was stirred in ethyl acetate (20 mL) for 15 minutes, filtered, and the filter cake was dried under reduced pressure to give [5-[5-(trifluoromethyl)-2-pyridyl]-2-pyridyl]methylamine 43d (1.5 g, hydrochloride), yield 80.4%. MS m / z (ESI): 254 [M+1] Referring to steps three through six of the method in Example 20, the title compound 4-amino-12-((5-(trifluoromethyl)-[2,3'-bipyridin-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 43 (20 mg) was obtained by passing compounds 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 43 (20 mg) in a yield of 6.8% by passing compounds 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 43 (20 mg). MS m / z(ESI): 536 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.32 (d, 1H), 9.15 - 9.07 (m, 1H), 8.57 (dd, 1H), 8.40 - 8.31 (m, 2H), 7.75 - 7.56 (m, 3H), 5.46 (d, 2H), 5.24 (d,1H), 5.08 (t, 2H), 4.76 (d, 1H), 4.63 (d, 1H), 4.47 - 4.37 (m, 1H), 3.82 (d,1H), 3.32 (d, 3H), 2.06 - 1.89 (m, 1H), 1.25 (d, 1H). Example 44 4-Amino-12-((5-chloro-[2,3'-bipyridin]-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: 5-chloro-2-iodopyridine 44b (9.5 g, 39.68 mmol) and 5-[5-(trifluoromethyl)-2-pyridyl]pyridine-2-onitrile 44a (9.13 g, 39.68 mmol) were dissolved in 1',4-Dioxane (200 mL) / Water (20 mL). Pd(dppf)Cl2 (2.90 g, 3.97 mmol) and K2CO3 (16.45 g, 119.03 mmol) were added sequentially. The mixture was purged with nitrogen three times under nitrogen protection. The reaction was carried out at 100°C with stirring for 16 hours. The reaction solution was filtered, and water (200 mL) was added to the filtrate. The mixture was extracted with ethyl acetate (200 mL × 3). The organic phases were combined and extracted with water (200 mL × 3). 3) Wash, dry with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and separate and purify the concentrated residue using purification system C to give 44c (5.7 g) of 5-(5-chloro-2-pyridyl)pyridine-2-onitrile, yield 66.6%. MS m / z (ESI): 217 [M+1] Step 2: 5-(5-chloro-2-pyridyl)pyridine-2-onitrile 44c (2 g, 9.27 mmol) was dissolved in MeOH (30 mL), followed by the addition of CoCl2 (1.45 g, 11.13 mmol) and Boc2O (4.05 g, 18.55 mmol). The reaction mixture was cooled to 0°C, and NaBH4 (2.46 g, 64.92 mmol) was added. The reaction was carried out at 25°C with stirring for 1 hour. The reaction solution was concentrated under reduced pressure, and water (60 mL) was added to the concentrated residue. The mixture was extracted with ethyl acetate (60 mL × 3), and the organic phases were combined and extracted with water (60 mL × 3). 3) Wash, dry with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and separate and purify the concentrated residue using purification system C to obtain N-[[5-(5-chloro-2-pyridinyl)-2-pyridinyl]methyl]tert-butyl carbamate; dissolve it in HCl (6 mL) methanol solution, purge three times with nitrogen, and maintain nitrogen protection. The reaction is carried out at 25 °C with stirring for 1 hour; concentrate the reaction solution under reduced pressure, concentrate the residue in ethyl acetate (30 mL) and stir for 15 minutes, filter, and dry the filter cake under reduced pressure to obtain [5-(5-chloro-2-pyridinyl)-2-pyridinyl]methylamine 44d (1.5 g, hydrochloride), yield 78.0%. MS m / z (ESI): 220 [M+1] Referring to steps three through six of the method in Example 11, the title compound 4-amino-12-((5-chloro-[2,3'-bipyridinyl]-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 44 (44 mg) was obtained by taking compounds 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 44 (44 mg) in 9.5% yield by taking compounds 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one. MS m / z (ESI): 502 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.24 (d, 1H), 8.77 (d, 1H), 8.48 (dd, 1H), 8.16 - 8.12 (m, 1H), 8.09 (dd, 1H), 7.73 - 7.55 (m, 3H), 5.45 (d, 2H), 5.23(d, 1H), 5.08 (d, 2H), 4.75 (d, 1H), 4.62 (d, 1H), 4.38 (d, 1H), 3.85 - 3.78(m, 1H), 3.10 (qd, 3H), 1.95 (d, 1H), 1.25 (d, 1H). Example 46 4-Amino-12-((2-(trifluoromethyl)thieno[2,3-b]pyridin-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: Add 55.5 mL of diisopropylaminolithium (2 M) to -70°C. o Under nitrogen protection, the solution was added dropwise to 100 mL of dry tetrahydrofuran containing 10.00 g (73.97 mmol) of thieno[2,3-b]pyridine. The reaction mixture was incubated at -70°C. o Stir at C for 20 minutes. Add a dry tetrahydrofuran (100 mL) solution of iodine (28.16 g, 110.96 mmol) to -70°C. oC was added dropwise to the reaction solution, and the mixture was stirred for 1 hour. The reaction solution was quenched with sodium sulfite aqueous solution and extracted with dichloromethane. The extract was concentrated and purified by silica gel column chromatography with eluent system B to give the title product 2-iodothieno[2,3-b]pyridine 46b (13.90 g), yield 72.0%. MS m / z (ESI): 262 [M+1] Step 2: 2-Iodothieno[2,3-b]pyridine 46b (10.00 g, 38.30 mmol) and m-chloroperoxybenzoic acid (10.60 g, 61.28 mmol) were dispersed in chloroform (100 mL) and stirred at room temperature for 16 hours. The reaction mixture was concentrated, slurried with ethyl acetate, and filtered to give the title product, 2-iodothieno[2,3-b]pyridine oxide 46c (8.70 g), in 82.0% yield. MS m / z (ESI): 278 [M+1] Step 3: Dissolve 2-iodothiophene[2,3-b]pyridine oxide 46c (1.50 g, 5.41 mmol), trimethylsilyl nitrile (806 mg, 8.12 mmol), and dimethylcarbamoyl chloride (1.16 g, 10.83 mmol) in acetonitrile (20 mL), 85 o Stirring at C for 16 hours. The reaction mixture was concentrated and purified by silica gel column chromatography using eluent system B to give the title product 2-iodothieno[2,3-b]pyridine-6-onitrile 46d (1.30 g), yield 83.9%. MS m / z (ESI): 287 [M+1] Step 4: Dissolve 46d (900 mg, 3.15 mmol) of 2-iodothieno[2,3-b]pyridin-6-onitrile, methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (1.21 g, 6.29 mmol), and cuprous iodide (599 mg, 3.15 mmol) in N,N-dimethylformamide (15 mL), 90 o Stir at C for 3 hours. Filter the reaction mixture to remove solids. Dilute the filtrate with ethyl acetate and wash with water and brine. Concentrate the organic phase and purify by silica gel column chromatography using eluent system B to give the title product 2-(trifluoromethyl)thieno[2,3-b]pyridine-6-nitrile 46d (620 mg), yield 86.4%. MS m / z (ESI): 229 [M+1] Following the synthetic method described in steps two through seven of Example 8, 4-amino-12-((2-(trifluoromethyl)thieno[2,3-b]pyridin-6-nitriles)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 46 (32 mg) was obtained from 2-(trifluoromethyl)thieno[2,3-b]pyridin-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 46 (32 mg) in yield of 2.3%. MS m / z (ESI): 515 [M+1] 1 H NMR (400 MHz, DMSO- d 6) δ 8.67 (s, 2H), 8.49 (d, 1H), 8.20 (d, 1H), 7.76 (d, 1H), 7.67 (d, 2H), 5.50 (m, 2H), 5.29 (d, 1H), 5.10 (m, 2H), 4.78(d, 1H), 4.63 (d, 1H), 4.52 (d, 1H), 3.83 (d, 1H), 3.32 (m, 3H), 1.94 (m,1H), 1.24 (m, 1H). Example 51 4-Amino-12-(2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenotin[7,8-g]quinoline-13(1H)-one Step 1: 2-Bromo-5-(trifluoromethyl)pyridine 51a (10 g, 44.24 mmol) was dissolved in 100 mL of tetrahydrofuran. At -70 °C, n-butyllithium (5.66 g, 88.48 mmol) was added, and the mixture was stirred for 30 minutes. Then, N-methoxy-N-methyl-2-methoxyacetamide (7.65 g, 57.5 mmol) was added, and the reaction was stirred at -70 °C for approximately 1 hour. Water (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL × 2). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethane-1-one 51b (2.2 g, 10 mmol), with a yield of 22%. MS m / z (ESI): 220 [M+1] Step 2: 2-Methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethane-1-one 51b (2.2 g, 10 mmol), hydroxylamine hydrochloride (901 mg, 13.1 mmol), and potassium carbonate (2.77 g, 20 mmol) were dissolved in 20 mL of dichloromethane. After reacting for 16 hours, the mixture was filtered and evaporated to dryness. The crude solid was then dissolved in methanol (20 mL) and reacted at 20 °C for 16 hours under hydrogen atmosphere. After filtration and evaporation, 2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethane-1-amine 51c (1.1 g) was obtained, with a yield of 50%. MS m / z (ESI): 221 [M+1] Following the synthetic methods described in steps four through eight of Example 1, 4-amino-12-(2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethane-1-amine 51c (1.1 g, 5.0 mmol) was synthesized to obtain 4-amino-12-(2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoinro[7,8-g]quinoline-13(1H)-one 51 (180 mg, 0.36 mmol) in 7.2% yield from compound 2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl.

[0104] MS m / z (ESI): 503 [M+1] Examples 51A & 51B (R)-4-amino-3-methyl-11-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11-tetrahydro-1H-furano[3,4-c][1,4]oxacino[6,7-g]quinoline-12(9H)-one (S)-4-amino-12-(2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoin[7,8-g]quinoline-13(1H)-one (S)-4-amino-12-(2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxacridine[7,8-g]quinoline-13(1H)-one 51 (180 mg, 0.358 mmol) was obtained by chiral preparative HPLC separation of 4-amino-12-(2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxacridine[7,8-g]quinoline-13(1H)-one 51A (50.9 mg). (mg), yield 28.0%; simultaneously (R)-4-amino-3-methyl-11-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11-tetrahydro-1H-furano[3,4-c][1,4]oxacoxinno[6,7-g]quinoline-12(9H)-one 51B (68.3 mg), yield 37.5%. MS m / z (ESI): 503 [M+1] 51A: 1 H NMR (400 MHz, DMSO-d6) 8.99 (m, 1H), 8.41 (s, 1H), 8.25 (m,1H), 7.89 (m, 1H), 7.63 (m, 1H), 7.46 (m, 1H), 5.56 (m, 1H), 5.48 - 5.38 (m,2H), 5.08 (m, 2H), 4.77 (m, 1H), 4.57 (m, 1H), 4.29 (m, 1H), 4.15 (m, 1H),4.04 (m, 1H), 3.91 (m, 1H), 3.52 - 3.45 (m, 2H), 3.27 - 3.11 (m, 4H), 1.29 -1.07 (m, 2H). 51B: 1H NMR (400 MHz, DMSO-d6) δ 9.02 - 8.96 (m, 1H), 8.25 (m, 1H), 7.89 (m, 1H), 7.57 (m, 1H), 7.36 (m, 1H), 5.56 (m, 1H), 5.39 (m, 2H), 5.04(m, 2H), 4.75 (m, 1H), 4.53 (m, 1H), 4.29 (m, 1H), 4.16 (m, 1H), 4.04 (m,1H), 3.89 (m, 1H), 3.47 (m, 1H), 3.38 (s, 2H), 3.34 (s, 2H), 3.27 - 3.09 (m, 2H), 1.30 - 1.10 (m, 2H). Example 52 4-Amino-12-((5-(2,6-difluorophenyl)thiazolyl-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxacono-nonanoin[7,8-g]quinoline-13(1H)-one Step 1: 5-Bromothiazolyl-2-carboxylonitrile 52a (2 g, 10.58 mmol), 2,6-difluorophenylboronic acid (3.3 g, 21.1 mmol), potassium carbonate (2.92 g, 21.6 mmol), and 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (773 mg, 1.06 mmol) were dissolved in 20 mL of dioxane and 4 mL of water. The reaction mixture was reacted at 100 °C for 2 hours. Water (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL × 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to obtain 5-(2,6-difluorophenyl)thiazolyl-2-carboxylonitrile 52b (0.32 g, 1.41 mmol), with a yield of 16%. MS m / z (ESI): 223 [M+1] Step 2: 5-(2,6-difluorophenyl)thiazolyl-2-carboxynitrile 52b (0.32 g, 0.61 mmol) and palladium on carbon (50 mg, 6 mmol) were dissolved in 20 mL of methanol and reacted at 20 °C for 16 hours under hydrogen atmosphere. The mixture was filtered and evaporated to dryness to give 2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethane-1-amine 52c (300 mg), yield 93%. MS m / z (ESI): 227 [M+1] Steps three through six follow the synthetic method of Example 1. Compound 2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethane-1-amine 52c (0.3 g, 1.32 mmol) was subjected to a three-step reaction involving substitution, hydrolysis, cyclization, and deprotection to yield 4-amino-12-((5-(2,6-difluorophenyl)thiazolyl-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoinro[7,8-g]quinoline-13(1H)-one 52 (70 mg, 0.137 mmol). Yield: 10.4%. MS m / z (ESI): 509 [M+1] 1 HNMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 8.15 (m, 1H), 7.67 (s, 1H),7.57-7.49 (m, 2H), 7.33 (m, 2H), 5.44 (m, 2H), 5.24 (m, 1H), 5.10-5.05 (m,2H), 4.75-4.68 (m, 2H), 4.60 (m, 1H), 3.73 (m, 1H), 3.31 m, 2H), 1.97 (m,1H), 1.31-1.22 (m, 2H). Example 57 4-Amino-12-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c]oxindo[4,3-g]quinoline-13(1H)-one Step 1: 5-Bromo-2-methylpyridine 57a (2 g, 11.63 mmol) and (2,6-difluorophenyl)boronic acid 57b (2.75 g, 17.44 mmol) were dissolved in 1'-4-Dioxane (50 mL) / Water (5 mL). Pd(dtbpf)Cl2 (751 mg, 1.16 mmol) and K2CO3 (4.82 g, 34.88 mmol) were added sequentially. The mixture was purged with nitrogen three times under nitrogen protection. The reaction was carried out at 100 °C with stirring for 16 hours. The reaction solution was filtered, and the filtrate was added to water (100 mL). The filtrate was extracted with ethyl acetate (100 mL × 3). The combined organic phases were then extracted with saturated brine (100 mL). ×2) Wash, dry with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and separate and purify the concentrated residue using purification system C to give 5-(2,6-difluorophenyl)-2-methylpyridine 57c (3 g), yield 62.9%. MS m / z (ESI): 206 [M+1] Step 2: 5-(2,6-difluorophenyl)-2-methylpyridine 57c (2.8 g, 13.65 mmol) was dissolved in CCl4 (6 mL), and NBS (4.86 g, 27.29 mmol) and AIBN (448.12 mg, 2.73 mmol) were added sequentially. The mixture was purged with nitrogen three times and kept under nitrogen protection. The reaction was carried out at 85 °C with stirring for 16 hours. Water (60 mL) was added to the reaction mixture, and the mixture was extracted with dichloromethane (100 mL × 3). The organic phases were combined, washed with water (100 mL × 3), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified using purification system C to separate and purify the concentrated residue, yielding 2-(bromomethyl)-5-(2,6-difluorophenyl)pyridine 57d (3.6 g), with a yield of 72.0%. MS m / z (ESI): 284 / 286 [M+1] Step 3: 7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 57e (6.10 g, 10.65 mmol) and lithium hydroxide (1.28 mg, 53.26 mmol) were dissolved in methanol (20 mL), tetrahydrofuran (20 mL), and water (15 mL) at 40 °C. oThe mixture was stirred at C for 24 hours. The reaction solution was concentrated and neutralized with hydrochloric acid, resulting in a large amount of solid. Filtration yielded the title product 7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 57f (5.0 g), yield 84.0%. MS m / z (ESI): 559 [M+1] Step 4: 57f of 7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid (57f, 5.90 g, 10.56 mmol), 57g of Miescherichia coli (3.04 g, 21.12 mmol), N,N-dimethylaminopyridine (2.58 g, 21.12 mmol) and N,N'-diisopropylcarbodiimide (2.67 g, 21.12 mmol) were dissolved in dichloromethane (50 mL) and tetrahydrofuran (50 mL), and stirred at room temperature for 16 hours. The reaction mixture was concentrated and purified by silica gel column chromatography using eluent system B to give the title product 5-(7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione 57 h (5.10 g), yield 70.5%. MS m / z (ESI): 685 [M+1] Step 5: Dissolve 5-(7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (57 h, 2.30 g, 3.36 mmol) in formic acid (2 mL) and methanol (30 mL) at 80 °C. o Stirring at C for 16 hours. The reaction mixture was concentrated and purified by silica gel column chromatography using eluent system B to give 57i (1.60 g) of the title product methyl 3-(7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate, yield 77.5%. MS m / z (ESI): 615 [M+1] Step 6: Dissolve 2 mL of boron trichloride in dichloromethane (1M) at 10 °C. oC was added dropwise to a solution of methyl 3-(4-(3,4-dimethoxybenzyl)amino)-7-(3-hydroxypropoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 57i (800 mg, 1.30 mmol) in dichloromethane (10 mL). The reaction solution was kept at -10°C. o Stirring at C for 1 hour, quenching with saturated sodium bicarbonate solution, and extraction with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography using eluent system B to give 57j (520 mg) of the title product methyl 3-(4-(3,4-dimethoxybenzyl)amino)-7-(3-hydroxypropoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate, yield 76.2%. MS m / z (ESI): 525 [M+1] Step 7: Methyl 3-(4-(3,4-dimethoxybenzyl)amino)-7-(3-hydroxypropoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 57j (630 mg, 1.20 mmol), triphenylphosphine (630 mg, 2.40 mmol), and carbon tetrabromide (797 mg, 2.40 mmol) were dissolved in dichloromethane (10 mL), and the mixture was stirred at room temperature for 2 hours under nitrogen purging. The reaction solution was concentrated. The residue was purified by silica gel column chromatography using eluent system B to give methyl 3-(7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 57k (510 mg), yield 72.3%. MS m / z (ESI): 587 [M+1] Step 8: Methyl 3-(7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 57kJ (560 mg, 0.95 mmol) and cesium carbonate (938 mg, 2.88 mmol) were dispersed in dioxane (10 mL) at 65°C. o The mixture was stirred at C for 16 hours; the reaction solution was filtered to remove solids, and the organic phase was concentrated. The residue was purified by silica gel column chromatography with eluent system B to give 57 l (400 mg) of methyl 4-((3,4-dimethoxybenzyl)amino)-13-oxo-1,3,7,9,10,11,12,13-octahydrofuran[3,4-c]oxo[4,3-g]quinoline-12-carboxylic acid, yield: 82.8%. MS m / z (ESI): 507 [M+1] Step 9: 4-((3,4-dimethoxybenzyl)amino)-13-oxo-1,3,7,9,10,11,12,13-octahydrofuran[3,4-c]oxo[4,3-g]quinoline-12-carboxylic acid methyl ester 57L (340 mg, 672 μmol), 2-(bromomethyl)-5-(2,6-difluorophenyl)pyridine 57D (228.83 mg, 806 μmol), and cesium carbonate (773 mg, 2.37 mmol) were heated at 65°C. o The mixture was stirred at C for 16 hours. The reaction solution was filtered to remove solids, the organic phase was concentrated, and purified by silica gel column chromatography using eluent system B to give 57 mg (90 mg) of the title product methyl 12-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-4-(3,4-dimethoxybenzyl)amino)-13-oxo-1,3,7,9,10,11,12,13-octahydrofuran[3,4-c]oxoquinoline[4,3-g]quinoline-12-carboxylic acid, in 15.0% yield. MS m / z (ESI): 711 [M+1] Step 10: Dissolve 57 mL (45 mg, 64 μmol) of methyl 12-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-4-(3,4-dimethoxybenzyl)amino)-13-oxo-1,3,7,9,10,11,12,13-octahydrofuran[3,4-c]oxoquinoline[4,3-g]quinoline-12-carboxylic acid in trifluoroacetic acid (5 mL) and heat at 90 °C. o The mixture was stirred at C for 16 hours; the reaction solution was concentrated and purified by prep-HPLC to give the title product 4-amino-12-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c]oxindo[4,3-g]quinoline-13(1H)-one 57 (1.8 mg), yield 6.0%. MS m / z (ESI): 502 [M+1] 1H NMR (400 MHz, DMSO-d6) δ 8.45 (s, 1H), 7.78 (d, 1H), 7.50 (tt, 1H), 7.45 - 7.36 (m, 2H), 7.22 (t, 2H), 7.06 (s, 1H), 6.62 (s, 2H), 5.32 (t, 1H),5.22 (dt, 1H), 5.09 (dt, 1H), 5.00 - 4.86 (m, 2H), 4.79 - 4.68 (m, 2H), 3.77- 3.68 (m, 1H), 3.60 (q, 1H), 3.19 (dd, 1H), 2.89 (dd, 1H), 2.00 (q, 2H), 1.63 (d, 2H). Examples 59A & 59B rel-(R,Z)-4-amino-12-(2-(pentafluoro-6-thioalkyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-1,3,9,10,11,12-hexahydro-13H-azanone[3,4-g]furano[3,4-c]quinoline-13-one & rel-(S,Z)-4-amino-12-(2-(pentafluoro-6-thioalkyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-1,3,9,10,11,12-hexahydro-13H-azanone[3,4-g]furano[3,4-c]quinoline-13-one Step 1: 2-(pentafluoro-6-thioalkyl)-6H-pyrano[3,4-b]pyridin-5(8H)-one 59a (2 g, 7.27 mmol) and hydroxylamine hydrochloride (505 mg, 7.27 mmol) were dissolved in water (10 mL) and ethanol (15 mL). Sodium acetate (1.79 g, 21.80 mmol) was added, and the reaction mixture was purged with nitrogen three times. The reaction mixture was heated to 80 °C and reacted for 1 hour. The reaction mixture was cooled to room temperature, quenched with water, extracted with ethyl acetate (600 mL × 3), and the organic phases were combined, washed with 30 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography with eluent system B to give 2-(pentafluoro-6-thioalkyl)-6H-pyrano[3,4-b]pyridine-5(8H)-one oxime 59b (1.77 g), in 83.9% yield. MS m / z (ESI): 291 [M+1] Step 2: 2-(pentafluoro-6-thioalkyl)-6H-pyrano[3,4-b]pyridine-5(8H)-ketooxime 59b (0.5 g, 1.72 mmol) and Raney nickel (101 mg, 1.72 mmol) were dissolved in methanol (20 mL), and the reaction was carried out under hydrogen balloon at 25 °C for 15 hours with three purgings. The mixture was filtered and concentrated to give 2-(pentafluoro-6-thioalkyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridine-5-amine 59c (0.41 g, crude). MS m / z (ESI): 277 [M+1] Referring to the synthesis method of Example 1, methyl (Z)-7-(5-bromopent-1-en-1-yl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 59d (1.00 g, 1.85 mmol) and 2-(pentafluoro-6-thioalkyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridine-5-amine 59c (1.02 g, 3.69 mmol) were used. (280 mg) of (Z)-4-amino-12-(2-(pentafluoro-16-thioalkyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-1,3,9,10,11,12-hexahydro-13H-aza[3,4-g]furano[3,4-c]quinoline-13-one was obtained in 27.3% yield. MS m / z (ESI): 555 [M+1] Step 7: Example 59 (280 mg, 0.51 mmol) was separated by chiral preparative HPLC to obtain rel-(R,Z)-4-amino-12-(2-(pentafluoro-6-thioalkyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-1,3,9,10,11,12-hexahydro-13H-azanone[3,4-g]furano[3,4-c]quinoline-13-one 59A (75 mg). The yield was 36.7%; simultaneously, rel-(S,Z)-4-amino-12-(2-(pentafluoro-6-thioalkyl)-5,8-dihydro-6H-pyrano[3,4-b]pyridin-5-yl)-1,3,9,10,11,12-hexahydro-13H-azanone[3,4-g]furano[3,4-c]quinoline-13-one 59B (83 mg) was obtained, with a yield of 40.6%.

[0105] 59A: MS m / z (ESI): 555 [M+1] 1H NMR (400 MHz, DMSO) δ 8.26 - 8.14 (m, 1H), 7.95 (dd, 1H), 7.46 (d,1H), 7.32 - 7.23 (m, 1H), 6.69 - 6.55 (m, 3H), 6.27 - 5.85 (m, 1H), 5.44 -5.21 (m, 3H), 5.01 (s, 2H), 4.87 - 4.70 (m, 2H), 4.33 - 4.09 (m, 2H), 3.79 -3.69 (m, 1H), 3.26 - 3.13 (m, 1H), 2.20 - 1.96 (m, 1H), 1.87 - 1.68 (m, 1H), 1.29 (dd, 2H). 59B: MS m / z (ESI): 555 [M+1] 1 H NMR (400 MHz, DMSO) δ 8.23 ​​- 8.13 (m, 1H), 7.95 (dd, 1H), 7.45 (d,1H), 7.28 (d, 1H), 6.73 - 6.51 (m, 3H), 6.26 - 5.90 (m, 1H), 5.44 - 5.20 (m,3H), 5.01 (s, 2H), 4.88 - 4.69 (m, 2H), 4.32 - 4.10 (m, 2H), 3.74 (q, 1H),3.26 - 3.12 (m, 1H), 2.16 - 1.97 (m, 1H), 1.75 (d, 1H), 1.46 - 1.19 (m, 2H). Example 60 (R)-4-amino-3-methyl-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoin[7,8-g]quinoline-13(1H)-one Step 1: Dissolve 20 g (120.48 mmol) of 3-(benzyloxy)propane-1-ol 60a in 400 mL of tetrahydrofuran. Add sodium hydride (5.78 g, 144.57 mmol, 60% purity) under ice bath conditions. After stirring for 15 minutes, add potassium (bromomethyl)trifluoroborate (24.09 g, 120.00 mmol) and allow the reaction to proceed at room temperature with stirring for approximately 16 hours. Add potassium fluoride solution (4.5 M) to the reaction mixture and stir at room temperature for 30 minutes. After evaporating the reaction mixture to dryness, add 2000 mL of hot acetone and stir at 80 °C for approximately 15 minutes. After hot filtration to remove impurities, distill the acetone under reduced pressure until a solid precipitates. Add twice the amount of diethyl ether, filter under ice bath conditions, and dry the residue to obtain potassium ((3-(benzyloxy)propoxy)methyl)trifluoroborate 60b (12.5 g), yield: 37.9%.

[0106] Step 2: Dissolve methyl 2-methyl-4-carbonyltetrahydrofuran-3-carboxylate 60c (50 g, 316.46 mmol) in 500 mL of dichloromethane, and add the following ingredients sequentially under ice bath conditions: N , N -Diisopropylethylamine (64.50 g, 500.00 mmol) and trifluoromethanesulfonic anhydride (116.80 g, 400.00 mmol). The reaction was stirred at room temperature for about 16 hours. 500 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (400 mL × 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 60d (82.5 g) of methyl 2-methyl-4-(((trifluoromethyl)sulfonyl)oxo)-2,5-dihydrofuran-3-carboxylic acid, in 89.9% yield. MS m / z (ESI): 291 [M+1] Step 3: Methyl 2-methyl-4-(((trifluoromethyl)sulfonyl)oxo)-2,5-dihydrofuran-3-carboxylic acid 60d (40.51 g, 139.69 mmol) and methyl 4-amino-2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxoboropentane-2-yl)benzoate 60e (40.43 g, 130.00 mmol) were dissolved in 400 mL of dioxane and 100 mL of water. Palladium dichloride (1,1'-bis(diphenylphosphino)ferrocene)dichloride (4.75 g, 6.50 mmol) and potassium carbonate (53.82 g, 390.00 mmol) were added. The reaction was carried out under nitrogen atmosphere and stirred at 100°C for approximately 16 hours. The reaction solution was filtered, and the filtrate was extracted with ethyl acetate (200 mL × 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 60 f (24.80 g) of methyl 7-chloro-3-methyl-4-carbonyl-1,3,4,5-tetrahydrofurano[3,4-c]quinoline-8-carboxylic acid, in 65.1% yield. MS m / z (ESI): 294 [M+1] Step 4: 60f of methyl 7-chloro-3-methyl-4-carbonyl-1,3,4,5-tetrahydrofurano[3,4-c]quinoline-8-carboxylic acid (24.80 g, 84.64 mmol) was dissolved in 200 mL of dimethyl sulfoxide. Then, 2,4-dimethoxybenzylamine (26.72 g, 160.00 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (36.48 g, 240.00 mmol), and Carter's condensing agent (70.72 g, 160.00 mmol) were added sequentially. The reaction was stirred at room temperature for approximately 2 hours under nitrogen atmosphere. The reaction mixture was poured into 2000 mL of water and 300 mL of ethyl acetate. A solid precipitated out and was filtered to give 60 g (26.97 g) of methyl 7-chloro-4-((2,4-dimethoxybenzyl)amino)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid, with a yield of 72.1%. MS m / z (ESI): 443 [M+1] Step 5: Dissolve 60 g (18.33 g, 41.47 mmol) of methyl 7-chloro-4-((2,4-dimethoxybenzyl)amino)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid, 60b (12.5 g, 45.62 mmol) of potassium trifluoroborate, 4.44 g (6.10 mmol) of [n-butyldi(1-adamantyl)phosphine](2-amino-1,1'-biphenyl-2-yl)palladium(II) (4.44 g, 6.10 mmol) and sodium carbonate (8.80 g, 83.00 mmol) in 200 mL of toluene and 40 mL of water. Allow the reaction to proceed at 100 °C for 16 hours under nitrogen atmosphere. The reaction solution was extracted with ethyl acetate (200 mL × 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give methyl 7-((3-(benzyloxy)propoxy)methyl)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid for 60 h (16.45 g), yield 67.7%. MS m / z (ESI): 587 [M+1] Step 6: Dissolve methyl 7-((3-(benzyloxy)propoxy)methyl)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 60h (16.45 g, 28.07 mmol) in 200 mL tetrahydrofuran, 100 mL methanol, and 3 mL acetic acid. Add palladium on carbon (5 g, 10%) and palladium hydroxide on carbon (5 g, 10%), and allow the reaction to proceed at 50°C for 16 hours under hydrogen atmosphere. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 60i (10.15 g) of methyl 4-((2,4-dimethoxybenzyl)amino)-7-((3-hydroxypropoxy)methyl)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid, in 72.9% yield. MS m / z (ESI): 497 [M+1] Step 7: Methyl 4-((2,4-dimethoxybenzyl)amino)-7-((3-hydroxypropoxy)methyl)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 60i (10.15 g, 20.46 mmol) and triphenylphosphine (13.40 g, 51.15 mmol) were dissolved in 200 mL of dichloromethane. Carbon tetrabromide (16.93 g, 51.15 mmol) was added, and the reaction was allowed to proceed at room temperature for 1 hour under nitrogen atmosphere. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system B to give methyl 7-((3-bromopropoxy)methyl)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 60j (9.87 g), yield 86.4%. MS m / z (ESI): 559 [M+1] Step 8: Dissolve methyl 7-((3-bromopropoxy)methyl)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 60j (3.4 g, 6.08 mmol), 3-trifluoromethylpyridine benzylamine hydrochloride 60k (2.58 g, 12.16 mmol), potassium carbonate (3.36 g, 24.33 mmol), and sodium iodide (1.82 g, 12.16 mmol) in 50 mL of acetonitrile. React at 80 °C for 1 hour under nitrogen atmosphere. The reaction solution was filtered, evaporated to dryness, and the residue was purified by silica gel column chromatography using eluent system B to give 60 μL (2.1 g) of methyl 4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid, yield 52.7%. MS m / z (ESI): 655 [M+1] Step 9: 4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 60L (2.1 g, 3.21 mmol) was separated by chiral preparative HPLC to obtain (S)-4-amino-12-(2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxacono-nonanoin[7,8-g]quinoline-13(1H)-one 60-A (783 (mg), yield 37%; simultaneously (R)-4-amino-3-methyl-11-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11-tetrahydro-1H-furano[3,4-c][1,4]oxacoxinno[6,7-g]quinoline-12(9H)-one 61-A (880 mg), yield 42%. MS m / z (ESI): 655 [M+1] Step 10: Dissolve (R)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 60-A (783 mg, 1.20 mmol) and lithium hydroxide (115 mg, 4.78 mmol) in 3 mL methanol, 3 mL tetrahydrofuran, and 3 mL water. React at 20°C for 1 hour under nitrogen atmosphere. The reaction solution was filtered, evaporated to dryness, and the residue was purified by silica gel column chromatography using eluent system B to give (R)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 60m (0.7 g), yield 91%. MS m / z (ESI): 641 [M+1] Step 11: Dissolve (R)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 60m (0.7 g, 1.09 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (830 mg, 2.18 mmol), and diisopropylethylamine (705 mg, 5.46 mmol) in 15 mL of N,N-dimethylformamide and react at 20°C for 1 hour under nitrogen atmosphere. The reaction solution was filtered, evaporated to dryness, and the residue was purified by silica gel column chromatography using eluent system B to give (R)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconitine[7,8-g]quinoline-13(1H)-one 60n (260 mg), yield 38%. MS m / z (ESI): 623 [M+1] Step 12: Dissolve (R)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoindo[7,8-g]quinoline-13(1H)-one 60n (260 mg, 0.417 mmol) in 5 mL of trifluoroacetic acid and react at 50 °C for 1 hour under nitrogen atmosphere. The reaction solution was filtered, evaporated to dryness, and the residue was purified by silica gel column chromatography using eluent system B to give 60 (184 mg) of methyl 4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid, in 93% yield. MS m / z (ESI): 473 [M+1] 1HNMR (400 MHz, DMSO-d6) δ 8.98 (d, 1H), 8.35 (s, 1H), 8.24 (dd, 1H), 7.77 (d, 1H), 7.65 (d, 2H), 5.55-5.50 (m, 1H), 5.50-5.38 (m, 2H), 5.20 (dd,1H), 4.76 (dd, 1H), 4.62 (dd, 1H), 4.47 (d, 1H), 3.84 (d, 1H), 3.36-3.25 (m,3H), 1.94 (d, 1H), 1.44 (d, 3H), 1.24 (d, 1H). Example 61 (S)-4-amino-3-methyl-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoin[7,8-g]quinoline-13(1H)-one Step 1: Dissolve (S)-4-amino-12-(2-methoxy-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoindo[7,8-g]quinoline-13(1H)-one 61-A (880 mg, 1.34 mmol) and lithium hydroxide (128 mg, 5.37 mmol) in 3 mL methanol, 3 mL tetrahydrofuran, and 3 mL water. React at 20°C for 1 hour under nitrogen atmosphere. The reaction solution was filtered, evaporated to dryness, and the residue was purified by silica gel column chromatography using eluent system B to give (S)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 61a (0.81 g), yield 94%. MS m / z (ESI): 641 [M+1] Step 2: Dissolve (S)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 61a (0.81 g, 1.26 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (960 mg, 2.52 mmol), and diisopropylethylamine (816 mg, 6.32 mmol) in 15 mL of N,N-dimethylformamide and react at 20°C for 1 hour under nitrogen atmosphere. The reaction solution was filtered, evaporated to dryness, and the residue was purified by silica gel column chromatography using eluent system B to give (S)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconitano[7,8-g]quinoline-13(1H)-one 61b (300 mg), yield 38%. MS m / z (ESI): 623 [M+1] Step 3: Dissolve (S)-4-((2,4-dimethoxybenzyl)amino)-3-methyl-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoindo[7,8-g]quinoline-13(1H)-one 61b (300 mg, 0.48 mmol) in 5 mL of trifluoroacetic acid and react at 50 °C for 1 hour under nitrogen atmosphere. The reaction solution was filtered, evaporated to dryness, and the residue was purified by silica gel column chromatography using eluent system B to give methyl 4-((2,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)propoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 61 (223 mg), yield 98%. MS m / z (ESI): 473 [M+1] 1H NMR (400 MHz, DMSO-d6) δ 8.97 (d, 1H), 8.23 ​​(dd, 1H), 7.77 (d, 1H), 7.64 (d, 2H), 5.51 (dd, 1H), 5.48-5.37 (m, 2H), 5.19 (dd, 1H), 4.75 (dd, 1H), 4.61 (dd, 1H), 4.46 (d, 1H), 3.83 (d, 1H), 3.47-3.23 (m, 5H), 1.93 (d, 1H), 1.43 (d, 3H), 1.23 (d, 1H). Example 62 (Z)-4-amino-3-methyl-13-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,12,13-tetrahydro-1H-furano[3,4-c][1,6]oxadecano[4,3-g]quinoline-14(9H)-one Step 1: Dissolve 62a (2 g, 3.57 mmol) and potassium tert-butoxide (1.6 g, 14.3 mmol) in 20 mL of tert-butanol and react at 50 °C for 1 hour. Add water (50 mL) to the reaction mixture and extract with ethyl acetate (200 mL × 2). After extraction, collect the organic phase, dry it over anhydrous sodium sulfate, filter, concentrate the filtrate under reduced pressure, and purify the residue by silica gel column chromatography with eluent system B to obtain 62b (1 g, 2.1 mmol), yield 60%. MS m / z (ESI): 465 [M+1] Step 2: 62b (1 g, 2.1 mmol), 62c (930 mg, 4.3 mmol), diisopropylethylamine (1.39 g, 10.7 mmol), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (1.63 g, 4.3 mmol) were dissolved in 15 mL of N,N-dimethylformamide and reacted at 20 °C for 2 hours. Water (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (200 mL × 2). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 62d (960 mg, 1.44 mmol), with a yield of 67%. MS m / z (ESI): 663 [M+1] Step 3: 62d (960 mg, 1.44 mmol) and Grubbs second-generation catalyst (245 mg, 0.29 mmol) were dissolved in 30 mL of 1,2-dichloroethane and reacted at 70 °C for 16 hours. Water (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL × 2). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 62e (80 mg, 0.126 mmol), with a yield of 8.7%. MS m / z (ESI): 635 [M+1] Step 4: Dissolve 62e (80 mg, 0.126 mmol) in 5 mL of trifluoroacetic acid and react at 50 °C for 1 hour. Dry the mixture and prepare the crude product by high-performance liquid chromatography (HPLC) to give (Z)-4-amino-3-methyl-13-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,12,13-tetrahydro-1H-furano[3,4-c][1,6]oxadecano[4,3-g]quinoline-14(9H)-one 62 (40 mg), yield 67%. MS m / z (ESI): 485 [M+1] 1 H NMR (400 MHz, DMSO- d 6) δ 8.98 – 8.95 (m, 1H), 8.23 ​​(dd, 2H), 7.83 (s, 1H), 7.72 (d, 1H), 7.61 (s, 1H), 6.14 (td, 1H), 5.81 (td, 1H), 5.51 (ddt,1H), 5.46 – 5.35 (m, 2H), 5.10 (d, 1H), 4.77 (d, 1H), 4.65 (s, 2H), 4.15 (dd,1H), 3.87 – 3.73 (m, 2H), 3.55 (dt, 1H), 1.43 (dd, 3H). Examples 64A & 64B (R)-4-amino-3-methyl-12-((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one & (S)-4-amino-3-methyl-12-((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: N-[(5-bromo-2-pyridinyl)methyl]tert-butyl carbamate 64a (700 mg, 2.44 mmol), butyric acid (307 mg, 3.66 mmol), 1,4-bis(diphenylphosphine)butane (207 mg, 0.49 mmol), and bis(triphenylphosphine)palladium dichloride (171 mg, 0.24 mmol) were dissolved in dimethyl sulfoxide (10 mL), purged with nitrogen, and stirred at 100 °C for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with water and brine, concentrated, and purified by silica gel column chromatography using eluent system B to give the title product (5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)tert-butyl carbamate 64b (530 mg), yield 88.3%. MS m / z (ESI): 247 [M+1] Step 2: 520 mg (2.11 mmol) of tert-butyl (5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)carbamate 64b was dissolved in dioxane hydrochloride solution (5 mL, 4 M) and tetrahydrofuran (5 mL), and stirred at room temperature for 16 hours. The reaction solution was concentrated to give the title product (5-(prop-1-yn-1-yl)pyridin-2-yl)methylamine hydrochloride 64c (260 mg), in 84.2% yield. MS m / z (ESI): 147 [M+1] Step 3: 7-(3-bromopropoxymethyl)-4-[(3,4-dimethoxyphenyl)methylamino]-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 64d (842 mg, 1.51 mmol), (5-(prop-1-yn-1-yl)pyridin-2-yl)methylamine hydrochloride 64c (550 mg, 3.01 mmol), potassium carbonate (415 mg, 3.01 mmol), and sodium iodide (451 mg, 3.01 mmol) were dispersed in acetonitrile (20 mL) at 80°C. o Stir for 16 hours. Filter the reaction mixture to remove solids, concentrate the organic phase, and purify by silica gel column chromatography using eluent system B to give the title product 4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((3-((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)amino)propoxy)methyl ester)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 64e (730 mg), yield 77.6%. MS m / z (ESI): 625 [M+1] Step 4: 4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((3-((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)amino)propoxy)methyl ester)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 64e (730 mg, 1.17 mmol) was separated by chiral preparative HPLC to obtain (R)-4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)amino)propoxy)methyl ester)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 64e-A (310 (mg), yield 42.0%; simultaneously, (S)-4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)amino)propoxy)methyl ester)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 64e-B (290 mg) was obtained, yield 39.7%. MS m / z (ESI): 625 [M+1] + Referring to steps seven through nine of Example 2, (R)-4-amino-3-methyl-12-((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)amino)propoxy)methyl ester)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 64e-A (310 mg, 0.50 mmol) was used to obtain (R)-4-amino-3-methyl-12-((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 64A (32 mg), yield: 14.5%. MS m / z (ESI): 443 [M+1] 1 H NMR (400 MHz, MeOD) δ 8.53 (d, 1H), 7.83 (m, 1H), 7.77 (s, 1H), 7.69 (s, 1H), 7.57 (d, 1H), 5.55 (m, 4H), 5.29 (m, 1H), 4.95 (s, 1H), 4.62(m, 1H), 4.39 (m, 1H), 3.94 (m, 1H), 3.40 (m, 2H), 2.08 (m, 5H), 1.52 (m,3H). Referring to steps seven through nine of Example 2, (S)-4-amino-3-methyl-12-((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)amino)propoxy)methyl ester)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid methyl ester 64e-B (290 mg, 0.46 mmol) was used to obtain (S)-4-amino-3-methyl-12-((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 64B (30 mg) in 14.8% yield from (S)-4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((3-(((5-(prop-1-yn-1-yl)pyridin-2-yl)methyl)-1,3-dihydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 64B. MS m / z (ESI): 443 [M+1] 1 H NMR (400 MHz, CD3OD) δ 8.52 (d, 1H), 7.80 (m, 1H), 7.69 (s, 1H), 7.64 (s, 1H), 7.55 (m, 1H), 5.40 (m, 5H), 4.93 (m 1H), 4.60 (m, 1H), 4.37 (m1H), 3.92 (m, 1H), 3.50 (m, 2H), 2.08 (m, 5H), 1.52 (m, 3H). Example 65 2-Amino-7-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-3-ethyl-7,8,9,10-tetrahydro-[1,5]oxazononanones[7,8- g Quinoxaline-6(12) H )-ketone Following the synthesis method of Example 1, 2-amino-7-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-3-ethyl-7,8,9,10-tetrahydro-[1,5]oxazononanones[7,8-]ethyl acrylate 65a (10.0 g, 78.13 mmol) was obtained from ethyl acrylate 65a (10.0 g, 78.13 mmol). g Quinoxaline-6(12) H )-Ketocone 65 (82 mg), yield 0.4%. MS m / z (ESI): 489 [M+1] 1H NMR (400 MHz, DMSO-d6) δ8.67 (s, 1H), 8.41 (s, 2H), 8.24 (s, 1H), 7.98 (d, 1H), 7.87 (s, 1H), 7.65 - 7.53 (m, 3H), 7.35 - 7.24 (m, 2H), 5.30(d, 1H), 4.68 (dd, 2H), 4.32 (d, 1H), 3.91 - 3.75 (m, 1H), 3.51 - 3.23 (m,4H), 2.65 (q, 2H), 1.98 (dd, 1H), 1.27 (t, 3H). Examples 67 & 68 4-Amino-13-oxo-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,7,9,10,11,12,13-octahydrofuran[3,4-c]oxoindo[4,3-g]quinoline-12-carboxylic acid methyl ester and 4-amino-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuran[3,4-c]oxoindo[4,3-g]quinoline-13(1H)-one Step 1: Methyl 7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 67a (6.10 g, 10.65 mmol) and lithium hydroxide (1.28 mg, 53.26 mmol) were dissolved in methanol (20 mL), tetrahydrofuran (20 mL), and water (15 mL) and stirred at 40 °C for 24 hours. The reaction mixture was concentrated and neutralized with hydrochloric acid, resulting in a large amount of solid. Filtration yielded the title product 7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 67b (5.00 g), yield 84.0%. MS m / z (ESI): 559 [M+1] Step 2: 7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 67b (5.90 g, 10.56 mmol), Miescherichia coli (3.04 g, 21.12 mmol), N,N-dimethylaminopyridine (2.58 g, 21.12 mmol) and N,N'-diisopropylcarbodiimide (2.67 g, 21.12 mmol) were dissolved in dichloromethane (50 mL) and tetrahydrofuran (50 mL) and stirred at room temperature for 16 hours. The reaction mixture was concentrated and purified by silica gel column chromatography using eluent system B to give the title product 5-(7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione 67c (5.10 g), yield 70.5%. MS m / z (ESI): 685 [M+1] Step 3: Dissolve 5-(7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione 67c (2.30 g, 3.36 mmol) in formic acid (2 mL) and methanol (30 mL) at 80 °C. o Stirring at C for 16 hours. The reaction mixture was concentrated and purified by silica gel column chromatography using eluent system B to give the title product methyl 3-(7-((3-(benzyloxy)propoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 67d (1.60 g), yield 77.5%. MS m / z (ESI): 615 [M+1] Step 4: Add 2 mL of boron trichloride solution in dichloromethane (1M) to a solution at 10 °C. o C was added dropwise to a solution of methyl 3-(4-(3,4-dimethoxybenzyl)amino)-7-(3-hydroxypropoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 67d (800 mg, 1.30 mmol) in dichloromethane (10 mL). The reaction solution was kept at -10°C. oStirred at C for 1 h, quenched with saturated sodium bicarbonate solution, and extracted with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography with eluent system B to give the title product methyl 3-(4-(3,4-dimethoxybenzyl)amino)-7-(3-hydroxypropoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 67e (520 mg), yield 76.2%. MS m / z (ESI): 525 [M+1] Step 5: Methyl 3-(4-(3,4-dimethoxybenzyl)amino)-7-(3-hydroxypropoxy)methyl)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 67e (630 mg, 1.20 mmol), triphenylphosphine (630 mg, 2.40 mmol), and carbon tetrabromide (797 mg, 2.40 mmol) were dissolved in dichloromethane (10 mL), and the mixture was stirred at room temperature for 2 hours under nitrogen purging. The reaction solution was concentrated. The residue was purified by silica gel column chromatography using eluent system B to give methyl 3-(7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 67f (510 mg), yield 72.3%. MS m / z (ESI): 587 [M+1] Step 6: Methyl 3-(7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-yl)-3-oxopropionate 67f (560 mg, 0.95 mmol) and cesium carbonate (938 mg, 2.88 mmol) were dispersed in dioxane (10 mL), 65 o The mixture was stirred at C for 16 hours. The reaction solution was filtered to remove solids, and the organic phase was concentrated. The residue was purified by silica gel column chromatography using eluent system B to give 67 g (400 mg) of methyl 4-((3,4-dimethoxybenzyl)amino)-13-oxo-1,3,7,9,10,11,12,13-octahydrofuran[3,4-c]oxo[4,3-g]quinoline-12-carboxylic acid, in 82.8% yield. MS m / z (ESI): 507 [M+1] Step 7: Mix 67g (400 mg, 0.79 mmol) of methyl 4-((3,4-dimethoxybenzyl)amino)-13-oxo-1,3,7,9,10,11,12,13-octahydrofuran[3,4-c]oxo[4,3-g]quinoline-12-carboxylic acid, 2-(bromomethyl)-5-(trifluoromethyl)pyridine (379 mg, 1.58 mmol), and cesium carbonate (773 mg, 2.37 mmol) at 65°C. o The mixture was stirred at C for 16 h. The reaction solution was filtered to remove solids, the organic phase was concentrated, and purified by silica gel column chromatography using eluent system B to give the title product methyl 4-((3,4-dimethoxybenzyl)amino)-13-oxo-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,7,9,10,11,12,13-octahydrofurano[3,4-c]oxoindo[4,3-g]quinoline-12-carboxylic acid 67 h (420 mg), yield 79.9%. MS m / z (ESI): 666 [M+1] Step 8: Dissolve methyl 4-((3,4-dimethoxybenzyl)amino)-13-oxo-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,7,9,10,11,12,13-octahydrofurano[3,4-c]oxoindo[4,3-g]quinoline-12-carboxylic acid 67h (160 mg, 0.24 mmol) in trifluoroacetic acid (5 mL) and heat at 90°C. o The mixture was stirred at C for 16 hours. The reaction solution was concentrated and purified by prep-HPLC to give methyl 4-amino-13-oxo-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1,3,7,9,10,11,12,13-octahydrofuran[3,4-c]oxoindo[4,3-g]quinoline-12-carboxylic acid 67 (30 mg), with a yield of 24.3%; and 4-amino-12-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuran[3,4-c]oxoindo[4,3-g]quinoline-13(1H)-one 68 (35 mg), with a yield of 31.9%.

[0107] Example 67: MS m / z (ESI): 516 [M+1] 1H NMR (400 MHz, MeOD) δ 8.75 (d, 1H), 8.03 (m, 2H), 7.58 (s, 1H), 7.43 (m, 1H), 5.43 (s, 2H), 5.15 (m, 2H), 4.37 (m, 1H), 3.86 (m, 4H), 3.50(m, 2H), 3.12 (m, 1H), 2.06 (m, 3H), 1.52 (m, 2H). Example 68: MS m / z (ESI): 458 [M+1] 1 H NMR (400 MHz, DMSO- d 6) δ 8.74 (d, 1H), 8.58 (s, 2H), 8.06 (d, J =8.2 Hz, 1H), 7.56 (m, 2H), 7.27 (s, 1H), 5.36 (m, 2H), 5.05 (m, 2H), 4.80 (m,2H), 3.79 (m, 1H), 3.65 (m, 1H), 3.33 (m, 1H), 3.25 (m, 1H), 2.99 m, 1H), 1.81 (m, 1H), 1.61 (m, 3H). Example 69 4-Amino-12-((5-(3,3,3-trifluoroprop-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: N-[(5-bromo-2-pyridinyl)methyl]tert-butyl carbamate 69a (300 mg, 1.04 mmol) and (3,3,3-trifluoro-1-propynyl)tributyltinane (800 mg, 2.09 mmol, 0.68 mL) were dissolved in toluene (10 mL). The mixture was purged with nitrogen three times. Tetraphenylphosphine palladium (241 mg, 0.21 mmol) was added to the system, and the mixture was heated to 130°C in a microwave reactor for 2 hours. The reaction was quenched with water, extracted with ethyl acetate (50 mL × 3), washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent system B to obtain (5-(3,3,3-trifluoroprop-1-yl)pyridin-2-yl)methyl)tert-butyl carbamate 69b (0.25 g), yield 79.7%. MS m / z (ESI): 301 [M+1] Step 2: Dissolve tert-butyl (5-(3,3,3-trifluoroprop-1-yl)pyridin-2-yl)methyl)carbamate 69b (0.25 g, 832.57 μmol) in dioxane hydrochloride (4 M, 5 mL), and react the mixture at 25°C for 0.5 h. Concentrate the reaction mixture, and directly add the crude product to the next step. This yields (5-(3,3,3-trifluoroprop-1-yl)pyridin-2-yl)methylamine 69c (0.16 g, crude product). MSm / z (ESI): 201 [M+1] Following the synthetic method described in steps six through nine of Example 2, methyl 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid 69d (250 mg, 0.49 mmol) and (5-(3,3,3-trifluoroprop-1-yl)pyridin-2-yl)methylamine 69c (180 mg, 0.92 mmol) yielded 4-amino-12-((5-(3,3,3-trifluoroprop-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 69 (8 mg), in a yield of 3.6%. MS m / z (ESI): 483 [M+1] 1H NMR (400 MHz, DMSO-d6) δ 8.92 (d, 1H), 8.21 (dd, 1H), 7.66 (d, 1H), 7.50 (s, 1H), 7.38 (s, 1H), 6.64 (s, 2H), 5.35 (s, 2H), 5.15 (d, 1H), 5.01(s, 2H), 4.70 (d, 1H), 4.53 (d, 1H), 4.40 (d, 1H), 3.76 (d, 1H), 3.47 (s,1H), 1.89 (d, 2H), 1.22 (d, 2H). Example 70 4-Amino-12-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-1,3,7,8,9,10,11,12-octahydro-13H-[1,5]diazoylnonanoin[7,8-g]furano[3,4-c]quinoline-13-one Referring to the synthetic method of steps four to seven of Example 1, methyl 70a (0.3 g, 0.448 mmol) of compound 7-(((3-bromopropyl)(3-chlorobenzyl)amino)methyl)-4-((2,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid was synthesized via a three-step reaction of substitution, hydrolysis, and cyclization to obtain 8-(3-chlorobenzyl)-12-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-4-((2,4-dimethoxybenzyl)amino)-1,3,7,8,9,10,11,12-octahydro-13H-[1,5]diazoylnonanoin[7,8-g]furano[3,4-c]quinoline-13-one 70e (120 mg, 0.154 mmol). (mmol), yield 34%. MS m / z (ESI): 777 [M+1] Step 4: Dissolve 8-(3-chlorobenzyl)-12-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-4-((2,4-dimethoxybenzyl)amino)-1,3,7,8,9,10,11,12-octahydro-13H-[1,5]diazoylnonano[7,8-g]furano[3,4-c]quinoline-13-one 70e (120 mg, 0.154 mmol) in trifluoroacetic acid (5 mL), purge with nitrogen three times, and react the system at 60 °C for 1 hour. The residue was concentrated and purified by high-performance liquid chromatography (HPLC) using eluent system A to give 70 (44.3 mg) of 4-amino-12-((5-(2,6-difluorophenyl)pyridin-2-yl)methyl)-1,3,7,8,9,10,11,12-octahydro-13H-[1,5]diazoylnonanointro[7,8-g]furano[3,4-c]quinoline-13-one, yield 57%. MS m / z (ESI): 502 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 2H), 8.67 (s, 1H), 8.05-7.95 (m,2H), 7.83 (s, 1H), 7.62 (m, 1H), 7.60-7.53 (m, 1H), 7.28 (m, 2H), 5.46 (s, 2H), 5.08 (m, 2H), 4.66 (s, 2H), 4.42 (m, 2H), 3.67 (m, 2H), 3.41 (s, 1H), 3.07 (s, 2H), 2.08 (m, 2H). Example 71 4-Amino-3-methyl-13-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1H-furano[3,4-c][1,6]oxadecano[4,3-g]quinoline-14(9H)-one Following the synthetic method of Example 1, methyl 4-((2,4-dimethoxybenzyl)amino)-7-((4-hydroxybutoxy)methyl)-3-methyl-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 71a (2 g, 3.92 mmol) was used to obtain 4-((2,4-dimethoxybenzyl)amino)-3-methyl-13-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1H-furano[3,4-c][1,6]oxaconitine[4,3-g]quinoline-14(9H)-one 71 (270 mg) in 12.6% yield from compound 4-((2,4-dimethoxybenzyl)amino)-3-methyl-13-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1H-furano[3,4-c][1,6]oxaconitine[4,3-g]quinoline-14(9H)-one 71.

[0108] MS m / z (ESI): 545 [M+1] Examples 71A & 71B (R)-4-amino-3-methyl-13-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1H-furano[3,4-c][1,6]oxadecano[4,3-g]quinoline-14(9H)-one & (S)-4-amino-3-methyl-13-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1H-furano[3,4-c][1,6]oxadecano[4,3-g]quinoline-14(9H)-one (R)-4-amino-3-methyl-13-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1H-furano[3,4-c][1,6]oxacacetin[4,3-g]quinoline-14(9H)-one 71 (270 mg, 0.496 mmol) was obtained by chiral preparative HPLC separation of 4-((2,4-dimethoxybenzyl)amino)-3-methyl-13-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1H-furano[3,4-c][1,6]oxacacetin[4,3-g]quinoline-14(9H)-one 71A (54.5 mg). (mg), yield 42%; simultaneously (R)-4-amino-3-methyl-11-((5-(pentafluoro-16-thioalkyl)pyridin-2-yl)methyl)-3,7,10,11-tetrahydro-1H-furano[3,4-c][1,4]oxacoxinno[6,7-g]quinoline-12(9H)-one 71B (57.1 mg), yield 44%. MS m / z (ESI): 545 [M+1] 71A: 1 HNMR (400 MHz, DMSO-d6) δ 9.13 - 9.05 (m, 1H), 8.44 - 8.33 (m,1H), 7.79 (m, 1H), 7.63 (m, 1H), 7.58 - 7.48 (m, 1H), 5.53 - 5.30 (m, 3H),5.20 (m, 1H), 4.83 (m, 1H), 4.62 - 4.41 (m, 2H), 3.86 - 3.52 (m, 3H), 3.23 -3.16 (m, 1H), 1.83 (s, 1H), 1.61 (s, 1H), 1.46-1.27 (m, 5H). 71B: 1HNMR (400 MHz, DMSO-d6) δ 9.13 - 9.05 (m, 1H), 8.44 - 8.33 (m,1H), 7.79 (m, 1H), 7.63 (m, 1H), 7.58 - 7.48 (m, 1H), 5.53 - 5.30 (m, 3H),5.20 (m, 1H), 4.83 (m, 1H), 4.62 - 4.41 (m, 2H), 3.86 - 3.52 (m, 3H), 3.23 -3.16 (m, 1H), 1.83 (s, 1H), 1.61 (s, 1H), 1.46 - 1.27 (m, 5H). Examples 72A & 72B 72A: ( R )-4-amino-3-methyl-13-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1 H -furano[3,4- c [1,6]Evodia Guiyingbing[4,3- g Quinoxaline-14(9) H )-ketone 72B: ( S )-4-amino-3-methyl-13-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1 H -furano[3,4- c [1,6]Evodia Guiyingbing[4,3- g Quinoxaline-14(9) H )-ketone Following the synthetic method of Example 1, 4-(benzyloxy)but-1-ol 72a (10.0 g, 55.56 mmol) was used to obtain ( R )-4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((4-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)butoxy)methyl)-1,3-dihydrofurano[3,4- c ] Quinoxalool-8-carboxylate methyl ester 72h-A (300 mg), yield 20.7%; simultaneously obtained ( S)-4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((4-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)butoxy)methyl)-1,3-dihydrofurano[3,4- c 300 mg methyl quinoxaline-8-carboxylate 72h-B, yield 20.7%. MS m / z (ESI): 669 [M+1] Referring sequentially to steps six through eight of Example 1, the synthesis method was carried out through ( R )-4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((4-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)butoxy)methyl)-1,3-dihydrofurano[3,4- c ] Quinoxalool-8-carboxylate methyl 72h-A (100 mg, 0.15 mmol) yielded ( R )-4-amino-3-methyl-13-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1 H -furano[3,4- c [1,6]Evodia Guiyingbing[4,3- g Quinoxaline-14(9) H )-Ketone 72A (17 mg), yield 23.3%. MS m / z (ESI): 487 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.96 (d, 1H), 8.54 (s, 2H), 8.28 – 8.11(m, 1H), 7.82 – 7.31 (m, 3H), 5.59 – 5.11 (m, 4H), 5.02 – 4.71 (m, 1H), 4.67– 4.27 (m, 2H), 3.76 - 3.63 (m, 1H), 3.61- 3.49 (m, 1H), 3.46 - 3.37 (m, 1H), 3.19 (d, 1H), 1.84 (s, 1H), 1.73 - 1.19 (m, 6H). Referring to the synthesis method in steps six to eight of Example 1, through ( S )-4-((3,4-dimethoxybenzyl)amino)-3-methyl-7-((4-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)butoxy)methyl)-1,3-dihydrofurano[3,4- c] Quinoxalool-8-carboxylate methyl ester 72h-B (100 mg, 0.15 mmol) was used to obtain ( S )-4-amino-3-methyl-13-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1 H -furano[3,4- c [1,6]Evodia Guiyingbing[4,3- g Quinoxaline-14(9) H )-Keto-72B (64 mg), yield 87.7%. MS m / z (ESI): 487 [M+1] 1H NMR (400 MHz, DMSO-d6) δ8.96 (d, 1H), 8.54 (s, 2H), 8.28 - 8.11(m, 1H), 7.82 - 7.31 (m, 3H), 5.59 - 5.11 (m, 4H), 5.02 - 4.71 (m, 1H), 4.67- 4.27 (m, 3H), 3.76 - 3.63 (m, 1H), 3.61 - 3.49 (m, 1H), 3.46 - 3.37 (m,1H), 3.19 (d, 1H), 1.84 (s, 1H), 1.73 - 1.19 (m, 6H). Example 73 4-Amino-12-((5-(4-phenylpiperazin-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: 12-((5-bromopyridin-2-yl)methyl)-4-((3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 73a (130 mg, 0.21 mmol), 1-phenylpiperazine (68 mg, 0.42 mmol), cesium carbonate (103 mg, 0.32 mmol), and dichloro[1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene](3-chloropyridinyl)palladium (20 mg, 0.02 mmol) were dispersed in dioxane (4 mL). [The solution was then added to a solution at 110 °C.] oStirred at C for 16 hours. The reaction mixture was concentrated and purified by silica gel column chromatography using eluent system B to give the title product 4-(3,4-dimethoxybenzyl)amino)-12-(5-(4-phenylpiperazin-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 73b (120 mg), yield 81.5%. MS m / z (ESI): 701 [M+1] Step 2: Dissolve 120 mg (0.17 mmol) of 4-(3,4-dimethoxybenzyl)amino)-12-(5-(4-phenylpiperazin-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 73b in trifluoroacetic acid (2 mL). o Stirred at C for 2 hours. The reaction mixture was concentrated and purified by prep-HPLC to give the title product 4-amino-12-((5-(4-phenylpiperazin-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 73 (60 mg), yield 64.0%. MS m / z (ESI): 551 [M+1] 1 H NMR (400 MHz, CD3OD) δ8.38 (m, 1H), 8.16 (m, 1H), 7.97 (s, 1H), 7.72 (s, 2H), 7.29 (m, 2H), 7.07 (m, 2H), 6.92 (m, 1H), 5.38 (m, 3H), 5.04(m, 2H), 4.65 (m, 2H), 4.10 (m, 2H), 3.61 (m, 10H), 3.18 (m, 1H), 2.00 (m,1H), 1.32 (m, 1H). Example 74 4-Amino-14-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12,13,14-octahydro-[1]oxo[6]azacycloundecano[4,3- g ]furano[3,4- c Quinoxaline-15(1) H )-ketone Following the synthetic method of Example 1, 4-amino-14-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12,13,14-octahydro-[1]oxo[6]azacycloundecano[4,3-] g ]furano[3,4- c Quinoxaline-15(1) H )-Ketone 74 (29 mg), yield 6.1%. MS m / z (ESI): 487 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.89 (d, 1H), 8.30 - 8.10 (m, 1H), 7.80 -6.47 (m, 5H), 5.47 - 3.95 (m, 9H), 3.50 (d, 1H), 3.14 (d, 2H), 1.90 - 0.78(m, 6H). Example 75 12-((5-(1H-1,2,3-triazol-1-yl)pyridin-2-yl)methyl)-4-amino-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Following steps one through six of the method in Example 11, the title compound 12-((5-(1H-1,2,3-triazol-1-yl)pyridin-2-yl)methyl)-4-amino-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 75 (35 mg) was obtained by reacting 5-fluoropyridin-2-onitrile 75a (150 mg, 1.23 mmol) with 5-fluoropyridin-2-onitrile 75a (150 mg, 1.23 mmol) in quinoline-13(1H)-one 75 (35 mg), with a yield of 6.2%. MS m / z (ESI): 458 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.12 (d, 1H), 8.95 (d, 1H), 8.37 (dd, 1H), 8.06 (d, 1H), 7.76 (d, 1H), 7.51 (s, 1H), 7.40 (s, 1H), 6.67 (s, 2H), 5.35(t, 2H), 5.22 (d, 1H), 5.01 (t, 2H), 4.72 (d, 1H), 4.54 (d, 1H), 4.41 (d,1H), 3.83 - 3.73 (m, 1H), 3.51 - 3.36 (m, 2H), 3.29 - 3.20 (m, 1H), 1.93 (q,1H), 1.23 (d, 1H). Example 76 4-Amino-12-((6-(trifluoromethyl)-[2,3'-dipyridin]-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H )-ketone Following the synthesis methods of Step 8 of Example 6 and Step 8 of Example 1, the synthesis was carried out via 12-((5-bromopyridin-2-yl)methyl)-4-((3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-13(1) H )-keto 76a (135 mg, 0.21 mmol) yielded 6-((4-amino-13-oxo-1,3,7,10,11,13-hexahydrofurano[3,4-) c [1,5]Evil Aren Yingbing[7,8- g Quinoxaline-12(9) H )-(methyl)-[3,4'-dipyridinium]-2'-carboxynitrile 76 (86 mg), yield 76.5%. MS m / z (ESI): 536 [M+1] 1H NMR (400 MHz, DMSO-d6) δ 9.28 (d, 1H), 8.53 (dd, 1H), 8.42 (d, 1H), 8.26 (t, 1H), 7.94 (d, 1H), 7.63 (dd, 5H), 5.43 (s, 2H), 5.24 (d, 1H), 5.06(s, 2H), 4.67 (dd, 2H), 4.40 (d, 1H), 3.80 (d, 1H), 3.50 - 3.21 (m, 3H), 1.96(d, 1H), 1.24 (d, 1H). Example 77 4-Amino-12-((5-chloro-[2,3'-bipyridin]-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Following steps one through two of the method in Example 43 and steps three through six of the method in Example 11, the title compound 4-amino-12-((5-(6-(trifluoromethyl)pyrimidin-4-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 77 (7 mg) was obtained by reacting compound 4-iodo-6-(trifluoromethyl)pyrimidin-4-yl)pyridin-2-yl)methyl with 200 mg, 730 μmol, in 1.8% yield. MS m / z (ESI): 538 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.55 (s, 1H), 9.49 (d, 1H), 8.74 (d, 2H), 7.76 (d, 1H), 7.67 (d, 2H), 5.48 (s, 2H), 5.23 (d, 1H), 5.09 (d, 2H), 4.77(d, 1H), 4.63 (d, 1H), 4.47 (d, 1H), 3.84 (d, 1H), 3.31 (s, 2H), 1.97 (d,1H), 1.25 (d, 2H). Example 78 4-Amino-12-((5-chloro-[2,3'-bipyridin]-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: 2-(trifluoromethyl)pyrimidin-4-ol 78a (6 g, 36.57 mmol) was dissolved in MeCN (60 mL) and added to POBr3 (12.58 g, 43.88 mmol, 4.37 mL). The mixture was purged with nitrogen three times and then subjected to nitrogen protection. The reaction was carried out at 100°C with stirring for 6 hours. Water (100 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (150 mL × 3). The organic phases were combined, washed with water (150 mL × 3), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified using purification system C to obtain 4-bromo-2-(trifluoromethyl)pyrimidin 78b (7.5 g), yield 83.7%. MS m / z (ESI): 228 [M+1] Following steps one through two of the method in Example 43 and steps three through six of the method in Example 11, the title compound 4-amino-12-((5-(2-(trifluoromethyl)pyrimidin-4-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 78 (20 mg) was obtained from compound 4-bromo-2-(trifluoromethyl)pyrimidin-4-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 78 (20 mg) in a yield of 4.2%. MS m / z (ESI): 538 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 9.40 (d, 1H), 9.18 (d, 1H), 8.65 (dd ,1H), 8.53 (d, 1H), 7.75 (d, 1H), 7.51 (s, 1H), 7.41 (s, 1H), 6.64 (s, 2H),5.36 (t, 2H), 5.23 (d, 1H), 5.01 (t, 2H), 4.72 (d, 1H), 4.55 (d, 1H), 4.43(d, 1H), 3.86 - 3.73 (m, 2H), 3.17 (s, 1H), 1.93 (q, 1H), 1.23 (s, 2H). Example 79 4-Amino-12-(3-methyl-4-(2H-1,2,3-triazol-2-yl)phenyl-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazonodecano[7,8-g]quinoline-13(1H)-one Step 1: 3-chloro-4-(triazol-2-yl)benzonitrile 79a (700 mg, 3.42 mmol), 1,4-dio×ane (10 mL), Water (2 mL), Cs₂CO₃ (2.22 g, 6.84 mmol), MeB(OH)₂ (410 mg, 6.84 mmol), and XPhos Pd G₂ (268 mg, 342 μmol) were added sequentially to a single-necked flask. The atmosphere was replaced with nitrogen, and the reaction was carried out at 100°C for 12 hours. After cooling to room temperature, the reaction solution was concentrated to dryness, and the residue was purified by silica gel column chromatography using eluent system A to give the title product 3-methyl-4-(triazol-2-yl)benzonitrile (572 mg, 3.10 mmol), in 90.8% yield. MS m / z (ESI): 185 [M+1] Following the synthetic methods described in Step 2 of Example 52 and Steps 5 through 8 of Example 1, 4-amino-12-(3-methyl-4-(2H-1,2,3-triazol-2-yl)phenyl-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolidinyldecano[7,8-g]quinoline-13(1H)-one 79 (26.0 mg) was obtained from 3-methyl-4-(triazol-2-yl)benzonitrile 79a (184 mg, 1.00 mmol), in yield of 5.5%. MS m / z (ESI): 471 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 2H), 7.56 (d, 1H), 7.51 (s, 1H), 7.48 (s, 1H), 7.45 (d, 1H), 7.41 (s, 1H), 6.70 (br s, 2H), 5.35 (t, 2H), 5.26(d, 1H), 5.01 (t, 2H), 4.71 (d, 1H), 4.54 (d, 1H), 4.18 (d, 1H), 3.74 (d,1H), 3.45 (t, 1H), 3.26 (d, 1H), 3.10 (d, 1H), 2.31 (s, 3H), 1.95 (q, 1H), 1.21 (d, 1H). Example 80 4-Amino-12-((5-(4-(pyridin-4-yl)piperazin-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuro[3,4-c][1,5]oxazolo[7,8-g]quinolin-13(1H)-one Referring to the synthesis method from the first step to the second step of Reference Example 73, 4-amino-12-((5-(4-(pyridin-4-yl)piperazin-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuro[3,4-c][1,5]oxazolo[7,8-g]quinolin-13(1H)-one 80 (36 mg) was obtained from 12-((5-bromopyridin-2-yl)methyl)-4-((3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofuro[3,4-c][1,5]oxazolo[7,8-g]quinolin-13(1H)-one 80a (130 mg, 0.21 mmol), with a yield of 31.0%. MS m / z (ESI): 552 [M+1] 1 H NMR (400 MHz, DMSO- d 6) δ 8.89 (s, 2H), 8.30 (m, 3H), 7.66 (s, 1H),7.60 (s, 1H), 7.51 (m, 2H), 7.33 (m, 2H), 5.46 (m, 2H), 5.10 (m, 3H), 4.66(m, 2H), 4.27 (d, 1H), 3.89 (m, 4H), 3.79 (m, 1H), 3.46 (m, 5H), 3.23 (m,2H), 1.91(m, 1H), 1.21 (m, 1H). Example 81 4-Amino-12-((6-methyl-5-(2 H -1,2,3-triazol-2-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuro[3,4- c [1,5]oxazino[7,8- g quinoxalin-13(1 H )-one Referring to the synthesis method from the first step to the second step of Reference Example 11, (6-methyl-5-(2 H-1,2,3-Triazol-2-yl)pyridin-2-yl)methanamine 81c (1.2 g), yield 44.1%. MS m / z (ESI): 190 [M+1] Referring to the synthesis method of the fifth to eighth steps of Reference Example 1, through (6-methyl-5-(2 H -1,2,3-Triazol-2-yl)pyridin-2-yl)methanamine 81c (200 mg, 1.06 mmol), 4-amino-12-((6-methyl-5-(2 H -1,2,3-Triazol-2-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofuro[3,4- c [1,5]oxazacyclononine[7,8- g quinoxalin-13(1 H )-one 81 (48 mg) was obtained, with a yield of 9.6%. MS m / z (ESI): 472 [M+1] 1 1H NMR (400 MHz, DMSO-d6) δ 8.65 - 7.84 (m, 5H), 7.61 (dd, 3H), 5.45(s, 2H), 5.19 (d, 1H), 5.08 (d, 2H), 4.69 (dd, 2H), 4.39 (d, 1H), 3.90 - 3.77(m, 1H), 3.54 - 3.35 (m, 3H), 2.55 (s, 3H), 1.96 (d, 1H), 1.26 (d, 1H). Example 82 4-Amino-13-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1 H -furo[3,4- c [1,6]oxazacyclodecine[4,3- g quinoxalin-14(9 H )-one Referring successively to the synthesis method of Example 1, through 4-benzyloxy-1-butanol 82a (740 mg, 4.11 mmol), 4-amino-13-((5-(trifluoromethyl)pyridin-2-yl)methyl)-3,7,10,11,12,13-hexahydro-1 H -furo[3,4- c [1,6]oxazacyclodecine[4,3- g quinoxalin-14(9 H)-Ketocone 82 (60 mg), yield 3.1%. MS m / z (ESI): 473 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ8.96 (d, 1H), 8.34 - 7.25 (m, 6H), 5.51 -4.76 (m, 6H), 4.64 - 4.30 (m, 2H), 3.62 (dt, 2H), 3.30 (dd, 2H), 2.08 - 1.12(m, 4H). Example 83 4-Amino-12-[(6-cyanopyridin-2-yl)methyl]-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazinedecano[7,8-g]quinoline-13(1H)-one Following the synthetic method described in steps five through seven of Example 1, 6-(4-(2,4-dimethoxybenzylamino)-13-oxo-1,3,7,10,11,13-hexahydrofurano[3,4-c][1,5]oxazhecyclodecano[7,8-g]quinoline-12(9H)-yl)methyl)nicotinamide 83d (80 mg) was obtained from 3-methyl-4-(triazol-2-yl)benzonitrile hydrochloride 83a (170 mg, 1.00 mmol) and 7-((3-bromopropyl)methyl)-4-(3,4-dimethoxybenzylamino)-1,3-dihydrofurano[3,4-c][1,5]oxazhecyclodecano[7,8-g]quinoline-12(9H)-yl)methyl)nicotinamide 83d (80 mg) in yield of 27.4% using 7-((3-bromopropyl)methyl)-4-(3,4-dimethoxybenzylamino)-1,3-dihydrofurano[3,4-c][1,5]oxazhecyclodecano[7,8-g]quinoline-12(9H)-yl)methyl)nicotinamide 83d. MS m / z (ESI): 584 [M+1] Step 4: Add 6-(4-(3,4-dimethoxybenzylamino)-13-oxo-1,3,7,10,11,13-hexahydrofurano[3,4-c][1,5]oxazyrocyclodecano[7,8-g]quinoline-12(9H)-yl)methyl)nicotinamide 83d (80 mg), acetonitrile (10 mL), ACN (10 mL), POCl3 (63.05 mg, 411 μmol, 42 μL), and DIEA (53.15 mg, 411 μmol, 72 μL) sequentially to a single-necked flask, replace the atmosphere with nitrogen, and react at 20°C for 3 hours. Quench the system in a saturated sodium bicarbonate solution, extract with EA, separate the layers, wash the organic phase with saturated NaCl solution, dry with anhydrous Na2SO4, filter, and concentrate the filtrate to dryness. The residue was purified by silica gel column chromatography with eluent system A to give the title product 6-(4-(3,4-dimethoxybenzylamino)-13-oxo-1,3,7,10,11,13-hexahydrofurano[3,4-c][1,5]oxazyrocyclodecano[7,8-g]quinoline-12(9H)-yl)methyl)nicotinamide 83e (40 mg) in 51.6%.

[0109] Following the synthetic method in step 8 of Example 1, 4-amino-12-[(6-cyanopyridin-2-yl)methyl]-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazetanedecano[7,8-g]quinoline-12(9H)-yl)methyl)nicotinamide 83e (40 mg, 71 μmol) was synthesized to yield 4-amino-12-[(6-cyanopyridin-2-yl)methyl]-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazetanedecano[7,8-g]quinoline-13(1H)-one 83 (5 mg), in 16.9% yield. MS m / z (ESI): 416 [M+1] 1H NMR (400 MHz, DMSO-d6) δ 8.10 (t, 1H), 7.99 (d, 1H), 7.85 (d, 1H), 7.51 (s, 1H), 7.41 (s, 1H), 6.65 (d, 2H), 5.35 (t, 1H), 5.13 (d, 1H), 5.01(t, 2H), 4.72 (d, 1H), 4.53 (d, 1H), 4.41 (d, 1H), 3.77 (d, 2H), 3.45 (d,1H), 3.39 (d, 1H), 3.20 (d, 1H), 1.88 (d, 1H), 1.18 (d, 1H). Example 84 4-Amino-12-((3'-chloro-2'-(trifluoromethyl)-[3,4-bipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Step 1: Dissolve (6-(((tert-Butoxycarbonyl)amino)methyl)pyridin-3-yl)boronic acid 84a (1.57 g, 6.22 mmol), 4-bromo-3-chloro-2-(trifluoromethyl)pyridine (1.08 g, 4.15 mmol), and potassium carbonate (1.15 g, 8.29 mmol) in 1',4-dioxane (20 mL) and water (4 mL). The mixture is purged with nitrogen three times. Add (1,1'-bis(diphenylphosphino)ferrocene palladium(II) chloride (306 mg, 0.41 mmol) to the system. React at 80°C for 15 hours. Quench with water, extract with ethyl acetate (80 mL × 3), and rinse with saturated brine (30 mL × 10 mL). Washed (mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography with eluent system B to give tert-butyl (3'-chloro-2'-(trifluoromethyl)-[3,4-bipyridin]-6-yl)methyl)carbamate 84b (1.05 g), yield: 65.3%. MS m / z (ESI): 388 [M+1] Step 2: (3'-chloro-2'-(trifluoromethyl)-[3,4-bipyridin]-6-yl)methyl)tert-butyl carbamate 84b (1 g, 2.58 mmol) was dissolved in dioxane hydrochloride (4 M, 10 mL), and the reaction was carried out at 25°C for 0.5 h. The reaction mixture was concentrated, and the crude product was directly added to the next step. This yielded (3'-chloro-2'-(trifluoromethyl)-[3,4-bipyridin]-6-yl)methylamine 84c (0.80 g, crude product). MS m / z (ESI): 288 [M+1] Following the synthetic method described in steps six through nine of Example 2, methyl 7-((3-bromopropoxy)methyl)-4-(3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4-c]quinoline-8-carboxylic acid ester 84d (250 mg, 0.49 mmol) and (3'-chloro-2'-(trifluoromethyl)-[3,4-bipyridin]-6-yl)methylamine 84c (390 mg, 1.32 mmol) yielded 4-amino-12-((3'-chloro-2'-(trifluoromethyl)-[3,4-bipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 84 (95 mg), in a yield of 34.1%. MS m / z (ESI): 570 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.80 (d, 1H), 8.74 (d, 1H), 8.07 (dd, 1H), 7.93 (d, 1H), 7.70 (d, 1H), 7.61 (d, 2H), 5.44 (t, 2H), 5.26 (d, 1H), 5.07(t, 2H), 4.75 (d, 1H), 4.61 (d, 1H), 4.40 (d, 1H), 3.88 - 3.79 (m, 1H), 3.49- 3.33 (m, 5H), 2.00 (t, 1H), 1.26 (d, 1H). Example 85 4-Amino-12-((2-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Following the synthetic method of steps one through ten of Example 46, 4-amino-12-((2-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 85 (61 mg) was obtained from thieno[3,2-b]pyridin-5-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 85 in yield of 0.3%. MS m / z (ESI): 515 [M+1] 1 H NMR (400 MHz, DMSO- d 6) δ 8.71 (d, 1H), 8.29 (s, 1H), 7.74 (d, 1H), 7.68 (d, 2H), 5.46 (m, 2H), 5.31 (d, 1H), 5.10 (m, 2H), 4.78 (d, 1H), 4.63(d, 1H), 4.50 (d, 1H), 3.86 (m, 1H), 3.39 (m, 3H), 1.90 (m, 1H), 1.23 (m,1H). Example 92 4-Amino-12-((6-methyl-5-(1H-1,2,3-triazol-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazanonane[7,8-g]quinoline-13(1H)-one Following steps one through two of Example 11 and steps five through eight of Example 1, 4-amino-12-((6-methyl-5-(1H-1,2,3-triazol-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazanonane[7,8-g]quinoline-13(1H)-one 92 (13 mg) were obtained by reacting 5-fluoro-6-methylpyridin-2-onitrile (272 mg, 2 mmol) with 5-fluoro-6-methylpyridin-2-onitrile (272 mg, 2 mmol), in a yield of 1.4%. MS m / z (ESI): 472 [M+1] 1 H NMR (400 MHz, DMSO- d6) δ 8.65 (broad s, 2H), 8.59 (s, 1H), 8.03 (s,1H), 7.93 (d, 1H), 7.73 (s, 1H), 7.71 (s, 1H), 7.61 (d, 1H), 5.49 (d, 2H),5.20 (d, 1H), 5.11 (s, 2H), 4.79 (d, 1H), 4.66 (d, 1H), 4.43 (d, 1H), 4.27(d, 1H), 3.87 (d, 1H), 3.30 (s, 2H), 2.38 (s, 3H), 1.97 (m, 1H), 1.27 (d, 1H). Example 93 4-Amino-12-((4-methyl-5-(1H-1,2,3-triazol-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazanonane[7,8-g]quinoline-13(1H)-one Following steps one through two of Example 11 and steps five through eight of Example 1, 4-amino-12-((4-methyl-5-(1H-1,2,3-triazol-1-yl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazanonane[7,8-g]quinoline-13(1H)-one 93 (26 mg) was obtained by reacting 5-fluoro-4-methylpyridin-2-onitrile (272 mg, 2 mmol) with 5-fluoro-4-methylpyridin-2-onitrile (272 mg, 2 mmol), in a yield of 2.8%. MS m / z (ESI): 472 [M+1] 1 H NMR (400 MHz, DMSO- d 6) δ 8.62 (s, 1H), 8.61 (s, 1H), 8.03 (s, 1H), 7.63 (s, 1H), 7.53 (s, 1H), 7.42 (s, 1H), 5.36 (s, 2H), 5.24 (d, 1H), 5.02(s, 2H), 4.73 (d, 1H), 4.56 (d, 1H), 4.35 (d, 1H), 3.80 (d, 1H), 3.47 (t,2H), 3.28 (m, 1H), 2.27 (s, 3H), 1.96 (m, 1H), 1.25 (d, 1H). Example 94 4-Amino-12-((2-O-2) H -[1,3'-dipyridin]-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Oxadione[7,8-g]quinoxaline-13(1 H )-ketone Step 1: Dissolve 94a (3 g, 10.49 mmol) in 30 mL of 1,4-dioxane, then add 2-hydroxypyridine (1.99 g, 20.98 mmol), cuprous iodide (399 mg, 2.10 mmol), and (…) sequentially. R , R )-(-)- N , N ′-Dimethyl-1,2-cyclohexanediamine (298 mg, 2.10 mmol). The reaction was stirred at 110 °C for approximately 16 hours. The reaction mixture was filtered to remove insoluble matter, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give 94b (500 mg), in 15.8% yield. MS m / z (ESI): 302 [M+1] 94b (500 mg, 1.66 mmol) was deprotected with trifluoroacetic acid to obtain 4-amino-12-((2-oxo-2) ... H -[1,3'-dipyridin]-6'-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4- c [1,5]Oxadione[7,8-g]quinoxaline-13(1 H )-Ketocone 94 (30 mg), yield 3.7%. MS m / z (ESI): 484 [M+1] 1 H NMR (400 MHz, DMSO- d 6) δ 8.62 (d, 1H), 7.93 (dd, 1H), 7.60 (dtd,7H), 6.53 (d, 1H), 6.37 (td, 1H), 5.44 (t, 2H), 5.27 (d, 1H), 5.10 (t, 2H),4.70 (dd, 2H), 4.38 (d, 1H), 3.83 (d, 1H), 3.57 – 3.46 (m, 1H), 3.33 (dd,2H), 1.99 (d, 1H), 1.29 (d, 1H). Example 95 4-Amino-12-((5-(cyclohexylfluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one Referring to steps eight and nine of Example 6, the synthesis was carried out using 12-((5-bromopyridin-2-yl)methyl)-4-((3,4-dimethoxybenzyl)amino)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 95a (100 mg, 0.16 mmol) and 2-(cyclohexylfluoromethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane (78 mg, 0.32 mmol), according to a known method, “Angew. Chem., 2022, vol. 134, # (41” Synthesis) 4-Amino-12-((5-(cyclohexylfluoromethyl)pyridin-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxazolo[7,8-g]quinoline-13(1H)-one 95 (62 mg), yield: 76.2%. MS m / z (ESI): 503 [M+1] 1 H NMR (400 MHz, DMSO-d6) δ 8.59 (s, 3H), 7.86 (d, 1H), 7.77–7.50 (m,3H), 5.48 (s, 2H), 5.20 (d, 1H), 5.10 (s, 2H), 4.75 (d, 1H), 4.63 (d, 1H), 4.34 (d, 1H), 3.82 (d, 1H), 3.28 (s, 4H), 2.38 (s, 2H), 2.19 (s, 2H), 1.95 (s, 1H), 1.58 (s, 5H), 1.24 (d, 1H). Example 98 4-Amino-12-((1'-methyl-1',2',3',6'-tetrahydro-[3,4'-bipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenotin[7,8-g]quinoline-13(1H)-one Step 1: 98a (200 mg, 0.32 mmol), tert-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxoboropentane-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid ester (130 mg, 0.42 μmol), tetraphenylphosphine palladium (75 mg, 0.065 mmol), sodium carbonate (103 mg, 0.97 mmol), dioxane (4 mL), and water (0.4 mL) were reacted at 85°C for 2 hours. Water (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL x 2). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 98b (0.2 g, 0.277 mmol), with a yield of 85%. MS m / z (ESI): 722 [M+1] Step 2: 98b (0.2 g, 0.277 mmol) was dissolved in 3 mL of methanol hydrochloric acid and reacted at 20 °C for 16 hours. The solution was filtered and evaporated to dryness to give 98c (140 mg), yield 81%. MS m / z (ESI): 622 [M+1] Step 3: Dissolve 98c (90 mg, 0.145 mmol), formaldehyde (22 mg, 0.72 mmol), sodium cyanoborohydride (27 mg, 0.43 mmol), and acetic acid (9 mg, 0.14 mmol) in methanol (4 mL). React at 20°C for 16 hours. Add water (10 mL) to the reaction mixture and extract with ethyl acetate (40 mL x 2). After extraction, collect the organic phase, dry it over anhydrous sodium sulfate, filter, concentrate the filtrate under reduced pressure, and purify the residue by silica gel column chromatography with eluent system B to obtain 98d (58 mg, 0.09 mmol), yield 63%. MS m / z (ESI): 636 [M+1] Step 4: Dissolve 98d (58 mg, 0.09 mmol) in 4 mL of trifluoroacetic acid and react at 50 °C for 1 hour. Filter and evaporate to dryness to give 16.2 mg of 4-amino-12-((1'-methyl-1',2',3',6'-tetrahydro-[3,4'-bipyridin]-6-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxaconoenoinro[7,8-g]quinoline-13(1H)-one, yield 42%. MS m / z (ESI): 486 [M+1] 1 H NMR (400 MHz, DMSO-d 6) δ 8.67 (d, 1H), 7.91 (dd, 1H), 7.50 (t, 2H), 7.35 (s, 1H), 6.64 (s, 2H), 6.34 – 6.30 (m, 1H), 5.36 – 5.32 (m, 2H), 5.17(d, 1H), 5.01 (d, 2H), 4.69 (d, 1H), 4.54 (d, 1H), 4.27 (d, 1H), 3.73 (dd,1H), 3.53 (s, 2H), 3.46 (d, 2H), 3.19 – 3.14 (m, 2H), 3.11 – 3.05 (m, 2H),2.68 (d, 2H), 2.64 (s, 2H), 2.03 – 1.97 (m, 1H), 1.90 (d, 1H). Example 101 4-Amino-12-((5-(2,6-difluorophenyl)thiazolyl-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxacono-nonanoin[7,8-g]quinoline-13(1H)-one Step 1: 101a (100 mg, 0.16 mmol), 3-trifluoromethyl-4-pyridineboronic acid (62 mg, 0.32 mmol), potassium carbonate (67 mg, 0.48 mmol), and 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (23 mg, 0.032 mmol) were dissolved in 2 mL of dioxane and 0.4 mL of water. The reaction mixture was reacted at 100 °C for 2 hours. Water (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (50 mL x 2). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 101b (30 mg, 0.043 mmol), with a yield of 27%. MS m / z (ESI): 686 [M+1] Step 2: 101b (30 mg, 0.043 mmol) was dissolved in 4 mL of trifluoroacetic acid and reacted at 50 °C for 2 hours. The mixture was filtered, evaporated to dryness, and the product was purified by high-performance liquid chromatography (HPLC) to give 4-amino-12-((5-(2,6-difluorophenyl)thiazol-2-yl)methyl)-3,7,9,10,11,12-hexahydrofurano[3,4-c][1,5]oxacono-[7,8-g]quinoline-13(1H)-one 1 (10.5 mg), yield 45%. MS m / z (ESI): 536 [M+1] 1 H NMR (400 MHz, DMSO- d 6) δ 9.10 (s, 1H), 8.97 (d, 1H), 8.58 (d, 1H), 7.90 (dd, 1H), 7.66 (d, 1H), 7.62 (d, 1H), 7.56 (s, 1H), 7.48 (s, 1H), 5.38(t, 2H), 5.24 (d, 1H), 5.03 (t, 2H), 4.73 (d, 1H), 4.57 (d, 1H), 4.41 (d,1H), 3.78 (d, 1H), 3.47 (d, 1H), 3.25 (d, 2H), 2.01 – 1.90 (m, 2H). Example 103 ( Z )-4-amino-11-methyl-9-(4-(1-methylpiperidin-4-yl)phenyl)-3,9,10,11-tetrahydroazacyclooctatetraeno[3,4-g]furano[3,4- c Quinoxaline-12(1) H )-ketone Step 1: Add 4-((3,4-dimethoxybenzyl)amino)-7-chloro-dihydrofuran[3,4- cQuinoxalo-8-carboxylic acid methyl ester 103a (1.0 g, 2.34 mmol) and potassium ethylene trifluoroborate (627 mg, 4.68 mmol) were dissolved in 20 mL of dioxane and 4 mL of water. Then, methanesulfonic acid [n-butyldi(1-adamantyl)phosphine](2-amino-1,1'-biphenyl-2-yl)palladium(II) (167 mg, 0.23 mmol) and cesium carbonate (5.37 g, 16.48 mmol) were added sequentially. The reaction was carried out at 100 °C for 12 hours under nitrogen atmosphere. Water (100 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (100 mL × 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 4-((3,4-dimethoxybenzyl)amino)-7-vinyl-dihydrofurano[3,4- c Quinoxalool-8-carboxylic acid methyl ester 103b (950 mg), yield: 96.7%. MS m / z (ESI): 421 [M+1] Step 2: Add 4-((3,4-dimethoxybenzyl)amino)-7-vinyl-dihydrofuran[3,4- c 103b (950 mg, 2.26 mmol) of quinoxalo-8-carboxylic acid methyl ester was dissolved in 10 mL of tetrahydrofuran and 10 mL of water with lithium hydroxide (475 mg, 11.30 mmol). The reaction was carried out at 70 °C for 12 hours. The reaction solution was concentrated under reduced pressure, and the residue was adjusted to pH 7 with 6 N hydrochloric acid. The solid precipitated, filtered, and dried to give 7-allyl-4-((3,4-dimethoxybenzyl)amino)-1,3-dihydrofuran[3,4- c Quinoxalo-8-carboxylic acid 103c (750 mg), yield 81.7%. MS m / z (ESI): 407 [M+1] Step 3: 103d of 4-(4-bromophenyl)piperidine (17.0 g, 71.13 mmol) was dissolved in 200 mL of dichloromethane. Triethylamine (10.0 g, 99.01 mmol) and di-tert-butyl dicarbonate (18.5 g, 85.00 mmol) were added, and the reaction was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system B to give 7-allyl-4-((3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4- c Quinoxalo-8-carboxylic acid 103e (24.0 g), yield 99.5%. MS m / z (ESI): 340 [M+1] Step 4: Add 7-allyl-4-((3,4-dimethoxybenzyl)amino)-1,3-dihydrofurano[3,4- c Quinoxalo-8-carboxylic acid 103e (24.0 g, 70.80 mmol), methyl acrylate (8.6 g, 100.00 mmol) and triethylamine (14.3 g, 141.60 mmol) were dissolved in 200 mL N , N - Dimethylformamide. Add bis(tri-o-tolylphosphine)palladium dichloride (5.6 g, 7.08 mmol), and allow the reaction to proceed at 100 °C for 12 hours under nitrogen atmosphere. Add water (1000 mL) to the reaction mixture, and extract with ethyl acetate (300 mL × 2). After extraction, collect the organic phase, dry it over anhydrous sodium sulfate, filter, concentrate the filtrate under reduced pressure, and purify the residue by silica gel column chromatography using eluent system B to obtain ( E 103 f (20.0 g) of 4-(4-(3-methoxy-3-oxoprop-1-en-1-yl)phenyl)piperidin-1-carboxylic acid tert-butyl ester, yield 81.9%. MS m / z (ESI): 346 [M+1] Step 5: Disperse cuprous iodide (8.3 g, 43.48 mmol) in tetrahydrofuran (50 mL), and add vinyl magnesium bromide (87.0 mL, 87.00 mmol, 1 M / L tetrahydrofuran solution) dropwise at -60°C. React at -60°C for 0.5 hours, then add ( E 103 f (5.0 g, 14.49 mmol) of 4-(4-(3-methoxy-3-oxoprop-1-en-1-yl)phenyl)piperidin-1-carboxylic acid tert-butyl ester was reacted at -60°C for 0.5 h. The reaction was quenched by adding 100 mL of saturated ammonium chloride aqueous solution to the reaction solution, and extracted with ethyl acetate (100 mL × 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with eluent system B to give 103 g (1.7 g) of 4-(4-(5-methoxy-5-oxopent-1-en-3-yl)phenyl)piperidin-1-carboxylic acid tert-butyl ester, yield 31.5%. MS m / z (ESI): 374 [M+1] Step 6: 103 g (1.7 g, 4.56 mmol) of 4-(4-(5-methoxy-5-oxopent-1-en-3-yl)phenyl)piperidine-1-carboxylic acid tert-butyl ester was dissolved in trifluoroacetic acid (10 mL), and the reaction mixture was reacted at 25 °C for 1 hour. The reaction solution was concentrated under reduced pressure to give 103 h (1.2 g) of 4-(4-(5-methoxy-5-oxopent-1-en-3-yl)phenyl)piperidine, yield 96.4%. MS m / z (ESI): 274 [M+1] Step 7: 4-(4-(5-methoxy-5-oxopent-1-en-3-yl)phenyl)piperidine 103h (1.2 g, 4.40 mmol) and triethylamine (889 mg, 8.80 mmol) were dissolved in dichloromethane (20 mL), and benzyl chloroformate (1.1 g, 6.60 mmol) was added. The reaction mixture was reacted at 25 °C for 1 hour. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system B to give 4-(4-(5-methoxy-5-oxopent-1-en-3-yl)phenyl)piperidine-1-carboxylic acid benzyl ester 103i (1.5 g), yield 83.8%. MS m / z (ESI): 408 [M+1] Step 8: Benzyl 4-(4-(5-methoxy-5-oxopent-1-en-3-yl)phenyl)piperidin-1-carboxylic acid ester 103i (580 mg, 1.43 mmol) and lithium hydroxide (172 mg, 7.15 mmol) were dissolved in 5 mL of tetrahydrofuran and 5 mL of water. The reaction mixture was reacted at 25 °C for 1 hour. The reaction solution was concentrated under reduced pressure to remove tetrahydrofuran. The residue was adjusted to pH 7 with 6 N hydrochloric acid, and a solid precipitated out. The solid was filtered and dried to give 3-(4-(1-((benzyloxy)carbonyl)piperidin-4-yl)phenyl)pent-4-enoic acid 103j (520 mg), yield: 92.6%. MS m / z (ESI): 394 [M+1] Step 9: 3-(4-(1-((benzyloxy)carbonyl)piperidin-4-yl)phenyl)pent-4-enoic acid 103k (520 mg, 1.32 mmol), triethylamine (160 mg, 1.58 mmol), and diphenyl azidophosphate (434 mg, 1.58 mmol) were dissolved in 10 mL of tert-butanol, and the reaction mixture was reacted at 85 °C for 12 hours. Water (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (30 mL × 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give 4-(4-(1-((tert-butoxycarbonyl)amino)but-3-en-2-yl)phenyl)piperidin-1-carboxylic acid benzyl ester 103k (430 mg), with a yield of 70.2%. MS m / z (ESI): 465 [M+1] Step 10: Benzyl 4-(4-(1-((tert-Butoxycarbonyl)(methyl)amino)but-3-en-2-yl)phenyl)piperidin-1-carboxylic acid ester 103k (430 mg, 0.93 mmol) was dissolved in 10 mL of tetrahydrofuran. Sodium hydrogen (45 mg, 1.86 mmol, 60%) and methyl iodide (385 mg, 2.79 mmol) were added sequentially, and the reaction system was reacted at 25 °C for 12 hours. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL × 2). The organic phase was collected after extraction, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to obtain benzyl 4-(4-(1-((tert-Butoxycarbonyl)(methyl)amino)but-3-en-2-yl)phenyl)piperidin-1-carboxylic acid ester 103l (390 mg), with a yield of 87.7%. MS m / z(ESI): 479 [M+1] Step 11: 103 μL (390 mg, 0.82 mmol) of benzyl 4-(4-(1-((tert-butoxycarbonyl)(methyl)amino)but-3-en-2-yl)phenyl)piperidin-1-carboxylic acid ester was dissolved in trifluoroacetic acid (5 mL), and the reaction mixture was reacted at 25 °C for 1 hour. The reaction solution was concentrated under reduced pressure to give the title product, 103 μL (290 mg), 4-(4-(1-(methylamino)but-3-en-2-yl)phenyl)piperidin-1-carboxylic acid ester, in 94.0% yield. MS m / z (ESI): 379 [M+1] Following the synthetic method described in steps four and five of Example 3, 103 mg (290 mg, 0.77 mmol) of benzyl 4-(4-(1-(methylamino)but-3-en-2-yl)phenyl)piperidin-1-carboxylic acid ester was used to obtain ( Z)-4-(4-(4-((3,4-dimethoxybenzyl)amino)-11-methyl-12-oxo-1,3,9,10,11,12-hexahydroazacyclooctatetraeno[3,4-g]furano[3,4- c 1030 (260 mg) quinoxalo-9-yl)phenyl)piperidine-1-carboxylic acid benzyl ester, yield 45.8%. MS m / z (ESI): 739 [M+1] Step 14: Place ( Z )-4-(4-(4-((3,4-dimethoxybenzyl)amino)-11-methyl-12-oxo-1,3,9,10,11,12-hexahydroazacyclooctatetraeno[3,4-g]furano[3,4- c 1030 mg (260 mg, 0.35 mmol) of quinoxalo-9-yl)phenyl)piperidin-1-carboxylic acid benzyl ester was dissolved in trifluoroacetic acid (5 mL), and the reaction mixture was reacted at 80°C for 2 hours. The reaction solution was concentrated under reduced pressure to give the title product ( Z )-4-amino-11-methyl-9-(4-(piperidin-4-yl)phenyl)-3,9,10,11-tetrahydroazacyclooctatetraeno[3,4-g]furano[3,4- c Quinoxaline-12(1) H )-Ketocone 103p (80 mg), yield 50.0%. MS m / z (ESI): 455 [M+1] Step 15: Place ( Z )-4-amino-11-methyl-9-(4-(piperidin-4-yl)phenyl)-3,9,10,11-tetrahydroazacyclooctatetraeno[3,4-g]furano[3,4- c Quinoxaline-12(1) H )-ketone 103p (80 mg, 0.18 mmol) was dissolved in 5 mL of methanol, and paraformaldehyde (54 mg, 1.80 mmol) and sodium cyanoborohydride (113 mg, 1.80 mmol) were added sequentially. The reaction system was reacted at 25°C for 2 hours. The reaction solution was filtered to remove insoluble matter, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography with eluent system A to obtain the title product ( Z )-4-amino-11-methyl-9-(4-(1-methylpiperidin-4-yl)phenyl)-3,9,10,11-tetrahydroazacyclooctatetraeno[3,4-g]furano[3,4- c Quinoxaline-12(1) H )-Ketone 103 (25 mg), yield 29.7%. MS m / z (ESI): 469 [M+1] 1H NMR (400 MHz, DMSO-d6) δ7.49 (dd, 2H), 7.13 (dd, 4H), 6.75 - 6.65 (m, 3H), 5.86 (dd, 1H), 5.30 (s, 2H), 5.00 (d, 2H), 4.12 - 3.96 (m, 1H), 3.76- 3.59 (m, 1H), 3.15 - 3.10 (m, 4H), 2.82 - 2.79 (m, 2H), 2.34 (d,1H), 2.15(s, 3H), 1.94 - 1.83 (m, 2H), 1.69 - 1.47 (m, 4H). Example 103 ( Z )-4-amino-11-methyl-9-(4-(1-methylpiperidin-4-yl)benzyl)-3,9,10,11-tetrahydroazacyclooctatetraeno[3,4-g]furano[3,4- c Quinoxaline-12(1) H )-ketone Following the synthesis method in step 2 of Example 3, 103a (13.0 g, 38.35 mmol) was reacted to yield 103b (11.0 g), with a yield of 95.3%. MS m / z (ESI): 302 [M+1] Step 2: 103b (11.0 g, 36.54 mmol) and methyl acrylate (6.02 g, 70.00 mmol) were dissolved in 200 mL of dichloromethane. A Janssen catalyst (2.68 g, 3.65 mmol) was added, and the reaction was allowed to proceed at 40 °C for 12 hours. The reaction solution was concen...

Claims

1. A compound of general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof: M1 is selected from -N- or -CR a -; M2 is selected from -N- or -CR b -; Preferred-CR b -; M3 is selected from N or C; N is preferred. Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 quinone heteroaryl; C is preferred 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl, or 5-6 membered heteroaryl; Ring B is selected from C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl or 5-14 quinone heteroaryl; C is preferred 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Fused cycloalkyl groups, 6-10 fused heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl groups; L1 is selected from the key, -CR aa R bb -、-C(O)-、-NR cc C(O), -S(O) m1 -or-NR cc -; Preferred-CR aa R bb -、-C(O)-、-S(O) m1 -or-NR cc -; L2 is selected from the bond, -CR aa R bb -、-C(O)-、-S(O) m1 -or NR cc Preferred - CR aa R bb -、-C(O)-、-S(O) m1 -or NR cc ; R1 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, -(CR cc R dd ) n1 -C 3-12 cycloalkyl, -(CR cc R dd ) n1 -3-12-membered heterocyclic group, -(CR cc R dd ) n1 -C 6-12 Aryl, -(CR cc R dd ) n1 -5-12-aryl heteroaryl, -SF5, -OR e -NR e R f -C(O)R e -C(O)OR e -C(O)NR e R f -N=S(O)R e R f -S(O)R e (=NR f ) or -P(O)R e R f The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl and =CR gg R hh One or more substituents are substituted in the group; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, -(CR cc R dd ) n1 -C 3-8 cycloalkyl, -(CR cc R dd ) n1 -3-8 membered heterocyclic group, -(CR cc R dd ) n1 -C 6-10 Aryl, -(CR cc R dd ) n1 -5-10% heteroaryl, -OR e -NR e R f -C(O)R e -C(O)NR e R f or -P(O)R e R f The amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; Or R1 and R a R b or R c Link formation C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents from 5-12 heteroaryl groups; preferably, a C13 group is formed. 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally further converted by deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R2 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic, C6-12 aryl, 5-12 membered heteroaryl, -(CH2) n2 OR ee -(CH2) n2 NR ee R ff -(CH2) n2 C(O)R ee -(CH2) n2 C(O)NR ee R ff -(CH2) n2 P(O)R ee R ff or =CR ee R ff The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -Y1-C 3-12 Cycloalkyl, -Y1-3-12-membered heterocyclic group, -Y1-C 6-12 Aryl, -Y1-5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h -C(=NR) i )NR g R h or =R g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl groups and =CR e R f One or more substituents are substituted in the group; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl and =CR e R f One or more substituents in it are replaced; Or any two R3 atoms can link with their adjacent atoms to form C. 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents from 5-12 heteroaryl groups; preferably, a C13 group is formed. 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally further converted by deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R a R b R c R e and R f Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic, C6-12 aryl, 5-12 membered heteroaryl, -(CH2) n2 OR ee -(CH2) n2 NR ee R ff -(CH2) n2 C(O)R ee -(CH2) n2 C(O)OR ee -(CH2) n2 C(O)NR ee R ff -(CH2) n2 N=S(O)R ee R ff -(CH2) n2 S(O)R ee (=NR ff ) or -(CH2) n2 P(O)R ee R ff The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl and =CR gg R hh One or more substituents are substituted in the group; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; Y1 is selected from key, -O-, -S-, -C(O), -NR j -、-C(O)NR j -、-NR j C(O)-、-S(O)2NR j -、-NR j S(O)2-, C 1-6 Alkylene, -OC 1-6 alkylene-, -C 1-6 Alkylene-O-, -NR j -C 1-6 alkylene-, -C 1-6 Alkylene-NR j -、C 2-6 imide or C 2-6 The acetylenic group, the C 1-6 Alkylene, C 2-6 imide and C 2-6 Alynyl group, optionally replaced by deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R g R h R i and R j Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; Or, R g With R h Link formation C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 aryl and 5-12 heteroaryl groups, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R aa R bb R cc and R dd Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R ee and R ff Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; R gg and R hh Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from aryl and 5-12 heteroaryl groups; preferably hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the amino group, C 1-3 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, oxo group, thio group, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents from 5-10 heteroaryl groups; x is selected from 0, 1, 2, 3, 4, 5 or 6; y is selected from 0, 1, 2, 3, 4, 5 or 6; m1 is selected from 0, 1 or 2; m2 is selected from 0, 1 or 2; n1 is selected from 0, 1, 2, 3 or 4; and n2 is selected from 0, 1, 2, 3 or 4.

2. The compound according to claim 1, its stereoisomers, or its pharmaceutically acceptable salts, characterized in that, The Selected from , , , or .

3. The compound according to claim 1 or 2, its stereoisomer, or a pharmaceutically acceptable salt thereof, characterized in that, Further, compounds of general formula (III-E), their stereoisomers, or pharmaceutically acceptable salts thereof: L5 is selected from the bond, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from 5-12 heteroaryl groups; preferably self-bonded, -O-, -S-, -C(O)-, -NR-. N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L6 is selected from the bond, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from 5-12 heteroaryl groups; preferably self-bonded, -O-, -S-, -C(O), -NR. N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; L7 is selected from the key, -O(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 O-, -S(CR) 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 S-、-C(O)(CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 C(O)-、-NR N (CR 9a R 9b ) n10 -、-(CR 9a R 9b ) n10 NR N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-、=CR 9a R 9b C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted with one or more substituents selected from 5-12 heteroaryl groups; preferably self-bonded, -O-, -S-, -C(O), -NR. N -、-C(O)NR N -、-NR N C(O)-、-S(O)2NR N -、-NR N S(O)2-, C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene or 5-12 quinone heteroarylene, wherein the C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-12 Cycloalkylene, 3-12 membered heterocyclic alkylene, C 6-12 arylene and 5-12 heteroarylene groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 It is substituted by one or more substituents in the aryl group and the 5-12 heteroaryl group.

4. The compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, according to any one of claims 1 to 3, characterized in that, Further, compounds as shown in general formula (IV-E), their stereoisomers, or their pharmaceutically acceptable salts: M5 is selected from N or CR. 3a M6 is selected from N or CR 3b ; R5 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 3a R 3b R 3d and R 3e Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or -C(=NR) i )NR g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl groups and =CR e R f One or more substituents in it are replaced; R 3c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or -C(=NR) i )NR g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl groups and =CR e R f One or more substituents in it are replaced.

5. The compound, its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that, Ring A is selected from 5-membered heterocyclic groups, 6-membered heterocyclic groups, 5-membered heteroaryl groups, or 6-membered heteroaryl groups; more preferably... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or ; Alternatively, ring B is selected from 3-6-membered heterocyclic benzophenyl or 3-6-membered heterocyclic benzo5-6-membered heteroaryl; preferably. , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

6. The compound, its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, characterized in that, Further, as shown in general formula (VI-A) or (VI-B): M5 is selected from N or CR. 3a ; M6 is selected from N or CR. 3b ; R5 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; R 3a R 3b R 3d and R 3e Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or -C(=NR) i )NR g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl groups and =CR e R f One or more substituents in it are replaced; R 3c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -SF5, -OR g -NR g R h -C(O)R g -C(O)OR g -C(O)NR g R h -N=S(O)R g R h -S(O)R g (=NR h -P(O)R g R h or -C(=NR) i )NR g R h The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl groups, optionally substituted with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, substituted or unsubstituted C 3-12 Cycloalkyl, substituted or unsubstituted 3-12 membered heterocyclic groups, substituted or unsubstituted C 6-12 aryl, substituted or unsubstituted 5-12 heteroaryl groups and =CR e R f One or more substituents in it are replaced; n11 is selected from 0, 1, or 2.

7. The compound, its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, characterized in that, L6 is selected from -O-, -S-, -C(O), and -NR. N -、C 1-3 Alkylene or C 2-4 Ideonyl, the C 1-3 Alkylene and C 2-4 alkenyl group, optionally replaced by deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, oxo group, thio group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group is substituted by one or more substituents in the 5-12 membered heteroaryl group; n8 is selected from 1, 2, or 3; n9 is selected from 0, 1, or 2; Or, R2 or R 2c Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, cyano-substituted C 1-3 Alkyl, C 3-8 cycloalkyl or -C(O)NR ee R ff The amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, cyano-substituted C 1-3 Alkyl and C 3-8 Cycloalkyl, optionally with deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, cyano-substituted C 1-3 Alkyl and C 3-8 One or more substituents in the cycloalkyl group are substituted; R ee and R ff Each is independently selected from hydrogen, deuterium, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 alkyl; Preferred elements include hydrogen, deuterium, fluorine, chlorine, methyl, deuterated methyl, difluoromethyl, and trifluoromethyl. , or ; Or, R c Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl or cyano-substituted C 1-3 Alkyl; more preferably hydrogen, deuterium, fluorine, chlorine, methyl, deuterated methyl, difluoromethyl or trifluoromethyl; Or, R a Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl or cyano-substituted C 1-3 Alkyl group; preferably hydrogen, deuterium, fluorine, chlorine, methyl, deuterated methyl, difluoromethyl or trifluoromethyl.

8. The compound, its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, characterized in that, The structure of the compound is as follows: or .

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

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

11. The use of the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 8, or the pharmaceutical composition according to claim 9, in the preparation of a treatment for cancer; wherein the cancer is MTAP-associated cancer.

12. The application according to claim 11, characterized in that, The cancers mentioned are selected from lung cancer, hepatocellular carcinoma, breast cancer, skin cancer, bladder cancer, liver cancer, pancreatic cancer, head and neck cancer, glioma, glioblastoma, esophageal cancer, pancreatic cancer, mesothelioma, melanoma, astrocytoma, undifferentiated pleomorphic sarcoma, leukemia, gastric adenocarcinoma, myxofibrosarcoma, cholangiosarcoma, brain cancer, gastric cancer, kidney cancer, endometrial cancer, ovarian tumor, prostate cancer, diffuse large B-cell lymphoma, non-Hodgkin lymphoma, urinary tract cancer, soft tissue cancer, pleural cancer, colorectal cancer, colorectal cancer, or bile duct cancer; the lung cancer is selected from non-small cell lung cancer, squamous cell carcinoma of the lung, or adenocarcinoma of the lung; the esophageal cancer is selected from esophageal squamous cell carcinoma or esophageal adenocarcinoma.

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