Polycyclic compound, and preparation method therefor and use thereof

Abstract

Disclosed in the present invention are a polycyclic compound, and a preparation method therefor and the use thereof. The polycyclic compound of the present invention is a compound as represented by formula (A-I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The polycyclic compound can be used as an effective modulator of human TNFα activity, and has good application prospects.

Description

A polycyclic compound, its preparation method and application

[0001] This application claims Chinese patent applications filed on July 26, 2024 (2024110156715), October 17, 2024 (2024114545214), November 19, 2024 (2024116549277), December 27, 2024 (2024119514034), January 6, 2025 (2025100177809), January 16, 2025 (2025100716984), and January 23, 2025 (202510110). Priority claims are made to Chinese patent applications 4203, 2025 / 2 / 25 2025102117056, 2025 / 2 / 27 2025 2025102250156, 2025 / 3 / 6 2025102638886, 2025 / 3 / 20 2025103352867, 2025 / 4 / 3 2025 2025104196813, 2025 / 4 / 30 2025105653572, and 2025 / 7 / 21 2025110094215. The full text of the aforementioned Chinese patent applications is incorporated herein by reference. Technical Field

[0002] This invention relates to a polycyclic compound, its preparation method, and its applications. Background Technology

[0003] TNFα (tumor necrosis factor) is a cytokine with multiple biological effects discovered in the 1970s and is the first typical member of the TNF superfamily (TNFSF) of ligands. TNFα is a type II transmembrane protein that can be secreted in a soluble form after being cleaved by metalloproteinases. In its native state, TNFα exists as a trimer. Only when the trimer form of TNFα binds to the extracellular region of TNFR1 can it induce the trimerization of TNFR1, thereby effectively activating downstream pathways. TNFα is secreted by monocytes, macrothiazides, and T cells activated by interaction with TNFRs. By binding to specific receptors on the cell membrane, it activates three signaling pathways: caspase, JNK, and the transcription factor NF-κB, thereby inducing multiple different biological processes and ultimately achieving its biological functions of regulating cell growth and apoptosis, tumorigenesis, immunity, inflammation, and stress responses.

[0004] Currently, many TNFα modulators have been developed and are commercially available. Clinically proven, inhibiting the binding of TNFα to TNFR1 and TNFR2 is used to treat or prevent many TNFα-mediated human diseases, including inflammatory and autoimmune diseases, and neurodegenerative diseases. All currently approved products are large molecules and work by inhibiting the binding of human TNFα to its receptors. Examples include adalimumab, golimumab, certoizumab pegol, infliximab, and etanercept.

[0005] Given the limited efficacy and certain clinical side effects of clinical antibody drugs, there is a need to develop small molecule inhibitors that can regulate TNFα signaling.

[0006] This invention relates to a new class of heterocyclic compounds that serve as effective inhibitors of TNFα activity. These compounds exhibit highly efficient TNFα inhibition and good drug-like properties. Summary of the Invention

[0007] This invention provides compounds of formula (AI), their stereoisomers, or pharmaceutically acceptable salts thereof.

[0008] in,

[0009] T1 is selected from N and C(R6);

[0010] T2 is selected from N and C (R7);

[0011] T3 is selected from N and C(R8);

[0012] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0013] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0014] Z is selected from -C(R) a )2-、-C(R b)2- and -C(=R c )-;

[0015] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0016] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0017] Selected from

[0018] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0019] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0020] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0021] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0022] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0023] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0024] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0025] R9 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0026] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0027] Alternatively, R6 and R1 can be connected together to form a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0028] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0029] Alternatively, R6 and L1, together with the atoms they are attached to, form a 5-6 membered monocyclic heteroaryl and a 5-10 membered heterocyclic alkenyl; wherein the heteroatoms in the monocyclic heteroaryl and heterocyclic alkenyl are independently selected from N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0030] Alternatively, R7 and L1 together with the atoms they are attached to form a 5-6 membered monocyclic heteroaryl and a 5-10 membered heterocyclic alkenyl; wherein the heteroatoms in the monocyclic heteroaryl and heterocyclic alkenyl are independently selected from N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0031] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0032] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0033] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0034] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0035] Alternatively, R9 and the substituent R on X1 aThey are linked together to form a 4-10 membered heterocyclic alkyl group, wherein the 4-10 membered heterocyclic alkyl group is optionally substituted with one or more R;

[0036] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0037] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0038] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0039] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0040] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1- 6-alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0041] n is selected from 0, 1, 2 or 3.

[0042] In some embodiments of the present invention, R9 is selected from F, Cl, Br, I, OH, NH2, CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0043] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0044] In some embodiments of the present invention, R9 is selected from -CH3 or -CD3.

[0045] In some embodiments of the present invention, the 5-6 membered monocyclic heteroaryl and 5-10 membered heterocyclic alkenyl group is Among them, #1 is connected to ring A, and #2 is connected to T2.

[0046] In some embodiments of the present invention, the compound represented by (AI), its stereoisomers, or pharmaceutically acceptable salts thereof, is selected from the compounds represented by formula (A-II-A) or (A-II-B) or pharmaceutically acceptable salts thereof.

[0047] in,

[0048] T1 is selected from N and C(R6);

[0049] T2 is selected from N and C (R7);

[0050] T3 is selected from N and C(R8);

[0051] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0052] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0053] Z is selected from -C(R) a )2-、-C(R b )2- and -C(=R c )-;

[0054] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0055] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0056] Selected from

[0057] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0058] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0059] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0060] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0061] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0062] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0063] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0064] R9 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0065] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0066] Alternatively, R6 and R1 can be connected together to form a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0067] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0068] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0069] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0070] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0071] R c Choose O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0072] Alternatively, R9 and the substituent R on X1 a They are linked together to form a 4-10 membered heterocyclic alkyl group, wherein the 4-10 membered heterocyclic alkyl group is optionally substituted with one or more R;

[0073] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0074] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0075] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0076] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0077] Alternatively, any substituent on Z can be linked to any substituent on X1 to form a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0078] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, Si(C 1-6 Alkyl)3, C 1-6 Alkyl, C 1- 6-alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0079] n is selected from 0, 1, 2 or 3.

[0080] In some embodiments of the present invention, R9 is selected from F, Cl, Br, I, OH, NH2, CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 The cycloalkyl or 3-10 membered heterocycloalkyl group may optionally be substituted with one or more R.

[0081] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0082] In some embodiments of the present invention, R9 is selected from -CH3 or -CD3.

[0083] This invention provides compounds of formula (AI), their stereoisomers, or pharmaceutically acceptable salts thereof.

[0084] in,

[0085] T1 is selected from N and C(R6);

[0086] T2 is selected from N and C (R7);

[0087] T3 is selected from N and C(R8);

[0088] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0089] X2 is selected from empty, -O-, -S-, -N(R) a)-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0090] Z is selected from -C(R) a )2-、-C(R b )2- and -C(=R c )-;

[0091] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0092] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0093] Selected from

[0094] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0095] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10-membered heterocyclic alkenyl, wherein R1 is optionally substituted with one or more R;

[0096] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0097] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0098] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0099] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0100] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0101] R9 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0102] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0103] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0104] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0105] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0106] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0107] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0108] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0109] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0110] Alternatively, any substituent on Z can be linked to any substituent on X1 to form a C 3-10Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0111] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, Si(C 1-6 Alkyl)3, C 1-6 Alkyl, C 1- 6-alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0112] n is selected from 0, 1, 2 or 3.

[0113] In some embodiments of the present invention, R9 is selected from F, Cl, Br, I, OH, NH2, CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0114] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0115] In some embodiments of the present invention, R9 is selected from -CH3 or -CD3.

[0116] In some embodiments of the present invention, the compound represented by (AI), its stereoisomers, or pharmaceutically acceptable salts thereof, is selected from the compounds represented by formula (A-II-A) or (A-II-B) or pharmaceutically acceptable salts thereof.

[0117] in,

[0118] T1 is selected from N and C(R6);

[0119] T2 is selected from N and C (R7);

[0120] T3 is selected from N and C(R8);

[0121] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0122] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(Rb )2C(R b )2-;

[0123] Z is selected from -C(R) a )2-、-C(R b )2- and -C(=R c )-;

[0124] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0125] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0126] Selected from

[0127] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0128] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0129] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0130] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0131] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0132] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0133] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0134] R9 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 Alkylamino, C 3-10Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0135] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0136] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0137] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0138] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0139] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0140] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0141] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0142] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0143] Alternatively, any substituent on Z can be linked to any substituent on X1 to form a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0144] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, Si(C 1-6 Alkyl)3, C 1-6 Alkyl, C 1- 6-alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C1-6 Alkyl)2-amino substitution;

[0145] n is selected from 0, 1, 2 or 3.

[0146] In some embodiments of the present invention, R9 is selected from F, Cl, Br, I, OH, NH2, CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0147] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0148] In some embodiments of the present invention, R9 is selected from -CH3 or -CD3.

[0149] This invention provides compounds of formula (A-III), formula (A-III-A), or formula (A-III-B), or pharmaceutically acceptable salts thereof.

[0150] in,

[0151] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0152] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0153] Z is selected from -C(R) a )2-、-C(R b)2- and -C(=R c )-;

[0154] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0155] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0156] Selected from

[0157] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0158] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0159] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0160] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0161] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0162] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0163] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0164] R9 is selected from F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0165] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0166] Alternatively, R6 and R1 can be connected together to form a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0167] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0168] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0169] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0170] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C.1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0171] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0172] Alternatively, R9 and the substituent R on X1 a They are linked together to form a 4-10 membered heterocyclic alkyl group, wherein the 4-10 membered heterocyclic alkyl group is optionally substituted with one or more R;

[0173] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0174] Or, R 10 With the substituent R on Z a Connected together, forming a C3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0175] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0176] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0177] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1- 6-alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0178] n is selected from 0, 1, 2 or 3.

[0179] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0180] In some embodiments of the present invention, R9 is selected from -CH3 or -CD3.

[0181] This invention provides compounds of formula (A-Ⅲ-1), formula (A-Ⅲ-1-A), or formula (A-Ⅲ-1-B), or pharmaceutically acceptable salts thereof.

[0182] in,

[0183] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0184] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0185] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0186] Selected from

[0187] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0188] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0189] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0190] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0191] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0192] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0193] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0194] R9 is selected from F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0195] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0196] Alternatively, R6 and R1 can be connected together to form a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0197] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0198] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0199] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0200] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0201] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0202] Alternatively, R9 and the substituent R on X1 a They are linked together to form a 4-10 membered heterocyclic alkyl group, wherein the 4-10 membered heterocyclic alkyl group is optionally substituted with one or more R;

[0203] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0204] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0205] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0206] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0207] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1- 6-alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0208] n is selected from 0, 1, 2 or 3.

[0209] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0210] In some embodiments of the present invention, R9 is selected from -CH3 or -CD3.

[0211] This invention provides compounds of formula (A-Ⅳ), formula (A-Ⅳ-A), formula (A-Ⅳ-B), formula (A-Ⅴ), formula (A-Ⅴ-A), formula (A-Ⅴ-B), or formula (A-Ⅵ), or pharmaceutically acceptable salts thereof.

[0212] in,

[0213] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0214] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0215] Z is selected from -C(R) a )2-、-C(R b )2- and -C(=R c )-;

[0216] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0217] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0218] Selected from

[0219] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0220] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0221] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0222] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0223] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0224] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0225] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0226] R9 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0227] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0228] Alternatively, R6 and R1 can be connected together to form a C5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0229] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0230] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0231] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0232] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0233] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0234] Alternatively, R9 and the substituent R on X1 a They are linked together to form a 4-10 membered heterocyclic alkyl group, wherein the 4-10 membered heterocyclic alkyl group is optionally substituted with one or more R;

[0235] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0236] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0237] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0238] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0239] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1- 6-alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0240] n is selected from 0, 1, 2 or 3.

[0241] In some embodiments of the present invention, R9 is selected from F, Cl, Br, I, OH, NH2, CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 The cycloalkyl or 3-10 membered heterocycloalkyl group may optionally be substituted with one or more R.

[0242] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0243] In some embodiments of the present invention, R9 is selected from -CH3 or -CD3.

[0244] In some embodiments of the present invention, the compound represented by formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof, wherein R9 and the substituent R on X1 a They are linked together to form a 4-10 membered heterocyclic alkyl group, wherein the 4-10 membered heterocyclic alkyl group is optionally substituted with one or more R;

[0245] In some embodiments of the present invention, R9 and X1 are substituents R a They are linked together to form a 4-membered, 5-membered, 6-membered, or 7-membered heterocyclic alkyl group, optionally substituted with one or more R groups.

[0246] This invention provides compounds of formula (A-VII), formula (A-VII-A), formula (A-IX), formula (A-IX-A), formula (A-X), or formula (A-X-A), or pharmaceutically acceptable salts thereof.

[0247] in,

[0248] T1 is selected from N and C(R6);

[0249] T2 is selected from N and C (R7);

[0250] T3 is selected from N and C(R8);

[0251] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0252] X2 is selected from empty, -O-, -S-, -N(R) a)-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0253] Z is selected from -C(R) a )2-、-C(R b )2- and -C(=R c )-;

[0254] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0255] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0256] Selected from

[0257] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0258] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0259] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0260] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0261] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0262] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0263] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0264] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0265] Alternatively, R6 and R1 can be connected together to form a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0266] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0267] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0268] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0269] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0270] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0271] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0272] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0273] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C1-6 Alkyl-OC(=O)-, C 1- 6-alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0274] n is selected from 0, 1, 2 or 3.

[0275] The present invention also provides a compound of formula (A-IX), formula (A-IX-A), formula (A-X) or formula (A-X-A) or a pharmaceutically acceptable salt thereof.

[0276] in,

[0277] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0278] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0279] Z is selected from -C(R) a )2-、-C(R b )2- and -C(=R c )-;

[0280] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0281] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0282] Selected from

[0283] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0284] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0285] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0286] Alternatively, R2 and R3 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0287] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0288] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0289] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0290] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0291] Alternatively, R6 and R1 can be connected together to form a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0292] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0293] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0294] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0295] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0296] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0297] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0298] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0299] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1- 6-alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0300] n is selected from 0, 1, 2 or 3.

[0301] In some embodiments of the present invention, R is selected from D.

[0302] The present invention also provides a compound of formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof.

[0303] in,

[0304] T1 is selected from N and C(R6);

[0305] T2 is selected from N and C (R7);

[0306] T3 is selected from N and C(R8);

[0307] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0308] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0309] Z is selected from -C(R) a )2-;

[0310] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0311] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0312] R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl-NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 Aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R1 is optionally substituted by one or more R;

[0313] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0314] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0315] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0316] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0317] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, Si(C 1-6 Alkyl)3, C 1-6 Alkyl, C 1- 6-alkoxy, C 1-6 Alkylthio, C1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 aryl and 5-10 heteroaryl groups, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamino substitution;

[0318] n is selected from 0, 1, 2 or 3.

[0319] In some embodiments of the present invention, the compound represented by formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from the compounds represented by formula (II-A) or formula (II-B), or pharmaceutically acceptable salts thereof.

[0320] in,

[0321] T1 is selected from N and C(R6);

[0322] T2 is selected from N and C (R7);

[0323] T3 is selected from N and C(R8);

[0324] X1 is selected from empty, -O-, -S-, -N(R) a)-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0325] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0326] Z is selected from -C(R) a )2;

[0327] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0328] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0329] R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl-NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 Aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R1 is optionally substituted by one or more R;

[0330] R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0331] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0332] R a Selected from H, C 1-6 Alkyl, C3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0333] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0334] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, Si(C) 1-6 Alkyl)3, C 1- 6-alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 aryl and 5-10 heteroaryl groups, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamino substitution;

[0335] n is selected from 0, 1, 2 or 3.

[0336] In some embodiments of the present invention, R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, Si(C 1-3 Alkyl)3, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C1-3 Alkyl-NH-S(=O)-, C 1-3 Alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-6 membered heteroaryl, C 3-6 Cycloalkyl-C(=O)-, 3-6 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10-membered heterocyclic alkenyl-C(=O)-, phenyl-C(=O)-, and 5-6-membered heteroaryl-C(=O)-, wherein R is optionally converted by one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-3 Alkoxy, C 1-3 alkylthio or C 1-3 Alkylamino substitution.

[0337] In some embodiments of the present invention, R is selected from D, F, Cl, Br, I, OH, NH2, CN, Si(CH3)3, methyl, ethyl, propyl, isopropyl, CD3,

[0338] In some embodiments of the present invention, R is selected from D, F, Cl, Br, I, OH, NH2, CN, methyl, ethyl, propyl, isopropyl,

[0339] In some embodiments of the present invention, when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)(=NH)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1-3 Alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 1-3 Alkyl-NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-10 membered heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 Aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted with one or more Rs.

[0340] In some embodiments of the present invention, when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)(=NH)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1-3 Alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 1-3 Alkyl-NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-10 membered heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0341] when Selected from When R1 is selected from C 1-3 Alkyl, C 3-6 Cycloalkyl, 4-6 membered heterocyclic alkyl, C 5-6 Cycloalkenyl, 5-6 membered heterocyclic alkenyl, C 3- 6-cyclic alkyl-CH2-, 4-6-membered heterocyclic alkyl-CH2-, C 5-6 Cycloalkenyl-CH2- and 5-6 membered heterocyclic alkenyl-CH2-.

[0342] In some embodiments of the present invention, when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, Methyl, ethyl, isopropyl, R1 may be arbitrarily replaced by one or more R;

[0343] when Selected from When, R1 is selected

[0344] In some embodiments of the present invention, when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, Methyl, ethyl, isopropyl, R1 may be replaced by one or more R.

[0345] In some embodiments of the present invention, when Selected from When R1 is selected from C 1-3 Alkyl, C 3-6 Cycloalkyl, 4-6 membered heterocyclic alkyl, C 5-6 Cycloalkenyl, 5-6 membered heterocyclic alkenyl, C 3-6 Cycloalkyl-CH2-, 4-6 membered heterocyclic alkyl-CH2-, C 5-6 Cycloalkenyl-CH2- and 5-6 membered heterocyclic alkenyl-CH2-.

[0346] In some embodiments of the present invention, when Selected from When, R1 is selected

[0347] In some embodiments of the present invention, R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)(=NH)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1-3 Alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 1-3 Alkyl-NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-10 membered heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 Aryl-CH2- and 5-10 heteroaryl-CH2-, wherein R1 is optionally substituted with one or more Rs.

[0348] In some embodiments of the present invention, R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, methyl, ethyl, isopropyl, R1 may be replaced by one or more R.

[0349] In some embodiments of the present invention, R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, methyl, ethyl, isopropyl, CD3, CF3,

[0350] In some embodiments of the present invention, R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, Methyl, ethyl, isopropyl, CD3, CF3

[0351] In some embodiments of the present invention, R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1-3 Alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-6 membered heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10Cycloalkenyl-O-, 5-10-membered heterocyclic alkenyl-O-, phenyl-O-, 5-6-membered heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10-membered heterocyclic alkenyl-S-, phenyl-S-, 5-6-membered heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, phenyl-NH-, 5-6 membered heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10-membered heterocyclic alkenyl-CH2-, phenyl-CH2-, 5-6-membered heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more Rs.

[0352] In some embodiments of the present invention, R2 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1- 3alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-6 membered heteroaryl, C 3-10Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10-membered heterocyclic alkenyl-O-, phenyl-O-, 5-6-membered heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10-membered heterocyclic alkenyl-S-, phenyl-S-, 5-6-membered heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, phenyl-NH-, 5-6 membered heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10-membered heterocyclic alkenyl-CH2-, phenyl-CH2-, 5-6-membered heteroaryl-CH2-, wherein R2 is optionally substituted with one or more Rs.

[0353] In some embodiments of the present invention, R3 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1- 3alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-6 membered heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10-membered heterocyclic alkenyl-O-, phenyl-O-, 5-6-membered heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 quinone / heterocyclic alkenyl-S-, phenyl-S-, 5-6 quinone heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, phenyl-NH-, 5-6 membered heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10-membered heterocyclic alkenyl-CH2-, phenyl-CH2-, 5-6-membered heteroaryl-CH2-, wherein R3 is optionally substituted with one or more Rs.

[0354] In some embodiments of the present invention, R4 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1- 3alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 3-10Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-6 membered heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10-membered heterocyclic alkenyl-O-, phenyl-O-, 5-6-membered heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10-membered heterocyclic alkenyl-S-, phenyl-S-, 5-6-membered heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, phenyl-NH-, 5-6 membered heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10-membered heterocyclic alkenyl-CH2-, phenyl-CH2-, 5-6-membered heteroaryl-CH2-, wherein R4 is optionally substituted with one or more Rs.

[0355] In some embodiments of the present invention, R5 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1-3 Alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1-3 Alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1- 3alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-6 membered heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10-membered heterocyclic alkenyl-O-, phenyl-O-, 5-6-membered heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10-membered heterocyclic alkenyl-S-, phenyl-S-, 5-6-membered heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, phenyl-NH-, 5-6 membered heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10-membered heterocyclic alkenyl-CH2-, phenyl-CH2-, 5-6-membered heteroaryl-CH2-, wherein R5 is optionally substituted with one or more Rs.

[0356] In some embodiments of the present invention, R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, ...

[0357] In some embodiments of the present invention, R2 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2,

[0358] In some embodiments of the present invention, R3 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2,

[0359] In some embodiments of the present invention, R3 is selected from H, D, F, and Cl.

[0360] In some embodiments of the present invention, R4 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2,

[0361] In some embodiments of the present invention, R4 is selected from H, D, F, and Cl.

[0362] In some embodiments of the present invention, R5 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2,

[0363] In some embodiments of the present invention, R5 is selected from H, D, F, and Cl.

[0364] In some embodiments of the present invention, R2 is derived from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, R3, R4, and R5 are each independently selected from H and F.

[0365] In some embodiments of the present invention, R6 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 Aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6 is optionally substituted by one or more Rs.

[0366] In some embodiments of the present invention, R6 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, wherein the alkanoylamino group is optionally substituted with one or more R groups.

[0367] In some embodiments of the present invention, R6 is selected from H, D, F, Cl, Br, I, OH, NH2 and CN.

[0368] In some embodiments of the present invention, R6 is selected from H.

[0369] In some embodiments of the present invention, R6 is selected from D.

[0370] In some embodiments of the present invention, R6 is selected from F.

[0371] In some embodiments of the present invention, R7 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 Aryl-CH2- or 5-10 heteroaryl-CH2-, wherein R7 is optionally substituted by one or more Rs.

[0372] In some embodiments of the present invention, R7 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, wherein the alkanoylamino group is optionally substituted with one or more R groups.

[0373] In some embodiments of the present invention, R7 is selected from H, D, F, Cl, Br, I, OH, NH2 and CN.

[0374] In some embodiments of the present invention, R7 is selected from H.

[0375] In some embodiments of the present invention, R7 is selected from D.

[0376] In some embodiments of the present invention, R7 is selected from F.

[0377] In some embodiments of the present invention, R8 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 Aryl-CH2-, 5-10 heteroaryl-CH2-, wherein the R8 is optionally substituted by one or more Rs.

[0378] In some embodiments of the present invention, R8 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, wherein the alkanoylamino group is optionally substituted with one or more R groups.

[0379] In some embodiments of the present invention, R8 is selected from H, D, F, Cl, Br, I, OH, NH2 and CN.

[0380] In some embodiments of the present invention, R8 is selected from H.

[0381] In some embodiments of the present invention, R8 is selected from D.

[0382] In some embodiments of the present invention, R8 is selected from F.

[0383] In some embodiments of the present invention, T1 is selected from C(R6).

[0384] In some embodiments of the present invention, T1 is selected from N.

[0385] In some embodiments of the present invention, T2 is selected from C(R7).

[0386] In some embodiments of the present invention, T2 is selected from N.

[0387] In some embodiments of the present invention, T3 is selected from C(R8).

[0388] In some embodiments of the present invention, T3 is selected from N.

[0389] In some embodiments of the present invention, T1 is selected from C(R6), T2 is selected from C(R7), and T3 is selected from C(R8).

[0390] In some embodiments of the present invention, T1 is selected from N, T2 is selected from C(R7), and T3 is selected from C(R8).

[0391] In some embodiments of the present invention, T1 is selected from C(R6), T2 is selected from N, and T3 is selected from C(R8).

[0392] In some embodiments of the present invention, T1 is selected from C(R6), T2 is selected from C(R7), and T3 is selected from N.

[0393] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CH, and T3 is selected from CH.

[0394] In some embodiments of the present invention, T1 is selected from CD, T2 is selected from CH, and T3 is selected from CH.

[0395] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CD, and T3 is selected from CH.

[0396] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CH, and T3 is selected from CD.

[0397] In some embodiments of the present invention, T1 is selected from CD, T2 is selected from CD, and T3 is selected from CH.

[0398] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CD, and T3 is selected from CD.

[0399] In some embodiments of the present invention, T1 is selected from CD, T2 is selected from CH, and T3 is selected from CD.

[0400] In some embodiments of the present invention, T1 is selected from CD, T2 is selected from CD, and T3 is selected from CD.

[0401] In some embodiments of the present invention, T1 is selected from CF, T2 is selected from CH, and T3 is selected from CH.

[0402] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CF, and T3 is selected from CH.

[0403] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CH, and T3 is selected from CF.

[0404] In some embodiments of the present invention, T1 is selected from CF, T2 is selected from CF, and T3 is selected from CH.

[0405] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CF, and T3 is selected from CF.

[0406] In some embodiments of the present invention, T1 is selected from CF, T2 is selected from CH, and T3 is selected from CF.

[0407] In some embodiments of the present invention, T1 is selected from N, T2 is selected from CH, and T3 is selected from CH.

[0408] In some embodiments of the present invention, T1 is selected from N, T2 is selected from CF, and T3 is selected from CH.

[0409] In some embodiments of the present invention, T1 is selected from N, T2 is selected from CH, and T3 is selected from CF.

[0410] In some embodiments of the present invention, T1 is selected from N, T2 is selected from CF, and T3 is selected from CF.

[0411] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from N, and T3 is selected from CH.

[0412] In some embodiments of the present invention, T1 is selected from CF, T2 is selected from N, and T3 is selected from CH.

[0413] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from N, and T3 is selected from CF.

[0414] In some embodiments of the present invention, T1 is selected from CF, T2 is selected from N, and T3 is selected from CF.

[0415] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CH, and T3 is selected from N.

[0416] In some embodiments of the present invention, T1 is selected from CF, T2 is selected from CH, and T3 is selected from N.

[0417] In some embodiments of the present invention, T1 is selected from CH, T2 is selected from CF, and T3 is selected from N.

[0418] In some embodiments of the present invention, T1 is selected from CF, T2 is selected from CF, and T3 is selected from N.

[0419] In some embodiments of the present invention, the R a Selected from H, C 1-3 Alkyl and C 3-6 cycloalkyl, the C 1-3 Alkyl groups may optionally be substituted with one or more R groups.

[0420] In some embodiments of the present invention, R8 is selected from H, D, and methyl.

[0421] In some embodiments of the present invention, R8 is selected from H.

[0422] In some embodiments of the present invention, R8 is selected from D.

[0423] In some embodiments of the present invention, R8 is selected from methyl.

[0424] In some embodiments of the present invention, R9 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, methyl, ethyl, isopropyl, cyclopropyl, CF3, CHF2, CH2F, CH2D, CD3,

[0425] In some embodiments of the present invention, R9 is selected from H, D, and methyl.

[0426] In some embodiments of the present invention, R9 is selected from H.

[0427] In some embodiments of the present invention, R9 is selected from D.

[0428] In some embodiments of the present invention, R9 is selected from methyl.

[0429] In some embodiments of the present invention, R8 is selected from H, and R9 is selected from H.

[0430] In some embodiments of the present invention, R8 is selected from D, and R9 is selected from H.

[0431] In some embodiments of the present invention, R8 is selected from H and R9 is selected from D.

[0432] In some embodiments of the present invention, R8 is selected from H and R9 is selected from methyl.

[0433] In some embodiments of the present invention, R8 is selected from methyl and R9 is selected from H.

[0434] In some embodiments of the present invention, the R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, methyl, ethyl, isopropyl, cyclopropyl, CF3, CHF2, CH2F, CH2D, CD3,

[0435] In some embodiments of the present invention, the R 10 Selected from H, D and methyl.

[0436] In some embodiments of the present invention, the R 10 Selected from H.

[0437] In some embodiments of the present invention, Ra is selected from H, methyl, -CD3, deuterated methyl, ethyl, propyl, isopropyl, cyclopropyl, ...

[0438] In some embodiments of the present invention, the R b Selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 Alkyl, C1-3 Alkoxy, C 1-3 alkylthio and C 1-3 Alkylamino, the R b It can be replaced by one or more R's.

[0439] In some embodiments of the present invention, the R b Selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, methyl, ethyl, propyl and isopropyl.

[0440] In some embodiments of the present invention, X1 is selected from -N(R) a X2 is selected from -C(=O)-.

[0441] In some embodiments of the present invention, X1 is selected from -N(CH3)- and X2 is selected from -C(=O)-.

[0442] In some embodiments of the present invention, the -X1-X2- is selected from -O-, -S-, -NH-, -N(CH3)-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -CH2-, -CH2CH2-, -C(=O)-O-, -C(=O)-NH-, -C(=O)-N(CH3)-, -C(=O)-CH2-, -S(=O)-O-, -S(=O)-NH-, -S( =O)-N(CH3)-, -S(=O)-CH2-, -S(=O)2-O-, -S(=O)2-NH-, -S(=O)2-N(CH3)-, -S(=O)2-CH2-, -O-CH2 -, -O-CH2CH2-, -S-CH2-, -S-CH2CH2-, -NH-CH2-, -NH-CH2CH2-, -N(CH3)-CH2-, -N(CH3)-CH2CH2-.

[0443] In some embodiments of the present invention, -X1-X2- is selected from...

[0444] In some embodiments of the present invention, -X1-X2- is selected from...

[0445] In some embodiments of the present invention, -X1-X2- is selected from...

[0446] In some embodiments of the present invention, Z is selected from -CH2-, -CHF-, -CF2-, -CH(CH3)-, -C(CH3)2- and -C(=CH2)-.

[0447] In some embodiments of the present invention, Z is selected from -CH2-.

[0448] In some embodiments of the present invention, the ring A is selected from furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazoleyl, oxazolyl, pyridyl, pyranoneyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, 2,3-dihydrofuran[3,2-b]pyridyl, 6,7-dihydro-5H-cyclopentan[b]pyridyl, 1H-pyrazolo[3,4-b]pyridyl, 3H-imidazo[4,5-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, 1,2,3,4-tetrahydro-1,8-naphthylpyridyl, 3,4-dihydro-2H-pyrido[3,2]pyridyl, 2,3,4-tetrahydro-1,8-naphthylpyridyl, 3,4-dihydro-2H-pyrido[3,2]pyridyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, 1,2,3,4-tetrahydro-1,8-naphthylpyridyl, 3,4-dihydro-2H-pyrido[3,2]pyridyl, 2,3 ... -b][1,4]oxazinyl, 3,4-dihydro-2H-pyrazino[2,3-b][1,4]oxazinyl, pyrazolo[1,5-a]pyrimidinyl, pyrrolo[2,1-f][1,2,4]triazinyl, 3H-[1,2,3]triazolo[4,5-b]pyridinyl, thiazo[5,4-b]pyridinyl, pyrrolo[1,2-a][1,3,5]triazinyl, 7H-pyrrolo[2,3-c]pyridazinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, 3,4-dihydro-2H-pyrano[3,2-b]pyridinyl, aziridine, pyrrolidinyl 2,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazolyl, spiro[3,3]heptyl, cyclopentyl, bicyclo[3,1,0]hexyl, 5a,6,7,7a-tetrahydrocyclobutane[4,5]furano[3,2-b]pyridyl, 5a,7,8,8a-tetrahydro-6H-cyclopentane[4,5]furano[3,2-b]pyridyl, 5a,6a-dihydro-6H-cyclopropane[4,5]furano[3,2-b]pyridyl, 5,5a,6,7,8,8a-hexahydropentene[1,2-b]pyridyl, 4b,5,5a,6-tetrahydrocyclopropane[3,4]cyclopentane[1,2-b]pyridyl, 5a,6,7,7a-tetrahydro-5H-cyclobutane[4, 5] Cyclopenta[1,2-b]pyridyl, 6a,7,8,8a-tetrahydro-6H-cyclobutane[4,5]pyrano[3,2-b]pyridyl, 2',3'-dihydrospiro[azacyclobutane-2,4'-pyrano[3,2-b]pyridyl]yl, 2',3'-dihydrospiro[aziridin-2,4'-pyrano[3,2-b]pyridyl]yl, 7,8-dihydro-6H-pyrano[2,3-b]pyrazinyl, 3,4-dihydro-2H-2,4-methanepyrano[3,2-b]pyridyl, 6,7-dihydro-5H-cyclopenta[b]pyrazinyl, 6,7-dihydro-5H-cyclopenta[c]pyridazinyl, phenyl, thiazolyl, isothiazolyl, isoxazolyl, 3-azabicyclo[4.2].[0] Octane-1(6),2,4-trienyl, 6,7-dihydro-5H-cyclopentan[c]pyridyl, 1,3-dihydrofuran[3,4-c]pyridyl, 2,3-dihydrofuran[2,3-c]pyridyl, nitropyridyl, nitropyridazinyl, nitropyrimidinyl, and nitropyrazinyl.

[0449] In some embodiments of the present invention, ring A is selected from furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazoleyl, oxazolyl, pyridyl, pyranoneyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, 2,3-dihydrofuran[3,2-b]pyridyl, 6,7-dihydro-5H-cyclopenta[b]pyridyl, 1H-pyrazolo[3,4-b]pyridyl, 3H-imidazo[4,5-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, 1,2,3,4-tetrahydro-1,8-naphthyridyl, 3,4-dihydro-2H- Pyrido[3,2-b][1,4]oxazinyl, 3,4-dihydro-2H-pyrazino[2,3-b][1,4]oxazinyl, pyrazolo[1,5-a]pyrimidinyl, pyrrolo[2,1-f][1,2,4]triazinyl, 3H-[1,2,3]triazolo[4,5-b]pyridinyl, thiazo[5,4-b]pyridinyl, pyrrolo[1,2-a][1,3,5]triazinyl, 7H-pyrrolo[2,3-c]pyridazinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, 3,4-dihydro-2H-pyrano[3,2-b] Pyridyl, aziridine, pyrrolidinyl, 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazolyl, spiro[3,3]heptyl, cyclopentyl, bicyclo[3,1,0]hexyl, 5a,6,7,7a-tetrahydrocyclobutane[4,5]furano[3,2-b]pyridyl, 5a,7,8,8a-tetrahydro-6H-cyclopentan[4,5]furano[3,2-b]pyridyl, 5a,6a-dihydro-6H-cyclopropane[4,5]furano[3,2-b]pyridyl, 5,5a,6,7,8,8a-hexahydropenten[1,2-b]pyridyl, 4b,5,5a,6-tetrahydrocyclopropane[3,4]cyclopentan[1,2-b]pyridyl, 5 a,6,7,7a-tetrahydro-5H-cyclobutane[4,5]cyclopentan[1,2-b]pyridyl, 6a,7,8,8a-tetrahydro-6H-cyclobutane[4,5]pyrano[3,2-b]pyridyl, 2',3'-dihydrospiro[azacyclobutane-2,4'-pyrano[3,2-b]pyridyl], 2',3'-dihydrospiro[aziridinium-2,4'-pyrano[3,2-b]pyridyl], 7,8-dihydro-6H-pyrano[2,3-b]pyrazinyl, 3,4-dihydro-2H-2,4-methanepyrano[3,2-b]pyridyl, 6,7-dihydro-5H-cyclopentan[b]pyrazinyl, 6,7-dihydro-5H-cyclopentan[c]pyridazinyl.

[0450] In some embodiments of the present invention, ring A is selected from furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazoleyl, oxazolyl, pyridyl, pyranoneyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, 2,3-dihydrofuran[3,2-b]pyridyl, 6,7-dihydro-5H-cyclopentan[b]pyridyl, 1H-pyrazolo[3,4-b]pyridyl, 3H-imidazo[4]pyridyl, etc. [5-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, 1,2,3,4-tetrahydro-1,8-naphthyridyl, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 3,4-Dihydro-2H-pyrazino[2,3-b][1,4]oxazinyl, pyrazolo[1,5-a]pyrimidinyl, pyrrolo[2,1-f][1,2,4]triazinyl, 3H-[1,2,3]triazolo[4,5-b]pyridinyl, thiazo[5,4-b]pyridinyl, pyrrolo[1,2-a][1,3,5]triazinyl, 7H-pyrazino The compounds are pyrrolo[2,3-c]pyridazinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, 3,4-dihydro-2H-pyrano[3,2-b]pyridinyl, aziridine, pyrrolidinyl, and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazolyl.

[0451] In some embodiments of the present invention, the structural unit Selected from

[0452] In some embodiments of the present invention, the structural unit Selected from

[0453] In some embodiments of the present invention, the structural unit Selected from

[0454] In some embodiments of the present invention, the ring L1 is selected from empty,

[0455] In some embodiments of the present invention, the structural unit Selected from

[0456] In some embodiments of the present invention, the structural unit Selected from

[0457] In some embodiments of the present invention, the structural unit Selected from

[0458] In some embodiments of the present invention, R2 and R3 are connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocyclic alkyl groups may optionally be substituted with one or more R groups.

[0459] This invention provides compounds of formula (A-XI), formula (A-XI-A), or formula (A-XI-B), or pharmaceutically acceptable salts thereof.

[0460] in,

[0461] T1 is selected from N and C(R6);

[0462] T2 is selected from N and C (R7);

[0463] T3 is selected from N and C(R8);

[0464] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0465] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(Rb )2- and -C(R b )2C(R b )2-;

[0466] Z is selected from -C(R) a )2-、-C(R b )2- and -C(=R c )-;

[0467] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0468] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0469] Selected from

[0470] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10 Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0471] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0472] R4 and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0473] Ring B is C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocyclic alkyl groups may optionally be substituted with one or more R groups.

[0474] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0475] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0476] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0477] R9 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0478] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0479] Alternatively, R6 and R1 can be connected together to form a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0480] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0481] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0482] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein R a It can be replaced by one or more R's;

[0483] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0484] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0485] Alternatively, R9 and the substituent R on X1 a They are linked together to form a 4-10 membered heterocyclic alkyl group, wherein the 4-10 membered heterocyclic alkyl group is optionally substituted with one or more R;

[0486] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0487] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0488] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0489] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0490] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1- 6-alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0491] n is selected from 0, 1, 2 or 3.

[0492] In some embodiments of the present invention, R9 is selected from F, Cl, Br, I, OH, NH2, CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 The cycloalkyl or 3-10 membered heterocycloalkyl group may optionally be substituted with one or more R.

[0493] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0494] This invention provides compounds of formula (A-XI-1), formula (A-XI-1-A), or formula (A-XI-1-B), or pharmaceutically acceptable salts thereof.

[0495] in,

[0496] X1 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(Rb )2-;

[0497] X2 is selected from empty, -O-, -S-, -N(R) a )-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, -C(R b )2- and -C(R b )2C(R b )2-;

[0498] L1 is selected from empty, -O-, -S-, -N(R) a )-、C 2-6 Olefins, C 2-6 Alkynes, C 1-6 Alkylene, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 4-10 heteroaryl groups;

[0499] Ring A is selected from C 3-15 Cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 Cycloalkenyl, 5-15 membered heterocyclic alkenyl, C 6-15 Aryl and 5-15 quinone heteroaryl groups;

[0500] Selected from

[0501] when Selected from When R1 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 1-6 Alkyl NH-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, C 3-10 Cycloalkyl-O-CH2-, 3-10 membered heterocyclic alkyl-O-CH2-, C 5-10 Cycloalkenyl-O-CH2-, 5-10 membered heterocyclic alkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 heteroaryl-O-CH2-, C 3-10 Cycloalkyl-S-CH2-, 3-10 membered heterocyclic alkyl-S-CH2-, C 5-10 Cycloalkenyl-S-CH2-, 5-10 membered heterocyclic alkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 heteroaryl-S-CH2-, C 3-10 Cycloalkyl-NH-CH2-, 3-10 membered heterocyclic alkyl-NH-CH2-, C 5-10Cycloalkenyl-NH-CH2-, 5-10 membered heterocyclic alkenyl-NH-CH2-, C 6-10 aryl-NH-CH2- and 5-10 heteroaryl-NH-CH2-, wherein R1 is optionally substituted by one or more R;

[0502] when Selected from When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R;

[0503] R4 and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R2, R3, R4, and R5 are optionally substituted by one or more R;

[0504] Ring B is C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocyclic alkyl groups may optionally be substituted with one or more R groups.

[0505] Alternatively, R3 and R4 can be connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0506] Alternatively, R4 and R5 can be connected together to form a C. 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0507] R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 heteroaryl-CH2-, wherein R6, R7, and R8 are optionally substituted by one or more R;

[0508] R9 is selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 Alkylamino, C3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0509] R 10 Selected from H, D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl or 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0510] Alternatively, R6 and R1 can be connected together to form a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0511] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0512] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-10 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0513] R a Selected from H, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, wherein Ra It can be replaced by one or more R's;

[0514] R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's;

[0515] R c Selected from O, S, CH2, CH-C 1-6 Alkyl, C(C) 1-6 Alkyl)2, the C 1-6 Alkyl groups may be substituted with one or more R groups;

[0516] Alternatively, R9 and the substituent R on X1 a They are linked together to form a 4-10 membered heterocyclic alkyl group, wherein the 4-10 membered heterocyclic alkyl group is optionally substituted with one or more R;

[0517] Alternatively, R9 with the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0518] Or, R 10 With the substituent R on Z a Connected together, forming a C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0519] Or, R9 and R 10 Connected together, forming a C 4-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 4-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0520] Alternatively, the two substituents R on Z a Connected together, forming a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R;

[0521] R is selected from D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1- 6-alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)(=NH)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-C(=O)-, 3-10 membered heterocycloalkyl-C(=O)-, C 5-10 Cycloalkenyl-C(=O)-, 5-10 membered heterocyclic alkenyl-C(=O)-, C 6-10 aryl-C(=O)- and 5-10 heteroaryl-C(=O)-, wherein the R is optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino or (C 1-6 Alkyl)2-amino substitution;

[0522] n is selected from 0, 1, 2 or 3.

[0523] In some embodiments of the present invention, R9 is selected from F, Cl, Br, I, OH, NH2, CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-10 The cycloalkyl or 3-10 membered heterocycloalkyl group may optionally be substituted with one or more R.

[0524] In some embodiments of the present invention, R9 is selected from C. 1-6 Alkyl groups may optionally be substituted with one or more R groups.

[0525] In some embodiments of the present invention, R2 and R3 are connected together to form

[0526] Alternatively, R3 and R4 can be connected together to form...

[0527] Alternatively, R4 and R5 can be connected together to form...

[0528] In some embodiments of the present invention, R2 and R3 are connected together to form

[0529] In some embodiments of the present invention, R3 and R4 are connected together to form

[0530] In some embodiments of the present invention, R4 and R5 are connected together to form

[0531] In some embodiments of the present invention, R6 and R1 are connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0532] Or, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0533] Or, R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocycloalkyl groups may optionally be substituted with one or more R;

[0534] Alternatively, R9 and the substituent R on X1 a They are linked together to form a 4-7 membered heterocyclic alkyl group, which may optionally be substituted with one or more R groups.

[0535] In some embodiments of the present invention, R6 and R1 are connected together to form a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocyclic alkyl groups may optionally be substituted with one or more R groups.

[0536] In some embodiments of the present invention, R6 and R 10 Connected together, forming a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7 Cycloalkyl and 5-7 membered heterocyclic alkyl groups may optionally be substituted with one or more R groups.

[0537] In some embodiments of the present invention, the R 10 Connected together with R2, forming a C 5-7 Cycloalkyl or 5-7 membered heterocycloalkyl, wherein C 5-7Cycloalkyl and 5-7 membered heterocyclic alkyl groups may optionally be substituted with one or more R groups.

[0538] In some embodiments of the present invention, the substituent R on R9 and X1 a They are linked together to form a 4-7 membered heterocyclic alkyl group, which may optionally be substituted with one or more R groups.

[0539] In some embodiments of the present invention, any substituent on Z is connected to any substituent on X1 to form a C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl, wherein C 3-10 Cycloalkyl and 4-10 membered heterocyclic alkyl groups may optionally be substituted with one or more R groups.

[0540] In some embodiments of the present invention, R6 is connected to R1 to form oxetyl, oxetylhexyl, azityl, azitylhexyl, oxetylheptyl or azitylheptyl, wherein the oxetyl, oxetyl, azityl, azityl, oxetylheptyl and azitylheptyl are optionally substituted by one or more R;

[0541] Or, R6 and R 10 They are linked together to form oxetyl, oxetylhexyl, azityl, azitylhexyl, oxetylheptyl or azitylheptyl, wherein the oxetyl, oxetyl, azityl, azitylhexyl, oxetylheptyl and azitylheptyl are optionally substituted with one or more R;

[0542] Or, R 10 When connected with R2, it forms an oxecyclopentyl, oxecyclohexyl, azicyclopentyl, azicyclohexyl, oxecycloheptyl, or azicycloheptyl, wherein the oxecyclopentyl, oxecyclohexyl, azicyclopentyl, azicyclohexyl, oxecycloheptyl, and azicycloheptyl are optionally substituted by one or more Rs.

[0543] Alternatively, R9 and the substituent R on X1 a They are linked together to form azircyclobutyl, azircyclopentyl, azircyclohexyl, or azircycloheptyl, wherein the azircyclobutyl, azircyclopentyl, azircyclohexyl, and azircycloheptyl may optionally be substituted with one or more R.

[0544] In some embodiments of the present invention, R6 is connected to R1 to form oxacyclopentyl, oxacyclohexyl, azicyclopentyl, azicyclohexyl, oxacycloheptyl, or azicycloheptyl, wherein the oxacyclopentyl, oxacyclohexyl, azicyclopentyl, azicyclohexyl, oxacycloheptyl, and azicycloheptyl are optionally substituted by one or more R.

[0545] In some embodiments of the present invention, R6 and R 10 They are linked together to form oxetyl, oxetylhexyl, aziretyl, aziretyl, oxetylheptyl, or aziretyl, wherein the oxetyl, oxetyl, aziretyl, aziretyl, oxetylheptyl, and aziretyl are optionally substituted with one or more R.

[0546] In some embodiments of the present invention, the R 10 When connected with R2, it forms an oxecyclopentyl, oxecyclohexyl, azicyclopentyl, azicyclohexyl, oxecycloheptyl, or azicycloheptyl, wherein the oxecyclopentyl, oxecyclohexyl, azicyclopentyl, azicyclohexyl, oxecycloheptyl, and azicycloheptyl are optionally substituted with one or more Rs.

[0547] In some embodiments of the present invention, the substituent R on R9 and X1 a They are linked together to form azircyclobutyl, azircyclopentyl, azircyclohexyl, or azircycloheptyl, wherein the azircyclobutyl, azircyclopentyl, azircyclohexyl, and azircycloheptyl may optionally be substituted with one or more R.

[0548] In some embodiments of the present invention, any substituent on Z is connected to any substituent on X1, namely, azircyclobutyl, azircyclopentyl, azircyclohexyl, or azircycloheptyl, wherein the azircyclobutyl, azircyclopentyl, azircyclohexyl, and azircycloheptyl are optionally substituted by one or more R.

[0549] In some embodiments of the present invention, R9 and the substituent R on Z are... a They connect together to form a cyclopropyl group.

[0550] In some embodiments of the present invention, the R 10 With the substituent R on Z a They connect together to form a cyclopropyl group.

[0551] In some embodiments of the present invention, R9 and R 10 They connect together to form a cyclopentyl or cyclohexyl group.

[0552] In some embodiments of the present invention, the two substituents R on Z a They connect together to form a cyclopropyl group.

[0553] In one aspect of the present invention, the compound represented by formula (I) is selected from any of the following compounds.

[0554] In one aspect of the present invention, the compound represented by formula (I) is selected from any of the following compounds.

[0555] On the other hand, the present invention also provides pharmaceutical compositions comprising the above-described compounds, their stereoisomers, or pharmaceutically acceptable salts thereof.

[0556] On the other hand, the present invention also provides the use of the above-described compounds, their stereoisomers or pharmaceutically acceptable salts thereof, or the above-described pharmaceutical compositions in the preparation of medicaments for treating diseases related to TNFα.

[0557] In one embodiment of the present invention, the TNFα-related diseases are selected from anti-inflammatory disorders or autoimmune disorders, neurological disorders or neurodegenerative disorders, pain or nociceptive disorders, cardiovascular disorders, metabolic disorders, eye disorders or oncological disorders.

[0558] In one aspect of the present invention, the TNFα-related diseases are preferably selected from rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, psoriasis, Crohn's disease, ulcerative colitis, psoriasis, spondyloarthritis, plaque psoriasis, septic shock, ankylosing spondylitis, juvenile idiopathic arthritis, hidradenitis suppurativa, uveitis, systemic lupus erythematosus (lupus), axial spondyloarthritis, polymyositis, pemphigus, multiple sclerosis, neuromyelitis optica, primary cholangitis, autoimmune hepatitis, lupus nephritis, pulmonary hemorrhage-nephritis syndrome, autoimmune oophoritis, or autoimmune orchitis.

[0559] definition

[0560] Unless otherwise stated, the following terms as used in this application shall have the following meanings. A particular term should not be considered uncertain or unclear unless specifically defined, but should be understood in accordance with its ordinary meaning in the art. When a trade name appears herein, it is intended to refer to the corresponding product or its active ingredient.

[0561] The term “pharmaceutically acceptable” as used herein refers to compounds, materials, compositions, and / or dosage forms that, within the bounds of reliable medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0562] The term "pharmaceutically acceptable salt" refers to a salt of the compounds of this invention, prepared by reacting a compound having specific substituents discovered in this invention with a relatively non-toxic acid or base. When the compounds of this invention contain relatively acidic functional groups, base addition salts can be obtained by contacting a neutral form of such compound with a sufficient amount of base in a pure solution or a suitable inert solvent. Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amines, magnesium salts, or similar salts. When the compounds of this invention contain relatively basic functional groups, acid addition salts can be obtained by contacting a neutral form of such compound with a sufficient amount of acid in a solution or a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include inorganic acid salts, such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, bicarbonate, phosphoric acid, monohydrogen phosphate, dihydrogen phosphate, sulfuric acid, hydrogen sulfate, hydroiodic acid, phosphorous acid, etc.; and organic acid salts, such as acetic acid, propionic acid, isobutyric acid, trifluoroacetic acid, maleic acid, malonic acid, benzoic acid, succinic acid, octanoic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, tartaric acid, and methanesulfonic acid; as well as salts of amino acids (such as arginine) and salts of organic acids such as glucuronic acid. Certain specific compounds of the present invention contain both basic and acidic functional groups, and thus can be converted into either a base or an acid addition salt.

[0563] The pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing acid radicals or bases by conventional chemical methods. Generally, such salts are prepared by reacting these compounds in free acid or base form with a stoichiometric amount of a suitable base or acid in water or an organic solvent or a mixture thereof.

[0564] "Pharmaceutical composition" means a mixture containing one or more of the compounds described herein or their pharmaceutically acceptable salts, along with other chemical components, such as pharmaceutically 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 its biological activity.

[0565] The term "substitution" refers to the substitution of one or more hydrogen atoms on a specific atom by a substituent, provided that the valence state of the specific atom is normal and the resulting compound is stable. When the substituent is oxo (i.e., =O), it means that two hydrogen atoms are substituted; oxo substitution does not occur on aromatic groups.

[0566] The terms “optional” or “optionally” mean that the event or condition subsequently described may or may not occur, including both the occurrence and non-occurrence of said event or condition. For example, the ethyl group “optionally” being halogenated means that the ethyl group can be unsubstituted (CH2CH3), monosubstituted (e.g., CH2CH2F), polysubstituted (e.g., CHFCH2F, CH2CHF2, etc.), or fully substituted (CF2CF3). Those skilled in the art will understand that for any group containing one or more substituents, no substitution or substitution pattern that is spatially impossible and / or cannot be synthesized is introduced.

[0567] In this document, "one or more" refers to an integer from one to ten. For example, "one or more" means one, two, three, four, five, six, seven, eight, nine, or ten; or, "one or more" means one, two, three, four, five, or six; or, "one or more" means one, two, or three. Those skilled in the art will understand that for any group containing one or more substituents, no substitution or substitution pattern that is spatially impossible and / or cannot be synthesized is introduced.

[0568] C in this article m-n This means that the part has an integer number of carbon atoms within a given range. For example, "C 1-6 "" means that the group can have 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms.

[0569] When any variable (e.g., R) appears more than once in the composition or structure of a compound, its definition is independent in each case. Therefore, for example, if a group is substituted by two Rs, each R has an independent option.

[0570] The term "alkyl" refers to a compound with the general formula C1. n H 2n+1 The alkyl group. This alkyl group can be straight-chain or branched. For example, the term "C 1-6 "Alkyl" refers to an alkyl group containing 1 to 6 carbon atoms (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neopentyl, hexyl, 2-methylpentyl, etc.). Similarly, the alkyl portion (i.e., alkyl) of alkoxy, alkylamino, dialkylamino, alkylsulfonyl, and alkylthio groups has the same definition as above.

[0571] The term "alkylene" refers to a compound with the general formula C1. n H 2n The divalent hydrocarbon group. For example, the term "C 1-6"Alkylene" refers to an alkylene containing 1 to 6 carbon atoms. Non-limiting examples of alkylene include, but are not limited to, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2- or -CH2CH(CH3)-), butylene (-CH2CH2CH2CH2-, -CH2CH(CH3)CH2- or -CH2CH2CH(CH3)-), pentylene, hexylene, etc.

[0572] The term "alkoxy" refers to alkyl-O-.

[0573] The term "alkylamino" refers to alkyl-NH-.

[0574] The term "alkylthio" refers to alkyl-S-.

[0575] The term "cycloalkyl" refers to a fully saturated carbon ring that can exist as a monocyclic, fused, bridged, or spirocyclic ring. Unless otherwise indicated, the carbon ring is typically a 3- to 10-membered ring; preferably a 3- to 6-membered ring. Non-limiting examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl (bicyclo[2.2.1]heptyl), bicyclo[2.2.2]octyl, adamantyl, decahydronaphthyl, etc.

[0576] The term "heterocyclic alkyl" refers to a fully saturated cyclic group that may exist as a monocyclic, bridged, or spirocyclic ring. Unless otherwise indicated, the heterocycle is typically a 3- to 8-membered ring containing 1 to 3 heteroatoms (preferably 1 or 2 heteroatoms) independently selected from sulfur, oxygen, silicon, phosphorus, boron, and / or nitrogen. Examples of 3-membered heterocyclic alkyl groups include, but are not limited to, ethylene oxide, cyclothioethylene, and cycloazoethylene; non-limiting examples of 4-membered heterocyclic alkyl groups include, but are not limited to, acridine, oxadiazolyl, thiobutyl, and silanidine; examples of 5-membered heterocyclic alkyl groups include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, imidazolyl, tetrahydropyrazolyl, and silanolyl; examples of 6-membered heterocyclic alkyl groups include, but are not limited to, piperidinyl, tetrahydropyranyl, tetrahydrothiaranyl, morpholinyl, piperazine, 1,4-thiaoxane, 1,4-dioxane, thiomorpholinyl, 1,3-dithiaalkyl, and 1,4-dithiaalkyl; and examples of 7-membered heterocyclic alkyl groups include, but are not limited to, azirheptanyl, oxeheptanyl, and thioheptanyl. Monocyclic heterocyclic alkyl groups having 4 or 6 ring atoms are preferred.

[0577] The term "heterocyclic alkenyl" includes cycloalkenyl groups in which one or more carbon atoms are replaced by heteroatoms, specifically, for example, cycloalkenyl groups in which up to three carbon atoms, in one embodiment up to two carbon atoms, or in another embodiment one carbon atom is independently replaced by O, S, or N, provided that at least one cycloalkenyl carbon-carbon double bond is retained. Cyclic groups can exist as monocyclic, bridged, or spirocyclic rings, and can be 3 to 12-membered rings (e.g., 5-, 6-, or 7-membered rings). Examples of heterocyclic alkenyl groups include, but are not limited to, dihydropyrroleyl, dihydrofuranyl, tetrahydropyridyl, tetrahydroazayl, or azaspirooctene.

[0578] The term "aryl" refers to a monocyclic all-carbon aromatic ring (i.e., monocyclic aryl) or a polycyclic aromatic ring system (i.e., polycyclic aryl) having a conjugated π-electron system, having 6 to 20 (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., 6 to 20-membered aryl). The aryl group is preferably an aryl group having 6 to 14 ring atoms (i.e., 6 to 14-membered aryl) or an aryl group having 6 to 10 ring atoms (i.e., 6 to 10-membered aryl). Monocyclic aryl groups include, for example, phenyl. Non-limiting examples of polycyclic aryl groups include naphthyl, anthracene, phenanthryl, etc. The polycyclic aryl group further includes fusion of a phenyl group with one or more of a heterocyclic group, a cycloalkyl group, a heterocyclic alkenyl group, or a cycloalkenyl group, or fusion of a naphthyl group with one or more of a heterocyclic group, a cycloalkyl group, a heterocyclic alkenyl group, or a cycloalkenyl group, and in this case, the number of ring atoms continues to represent the number of ring atoms in the polycyclic aromatic ring system, wherein the connection point can be at any site of the fused ring, and non-limiting examples include: wait.

[0579] The term "heteroaryl" refers to a monocyclic heteroaryl ring (i.e., monocyclic heteroaryl) or a polycyclic heteroaryl ring system (i.e., polycyclic heteroaryl) having a conjugated π-electron system, wherein the ring contains at least one (e.g., 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, and sulfur (the nitrogen may optionally be oxidized, i.e., to form nitrogen oxides; the sulfur may optionally be oxidized, i.e., to form sulfoxides or sulfones, but excluding -OO-, -OS-, or -SS-), having 5 to 14 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) ring atoms (i.e., 5 to 14-membered heteroaryl). The heteroaryl is preferably a heteroaryl having 5 to 10 ring atoms (i.e., 5 to 10-membered heteroaryl), more preferably a heteroaryl having 5 or 6 ring atoms (i.e., 5 or 6-membered heteroaryl).

[0580] Non-limiting examples of the monocyclic heteroaryl groups include: furanyl, thiopheneyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, imidazoleyl, pyrazolyl, triazolyl, tetrazolyl, furazolyl, pyrroleyl, N-alkylpyrroleyl, pyridyl, pyrimidinyl, pyridoneyl, N-alkylpyridoneyl, pyrazinyl, pyridazinyl, etc.

[0581] Non-limiting examples of the aforementioned polycyclic heteroaryl groups include: indolyl, indazole, quinolinyl, isoquinolinyl, quinoxalinyl, phthalazinyl, benzimidazolyl, benzothiophene, quinazolinyl, benzothiazolyl, carbazole, etc. The polycyclic heteroaryl groups also include monocyclic heteroaryl groups fused with one or more aryl groups, wherein the bonding site is on the aromatic ring, and in this case, the number of ring atoms continues to represent the number of ring atoms in the polycyclic heteroaryl ring system. The polycyclic heteroaryl groups also include monocyclic heteroaryl groups fused with one or more of heterocyclic groups, cycloalkyl groups, heterocyclic alkenyl groups, or cycloalkenyl groups, and in this case, the number of ring atoms continues to represent the number of ring atoms in the polycyclic heteroaryl ring system. Non-limiting examples include: wait.

[0582] The compounds disclosed in this application can exist in specific stereoisomer forms. The term "stereoisomer" refers to isomers with the same structure but different spatial arrangements of atoms. These include cis and trans (or Z and E) isomers, (-)- and (+)- isomers, (R)- and (S)- enantiomers, diastereomers, (D)- and (L)- isomers, tautomers, transisomers, conformational isomers, and mixtures thereof (such as racemic mixtures and mixtures of diastereomers). Substituents in the compounds disclosed in this application may contain additional asymmetric atoms. All such stereoisomers and mixtures thereof are included within the scope of this application. Optically active (-)- and (+)- isomers, (R)- and (S)- enantiomers, and (D)- and (L)- isomers can be prepared by chiral synthesis, chiral reagents, or other conventional techniques. This application discloses an isomer of a compound, which can be prepared by asymmetric synthesis or with chiral auxiliaries. Alternatively, when the molecule contains a basic functional group (such as an amino group) or an acidic functional group (such as a carboxyl group), it can form a salt of the diastereomer with a suitable optically active acid or base, and then the diastereomer can be resolved by conventional methods known in the art to obtain the pure isomer. Furthermore, the separation of enantiomers and diastereomers is usually accomplished by chromatography.

[0583] In the chemical structure of the compounds described in this disclosure, the bonds... This indicates that the configuration is not specified; that is, if chiral isomers exist in the chemical structure, the bond... It can be Or simultaneously include Two configurations. For all carbon-carbon double bonds, even if only one configuration is named, both the Z-type and E-type are included.

[0584] The compounds disclosed in this application may exist in different tautomer forms, and all such forms are included within the scope of this disclosure. The terms "tautomer" or "tautomer form" refer to a structural isomer that exists in equilibrium and readily transforms from one isomer to another. This includes all possible tautomers, i.e., existing as a single isomer or as a mixture of said tautomers in any proportion. Non-limiting examples include: keto-enols, imine-enamines, lactam-lactamimides, etc. Examples of lactam-lactamimide equilibrium are shown below:

[0585] All tautomers are disclosed within the scope of this application, and the naming of compounds does not exclude any tautomers.

[0586] When one of the variables is selected as empty, it indicates that the two groups it connects to are directly connected, for example... In the middle, L represents spacetime, indicating that the structure is actually

[0587] When the listed linking groups do not specify their linking direction, the linking direction is arbitrary, for example... The connecting group L is -C(=O)-NH-. In this case, -C(=O)-NH- can be connected to cyclohexane and cyclopentane in the same direction as the reading order from left to right to form a compound. Alternatively, cyclohexane and cyclopentane can be connected in the reverse order of reading from left to right to form the compound. The combination of linking groups, substituents, and / or their variants is permitted only if such a combination produces a stable compound.

[0588] The compounds disclosed in this application include all suitable isotopic derivatives thereof. The term "isotopic derivative" refers to a compound in which at least one atom is replaced by an atom having the same atomic number but a different atomic mass. Examples of isotopes that can be introduced into the compounds disclosed in this application include stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine, for example, […]. 2 H (deuterium, D) 3 H (tritium, T) 11 C 13 C 14 C 15 N、 17 O、 18 O、 32 p、 33 p、 33S, 34 S, 35 S, 36 S, 18 F, 36 Cl、 82 Br、 123 I, 124 I, 125 I, 129 I and 131 Grade I, with deuterium as the preferred grade.

[0589] Compared to undeuterated drugs, deuterated drugs offer advantages such as reduced toxicity, increased drug stability, enhanced efficacy, and prolonged biological half-life. All isotopic variations of the compounds disclosed herein, regardless of radioactivity, are included within the scope of this disclosure. Each available hydrogen atom bonded to a carbon atom can be independently replaced by a deuterium atom, wherein the deuterium substitution can be partial or complete; partial deuterium substitution refers to the replacement of at least one hydrogen atom with at least one deuterium atom.

[0590] When a position is specifically designated as deuterium (D), the position should be understood as having a deuterium abundance of at least 1,000 times greater than the natural abundance of deuterium (which is 0.015%) (i.e., at least 15% deuterium incorporation). The compounds in the examples having a natural abundance greater than deuterium can be at least 1000 times abundant deuterium (i.e., at least 15% deuterium doping), at least 2000 times abundant deuterium (i.e., at least 30% deuterium doping), at least 3000 times abundant deuterium (i.e., at least 45% deuterium doping), at least 3340 times abundant deuterium (i.e., at least 50.1% deuterium doping), at least 3500 times abundant deuterium (i.e., at least 52.5% deuterium doping), at least 4000 times abundant deuterium (i.e., at least 60% deuterium doping), or at least 4500 times abundant deuterium (i.e., at least 67.5% deuterium doping). The abundance of deuterium is at least 5000 times (i.e., at least 75% deuterium doping), at least 5500 times (i.e., at least 82.5% deuterium doping), at least 6000 times (i.e., at least 90% deuterium doping), at least 6333.3 times (i.e., at least 95% deuterium doping), at least 6466.7 times (i.e., at least 97% deuterium doping), at least 6600 times (i.e., at least 99% deuterium doping), at least 6633.3 times (i.e., at least 99.5% deuterium doping), or higher. Detailed Implementation

[0591] For clarity, this application is further illustrated with examples, but these examples are not intended to limit the scope of this application. It will be apparent to those skilled in the art that various changes and modifications can be made to the specific embodiments of this application without departing from the spirit and scope thereof. All reagents used in this application are commercially available and can be used without further purification.

[0592] The compounds of this application can be prepared by those skilled in the art of organic synthesis with reference to the routes or methods of the following embodiments. The resulting compounds can be characterized by known instruments or methods, including but not limited to mass spectrometry, nuclear magnetic resonance, etc.

[0593] This application uses the following abbreviations:

[0594] AcOH represents acetic acid; Ar represents argon; BBr3 represents boron tribromide; BH3 represents borane; Boc represents tert-butyloxycarbonyl; br represents a broad peak; ℃ represents degrees Celsius; CD3OD represents deuterated methanol; CDCl3 represents deuterated chloroform; CO represents carbon monoxide; (COCl)2 represents oxalyl chloride; Cs2CO3 represents cesium carbonate; CuCl represents cuprous chloride; CuI represents cuprous iodide; d represents a doublet; DCE represents dichloroethane; DCM represents dichloromethane; Dioxane or 1,4-dioxane represents dioxane; DIPEA or DIEA represents N,N-diisopropylethylamine; DMF represents... Table 1: Dimethylformamide; DMSO represents dimethyl sulfoxide; EA or EtOAc represents ethyl acetate; ESI represents electrospray ionization; FeCl3 represents ferric chloride; g represents grams; H2O represents water; HCl represents hydrochloric acid; HPLC represents high performance liquid chromatography; K2CO3 represents potassium carbonate; KOAc represents potassium acetate; K3PO4 represents potassium phosphate; LDA represents lithium diisopropylamino; LC-MS represents liquid chromatography-mass spectrometry; LiCl represents lithium chloride; LiHMDS represents bis(trimethylsilyl)aminolithium; LiOH represents lithium hydroxide; m represents multiplet; m / z represents mass-to-charge ratio; MeCN or AC N represents acetonitrile; MeOH represents methanol; MeONa represents sodium methoxide; M represents mol; min represents minutes; mg represents milligrams; mL represents milliliters; mmol represents millimoles; N2 represents nitrogen; NaBH4 represents sodium borohydride; Na2CO3 represents sodium carbonate; NaCl represents sodium chloride; NaHCO3 represents sodium bicarbonate; NaH represents sodium hydride; NaOH represents sodium hydroxide; Na2SO4 represents sodium sulfate; NBS represents N-bromosuccinimide; n-BuLi represents n-butyllithium; NH4Cl represents ammonium chloride; NIS represents N-iodosuccinimide; PE represents petroleum ether; Pd(dppf) Cl2 represents [1,1′-bis(diphenylphosphine)ferrocene]palladium(II) dichloride; Pd(OAc)2 represents palladium acetate; THF represents tetrahydrofuran; tBuOK represents potassium tert-butoxide; rt or RT represents room temperature; Xantphos represents 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene; X-Phos represents 2-biscyclohexylphosphine-2',4',6'-triisopropylbiphenyl; XPhosPdG2 represents chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II); UV represents ultraviolet light.

[0595] Example 1: Preparation of Compound 1

[0596] Synthesis of Compound 1-1

[0597] 2-Bromo-6-hydroxybenzaldehyde (25 g) and KOH (34.89 g) were dissolved in ACN / H₂O (V / V = 10:1, 622 mL). Diethyl bromofluoromethyl phosphate (39.85 g) was slowly added dropwise at 0 °C, and the mixture was stirred at 0 °C for 0.5 hours. After adjusting the pH to approximately 5 with 1 M HCl, the mixture was extracted three times with EA (500 mL). The combined organic phases were washed with brine (1500 mL) and dried over anhydrous Na₂SO₄. The residue was concentrated and purified to give compound 1-1 (15.5 g).

[0598] 1 H-NMR (400MHz, CDCl3) δ10.35(s,1H),7.58(dd,J=8.1,1.0Hz,1H),7.42(t,J=8.2Hz,1H),7.26(d,J=9.1Hz,1H),6.61(t,J=73.4Hz,1H).

[0599] Synthesis of Compounds 1-2

[0600] A mixture of tetraisopropyl titanate (304.12 g) and cyclobutanone (50 g) in THF (400 mL) was stirred for 10 minutes. Tert-butylsulfinamide (69.17 g) was then added, and the reaction mixture was stirred at 70 °C for 5 hours. After the reaction was complete, water (200 mL) was added, the mixture was filtered, and the filtrate was collected, concentrated, and purified to give compounds 1-2 (41.00 g).

[0601] 1 H-NMR (400MHz, DMSO-d6) δ3.41-3.30(m,1H),3.24-2.99(m,3H),2.09-1.96(m,2H),1.15(d,J=8.8Hz,9H).

[0602] Synthesis of compounds 1-3

[0603] At -78°C, n-BuLi (1.6M, 148.97mL) was added dropwise to a dry toluene (1200mL) solution of 67.90g of 2-iodo-5-bromopyrimidine and reacted at -78°C for 40 minutes. Then, a dry toluene (120mL) solution of 41.3g of compound 1-2 was added. The mixture was stirred at -78°C for 40 minutes, then heated to 0°C and reacted for another 2 hours. Saturated NH4Cl (1500mL) was added to the reaction system, and the mixture was extracted twice with EA (1000mL). The organic phase was concentrated and purified to give compound 1-3 (13.00g).

[0604] LC-MS(ESI)m / z:[M+H] + =332.1

[0605] Synthesis of compounds 1-4

[0606] Compounds 1-3 (800 mg), pinacol borate (742.77 mg), and Pd(dppf)Cl2 (177.94 mg) were dissolved in 1,4-dioxane (8 mL). KOAc (717.65 mg) was added, the mixture was heated to 100 °C, stirred for 1 hour, concentrated, and then PE was added to slurry. The mixture was filtered, the filter cake was washed with PE, and the filtrate was concentrated to obtain compounds 1-4 (600.00 mg).

[0607] LC-MS(ESI)m / z:[M+H] + =298.2

[0608] Synthesis of compounds 1-5

[0609] 4-Chloro-2-pyridinecarboxaldehyde (8 g) and methyl azide acetate (16.26 g) were dissolved in methanol (200 mL) and cooled to -15 °C. Sodium methoxide (7.63 g) was added and the mixture was stirred overnight at 0 °C. Ice water was added to the reaction solution, the precipitate was collected, and the solution was washed with water (2 x 100 mL) to give compounds 1-5 (6.14 g).

[0610] LC-MS(ESI)m / z:[M+H] + =239.

[0611] Synthesis of compounds 1-6

[0612] Compounds 1-5 (23 g) were dissolved in benzene (200 mL), and the mixture was stirred at 180 °C for one hour. Upon natural return to room temperature, a solid precipitated. The solid was collected and washed with EA (20 mL) to give compounds 1-6 (10.64 g).

[0613] LC-MS(ESI)m / z:[M+H] + =211.

[0614] Synthesis of compounds 1-7

[0615] Compounds 1-6 (3.4 g) were dissolved in ACN (105 mL), and NIS (5.45 g) was added in portions. The reaction mixture was stirred at 25 °C for 16 hours, quenched with water (100 mL), and extracted with EA (200 x 3 mL). The organic phases were combined, dried, concentrated and purified to give compounds 1-7 (4.30 g).

[0616] LC-MS(ESI)m / z:[M+H] + =336.6

[0617] Synthesis of compounds 1-8

[0618] Compound 1-7 (4.3 g) and hexamethylphosphoramide (6.87 g) were added to THF (86.00 mL), the temperature was lowered to -30 °C, and isopropyl magnesium chloride-lithium chloride (1.3 M, 19.66 mL) was slowly added dropwise. The mixture was stirred and reacted for 1 h. Then, a THF (8.6 mL) solution of compound 1-1 (3.53 g) was added, and the temperature was maintained at -30 °C for 2 h. After the reaction was completed, the reaction solution was poured into saturated ammonium chloride (100 mL), extracted with EA (100 x 3 mL), the combined organic phases were washed with brine (200 mL), dried over Na2SO4, and concentrated and purified to obtain compound 1-8 (3.60 g).

[0619] LC-MS(ESI)m / z:[M+H] + =443.0

[0620] Synthesis of compounds 1-9

[0621] Compounds 1-8 (3.6 g), dimethyl malonate (1.24 g), and FeCl3 (252.98 mg) were added to a DCE (36 mL), and the mixture was stirred at 80 °C for 2 hours. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, water (50 mL) was added, and the mixture was extracted with EA (50 x 3 mL). The combined organic phases were washed with brine (150 mL) and dried over Na2SO4. The purified mixture was concentrated under reduced pressure to give compounds 1-9 (1.51 g).

[0622] LC-MS(ESI)m / z:[M+H] + =575.1

[0623] Synthesis of compounds 1-10

[0624] Compounds 1-9 (1.45 g) and LiCl (2.14 g) were added to DMSO (29 mL) and H2O (2.9 mL), and the mixture was stirred at 130 °C for 8 hours. The reaction mixture was quenched in water (50 mL), extracted with EA (50 x 3 mL), and the combined organic phases were washed with brine (150 mL) and dried over Na2SO4. The mixture was concentrated and purified under reduced pressure to give compound 1-10 (817.00 mg).

[0625] LC-MS(ESI)m / z:[M+H] + =517.0

[0626] Synthesis of compounds 1-11

[0627] Compound 1-10 (810 mg) was added to THF (16.2 mL), cooled to -10 °C, and tBuOK (1 M, 2.50 mL) was slowly added dropwise while stirring at -10 °C for 0.5 h. The reaction mixture was quenched in saturated ammonium chloride (50 mL), extracted with EA (50 x 3 mL), and the combined organic phases were washed with brine (150 mL) and dried over Na₂SO₄. After purification by vacuum concentration, compound 1-11 (560.00 mg) was obtained.

[0628] LC-MS(ESI)m / z:[M+H] + =485.0

[0629] Synthesis of compounds 1-12

[0630] Compound 1-11 (560 mg) was added to DMSO / H2O (V / V = 5:1, 12 mL), and the mixture was heated to 100 °C and reacted for 4 hours. The reaction mixture was cooled to room temperature, quenched in ice water (20 mL), and filtered to obtain compound 1-12 (418.00 mg).

[0631] LC-MS(ESI)m / z:[M+H] + =427.0

[0632] Synthesis of compounds 1-13

[0633] At room temperature, (S)-tert-butylsulfinamide (236.94 mg) was added to a THF solution (8 mL) of tetraisopropyl titanate (416.73 mg) containing 418 mg of compound 1-12. The mixture was stirred at 75 °C for 24 hours. The mixture was cooled to 0 °C, and sodium borohydride (73.83 mg) was added. The mixture was stirred at 0 °C for 1 hour. The reaction mixture was quenched in water (20 mL), filtered through diatomaceous earth, and the filtrate was extracted with EA (3 x 20 mL). The combined organic phases were washed with brine (100 mL) and dried over Na₂SO₄. The mixture was concentrated under reduced pressure to give compound 1-13 (524.00 mg).

[0634] LC-MS(ESI)m / z:[M+H] + =532.0

[0635] Synthesis of compounds 1-14

[0636] Compound 1-13 (524 mg) was added to HCl / 1,4-dioxane (5 mL) and stirred at 25 °C for 1 hour. The reaction mixture was concentrated to dryness, dissolved in EA (10 mL), and the pH was adjusted to neutral by adding ammonia. Water (20 mL) was added, and the mixture was extracted with EA (3 x 20 mL). The combined organic phases were washed with brine (50 mL) and dried over anhydrous Na₂SO₄. After purification by concentration under reduced pressure, compound 1-14 (240.00 mg) was obtained.

[0637] LC-MS(ESI)m / z:[M+H] + =411.0

[0638] Synthesis of compounds 1-15

[0639] Compound 1-14 (170 mg) was dissolved in 1,4-dioxane (17 mL) at room temperature, and K₂CO₃ (109.62 mg), Xantphos (22.95 mg), and Pd(OAC)₂ (8.90 mg) were added. The gas was purged three times with a CO balloon, and the flask was placed in an oil bath and heated to 110 °C. The reaction was stirred for 16 hours. Compound 1-15 (25.00 mg) was obtained by concentration and purification.

[0640] LC-MS(ESI)m / z:[M+H] + =376.1

[0641] Synthesis of compounds 1-16

[0642] Compound 1-15 (25 mg) was dissolved in DMF (1 mL) at 0 °C. NaH (1.92 mg) was slowly added under ice bath conditions. After stirring for 30 minutes, iodomethane (18.89 mg) was slowly added dropwise to the solution, and the reaction was carried out at 0 °C for 1.5 hours. After quenching with saturated NH4Cl (20 mL), the mixture was extracted with EA (30 x 3 mL). The organic phases were combined and concentrated to obtain compound 1-16 (25.00 mg).

[0643] LC-MS(ESI)m / z:[M+H] + =390.1

[0644] Synthesis of compounds 1-17

[0645] Compound 1-16 (25 mg) was dissolved in 1,4-dioxane (1.2 mL), followed by the addition of compound 1-4 (48.14 mg), XPhos Pd G2 (5.03 mg), X-PHOS (6.12 mg), and K3PO4 (27.19 mg). The mixture was then purged with nitrogen and stirred at 100 °C for 2 hours. The reaction mixture was concentrated and purified to give compound 1-17 (26.00 mg).

[0646] LC-MS(ESI)m / z:[M+H] + =607.3

[0647] Synthesis of Compound 1

[0648] Compound 1-17 (26 mg) was added to a mixed solvent of HCl / 1,4-dioxane (1 mL) and DCM (1 mL), and the mixture was stirred at 25 °C for 1 hour. After concentration, ammonia was added to adjust the pH to alkaline, and the mixture was concentrated and purified to obtain compound 1 (20.00 mg).

[0649] LC-MS(ESI)m / z:[M+H] + =503.2

[0650] 1 H-NMR (400MHz, CDCl3) δ8.95 (s, 2H), 8.51-8.43 (m, 2H), 7.69 (d, J = 1.6Hz, 1H ),7.29(t,J=8.0Hz,2H),7.26-7.21(m,2H),7.00-6.59(m,2H),5.12(d,J=6.6 Hz,1H),4.91(d,J=7.1Hz,1H),3.44(s,3H),3.33-3.26(m,1H),2.83-2.77(m, 2H), 2.65 (d, J=13.2Hz, 1H), 2.26-2.13 (m, 3H), 2.00 (td, J=10.0, 3.8Hz, 1H).

[0651] Preparation of Compound 1A and Compound 1B

[0652] Compound 1 was chirally purified under SFC conditions on a Chiralpak AD column (250*30mm, ID, 10mm; flow rate 120mL / min; mobile phase: CO2 + 45% Ethanol (0.1% NH3·H2O)) to obtain compound 1A (shorter retention time) and compound 1B (longer retention time).

[0653] Compound 1A:

[0654] LC-MS(ESI)m / z:[M+H] + =503.2

[0655] 1H-NMR (400MHz, CDCl3) δ8.95(s,2H),8.51-8.43(m,2H),7.68(d,J=1.6Hz,1H),7.29(t,J=8.0Hz,2H),7.27-7.22(m,2H),7.96-6.59(m,2H), 5.12(d,J=6.6Hz,1H),4.91(d,J=7.1Hz,1H),3.45(s,3H),3.34-3.26(m,1H),2.83-2.77(m,2H),2.65(d,J=13.2Hz,1H),2.26-1.96(m,4H).

[0656] Compound 1B

[0657] LC-MS(ESI)m / z:[M+H] + =503.2

[0658] Example 2: Preparation of Compound 2

[0659] Synthesis of Compound 2-1

[0660] Compound 1-16 (80 mg), xphos (9.78 mg), and trimethylsilylacetylene (201.59 mg) were dissolved in TEA (1.6 mL). After adding xphos-Pd-G2 (16.15 mg), the mixture was heated to 110 °C and stirred for 18 hours. After concentration, 67 mg of crude product was obtained, which was redissolved in MeOH (4 mL). After adding KF (35.77 mg), the mixture was heated to 50 °C and stirred for 20 hours. After concentration and purification, compound 2-1 (52.00 mg) was obtained.

[0661] LC-MS[M+1] + =380.2

[0662] Synthesis of Compound 2

[0663] Compound 2-1 (25 mg), compound 5-bromo-3-methylpyridinecarboxamide (20.41 mg), and TEA (40.01 mg) were dissolved in THF (2 mL). After adding Pd(PPh3)4 (9.14 mg), the mixture was heated to 80 °C and stirred for 16 hours under nitrogen protection. After concentration and purification, compound 2 (21.00 mg) was obtained.

[0664] LC-MS[M+1] + =514.3

[0665] 1H-NMR (400MHz, CDCl3) δ8.59 (s, 1H), 8.45-8.39 (m, 2H), 8.08 (d, J = 44.0Hz, 1H), 7.89 (s, 1H), 7.67 (s, 1H), 7.41-7.29 (m, 2H), 7.00-6.47 (m,2H),5.72(s,1H),5.09(d,J=6.6Hz,1H),4.91(d,J=7.1Hz,1H),3.43(s,3H),3.32-3.25(m,1H),2.78(s,3H),2.65(d,J=13.7Hz,1H).

[0666] Preparation of Compound 2A and Compound 2B

[0667] Compound 2 was chirally purified under SFC conditions on a Chiralpak AD column (250*30mm, ID, 10μm; flow rate 120mL / min; mobile phase: CO2 + 30% Ethanol (0.1% NH3·H2O)) to obtain compound 2A (shorter retention time) and compound 2B (longer retention time).

[0668] Compound 2A:

[0669] LC-MS[M+1] + =514.2

[0670] 1 H-NMR (400MHz, CDCl3) δ8.53(s,1H),8.44(dd,J=7.8,1.8Hz,1H),8.35(d,J=7.4Hz ,1H),7.87(s,1H),7.75(s,1H),7.64(s,1H),7.29(d,J=8.0Hz,1H),7.24(d,J=8.2 Hz,1H),6.96-6.59(m,2H),5.51(s,1H),5.08(d,J=6.9Hz,1H),4.90(d,J=6.9Hz,1 H),3.42(d,J=4.7Hz,3H),3.31-3.24(m,1H),2.75(s,3H),2.64(d,J=13.2Hz,1H).

[0671] Compound 2B:

[0672] LC-MS[M+1] + =514.2

[0673] 1H-NMR (400MHz, CDCl3) δ8.54(s,1H),8.44(dd,J=7.7,1.6Hz,1H),8.35(d,J=7.1 Hz,1H),7.87(s,1H),7.75(s,1H),7.64(s,1H),7.29(d,J=8.2Hz,1H),7.24(d,J =8.0Hz,1H),7.00-6.59(m,2H),5.51(s,1H),5.08(d,J=6.6Hz,1H),4.90(d,J=6 .9Hz,1H),3.43(s,3H),3.31-3.24(m,1H),2.75(s,3H),2.64(d,J=13.2Hz,1H).

[0674] Example 3

[0675] Following the synthesis and purification methods of compound 2, compound 3 was synthesized.

[0676] LC-MS[M+1] + =500.2

[0677] 1 H-NMR (400MHz, DMSO-d6) δ8.83(d,J=1.6Hz,1H),8.75(d,J=7.4Hz,1H),8.21(q,J=8.0Hz,3H),8.08(d,J=8.0Hz,1H), 7.77(s,1H),7.72-7.32(m,4H),6.98(d,J=5.5Hz,1H),5.09(d,J=6.9Hz,1H),4.99(d,J=6.6Hz,1H),3.30-3.27(m,3H)

[0678] Example 4: Preparation of Compound 4

[0679] Compounds 1-16 were chirally purified under SFC conditions on a Chiralpak IG column (250*30mm, ID, 10μm; flow rate 120mL / min; mobile phase: CO2 + 30% Ethanol (0.1% NH3·H2O)) to obtain compound 1-16A (shorter retention time) and compound 1-16B (longer retention time).

[0680] Synthesis of compound 4-1

[0681] At room temperature, tert-butylsulfinamide (2.02 g) and tetraisopropyl phthalate (11.82 g) were added to a solution of 1 g of 2-butanone in 10 mL of THF. The mixture was stirred at 75 °C for 5 hours, quenched with water (3 mL), filtered through diatomaceous earth, and purified by vacuum concentration to obtain compound 4-1 (1.00 g).

[0682] LC-MS[M+1] + =176.1

[0683] Synthesis of compound 4-2

[0684] Compound 4-1 (1 g) was dissolved in dry DCM (10 mL). n-BuLi (1.6 M, 2.45 mL) was added at -78 °C, and the mixture was stirred at -78 °C for 30 minutes. Then, a dry DCM (1 mL) solution of 5-bromo-3-fluoro-2-iodopyridine (550.19 mg) was added. The mixture was stirred at -78 °C for 2 hours. The mixture was quenched with NH4Cl (20 mL), extracted with EA (3 x 20 mL), dried over Na2SO4, and the organic phase was concentrated and purified to give compound 4-2 (700.00 mg).

[0685] LC-MS[M+1] + =351.1

[0686] Synthesis of compound 4-3

[0687] Compound 4-2 (100 mg), pinacol diborate (79.52 mg), and potassium acetate (55.88 mg) were dissolved in 1,4-dioxane (2 mL). Pd(dppf)Cl2 (20.81 mg) was added, and the mixture was heated to 100 °C under N2 protection and stirred for 3 hours. The solution was then concentrated and purified under reduced pressure to obtain compound 4-3 (120.00 mg).

[0688] LC-MS[M+1] + =399.2

[0689] Synthesis of compound 4-4

[0690] Compound 1-16A (15.00 mg) was dissolved in 1,4-dioxane (1 mL) and H₂O (0.1 mL), and compound 4-3 (30.66 mg), K₃PO₄ (24.48 mg), Xphos (3.66 mg), and Xphos-Pd-G₂ (3.02 mg) were added. The reaction mixture was stirred at 100 °C for 2 hours under nitrogen protection. The reaction solution was concentrated and purified under reduced pressure to obtain compound 4-4 (20.00 mg).

[0691] LC-MS[M+1] + =626.3

[0692] Synthesis of Compound 4

[0693] Compound 4-4 (20 mg) was dissolved in DCM (1 mL), and HCl / Dioxane (1 mL) was added. The mixture was stirred at 25 °C for 1 hour. The reaction solution was concentrated and purified under reduced pressure to obtain compound 4 (12.49 mg).

[0694] LC-MS[M+1] + =522.3

[0695] 1 H NMR(400MHz, DMSO-d6)δ8.80-8.75(m,2H),8.22(dd,J=7.7,1.1Hz,1H),8.02(dd,J=13.2,1.6Hz,1H),7.78-7.27(m, 5H),5.05(dd,J=24.7,6.6Hz,2H),3.28(s,3H),2.53(s,2H),1.92-1.73(m,2H),1.46(s,3H),0.72(t,J=7.4Hz,3H).

[0696] Example 5

[0697] Following the synthesis and purification methods of compound 4, compound 5 was synthesized.

[0698] LC-MS[M+1] + =521.4

[0699] 1H-NMR (400MHz, CDCl3) δ8.97 (d, J = 15.1Hz, 2H), 8.49 (d, J = 7.4Hz, 1H), 8.44 (d, J = 6.9Hz, 1H),7.68(s,1H),7.29(s,1H),7.22(d,J=7.7Hz,1H),6.97-6.60(m,2H),6.90(d,J=5.5Hz, 1H),5.11(d,J=6.6Hz,1H),4.91(d,J=6.9Hz,1H),4.02(d,J=8.8Hz,1H),3.81(d,J=8.8Hz, 1H),3.44(s,3H),3.35(s,3H),3.28(q,J=6.7Hz,1H),2.65(d,J=13.2Hz,1H),1.70(s,3H).

[0700] Example 6

[0701] Following the synthesis and purification methods of compound 4, compound 6 was synthesized.

[0702] LC-MS[M+H] + =505.3

[0703] 1 H-NMR (400MHz, CD3OD) δ9.09 (s, 2H), 8.63 (d, J = 7.4Hz, 1H), 8.30 (d, J = 8.2Hz, 1H), 7.81 (s, 1H), 7.42-7.05 (m, 4H), 5.16 (d, J = 6.9Hz, 1H), 5.06(d,J=6.9Hz,1H),4.59-4.55(m,2H),3.40-3.33(m,4H),2.62(d,J=13.5Hz,1H),2.1-1.94(m,2H),1.61(s,3H),0.79(t,J=7.4Hz,3H).

[0704] Example 7

[0705] Following the synthesis and purification method of compound 4, compound 7 was synthesized. Compound 7 was purified by preparative HPLC (Mobile phase: (0.1% FA) H2O-CAN; Column: Welch Ultimate 10μm 21.2*250mm) to obtain compound 7A (shorter retention time) and compound 7B (longer retention time).

[0706] Compound 7A

[0707] LC-MS[M+1] + =560.3

[0708] 1 H-NMR (400MHz, DMSO-d6) δ9.16 (s, 2H), 8.94-8.83 (m, 1H), 8.22 (d, J = 6.9Hz, 1H), 7.77-7.58 (m, 3H), 7.40-7.17 (m, 5H), 6.74 (s, 1H), 5.05(dd,J=26.2,6.7Hz,2H),3.60-3.42(m,2H),3.28(s,3H),3.13(d,J=13.2Hz,2H),2.11(d,J=12.9Hz,2H),1.56(d,J=11.0Hz,3H).

[0709] Compound 7B

[0710] LC-MS[M+1] + =560.3

[0711] 1H-NMR (400MHz, DMSO-d6) δ9.16(s,2H),8.83(d,J=7.1Hz,1H),8.22(d,J=6.6Hz,1H),7.77-7.59(m,4H),7.40-7.31(m,4H),6.87( s,1H),5.06(dd,J=24.7,6.9Hz,2H),3.51-3.48(m,2H),3.28(s,4H),3.17(d,J=5.2Hz,1H),2.63(d,J=12.9Hz,2H),1.26(s,3H).

[0712] Example 8

[0713] Following the synthesis and purification method of compound 4, compound 8 was synthesized. Compound 8 was purified by preparative HPLC (Mobile phase: (0.1% FA) H2O-CAN; Column: Welch Ultimate 10μm 21.2*250mm) to obtain compound 8A (shorter retention time) and compound 8B (longer retention time).

[0714] Compound 8A

[0715] LC-MS[M+1] + =550.48

[0716] Compound 8B

[0717] LC-MS[M+1] + =550.48

[0718] Example 9

[0719] Following the synthesis and purification methods of compound 4, compound 9 was synthesized.

[0720] LC-MS[M+1] + =517.2

[0721] 1H-NMR(400MHz, CDCl3)δ8.94(d,J=13.2Hz,2H),8.48-8.42(m,2H),7.67(d,J=9.9 Hz,1H),7.28(d,J=8.2Hz,1H),7.22(d,J=7.7Hz,1H),6.96-6.59(m,2H),5.11(d,J =6.6Hz,1H),4.91(d,J=6.6Hz,1H),3.44(s,3H),3.32-3.25(m,1H),2.99-2.82(m ,2H),2.69-2.63(m,1H),2.24-2.16(m,2H),2.06-1.88(m,1H),1.25-1.21(m,3H).

[0722] Example 10

[0723] Following the synthesis and purification methods of compound 4, compound 10 was synthesized.

[0724] LC-MS[M+1] + =560.49

[0725] Example 11

[0726] Following the synthesis and purification methods of compound 4, compound 11 was synthesized.

[0727] LC-MS[M+1] + =453.5

[0728] Example 12

[0729] Following the synthesis and purification methods of compound 4, compound 12 was synthesized.

[0730] LC-MS[M+1] + =476.41

[0731] Example 13

[0732] Following the synthesis and purification methods of compound 4, compound 13 was synthesized.

[0733] LC-MS[M+1] + =573.4

[0734] 1¹H NMR (400MHz, DMSO-d⁶) δ 8.56 (d, J = 7.4Hz, 1H), 8.41 (d, J = 4.7Hz, 2H), 8.21 (d, J = 8.0Hz, 1H), 7.69–7.30 (m, 4H), 7.00 (dd, J = 16.2, 2.2Hz, 1H), 6.69 (t, J = 4.8Hz, 1H), 4.99–4.83 (m, 3H), 4.70 (d, J = 11.0Hz, 1H), 3.98–3.93 (m, 1H), 3.83 (d, J = 9.9Hz, 2H), 3.60–3.47 (m, 4H), 3.25 (s, 3H), 2.99–2.81 (m, 2H). Example 14: Synthesis of Compound 14

[0735] Synthesis of Compound 14-1

[0736] 24 g of 5-bromo-2,2-difluoro-1,3-benzodioxazole was added to a three-necked flask under nitrogen protection. 200 mL of THF was added, and 60.8 mL of LDA was slowly added dropwise at -78 °C. The reaction was maintained at this temperature for 40 minutes. 14.8 g of DMF was added, and the reaction was continued for another 30 minutes. The temperature was then raised to room temperature and reacted for another 30 minutes. The reaction was quenched with 200 mL of citric acid solution and extracted with EA (3 x 100 mL). The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was filtered, evaporated to dryness, and the crude product was purified by column chromatography to obtain 14-1.

[0737] 1 H NMR (400MHz, CDCl3) δ10.30 (s, 1H), 7.41 (d, J = 8.5Hz, 1H), 7.15 (d, J = 8.5Hz, 1H).

[0738] Synthesis of Compound 14-2

[0739] Following the synthesis and purification methods of compounds 1-15, compound 14-2 was synthesized.

[0740] LC-MS[M+1] + =390.0

[0741] Synthesis of Compound 14-3

[0742] Compound 14-2 (15 mg) was dissolved in DMF (0.8 mL) at 0 °C. NaH (1.11 mg) was slowly added under ice bath conditions, followed by stirring for 30 minutes. CH3I (10.93 mg) was then slowly added dropwise, and the reaction was allowed to proceed at 0 °C for 1 hour. The reaction was quenched with saturated NH4Cl (20 mL), extracted with EA (3 x 30 mL), and the organic phases were combined, dried, concentrated, and purified to obtain 14-3.

[0743] LC-MS[M+1]+=404.2

[0744] Synthesis of compound 14-4

[0745] 14-3 (13 mg) was dissolved in Dioxane (0.4 mL), followed by the addition of 1-4 (24.43 mg), XPhos Pd G2 (2.53 mg), X-PHOS (3.07 mg), and K3PO4 (20.48 mg). The mixture was then purged with nitrogen and stirred at 100 °C for 2 hours. The reaction mixture was concentrated and purified to obtain 14-4.

[0746] LC-MS[M+1]+=621.4

[0747] Synthesis of Compound 14

[0748] 14-4 (16 mg) was added to a mixed solvent of DCM (1 mL) and HCl / Dioxane (1 mL), and the mixture was stirred at 25 °C for 1 hour. After concentration, one drop of ammonia was added to adjust the pH to alkaline, and the mixture was purified to obtain compound 14. Compound 14 was chirally purified under SFC conditions on a Chiralpak AD column (250*30 mm, ID, 10 μm; flow rate 120 mL / min; mobile phase: CO2 + 50% Ethanol (0.05% DEA)) to obtain compound 14A (shorter retention time) and compound 14B (longer retention time).

[0749] Compound 14A

[0750] LC-MS[M+1] + =517.4

[0751] 1 H-NMR (400MHz, CDCl3) δ8.95 (s, 2H), 8.51 (d, J = 7.4Hz, 1H), 8.42 (d, J = 8.8Hz, 1H), 7.60 (s, 1H), 6.96-6.91 (m, 2H), 4.97 (d,J=7.1Hz,1H),4.81(d,J=6.3Hz,1H),3.45(d,J=4.4Hz,3H),3.34-3.27(m,1H),2.88-2.62(m,5H),2.38-2.22(m,2H).

[0752] Compound 14B

[0753] LC-MS[M+1] + =517.3

[0754] Example 15: Synthesis of Compound 15

[0755] Synthesis of Compound 15-1

[0756] 200 mg of 7-bromo-2H-pyrano[3,2-b]pyridin-4(3H)-one was dissolved in toluene (4 mL), and 0.88 mL of 3 M magnesium bromide was added at 0 °C. The mixture was heated and stirred at 25 °C for 3 hours. The mixture was quenched with 20 mL of saturated ammonium chloride, extracted with EA (3 x 30 mL), and the organic phases were combined, washed with 90 mL of brine, and dried over anhydrous sodium sulfate. The purified compound 15-1 was obtained by concentration.

[0757] LC-MS[M+1] + =244.1

[0758] Synthesis of Compound 15-2

[0759] Dissolve 15-1 (140 mg) in DCM (3 mL), add NaN3 (372.82 mg), lower the temperature to 0 °C, add TFA (6 mL), stir and react at 25 °C for 48 hours, pour into ice-saturated NaHCO3 (30 mL), extract with EA (3 x 10 mL), combine the organic phases, dry and concentrate, dissolve in THF (3 mL) and use directly in the next step of the reaction.

[0760] LC-MS[M+1] + =269.1

[0761] Synthesis of Compound 15-3

[0762] 15-2 (100 mg) was dissolved in THF / H2O (3:1 mL), and zinc powder (96.62 mg) and NH4Cl (200.67 mg) were added. The mixture was stirred at 25 °C for 1 hour until the reaction was complete. The solution was filtered, and the filtrate was concentrated to obtain the crude product. The crude product was dissolved in DCM (3 mL), and TEA (112.81 mg) and (Boc)2O (80.27 mg) were added. The mixture was stirred at 25 °C for 18 hours. After concentration and purification, 15-3 was obtained.

[0763] LC-MS[M+1] + =343.1

[0764] Synthesis of Compound 15-4

[0765] Dissolve 15-3 (24 mg), pinacol diboryl ester (19.53 mg), and potassium acetate (20.59 mg) in 1,4-dioxane (0.6 mL), add Pd(dppf)Cl2 (5.10 mg), raise the temperature to 80 °C, and stir for 1 hour. Concentrate to obtain crude 15-4, which is then directly added to the next reaction step.

[0766] Synthesis of Compound 15-5

[0767] Compound 1-16 (20 mg) was dissolved in Dioxane / water (V / V = 10 / 1, 0.6 mL), and 15-4 (24.03 mg), XPhos Pd G2 (4.03 mg), X-PHOS (4.89 mg), and K3PO4 (32.63 mg) were added. The mixture was then purged with nitrogen and stirred at 100 °C for 2 hours. After the reaction was complete, the mixture was concentrated and purified to obtain 15-5.

[0768] LC-MS[M+1] + =618.5

[0769] Synthesis of Compound 15

[0770] Compound 15-5 (30 mg) was added to a mixed solvent of HCl / Dioxane (1 mL) and DCM (1 mL), and the mixture was stirred at 25 °C for 1 hour. After concentration and purification, compound 15 was obtained.

[0771] Compound 15 was chirally purified under SFC conditions on a Chiralpak OD column (250*30mm, ID, 10μm; flow rate 120mL / min; mobile phase: CO2 + 50% Ethanol (0.05% DEA)) to obtain compound 15A (shorter retention time) and compound 15B (longer retention time).

[0772] Compound 15A

[0773] LC-MS[M+1] + =518.4

[0774] 1H-NMR (400MHz, CDCl3) δ8.43-8.37(m,3H),7.55(d,J=25.6Hz,1H),7.33-7.27(1H),7.25-7.21(m,4H),6.89(d,J=83.3Hz,2H),5.08(d,J=6.6Hz,1H ),4.88(d,J=7.1Hz,1H),4.51-4.12(2H),3.74(s,1H),3.43(s,3H),3.34 -3.16(m,1H),2.62(d,J=13.2Hz,1H),2.26(d,J=29.4Hz,1H),1.25(s,3H)

[0775] Compound 15B

[0776] LC-MS[M+1] + =518.3

[0777] 1 H-NMR (400MHz, CDCl3) δ8.49-8.35(m,3H),7.55(d,J=25.6Hz,1H),7.33-7.27(1H),7.24-7.21(m,4H),6.89(d,J=83.3Hz,2H),5.1 5-5.04(m,1H),4.82(d,J=7.1Hz,1H),4.52-4.1(2H),3.74(s,1H),3.43(s,3H),3.33-3.15(m,1H),2.62-2.26(m,2H),0.87(s,3H)

[0778] Example 16

[0779] Compound 16 was synthesized using the same synthesis and purification methods as compound 15.

[0780] LC-MS[M+H] + =485.3

[0781] 1H-NMR(400MHz, METHANOL-d4)δ8.71(s,1H),8.56(d,J=7.1Hz,1H),8.29(d,J=7.7Hz,1H),7.96(s,1H),7.72(s,1H),7.41-7.04(m,4H), 5.09(dd,J=36.3,6.6Hz,2H),3.40(s,3H),3.37-3.31(m,1H),3.12-3.04(m,2H),2.60(d,J=13.2Hz,1H),2.34-2.27(m,2H),1.55(s,3H)

[0782] Example 17

[0783] Following the synthesis and purification methods of compound 15, compound 17 was synthesized.

[0784] LC-MS[M+1] + =519.4

[0785] 1 H-NMR (400MHz, CDCl3) δ8.45-8.40(m,3H),7.63(s,1H),7.31-7.28(m,2H),7.22(t,J=8.1Hz,1H),6.95-6.59(m,2H),5.10(d,J=6.6Hz,1H),4 .90(d,J=6.9Hz,1H),4.43-4.26(m,2H),3.43(s,3H),3.32-3.25(m,1H ),3.17(s,1H),2.64(d,J=13.2Hz,1H),2.33-2.15(m,2H),1.69(s,3H).

[0786] Example 18

[0787] Following the synthesis and purification methods of compound 15, compound 18 was synthesized.

[0788] LC-MS[M+1] + =503.4

[0789] 1H NMR (400MHz, CDCl3) δ8.65(s,1H),8.49-8.43(m,2H),7.96(s,1H),7.64(s,1H),7.28(d,J=8.0Hz,1H),7.22(d,J=8.0Hz,1H),6.78(s,2H),5.11( d,J=6.6Hz,1H),4.91(d,J=6.9Hz,1H),3.43(s,3H),3.29(t,J=6.6Hz,1 H),2.90-3.21(m,2H),2.65(d,J=13.5Hz,1H),2.42(s,2H),1.76(s,3H).

[0790] Example 19

[0791] Following the synthesis and purification methods of compound 15, compound 19 was synthesized.

[0792] LC-MS[M+1] + =505.3

[0793] 1 H-NMR (400MHz, DMSO-d6) δ8.76(d,J=7.4Hz,1H),8.43(d,J=1.6Hz,1H),8.22(d,J=6.9Hz,1H),7.78-7.41(m,3H),7.39-7.31(m,2H),7.20(dd ,J=7.4,1.9Hz,1H),5.74(s,1H),5.04(dd,J=25.4,7.0Hz,2H),4.46(dd,J=23.4,9.9Hz,2H),3.26(t,J=7.3Hz,4H),2.52(s,1H),1.58(s,3H).

[0794] Example 20

[0795] Compound 20 was synthesized using the same synthesis and purification method as compound 15.

[0796] LC-MS[M+1] + =499.4

[0797] 1H-NMR (400MHz, CDCl3) δ8.65 (s, 1H), 8.45-8.42 (m, 2H), 7.66 (d, J = 28.0Hz, 2H), 7.28 (s,1H),7.24-7.20(m,1H),6.95-6.58(m,2H),5.10(d,J=6.9Hz,1H),4.90(d,J=6.9Hz ,1H),3.44(s,3H),3.32-3.25(m,1H),3.04-2.86(m,2H),2.64(d,J=13.2Hz,1H),2.40 -2.33(m,1H),2.07-1.99(m,1H),1.85(qd,J=14.2,6.9Hz,2H),0.94(t,J=7.4Hz,3H).

[0798] Example 21: Synthesis of Compound 21

[0799] Synthesis of Compound 21-1

[0800] Compound 1-15 (900 mg) and CD3I (694.41 mg) were dissolved in DMF (9 mL). Under nitrogen protection, NaH (114.97 mg, 60% purity) was slowly added in an ice bath, and the reaction was stirred at room temperature for 6 hours. The reaction solution was quenched with saturated NH4Cl solution (20 mL), extracted three times with EA (10 x 3 mL), and the organic phases were combined, washed with saturated brine (30 mL x 3), dried, concentrated, and purified to obtain compound 21-1.

[0801] LC-MS[M+1] + =393.1

[0802] Compound 21-1 was chirally purified under SFC conditions on a Chiralpak AD column (250*30mm, ID, 10μm; flow rate 120mL / min; mobile phase: CO2 + 30% Ethanol (0.05% DEA)) to obtain compound 21-1A (shorter retention time) and compound 21-1B (longer retention time).

[0803] Synthesis of compound 21-2

[0804] Compound 21-1A (25 mg) and compound 1-4 (36.21 mg) were dissolved in a mixed solution of 1,4-dioxane (1 mL) and water (0.1 mL). K3PO4 (40.48 mg), Xphos (6.06 mg), and Xphos Pd G2 (5.00 mg) were added. The mixture was purged with nitrogen and stirred at 100 °C for 16 hours. The reaction mixture was concentrated and purified to give compound 21-2.

[0805] LCMS[M+1] + =610.5

[0806] Synthesis of Compound 21

[0807] Compound 21-2 (20 mg) was dissolved in DCM (0.5 mL), and 4 M HCl / (dioxane) (0.5 mL) was added. The mixture was stirred at room temperature (25 °C) for 30 minutes. The reaction solution was concentrated and purified to obtain compound 21.

[0808] LC-MS[M+1] + =506.4

[0809] 1 H-NMR (400MHz, CDCl3) δ8.95(s,2H),8.50(d,J=7.1Hz,1H),8.44(dd,J=8.1,1.2Hz,1H),7.68(s,1H),7.28(d,J=8.2Hz,1H),7.22(d,J=7.7Hz,1H) ,6.96-6.60(m,2H),5.12(d,J=6.6Hz,1H),4.90(d,J=6.9Hz,1H),3.33-3 .26(m,1H),2.83-2.78(m,2H),2.65(d,J=13.2Hz,1H),2.27-2.00(m,4H).

[0810] Example 22

[0811] Following the synthesis and purification methods of compound 21, compound 22 was synthesized.

[0812] LC-MS[M+1] + =506.4

[0813] 1 H-NMR (400MHz, CDCl3) δ8.95(s,2H),8.47(dd,J=24.9,7.6Hz,2H),7.69(s,1H),7.28(d,J=8.2Hz,1H),7.25-7.21(m,1H), 6.97-6.60(m,2H),5.12(d,J=6.6Hz,1H),4.91(d,J=6.9Hz,1H),3.33-3.26(m,1H),2.84-2.64(m,3H),2.29-2.03(m,4H).

[0814] Example 23

[0815] Following the synthesis and purification methods of compound 1, compound 23 was synthesized.

[0816] LC-MS[M+1] + =517.2

[0817] Example 24

[0818] Following the synthesis and purification methods of compound 1, compound 24 was synthesized.

[0819] LC-MS[M+1] + =529.2

[0820] Example 25: Synthesis of Compound 25

[0821] Synthesis of Compound 25-1

[0822] 500 mg of methyl 5-bromo-3-(bromomethyl)-pyridine-2-carboxylic acid was dissolved in 5 mL of MeOH, and sodium methoxide (5.4 M, 389.61 μL, 30% purity) was added. The mixture was stirred at 0-25 °C for 1 hour under nitrogen protection. The reaction solution was poured into 10 mL of 1 M HCl and extracted with EA (3 x 5 mL). The organic phases were combined, dried, concentrated, and purified to give compound 25-1.

[0823] LC-MS[M+1] + =262.1

[0824] Synthesis of Compound 25-2

[0825] Compound 25-1 (400 mg) was dissolved in THF (4 mL), and NH4OH / MeOH (3 M, 12 mL) was added. The mixture was stirred at 25 °C for 18 hours. The reaction solution was then concentrated and purified under reduced pressure to obtain compound 25-2.

[0826] LC-MS[M+1] + =245.0

[0827] Synthesis of Compound 25-3

[0828] Compound 25-2 (40 mg), xphos (7.78 mg), and trimethylsilylacetylene (160.31 mg) were dissolved in TEA / THF (0.8 mL), and xphos-Pd-G2 (12.85 mg) was added. Under nitrogen protection, the mixture was heated to 110 °C and stirred for 2 hours. The reaction solution was directly concentrated under reduced pressure, redissolved in MeOH (2 mL), and KF (28.45 mg) was added. The mixture was heated to 50 °C and stirred for 12 hours. The reaction solution was then directly concentrated and purified under reduced pressure to obtain compound 25-3.

[0829] LC-MS[M+1] + =191.1

[0830] Synthesis of Compound 25

[0831] Compound 1-4 (15 mg), compound 25-3 (21.96 mg), Xphos-Pd-G2 (3.02 mg), and Xphos (3.66 mg) were added to THF (0.5 mL), and the mixture was heated to 80 °C and stirred for 16 hours under nitrogen protection. The reaction mixture was quenched with water (1 mL), extracted with ethyl acetate (3 x 0.5 mL), washed with saturated brine (2 mL), dried over anhydrous sodium sulfate, and purified by vacuum concentration to obtain compound 25.

[0832] LC-MS[M+1] + =544.3

[0833] 1 H NMR (400MHz, DMSO-d6) δ8.75-8.71 (m, 2H), 8.23 ​​(dd, J = 8.0, 1.2Hz, 1H), 8.15 (s, 2H), 7.72-7. 32(m,5H),7.00-6.97(m,1H),5.09-4.99(m,2H),4.86(s,2H),3.45-3.31(m,5H),3.27(s,3H).

[0834] Example 26: Synthesis of Compound 26

[0835] Synthesis of Compound 26-1

[0836] Compound 14-2 (3.44 g) and CD3I (2.56 g) were dissolved in DMF (35 mL), and NaH (423 mg, 60% purity) was slowly added under ice bath conditions. The mixture was stirred at room temperature for 3 hours. The reaction solution was quenched with saturated NH4Cl solution (50 mL), extracted three times with EA (3 x 30 mL), and the organic phases were combined, washed with saturated brine (3 x 20 mL), dried, concentrated, and purified to obtain compound 26-1.

[0837] LC-MS[M+1] + =407.3

[0838] Compound 26-1 was chirally purified under SFC conditions in a Chiralpak AD column (250*30mm, ID, 10μm; flow rate 120mL / min; mobile phase: A for CO2 and B for Ethanol:MeCN = 7:3 (Gradient: B 45%) to obtain compound 26-1A (shorter retention time) and compound 26-1B (longer retention time).

[0839] Synthesis of compound 26-2

[0840] Compound 26-1A (100 mg) was dissolved in Dioxane (2 mL), followed by the sequential addition of compound 1-4 (103 mg), XPhos Pd G2 (20 mg), X-PHOS (12 mg), and K3PO4 (156 mg). The mixture was then purged with nitrogen and stirred at 100 °C for 2 hours. The reaction mixture was concentrated and purified to obtain compound 26-2.

[0841] LC-MS[M+1]+=621.4

[0842] Synthesis of Compound 26

[0843] Compound 26-2 (130 mg) was added to a mixed solvent of Dioxane (2 mL) and HCl / Dioxane (2 mL), and the mixture was stirred at 25 °C for 1 hour. After concentration, one drop of ammonia was added to adjust the pH to alkaline, and the mixture was purified to obtain compound 26.

[0844] LC-MS[M+1]+=520.4

[0845] 1 H NMR (400MHz, DMSO-d6) δ9.19(s,1H),8.85(d,J=7.4Hz,1H),8.25(d,J=8.9Hz,1H),7.77(s,1H),7.33(dd,J=7.4,2.1Hz,1H),7.29(d,J =8.9Hz,1H),5.16(d,J=7.0Hz,1H),4.79(d,J=6.2Hz,1H),3.31-3.26(m,1H),2.67-2.64(m,3H),2.26-2.16(m,2H),2.08-1.85(m,2H).

[0846] Examples 27 and 28

[0847] Compound 17 was chirally purified under SFC conditions on a Chiralpak OD column (250*30mm, ID, 10μm; flow rate 120mL / min; mobile phase: CO2 + 50% Ethanol (0.05% DEA)) to obtain compound 27 (shorter retention time) and compound 28 (longer retention time).

[0848] Compound 27

[0849] LC-MS[M+1] + =519.4

[0850] 1 H NMR (400MHz, DMSO-d6) δ8.75(d,J=7.4Hz,1H),8.49(d,J=2.1Hz,1H),8.21(d,J=7.6Hz,1H),7.83 -7.61(m,2H),7.48(d,J=2.0Hz,1H),7.38-7.31(m,2H),7.21(dd,J=7.4,2.1Hz,1H),5.32(s,1H),5.07(d,J=6.9Hz, 1H), 5.00 (d, J = 6.6Hz, 1H), 4.35-4.25 (m, 2H), 3.29-3.26 (m, 4H), 2.52-2.51 (m, 1H), 2.04-2.02 (m, 2H), 1.57 (s, 3H).

[0851] Compound 28

[0852] LC-MS[M+1] + =519.4

[0853] 1 H NMR (400MHz, DMSO-d6) δ8.75(d,J=7.4Hz,1H),8.49(d,J=2.1Hz,1H),8.22(d,J=7.6Hz,1H),7.83 -7.61(m,2H),7.48(d,J=2.0Hz,1H),7.38-7.31(m,2H),7.21(dd,J=7.4,2.1Hz,1H),5.32(s,1H),5.07(d,J=6.9Hz, 1H), 5.00 (d, J = 6.6Hz, 1H), 4.35-4.25 (m, 2H), 3.29-3.26 (m, 4H), 2.52-2.51 (m, 1H), 2.04-2.02 (m, 2H), 1.57 (s, 3H).

[0854] Example 29: Synthesis of Compound 29

[0855] Synthesis of Compound 29-1

[0856] Compound 15-1 was chirally resolved on a Chiralpak IA column (250*30mm, 10μm; flow rate: 25mL / min; mobile phase: HEX / ETOH=20 / 80) to obtain compound 15-1A (shorter retention time) and compound 15-1B (longer retention time).

[0857] Compound 15-1A (25 mg) and pinacol diborate (31 mg) were dissolved in 1,4-dioxane (1 mL), followed by the addition of Pd(dppf)Cl2 (7 mg) and KOAc (30 mg). The mixture was then purged with nitrogen and stirred at 100 °C for 1 hour. The reaction solution was concentrated, slurried with PE (10 mL), and filtered. The filtrate was concentrated to obtain compound 29-1.

[0858] LC-MS[M+1]+=210.2.

[0859] Synthesis of Compound 29

[0860] Compound 29-1 (12 mg) was dissolved in 1,4-dioxane (1 mL), followed by the sequential addition of compound 21-1A (10 mg), XPhos Pd G2 (3 mg), X-PHOS (2 mg), and K3PO4 (20 mg). The mixture was then purged with nitrogen and stirred at 100 °C for 2 hours. The reaction mixture was concentrated and purified to obtain compound 29.

[0861] LC-MS[M+1]+=522.4

[0862] 1 H NMR(400MHz, DMSO-d6)δ8.75(d,J=7.4Hz,1H),8.49(d,J=2.1Hz,1H),8.22(d, J=9.5Hz,1H),7.81–7.57(m,2H),7.48(d,J=2.0Hz,1H),7.37–7.28(m,2H),7. 21(dd,J=7.4,2.1Hz,1H),5.32(s,1H),5.06(d,J=7.0Hz,1H),5.00(d,J=6.6H z,1H),4.35–4.25(m,2H),3.27–3.24(m,1H),2.05–2.02(m,2H),1.57(s,3H).

[0863] Example 30: Synthesis of Compound 30

[0864] Synthesis of Compound 30

[0865] Compound 29-1 (10 mg) was dissolved in Dioxane (1 mL), and then compound 26-1A (8 mg), XPhos Pd G2 (3 mg), X-PHOS (2 mg), and K3PO4 (16 mg) were added sequentially. The mixture was purged with nitrogen and stirred at 100 °C for 2 hours. The reaction mixture was concentrated and purified to give compound 30.

[0866] LC-MS[M+1]+=536.31

[0867] 1 H NMR (400MHz, DMSO-d6) δ8.76(d,J=8.3Hz,1H),8.49(d,J=2.0Hz,1H),8.25(d ,J=8.9Hz,1H),7.62(d,J=2.1Hz,1H),7.49(d,J=2.0Hz,1H),7.28(d,J=8.9Hz ,1H),7.22(dd,J=7.4,2.1Hz,1H),5.32(s,1H),5.14(d,J=6.9Hz,1H),4.78(d ,J=6.2Hz,1H),4.35-4.11(m,2H),3.28-3.25(m,1H),2.63-2.60(m,1H),2.05 -2.02 (m, 2H), 1.57 (s, 3H).

[0868] Example 31

[0869] Following the synthesis and purification methods of compound 25, compound 31 was synthesized.

[0870] LC-MS[M+1]+=561.17

[0871] Examples 32 and 33

[0872] Following the synthesis and purification methods of compound 14, compounds 32 and 33 were synthesized.

[0873] Compound 32

[0874] LC-MS[M+1]+=557.4

[0875] 1H-NMR (400MHz, CDCl3) δ8.96 (s, 2H), 8.53 (d, J = 7.4Hz, 1H), 8.42 (d, J = 8.8Hz, 1H), 7.63-7.52 (m, 1H), 7.00-6.92 (m, 2H), 5.00-4.9 8(m,2H),4.82(d,J=6.3Hz,1H),3.46(s,3H),3.35-3.29(m,1H),2.97(dd,J=42.5,13.6Hz,4H),2.73(d,J=13.2Hz,1H),1.77(s,3H)

[0876] Compound 33

[0877] LC-MS[M+1]+=557.4

[0878] Examples 34 and 35

[0879] Compounds 34 and 35 were synthesized using the same methods as those used for the synthesis and purification of compound 15.

[0880] Compound 34

[0881] LC-MS[M+1]+=535.4

[0882] 1 H-NMR (400MHz, CDCl3) δ8.46-8.40(m,3H),7.54(d,J=10.2Hz,1H),7.31(m,1H),7.01-6.90(m,2H),4.95(d,J=6.9Hz,1 H),4.79(d,J=6.0Hz,1H),4.39-4.30(m,2H),3.33-3.26(m,1H),2.70(d,J=13.2Hz,1H),1.86-2.19(m,2H),1.67(s,3H)

[0883] Compound 35

[0884] LC-MS[M+1]+=535.4

[0885] Examples 36 and 37

[0886] Following the synthesis and purification methods of compound 4, compounds 36 and 37 were synthesized.

[0887] Compound 36

[0888] LC-MS[M+1]+=536.4

[0889] Compound 37

[0890] LC-MS[M+1]+=536.4

[0891] Example 38

[0892] Following the synthesis and purification methods of compound 2, compound 38 was synthesized.

[0893] LC-MS[M+1]+=489.17.

[0894] Examples 39 and 40

[0895] Following the synthesis and purification method of compound 4, compounds 39 and 40 were synthesized and purified by preparative HPLC (Mobile phase: (0.1% FA) H2O-CAN; Column: Welch Ultimate 10μm 21.2*250mm) to obtain compound 39 (shorter retention time) and compound 40 (longer retention time).

[0896] Compound 39

[0897] LC-MS[M+1] + =553.39

[0898] 1 H NMR(400MHz, DMSO-d6)δ8.79(d,J=7.4Hz,1H),8.69-8.66(m,1H),8.22-8.01(m,2H),7.78-7.42(m,2H),7.44- 7.25(m,3H),5.07(d,J=6.9Hz,1H),5.01(d,J=6.9Hz,1H),3.26-2.53(m,4H),2.20-2.15(m,2H),0.99(s,3H).

[0899] Compound 40

[0900] LC-MS[M+1] + =553.44

[0901] 1H NMR(400MHz,DMSO-d6)δ8.79(d,J=7.4Hz,1H),8.69-8.66(m,1H),8.22(dd,J=7.9,1.5Hz,1H),7.99(dd,J=12.0,1.9Hz,1H),7.81-7.59(m,2H),7.44-7 .31(m,2H),7.25(dd,J=7.3,2.1Hz,1H),5.07(d,J=6.9Hz,1H),5.01(d,J=6 .7Hz,1H),4.70(s,1H),3.25-2.61(m,4H),2.20-2.15(m,2H),1.51(s,3H).

[0902] Example 41: Synthesis of Compound 41

[0903] Synthesis of compound 41-1

[0904] 10 g of 4-bromo-2-fluorophenylacetic acid was dissolved in 20 mL of THF. At 0 °C, 47.20 mL of 2 M magnesium chloride was added dropwise, followed by 7.15 g of epichlorohydrin. The mixture was stirred at 0 °C for 1 hour. After further addition of 21.46 mL of 2 M magnesium chloride, the temperature was raised to 60 °C and stirred for 18 hours. The temperature was then lowered to -20 °C and quenched with 10 mL of 6 M HCl. Extraction was performed with EA (3 x 100 mL). The organic phases were combined, dried, concentrated, and purified to give compound 41-1.

[0905] LC-MS[M+1] + =287.1

[0906] Synthesis of compound 41-2

[0907] Compound 41-1 (1.8 g) and triethylamine (756.04 mg) were dissolved in tert-butanol (18 mL), and diphenyl azidophosphate (2.06 g) was added. The mixture was heated to 80 °C and stirred for 18 hours. After concentration and purification, compound 41-2 was obtained.

[0908] LC-MS[M+1] + =286.0

[0909] Synthesis of compound 41-3

[0910] Compound 41-2 (1.55 g) was dissolved in isopropanol (18 mL) and water (18 mL), and KOH (1.52 g) was added. The mixture was heated to 100 °C and stirred for 5 hours. The solution was concentrated and extracted with DCM (3 x 20 mL). The organic phases were combined, dried, concentrated, and purified to obtain compound 41-3.

[0911] LC-MS[M+1] + =260.1

[0912] Synthesis of compound 41-4

[0913] Compound 41-3 (1.4 g) was dissolved in THF (20 mL), and TEA (2.18 g) and (Boc)₂O (2.33 g) were added respectively. The mixture was stirred at 30 °C for 2 hours. Compound 41-4 was obtained by concentration and purification.

[0914] LC-MS[M+Na] + =382.2

[0915] Synthesis of Compound 41-5

[0916] Compound 41-4 (240 mg) was dissolved in DCM (5 mL), and DMP (290.49 mg) was added. After stirring at 30 °C for 2 hours, saturated Na2SO3 (10 mL) and saturated NaHCO3 (10 mL) were added to quench the reaction. The mixture was then extracted with DCM (3 x 20 mL). The organic phases were combined, dried, concentrated and purified to obtain compound 41-5.

[0917] LC-MS[M+Na] + =380.1

[0918] Synthesis of Compound 41-6

[0919] Compound 41-5 (200 mg) was dissolved in THF (5 mL), and methyl magnesium bromide (3 M, 837.52 μL) was added dropwise at 0 °C. The mixture was stirred at 0 °C for 2 hours. The reaction solution was poured into ice-cold saturated NH4Cl (20 mL), extracted with EA (3 x 20 mL), and the organic phases were combined, dried, concentrated, and purified to give compound 41-6.

[0920] LC-MS[M+Na] + =396.1

[0921] Synthesis of Compound 41-7

[0922] Compound 41-6 (27 mg), bis(boron) (20.77 mg), and KOAc (14.16 mg) were dissolved in dioxane (1 mL), and Pd(dppf)Cl2 (5.27 mg) was added. The mixture was heated to 100 °C and reacted under nitrogen protection for 3 hours. The crude compound 41-7 was concentrated and used directly in the next reaction step.

[0923] Synthesis of Compounds 41-8

[0924] Compound 1-16A (15 mg) was dissolved in 1,4-dioxane (1 mL) and water (0.1 mL). Compound 41-7 (24.32 mg), XPhos Pd G2 (3.02 mg), X-PHOS (3.66 mg), and K3PO4 (24.48 mg) were added. The mixture was purged with nitrogen and stirred at 100 °C for 2 hours. The reaction mixture was concentrated to dryness, dissolved in methanol, and purified to give compound 41-8.

[0925] LC-MS[M+1] + =649.5

[0926] Synthesis of compounds 41 and 42

[0927] Compound 41-8 (18 mg) was dissolved in HCl-Dioxane (3 mL) and reacted at 25 °C for 2 hours. After concentration, the mixture was purified by Pre-HPLC ((0.1% FA)H2O-ACN, Welch Ultimate 10 μm 21.2*250 mm) to obtain compound 41 (shorter retention time) and compound 42 (longer retention time).

[0928] Compound 41

[0929] LC-MS[M+1] + =540.2

[0930] 1 H-NMR (400MHz, CDCl3) δ8.44-8.40(m,2H),7.62(s,1H),7.38-7.34(m,3H),7.20(d,J=7.7Hz,2H),7.00-6.59( m,2H),5.09(d,J=6.6Hz,1H),4.89(d,J=6.9Hz,1H),3.43-3.26(m,4H),2.71-2.50(m,4H),1.30-1.25(m,4H).

[0931] Compound 42

[0932] LC-MS[M+1] + =540.2

[0933] 1H-NMR (400MHz, CDCl3) δ8.42-8.37(m,2H),7.60-7.36(m,3H),7.30(s,1H),7.26-7.21(m,2H),6.98-6.61 (m,2H),5.07(d,J=6.9Hz,1H),4.88(d,J=7.1Hz,1H),3.42-3.25(m,4H),2.81-2.61(m,5H),1.26(s,3H).

[0934] Example 43: Synthesis of Compound 43

[0935] Synthesis of Compound 43-1

[0936] Compound 41-5 (200 mg) was dissolved in toluene (2 mL), and bis(2-methoxyethyl)aminosulfur trifluoride (1 mL) was added. The mixture was stirred at 50 °C for 2 hours. Saturated NaHCO3 (10 mL) was added to quench the reaction, and the mixture was extracted with EA (3 x 10 mL). The organic phases were combined, dried, concentrated, and purified to give compound 43-1.

[0937] LC-MS[M+1] + =324.0

[0938] Synthesis of Compound 43-2

[0939] Compound 43-1 (30 mg), pinacol diborate (22.04 mg), and potassium acetate (22.18 mg) were dissolved in 1,4-dioxane (0.6 mL). Pd(dppf)Cl2 (5.76 mg) was added, and the mixture was heated to 80 °C and stirred for 2 hours. After the reaction was complete, the reaction solution was used directly for the next reaction.

[0940] LC-MS[M+1] + =372.3

[0941] Synthesis of compound 43-3

[0942] Compound 1-16A (15 mg) was dissolved in 1,4-dioxane / water (0.6 mL, V / V = 10 / 1), and compound 43-2 (28.81 mg), XPhos Pd G2 (3.02 mg), X-PHOS (3.67 mg), and K3PO4 (24.48 mg) were added. The mixture was then purged with nitrogen, and the reaction was stirred at 100 °C for 2 hours. After concentration and purification, compound 43-3 was obtained.

[0943] LC-MS[M+1] + =655.4

[0944] Synthesis of Compound 43

[0945] Compound 43-3 (17 mg) was added to DCM (1 mL), followed by HCl / dioxane (1 mL). The mixture was stirred at 25 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, dissolved in methanol, and the pH was adjusted to alkaline by adding two drops of ammonia. After concentration and purification, compound 43 was obtained.

[0946] LC-MS[M+1] + =555.4

[0947] 1 H-NMR (400MHz, CDCl3) δ8.43 (d, J = 7.7Hz, 2H), 7.63 (s, 1H), 7.39-7.29 (m, 3H), 7.25-7.20 (m, 2H), 6.96-6.60 (m, 2H), 5 .10(d,J=6.6Hz,1H),4.90(d,J=7.1Hz,1H),3.43(s,3H),3.30-3.12(m,3H),2.93-2.86(m,2H),2.64(d,J=13.2Hz,1H).

[0948] Example 44: Synthesis of Compound 44

[0949] Synthesis of Compound 44-1

[0950] 1.3 g of 5-bromo-2-iodopyridin-3-ol and 839.59 mg of 2-bromocyclobutanone were dissolved in 13 mL of DMF, and 919.00 mg of Na2CO3 was added. The mixture was reacted at 50 °C for 16 hours. The reaction solution was poured into 100 mL of water, extracted with ethyl acetate (2 x 200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain purified compound 44-1.

[0951] LC-MS[M+1] + =368.0

[0952] Synthesis of compound 44-2

[0953] Compound 44-1 (197.63 mg) and tert-butylsulfinamide (197.63 mg) were added to THF (3 mL), followed by tetraisopropyl phthalate (286.98 mg). The reaction mixture was incubated at 70 °C for 16 hours. The reaction mixture was cooled, and 3 mL of water was added, causing a solid to precipitate. The solid was filtered, and the filtrate was concentrated and purified under reduced pressure to obtain compound 44-2.

[0954] LC-MS[M+1] + =471.1

[0955] 1 H-NMR (400MHz, CDCl3) δ8.13 (d, J=1.6Hz, 1H), 7.46 (dd, J=13.2, 1.9Hz, 1H), 5.36 (d, J= 6.9Hz,1H),3.80-3.33(m,1H),3.28-3.09(m,1H),2.74-2.47(m,2H),1.27-1.23(m,9H)

[0956] Synthesis of compound 44-3

[0957] Compound 44-2 (50 mg) was added to toluene (1 mL), the mixture was cooled to -78 °C, and a mixture of sec-butylmagnesium chloride and lithium chloride (212.25 μmol, 163.27 μL) was slowly added dropwise. The reaction was maintained at -78 °C for 1 hour. The reaction solution was then poured into saturated ammonium chloride (50 mL), concentrated and purified under reduced pressure to obtain compound 44-3.

[0958] LCMS[M+1] + =435.1

[0959] Synthesis of compound 44-4

[0960] Compound 44-3 (35 mg), pinacol diboryl ester (25.74 mg), and Pd(dppf)Cl2 (3.70 mg) were dissolved in 1,4-dioxane (1 mL), and KOAc (29.80 mg) was added. Under nitrogen protection, the mixture was heated to 105 °C and stirred for 2 hours. The reaction solution was directly concentrated to obtain compound 44-4, which was used directly in the next step.

[0961] LCMS[M+1] + =311.2

[0962] Synthesis of compound 44-5

[0963] Compound 1-16A (30.00 mg) and compound 44-4 (26.00 mg) were dissolved in a mixed solution of 1,4-dioxane (1 mL) and water (0.2 mL). Xphos-Pd-G2 (4.03 mg), Xphos (4.88 mg), and K3PO4 (32.63 mg) were added, and the mixture was purged with nitrogen and stirred at 102 °C for 2 hours. The reaction mixture was concentrated and purified to give compound 44-5.

[0964] LCMS[M+1] + =620.4

[0965] Synthesis of Compound 44

[0966] Compound 44-5 (26 mg) was dissolved in DCM (1 mL), and TFA (0.3 mL) was added. The mixture was stirred at room temperature (30 °C) for 1 hour. The reaction solution was concentrated, dissolved in methanol (2 mL), and two drops of ammonia were added to make it alkaline. The mixture was filtered, and the filtrate was concentrated and purified to obtain compound 44.

[0967] LC-MS[M+1] + =534.4

[0968] 1 H-NMR (400MHz, CDCl3) δ8.44(t,J=7.0Hz,3H),7.64(s,1H),7.32(s,1H),7.25-7.21(m,1H),6.96-6.59(m,2H),5.11(d,J=6.9Hz,1H),5.03(dd,J=7 .3,5.4Hz,1H),4.90(d,J=6.9Hz,1H),3.44(s,3H),3.32-3.25(m,1H),2. 66-2.56(m,2H),2.45-2.41(m,1H),2.30-2.20(m,1H),2.02-1.82(m,2H).

[0969] Example 45

[0970] Compound 45 was synthesized using the same synthesis and purification methods as compound 15.

[0971] LC-MS[M+1] + =504.4

[0972] 1 H-NMR (400MHz, CDCl3) δ8.44-8.41(m,3H),7.63(s,1H),7.27(s,2H),7.22(t,J=7.8Hz,1H),6.95-6.58(m,2H),5.10(d,J=6.6 Hz,1H),4.89(d,J=6.9Hz,1H),4.38-4.26(m,2H),3.43(s,3H),3.31-3.25(m,1H),2.64(d,J=13.2Hz,1H),2.17-2.11(m,2H).

[0973] Example 46

[0974] Following the synthesis and purification methods of compound 15, compound 46 was synthesized.

[0975] LC-MS[M+1] + =506.4.

[0976] 1 H NMR (400MHz, DMSO-d6) δ8.75(d,J=7.4Hz,1H),8.48(d,J=2.0Hz,1H),8.22(dd,J=7.9,1.6Hz,1H),7.78-7.42(m,3H),7.38-7.30(m,2H),7.21(dd,J=7 .4,2.1Hz,1H),5.58(s,1H),5.07(d,J=6.9Hz,1H),5.00(d,J=6.6Hz,1H),4 .34-4.21(m,2H),3.29-3.24(m,4H),2.52-2.51(m,1H),2.13-1.98(m,2H).

[0977] Examples 47 and 48

[0978] Compounds 47 and 48 were synthesized using the same methods as those used for the synthesis and purification of compound 14.

[0979] Compound 47

[0980] LC-MS[M+1] + =560.4

[0981] 1 H-NMR (400MHz, CDCl3) δ8.96(s,2H),8.53(d,J=8.2Hz,1H),8.42(d,J=8.8Hz,1H),7.61(d,J=1.1Hz,1H),6.97-6.92(m,2H),4.98(d ,J=7.1Hz,2H),4.82(d,J=6.0Hz,1H),3.35-3.28(m,1H),3.04-3.01(m,2H),2.93-2.90(m,2H),2.73(d,J=13.2Hz,1H),1.77(s,3H).

[0982] Compound 48

[0983] LC-MS[M+1] + =560.3.

[0984] Examples 49 and 50

[0985] Following the synthesis and purification methods of compound 42, compounds 49 and 50 were synthesized.

[0986] Compound 49

[0987] LC-MS[M+1] + =534.46

[0988] Compound 50

[0989] LC-MS[M+1] + =534.46.

[0990] Example 51

[0991] Following the synthesis and purification methods of compound 42, compound 51 was synthesized.

[0992] LC-MS[M+1] + =547.4

[0993] 1 H-NMR (400MHz, CD3OD) δ8.54(s,1H),8.34(s,1H),7.55(s,1H),7.32-7.22(m,3H),7.12-7.03(m,1H),7.00-6.89( m,1H),4.98-4.92(m,2H),3.12-2.22(m,1H),2.78-2.77(m,2H),2.68-2.66(m,1H),2.56-2.55(m,2H),1.20(s,3H)

[0994] Example 52

[0995] Following the synthesis and purification methods of compound 42, compound 52 was synthesized.

[0996] LC-MS[M+1] + =535.4

[0997] Example 53

[0998] Following the synthesis and purification methods of compound 43, compound 53 was synthesized.

[0999] LC-MS[M+1] + =572.4

[1000] 1H NMR (400MHz, CD3OD) δ8.56(d,J=7.1Hz,1H),8.33(d,J=8.8Hz,1H),7.65(d,J=1.1Hz,1H),7.52-7.45(m,3H),7.16(dd,J=7.1,2.2Hz,1H),7.09(d, J=8.8Hz,1H),5.12(d,J=7.1Hz,1H),4.98(d,J=14.8Hz,1H),3.40-3.34( m,1H),3.21(q,J=13.0Hz,2H),2.94-2.85(m,2H),2.69(d,J=13.2Hz,1H).

[1001] Example 54

[1002] Following the synthesis and purification methods of compound 43, compound 54 was synthesized.

[1003] LC-MS[M+1] + =505.4

[1004] Example 55

[1005] Following the synthesis and purification methods of compound 43, compound 55 was synthesized.

[1006] LC-MS[M+1] + =519.4

[1007] 1 H NMR (400MHz, CD3OD) δ8.56(d,J=8.2Hz,1H),8.34(d,J=9.3Hz,1H),7.63(t,J=1.1Hz,1H),7.50-7.40(m,3H),7.16(dd,J=7.1,2.2Hz,1H),7.09(d, J=8.8Hz,1H),5.12(d,J=7.1Hz,1H),4.98(d,J=14.8Hz,1H),3.40-3.35( m,1H),2.71-2.65(m,3H),2.33-2.20(m,3H),1.84(qd,J=9.8,5.1Hz,1H).

[1008] Example 56

[1009] Following the synthesis and purification methods of compound 43, compound 56 was synthesized.

[1010] LC-MS[M+1] + =540.23.

[1011] Example 57

[1012] Following the synthesis and purification methods of compound 43, compound 57 was synthesized.

[1013] LC-MS[M+1] + =558.4.

[1014] 1 H NMR (400MHz, CD3OD) δ8.53(dd,J=7.4,0.5Hz,1H),8.29(dd,J=8.1,1.2Hz,1H),7.72(t,J=1.0Hz,1H),7.53-7.04(m,7H),5.14(d,J=6 .6Hz,1H),5.03(d,J=6.9Hz,1H),3.35(t,J=6.9Hz,1H),3.21(q,J=13.1Hz,2H),2.90(td,J=13.6,9.4Hz,2H),2.60(d,J=13.5Hz,1H).

[1015] Example 58

[1016] Following the synthesis and purification methods of compound 21, compound 58 was synthesized.

[1017] LC-MS[M+1] + =546.46

[1018] Example 59

[1019] Following the synthesis and purification methods of compound 43, compound 59 was synthesized.

[1020] LC-MS[M+1] + =501.4

[1021] 1H-NMR (400MHz, DMSO-d6) δ8.76-8.73(m,1H),8.24(t,J=9.2Hz,1H),7.72(d,J= 8.4Hz,2H),7.60(d,J=8.4Hz,3H),7.28(d,J=8.8Hz,1H),7.20(dd,J=7.7,2.2Hz ,1H),5.14(d,J=7.2Hz,1H),4.78(d,J=6.4Hz,1H),3.11-3.24(m,1H),2.68-2.6 0(m,1H),2.46(s,2H),2.33-2.24(m,2H),2.11-1.99(m,1H),1.78-1.67(m,1H).

[1022] Example 60

[1023] Following the synthesis and purification methods of compound 43, compound 60 was synthesized.

[1024] LC-MS[M+1] + =520.4

[1025] 1 H-NMR (400MHz, CDCl3) δ9.15 (s, 1H), 9.04-9.01 (m, 1H), 8.47 (d, J = 7.7Hz, 1H), 8.40-8.37 (m, 1H), 8.11 (s, 1H), 7.52-7.46 (m, 1H), 6.95-6.89 (m ,1H),4.96-4.90(m,1H),4.50(s,1H),3.16(q,J=6.4Hz,1H),2.79-2.74 (m,2H),2.64(d,J=13.2Hz,3H),2.37(d,J=8.2Hz,1H),2.09-2.05(m,1H)

[1026] Example 61

[1027] Following the synthesis and purification methods of compound 43, compound 61 was synthesized.

[1028] LC-MS[M+1] + =525.4

[1029] 1H-NMR (400MHz, CDCl3) δ8.47-8.37(m,2H),7.96(d,J=23.9Hz,1H),7.60-7.52(m,1H),7.00-6. 87(m,2H),4.93(d,J=7.2Hz,1H),4.77(d,J=6.4Hz,1H),3.35-3.25(m,1H),3.07-2.21(m,7H).

[1030] Example 62

[1031] Following the synthesis and purification methods of compound 43, compound 62 was synthesized.

[1032] LC-MS[M+1] + =511.2

[1033] 1 H NMR (400MHz, DMSO-d6) δ8.71(d,J=7.4Hz,1H),8.23(d,J=8.1Hz,1H),8.20(s,1 H),7.8–7.48(m,2H),7.41(d,J=8.6Hz,1H),7.35(d,J=8.1Hz,1H),7.21(dd,J= 7.5,2.1Hz,1H),5.06(d,J=6.9Hz,1H),4.99(d,J=6.6Hz,1H),3.31–3.25(m,1H ),2.58–2.56(m,2H),2.49–2.45(m,1H),2.21–2.14(m,2H),2.00–1.89(m,2H).

[1034] Examples 63 and 64

[1035] Following the synthesis and purification methods of compound 14, compounds 63 and 64 were synthesized.

[1036] Compound 63

[1037] LC-MS[M+1] + =558.4

[1038] 1H NMR (400MHz, CDCl3) δ8.46-8.40(m,2H),7.63(d,J=8.5Hz,2H),7.58-7.52(m,3H),6.99(dd,J=7.6,2.1Hz,1H),6.93(q,J=4.4Hz,1H),4.96(d,J=7 .1Hz,1H),4.80(d,J=6.3Hz,1H),3.34-3.27(m,1H),3.23-3.20(m,2H),2 .71(d,J=12.9Hz,1H),2.57(dd,J=11.5,2.2Hz,2H),1.80(d,J=4.7Hz,3H)

[1039] Compound 64

[1040] LC-MS[M+1] + =558.4.

[1041] 1 H-NMR (400MHz, CDCl3) δ8.44-8.40(m,2H),7.62-7.57(m,3H),7.50-7.47(m,2H),6.98-6.93(m,2H),4.95(d,J=6 .9Hz,1H),4.79(d,J=6.3Hz,1H),3.33-3.27(m,1H),3.04-3.01(m,2H),2.76-2.69(m,3H),1.52(d,J=9.3Hz,3H)

[1042] Examples 65 and 66

[1043] Following the synthesis and purification methods of compound 26, compounds 65 and 66 were synthesized.

[1044] Compound 65

[1045] LC-MS[M+1] + =534.34

[1046] 1 H NMR (400MHz, DMSO-d6) δ8.90(s,2H),8.73(s,1H),8.24(d,J=8.9Hz,1H),7.32(s,1H),7.28(d,J=8.9Hz,1H),5.13( d,J=6.9Hz,1H),4.73(d,J=6.2Hz,1H),3.30-3.24(m,1H),2.67-2.58(m,3H),2.18-2.12(m,5H),2.05-1.82(m,2H).

[1047] Compound 66

[1048] LC-MS[M+1] + =534.4

[1049] Example 67

[1050] Following the synthesis and purification methods of compound 43, compound 67 was synthesized.

[1051] LC-MS[M+1] + =539.4

[1052] Example 68

[1053] Following the synthesis and purification methods of compound 43, compound 68 was synthesized.

[1054] LC-MS[M+1] + =509.2

[1055] 1 H-NMR (400MHz, CDCl3) δ8.41(d,J=8.8Hz,1H),8.35(d,J=7.4Hz,1H),7.64(s,1H),7.33(d,J=18.4Hz,1H),6.94-6.90(m,2H),4.94( d,J=6.9Hz,1H),4.78(d,J=6.3Hz,1H),3.32-3.26(m,1H),2.83(s,2H),2.71(d,J=13.2Hz,1H),2.62(s,2H),2.26(d,J=71.5Hz,2H)

[1056] Example 69

[1057] Following the synthesis and purification methods of compound 43, compound 69 was synthesized.

[1058] LC-MS[M+1] + =511.2

[1059] 1H-NMR (400MHz, CD3OD) δ8.49(d,J=7.1Hz,1H),8.33(d,J=9.3Hz,1H),7.94-7.90(m,1H),7.52-7.49(m,1H),7.14- 7.08(m,2H),5.10(d,J=7.1Hz,1H),4.57(s,2H),3.36(q,J=6.8Hz,1H),2.68(d,J=13.2Hz,1H),1.43-1.22(m,5H).

[1060] Example 70

[1061] Following the synthesis and purification methods of compound 43, compound 70 was synthesized.

[1062] LC-MS[M-NH3] + =596.3

[1063] 1 H-NMR (400MHz, CDCl3) δ8.42-8.35(m,2H),7.89(s,1H),7.52-7.49(m,1H),7.00-6.83(m,2H),4.93(d ,J=6.4Hz,1H),4.79-4.75(m,1H),3.31-3.24(m,1H),2.70(dd,J=13.2,4.4Hz,1H),2.05-1.64(m,6H)

[1064] Example 71: Synthesis of Compound 71

[1065] Synthesis of Compound 71-1

[1066] Compound 21-1A (500 mg) was dissolved in a 15 mL, 30% sodium methoxide methanol solution. The reaction mixture was stirred at 80 °C for 2 hours. The reaction mixture was concentrated, and the residue was purified by reversed-phase chromatography to give compound 71-1.

[1067] LC-MS[M+1] + =343.2.

[1068] Synthesis of Compound 71-2

[1069] Compound 71-1 (300 mg) was dissolved in dry tetrahydrofuran (10 mL), and NaH (700 mg) was added at 0 °C with stirring for half an hour. Heavy water (3 mL) and diethyl bromofluoromethylphosphonate (700 mg) were added to the reaction solution, and the reaction solution was stirred for 2 hours. The reaction solution was concentrated and purified to obtain compound 71-2.

[1070] LC-MS[M+1] + =394.2.

[1071] Synthesis of Compound 71-3

[1072] Compound 71-2 (180 mg) and compound 1-4 (190 mg) were dissolved in Dioxane (5 mL), and X-phos Pd G2 (36 mg), X-phos (22 mg), and K3PO4 (291 mg) were added sequentially. The mixture was purged with nitrogen and stirred at 100 °C for 2 hours. The reaction solution was concentrated and purified to obtain compound 71-3.

[1073] LC-MS[M+1] + =611.4.

[1074] Synthesis of Compound 71

[1075] Compound 71-3 (230 mg) was dissolved in dioxane (2 mL), and 4 M / L dioxane hydrochloride solution (1 mL) was added. The reaction mixture was stirred at 25 °C for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was prepared by high performance liquid chromatography (formic acid) to obtain compound 71.

[1076] LC-MS[M+1] + =507.27

[1077] 1 H NMR(400MHz, DMSO-d6)9.20(s,2H),8.87(d,J=7.3Hz,1H),8.25–8.24(m,1H),7.74(s,1H),7.42–7.40(m,1H),7.36(t,J=8.0Hz,2H),5.1 1(d,J=6.9Hz,1H),5.05(d,J=6.6Hz,1H),3.33–3.28(m,1H),2.71–2.64(m,2H),2.59–2.56(m,1H),2.27–2.20(m,2H),2.06–1.89(m,2H).

[1078] Example 72

[1079] Following the synthesis and purification methods of compound 2, compound 72 was synthesized.

[1080] LC-MS[M+1] + =515.40

[1081] 1H NMR(400MHz, DMSO-d6)δ9.15(s,2H),8.78(dd,J=7.3,1.0Hz,1H),8.26(s,1H),7.89(s,1H),7.67-7.65(m,1H),7.31(d,J=8.9Hz, 1H),7.00(dd,J=7.3,1.9Hz,1H),5.16(d,J=6.9Hz,1H),4.78(d,J=6.3Hz,1H),3.29(s,3H),3.27–3.24(m,1H),2.63–2.59(m,1H).

[1082] Example 73

[1083] Following the synthesis and purification methods of compound 43, compound 73 was synthesized.

[1084] LC-MS[M-NH3] + =550.23

[1085] Example 74

[1086] Following the synthesis and purification methods of compound 43, compound 74 was synthesized.

[1087] LC-MS[M-NH3] + =553.17

[1088] Example 75

[1089] Following the synthesis and purification methods of compound 43, compound 75 was synthesized.

[1090] LC-MS[M-NH3] + =537.37

[1091] Example 76

[1092] Following the synthesis and purification methods of compound 43, compound 76 was synthesized.

[1093] LC-MS[M-NH3] + =533.34

[1094] Example 77

[1095] Following the synthesis and purification methods of compound 43, compound 77 was synthesized.

[1096] LC-MS[M+1] + =554.28

[1097] 1 H NMR (400MHz, DMSO-d6) δ9.18(d,J=4.9Hz,1H),8.85(d,J=7.5Hz,1H),8.32(s,1H),8.27(d,J=9.0Hz,1H),8.16(d,J=2.0Hz,1H),7.5 8(dd,J=7.5,2.1Hz,1H),7.31(d,J=8.9Hz,1H),5.19(d,J=7.0Hz,1H),4.85(d,J=6.3Hz,1H),3.25–2.62(m,6H),2.17-2.07(m,2H).

[1098] Example 78

[1099] Following the synthesis and purification methods of compound 43, compound 78 was synthesized.

[1100] LC-MS[M+1] + =555.3

[1101] Example 79

[1102] Following the synthesis and purification methods of compound 43, compound 79 was synthesized.

[1103] LC-MS[M+1] + =534.19

[1104] 1 H NMR (400MHz, DMSO-d6) δ9.18(d,J=4.9Hz,1H),8.85(d,J=7.5Hz,1H),8.32(s,1H),8.27(d,J=9.0Hz,1H),8.16(d,J=2.0Hz,1H),7.5 8(dd,J=7.5,2.1Hz,1H),7.31(d,J=8.9Hz,1H),5.19(d,J=7.0Hz,1H),4.85(d,J=6.3Hz,1H),3.25–2.62(m,6H),2.17-2.07(m,2H).

[1105] Example 80

[1106] Following the synthesis and purification methods of compound 43, compound 80 was synthesized.

[1107] LC-MS[M+1]+=525.31

[1108] 1H NMR (400MHz, DMSO-d6) δ8.70(d,J=7.4Hz,1H),8.25(d,J=8.9Hz,1H),8.20(s,1H),7.43(d,J=2.0Hz,1H),7.28(d,J=8.9Hz,1H),7.21(dd,J =7.4,2.1Hz,1H),5.13(d,J=7.0Hz,1H),4.76(d,J=6.2Hz,1H),3.28–3.23(m,1H),2.62–2.54(m,3H),2.20–2.13(m,2H),1.99–1.86(m,2H).

[1109] Examples 81 and 82

[1110] Following the synthesis and purification methods of compound 42, compounds 81 and 82 were synthesized.

[1111] Compound 81

[1112] LC-MS[M+1] + =548.34

[1113] Compound 82

[1114] LC-MS[M+1] + =548.37

[1115] Examples 83 and 84

[1116] Following the synthesis and purification methods of compound 14, compounds 83 and 84 were synthesized.

[1117] Compound 83

[1118] LC-MS[M+1] + =565.3

[1119] 1 H-NMR (400MHz, CDCl3) δ8.34-8.30(m,2H),7.86(d,J=6.9Hz,1H),7.45-7.43(m,1H),6.86(d,J=8.8Hz,1H),6.81(dd,J=7.4,2.2Hz, 1H),4.87(d,J=7.1Hz,1H),4.70(d,J=6.3Hz,1H),3.51(s,1H),3.25-3.18(m,1H),2.96-2.85(m,4H),2.67-2.61(m,1H),1.62(s,3H)

[1120] Compound 84

[1121] LC-MS[M+1] + =565.4

[1122] 1 H-NMR (400MHz, CDCl3) δ8.34-8.31(m,2H),7.87(s,1H),7.45(d,J=1.4Hz,1H),6.88-6.81(m,2H),4.87(d,J=6.9Hz,1H),4.71 (d,J=6.3Hz,1H),3.33-3.27(m,3H),3.21(q,J=6.7Hz,1H),2.63(d,J=13.2Hz,1H),2.52(dd,J=10.6,3.4Hz,2H),1.73(s,3H)

[1123] Example 85

[1124] Following the synthesis and purification methods of compound 43, compound 85 was synthesized.

[1125] LC-MS[M+1] + =519.4

[1126] 1 H NMR (400MHz, CDCl3) δ8.89 (d, J = 20.0Hz, 1H), 8.48-8.37 (m, 2H), 8.01-7.77 (m, 3H), 7.41 (d, J = 6.0Hz, 1H), 6.92 (dd, J = 15.4, 8. 8Hz,1H),4.97-4.91(m,1H),4.68(d,J=6.0Hz,1H),3.26-3.20(m,1H),2.68-2.62(m,3H),2.43-2.29(m,2H),1.87-1.81(m,2H).

[1127] Example 86

[1128] Following the synthesis and purification methods of compound 14, compound 85 was synthesized.

[1129] LC-MS[M+1] + =557.5

[1130] 1H-NMR (400MHz, CDCl3) δ8.44-8.40(m,2H),7.62-7.39(m,5H),7.00-6.93(m,2H),4.95(d,J=6.9Hz,1H),4.79(dd,J =6.3,2.5Hz,1H),3.33-3.21(m,2H),2.86(d,J=12.9Hz,1H),2.73-2.69(m,2H),2.46(d,J=12.9Hz,1H),1.78(s,3H)

[1131] Example 87

[1132] Following the synthesis and purification methods of compound 14, compound 87 was synthesized.

[1133] LC-MS[M+1] + =558.4

[1134] 1 H-NMR (400MHz, CDCl3) δ8.44-8.40(m,2H),7.62-7.57(m,3H),7.50-7.47(m,2H),6.98-6.93(m,2H),4.95(d,J=6 .9Hz,1H),4.79(d,J=6.3Hz,1H),3.33-3.27(m,1H),3.04-3.01(m,2H),2.76-2.69(m,3H),1.52(d,J=9.3Hz,3H)

[1135] Example 88

[1136] Following the synthesis and purification methods of compound 43, compound 88 was synthesized.

[1137] LC-MS[M+1] + =520.4

[1138] 1 H-NMR (400MHz, CDCl3) δ8.94(s,2H),8.59(s,1H),8.47-8.38(m,2H),7.82-7.80(m,1H),6.92(d,J=8.8Hz,1H),4.96(d, J=7.1Hz,1H),4.83(d,J=6.3Hz,1H),3.34-3.27(m,1H),2.71-2.63(m,3H),2.34(d,J=6.6Hz,3H),1.87(d,J=8.5Hz,1H)

[1139] Example 89: Synthesis of Compound 89

[1140] Synthesis of Compound 89-2

[1141] At room temperature, methyl magnesium bromide (3M, 1.5 mL) was added to a mixed solution of compound 89-1 (530 mg) and toluene (9 mL), and the mixture was stirred at 50 °C for 4 hours. The reaction was cooled to room temperature and then slowly added to saturated ammonium chloride (50 mL). The mixture was extracted with ethyl acetate (50 x 3 mL), and the organic phases were combined, dried, concentrated, and purified to give compound 89-2 (260 mg).

[1142] LC-MS[M+1] + =546.2

[1143] Synthesis of Compound 89-3

[1144] Iodine (181 mg) was added to a mixed solution of compound 89-2 (260 mg) in tetrahydrofuran / water (24 mL) at room temperature, and the mixture was stirred at 50 °C for 2 hours. After quenching with saturated sodium sulfite (30 mL), the aqueous phase was extracted with ethyl acetate (30 x 3 mL), the organic phases were combined, dried, concentrated and purified to give compound 89-3 (200 mg).

[1145] LC-MS[M+1] + =425.1

[1146] Synthesis of Compound 89-4

[1147] Compound 89-3 (50 mg) was dissolved in dioxane (5 mL), potassium carbonate (31.22 mg) and Xantphos (6.54 mg) were added, and the gas was purged once with a CO2 balloon. Then, palladium acetate (1.78 mg) was added, and the gas was purged three times with a CO2 balloon. The mixture was placed in an oil bath and heated to 110 °C, and stirred for 20 hours. LC-MS monitoring showed that the starting material disappeared, and most of the product was present. The reaction solution was quenched with water (30 mL), extracted with ethyl acetate (20 x 3 mL), and the organic phases were combined, washed with saturated brine, dried, concentrated, and purified to give compound 89-4 (12.00 mg).

[1148] LC-MS[M+1] + =390.2

[1149] Synthesis of Compound 89-5

[1150] Compound 89-4 (12 mg) and deuterated iodomethane (26.78 mg) were dissolved in DMF (1 mL). NaH (4.06 mg, 60% purity) was added at 0 °C, and the mixture was stirred at room temperature for 1 hour. After quenching with saturated ammonium chloride (10 mL), the mixture was extracted with ethyl acetate (20 x 3 mL). The organic phases were combined, dried, and concentrated to give compound 89-5 (15.00 mg).

[1151] LC-MS[M+1] + =407.2

[1152] Synthesis of compound 89-6

[1153] Compound 89-5 (50 mg) was dissolved in a mixed solution of dioxane / water (3 mL), and compounds 1-4 (93 mg), K3PO4 (52 mg), Xphos (12 mg), and Xphos-Pd-G2 (9.60 mg) were added. The mixture was purged with nitrogen and stirred at 100 °C for 2 hours. The reaction solution was then concentrated and purified by column chromatography (ethyl acetate:methanol = 30:1) to obtain compound 89-6 (50.00 mg).

[1154] LC-MS[M+1] + =624.5

[1155] Synthesis of Compound 89

[1156] Compound 89-6 (65 mg) was dissolved in a mixed solution of tetrahydrofuran / water (3 mL, 5 / 1), iodine (39.67 mg μmol) was added, nitrogen was purged, and the mixture was stirred at 50 °C for 4 hours. After quenching with saturated sodium sulfite (10 mL), the mixture was extracted with ethyl acetate (10 x 3 mL), the organic phases were combined, dried, concentrated and purified to obtain compound 89 (50.00 mg).

[1157] LC-MS[M+1] + =520.4

[1158] 1H-NMR (400MHz, CDCl3) δ8.96(d,J=4.9Hz,2H),8.73(d,J=4.9Hz,0H),8.50-8.43(m,2H),7.72(q,J=1.0Hz,1H),7.28(d,J=8.2Hz,1H),7.20(d, J=7.1Hz,1H),6.97-6.60(m,2H),4.99(d,J=7.1Hz,1H),3.21(dd,J=13.3,7.3Hz,1H),2.85-2.73(m,3H),2.26-2.13(m,3H),2.05-1.98(m,4H).

[1159] Examples 90 and 91

[1160] Compound 89 was chirally purified under SFC conditions in a CHIRALPAK column (250*30mm, IC, 10mm; flow rate 25mL / min; mobile phase: 40% HEX (0.2% DEA) + 60% Ethanol (0.2% DEA)) to obtain compound 90 (shorter retention time) and compound 91 (longer retention time).

[1161] Compound 90

[1162] LC-MS[M+1] + =520.22

[1163] 1 H NMR(400MHz, DMSO-d6)δ9.17(s,2H),8.84(d,J=7.3Hz,1H),8.23(d,J=2.0Hz,1H),7.80-7.60(m,2H),7.44 -7.36(m,1H),7.36-7.31(m,2H),4.91(d,J=7.1Hz,1H),2.90-2.70(m,2H),2.23-2.01(m,4H),1.95(s,3H),1.93-1.80(m,2H).

[1164] Compound 91

[1165] LC-MS[M+1] + =520.22

[1166] 1H NMR (400MHz, DMSO-d6) δ9.19 (s, 2H), 8.85 (d, J = 7.3Hz, 1H), 8.23 ​​(dd, J = 7.7, 1.8Hz, 1H), 7.82-7.59 (m, 2H), 7.43 -7.32(m,3H),4.91(d,J=7.1Hz,1H),2.75-2.61(m,4H),2.31-2.03(m,4H),1.95(s,3H).

[1167] Example 92

[1168] Following the synthesis and purification methods of compound 89, compound 92 was synthesized.

[1169] LC-MS[M+1] + =538.5

[1170] 1 H-NMR (400MHz, CDCl3) δ9.49(d,J=31.3Hz,2H),8.99(s,2H),8.47(dd,J=9.3,5.8Hz,2H),7.72(s,1H),7.09-6.71(m,3H),5.04(d,J=7.1Hz ,1H),3.23(dd,J=13.3,7.3Hz,1H),3.15-3.08(m,2H),2.91(dd,J=15.7,9.6Hz,2H),2.81(d,J=13.5Hz,1H),2.58-2.33(m,2H),2.03(s,3H)

[1171] Example 93

[1172] Following the synthesis and purification methods of compound 89, compound 93 was synthesized.

[1173] LC-MS[M+1] + =534.4

[1174] 1H-NMR (400MHz, CDCl3) δ9.32-9.54(s,2H),8.96(s,2H),8.41-8.60(d,J=7.1Hz,1H),8.34(d,J=8.5Hz,1H),7.69(s,1H),7.13(d,J=8.5Hz,1H ),6.39-6.97(m,2H),5.02(d,J=7.1Hz,1H),3.00-3.25(m,3H),2.80(m,3H),2.47-2.61(m,1H),2.36(d,J=17.0Hz,3H),2.02(d,J=3.6Hz,4H)

[1175] Examples 94 and 95

[1176] Following the synthesis and purification methods of compound 15, compounds 94 and 95 were synthesized.

[1177] Compound 94

[1178] LC-MS[M+1] + =540.43

[1179] 1 H NMR (400MHz, DMSO-d6) δ8.78(d,J=7.4Hz,1H),8.52(d,J=2.0Hz,1H),8.28(d,J=9.0Hz,1H),7.66(d,J=2.0Hz,1H),7.51(d,J=2.0Hz,1H),7.31(d,J =8.9Hz,1H),7.25(dd,J=7.4,2.1Hz,1H),5.17(d,J=7.0Hz,1H),4.80(d,J =6.2Hz,1H),3.25-3.20(m,1H),2.70-2.60(m,1H),2.04(d,J=2.6Hz,2H).

[1180] Compound 95

[1181] LC-MS[M+1] + =340.34

[1182] 1H NMR (400MHz, DMSO-d6) δ8.79(d,J=7.4Hz,1H),8.52(d,J=2.0Hz,1H),8.27(d,J=9.0Hz,1H),7.66(d,J=2.0Hz,1H),7.52(d,J=2.0Hz,1H),7.31(d,J =8.9Hz,1H),7.25(dd,J=7.4,2.1Hz,1H),5.17(d,J=7.0Hz,1H),4.80(d,J =6.2Hz,1H),3.23-3.19(m,1H),2.68-2.62(m,1H),2.05(d,J=2.6Hz,2H).

[1183] Examples 96 and 97

[1184] Following the synthesis and purification methods of compound 89, compounds 96 and 97 were synthesized.

[1185] Compound 96

[1186] LC-MS[M+1] + =523.3

[1187] 1 H NMR(400MHz, DMSO-d6)δ9.18(s,2H),8.86(d,J=7.4Hz,1H),8.25(dd,J=7.8,1.7Hz,1H),7.82-7.45(m,2H),7.41-7.33(m,3H),4.9 3(d,J=7.1Hz,1H),3.28(dd,J=13.5,7.2Hz,1H),2.73(d,J=13.5Hz,1H),2.69-2.62(m,2H),2.21-2.14(m,2H),2.08-1.83(m,2H).

[1188] Compound 97

[1189] LC-MS[M+1] + =523.3

[1190] 1H NMR(400MHz, DMSO-d6)δ9.18(s,2H),8.86(d,J=7.4Hz,1H),8.25(dd,J=7.8,1.7Hz,1H),7.85-7.43(m,2H),7.43-7.29(m,3H),4.9 3(d,J=7.1Hz,1H),3.28(dd,J=13.6,7.3Hz,1H),2.73(d,J=13.6Hz,1H),2.69-2.61(m,2H),2.22-2.12(m,2H),2.09-1.80(m,2H).

[1191] Example 98: Synthesis of Compound 98

[1192] Synthesis of compounds 98-1 and 98-2

[1193] Compound 1-12 (15 g) was dissolved in toluene (150 mL), and 3-methoxypropylamine (4.69 g) and PTSA (604.03 mg) were added. Under nitrogen protection, the mixture was stirred at 110 °C for 3 hours. The reaction solution was directly concentrated under reduced pressure, and the crude product was dissolved in acetonitrile (150 mL). Anhydrous sodium sulfate (24.90 g) and the selective fluoride reagent F-TEDA (37.28 g) were added. Under nitrogen protection, the mixture was stirred at 60 °C for 3 hours. The reaction solution was quenched with water (300 mL), and the pH was adjusted to acidic with 1 N hydrochloric acid. The mixture was extracted with ethyl acetate (100 mL x 3), washed with saturated brine (300 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a mixture of compounds 98-1 and 98-2 (2.5 g).

[1194] Compound 98-1

[1195] LC-MS[M+1] + =463.2

[1196] Compound 98-2

[1197] LC-MS[M+1] + =445.0

[1198] Synthesis of compounds 98-3 and 98-4

[1199] At room temperature, (R)-tert-butylsulfinamide (870.24 mg) was added to a mixed solution of compounds 98-1 and 98-2 (2.13 g) in tetraisopropyl titanate (15 mL), and the mixture was stirred at 85 °C for 16 hours. LC-MS showed that the starting material reacted completely. Tetrahydrofuran (THF) (15 mL) was added, and under nitrogen protection, sodium borohydride (1.52 g) was added at 0 °C. The mixture was then brought to room temperature and reacted for 2 hours. The reaction solution was slowly poured into ice water (20 mL), and a large amount of solid precipitated. The solid was filtered through diatomaceous earth, and the filtrate was extracted with ethyl acetate (20 x 2 mL). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to give a crude product mixture of compounds 98-3 and 98-4 (2.5 g).

[1200] Compound 98-3

[1201] LC-MS[M+1] + =568.2

[1202] Compound 98-4

[1203] LC-MS[M+1] + =550.3

[1204] Synthesis of compounds 98-5 and 98-6

[1205] Compounds 98-3 and 98-4 (2.50 g) were dissolved in a mixed solvent of tetrahydrofuran (30 mL) and water (6 mL), and elemental iodine (319.98 mg) was added. The reaction mixture was reacted at 50 °C for 3 hours. The reaction solution was poured into 10 mL of saturated sodium sulfite aqueous solution, extracted with ethyl acetate (20 x 3 mL), washed with saturated brine (10 mL), and the combined organic phases were dried over anhydrous sodium sulfate. The mixture was concentrated and purified to give a mixture of compounds 98-5 and 98-6 (260 mg).

[1206] Compound 98-5

[1207] LC-MS[M+1] + =464.1

[1208] Compound 98-6

[1209] LC-MS[M+1] + =446.1

[1210] Synthesis of Compound 98-7

[1211] Compound 98-5 (410 mg) was dissolved in 1,4-dioxane (5 mL), and Xantphos (175.40 mg), Pd2(dba)3 (138.83 mg), and potassium carbonate (418.78 mg) were added. The mixture was purged with CO gas three times, and the reaction solution was placed at 110 °C for 16 hours. The reaction solution was then directly concentrated and purified to obtain compound 98-7 (63 mg).

[1212] LCMS[M+1] + =412.1

[1213] Synthesis of Compound 98-8

[1214] Compound 98-7 (70 mg) was dissolved in N,N-dimethylformamide (1.5 mL), and deuterated iodomethane (49.29 mg) was added. Under nitrogen protection, NaH (13.60 mg, 60% purity) was added at 0 °C, and the mixture was heated to room temperature (20 °C) and reacted for 1 hour. The reaction solution was poured into a saturated ammonium chloride aqueous solution (1 mL), extracted with ethyl acetate (3 x 2 mL), washed with saturated brine (2 mL), and purified by drying with anhydrous sodium sulfate to obtain compound 98-8 (52 mg).

[1215] LC-MS[M+1]+=429.1

[1216] Synthesis of compound 98-9

[1217] Compound 98-8 (50 mg) was dissolved in a mixed solution of 1,4-dioxane (1 mL) and water (0.1 mL). Compound 1-4 (66.35 mg), XPhos-Pd-G2 (9.15 mg), XPhos (11.10 mg), and potassium phosphate (74.16 mg) were added. The mixture was purged with nitrogen and stirred at 100 °C for 1 hour. The reaction solution was concentrated and purified by preparative chromatography to obtain compound 98-9 (70 mg).

[1218] LC-MS[M+1] + =646.5

[1219] Synthesis of Compound 98

[1220] Compound 98-9 (67 mg) was added to a mixed solvent of tetrahydrofuran (2 mL) and water (0.2 mL), and elemental iodine (24.38 mg) was added. The reaction mixture was reacted at 50 °C for 1 hour. The reaction solution was poured into a saturated sodium sulfite aqueous solution (1 mL), extracted with ethyl acetate (1 x 2 mL), washed once with a saturated brine solution (2 mL), dried over anhydrous sodium sulfate, and the filtrate was concentrated and purified to give compound 98 (42 mg).

[1221] LC-MS[M+1]+ =542.2

[1222] 1 H-NMR (400MHz, CDCl3) δ8.98(s,2H),8.56(dd,J=7.3,1.0Hz,1H),8.41(dd,J=8.0,1.4Hz,1H),7.70(d,J=1.1Hz,1H),7.35(t,J=8.1Hz,1H),7.2 9(d,J=7.7Hz,1H),7.02-6.63(m,2H),5.43(d,J=12.6Hz,1H),4.98(d,J =11.8Hz,1H),2.90-2.83(m,2H),2.77-2.70(m,2H),2.40-2.17(m,2H).

[1223] Example 99

[1224] Following the synthesis and purification methods of compound 98, compound 99 was synthesized.

[1225] LC-MS[M+1] + =524.4

[1226] 1 H-NMR(400MHz, CDCl3)δ8.98(s,2H),8.53(dd,J=7.4,0.8Hz,1H),8.40(dd,J=8.0,1.6Hz,1H),7.69(d,J=1.1Hz,1H),7.35-7.27(m,2H), 7.01-6.65(m,2H),5.69(d,J=49.2Hz,1H),5.22(d,J=16.5Hz,1H),4.94(d,J=15.7Hz,1H),2.86(dd,J=14.8,6.9Hz,4H),2.16-2.52(2H).

[1227] Example 100: Synthesis of Compound 100

[1228] Synthesis of Compound 100-1

[1229] Compound 89-1 (3.5 g) was dissolved in THF (70 mL), purged with nitrogen, and allyl magnesium bromide (1 M, 13.19 mL) was added dropwise at -78 °C. After the addition was complete, the mixture was stirred at -78 °C for 2 hours. The reaction solution was quenched with saturated ammonium chloride (20 mL), extracted with ethyl acetate (30 x 2 mL), and the organic phases were combined, dried, concentrated, and purified to give compound 100-1 (3.20 g).

[1230] LC-MS[M+1] + =572.2

[1231] Synthesis of Compound 100-2

[1232] Potassium osmium tetroxide (289.41 mg) and NMO (920.20 mg) were added to an acetone / water (15 mL, 5 / 1) solution of compound 100-1 (1.5 g). The reaction mixture was stirred at 25 °C for 18 hours. The reaction solution was quenched in sodium sulfite, extracted with ethyl acetate (20 x 4 mL), and the organic phases were combined. The organic phases were washed with saturated sodium chloride (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give compound 100-2 (930 mg).

[1233] LC-MS[M+1] + =606.2

[1234] Synthesis of Compound 100-3

[1235] Lead tetraacetate (2.34 g) was added in portions over 5 minutes to a 32 mL solution of acetonitrile containing 930 mg of compound 100-2. The reaction mixture was stirred at room temperature for 1 hour. After filtration, the filtrate was collected, concentrated, and compound 100-3 (590 mg) was obtained.

[1236] LC-MS[M+1] + =574.2

[1237] Synthesis of Compound 100-4

[1238] The mixture was cooled to 0°C, and sodium borohydride (210.58 mg) was added in portions to a THF (32 mL) solution of compound 100-3 (590 mg). The reaction mixture was stirred at room temperature for 2 hours. After quenching with saturated ammonium chloride (10 mL), the mixture was extracted with ethyl acetate (20 x 3 mL), and the organic phases were combined, dried, concentrated, and purified to give compound 100-4 (520 mg).

[1239] LC-MS[M+1] + =576.2

[1240] Synthesis of Compound 100-5

[1241] The mixture was cooled to 0°C, and iodine (264 mg) was added in portions to a tetrahydrofuran / water (3 mL, 5 / 1) solution of compound 100-4 (520 mg). The reaction mixture was stirred at room temperature for 2 hours. After quenching with saturated sodium sulfite (20 mL), the mixture was extracted with ethyl acetate (20 x 3 mL), and the organic phases were combined, dried, concentrated, and purified to give compound 100-5 (345 mg).

[1242] LC-MS[M+1] + =472.2

[1243] Synthesis of Compound 100-6

[1244] Compound 100-5 (345 mg), TBSCl (108.41 mg), and imidazole (73.45 mg) were added to DCM (5 mL) and stirred at room temperature for 2 hours. The reaction solution was then concentrated and purified to obtain compound 100-6 (360 mg).

[1245] LCMS[M+1] + =586.3

[1246] Synthesis of Compound 100-7

[1247] Compound 100-6 (23 mg) was dissolved in dioxane (2 mL), potassium carbonate (120 mg), Pd2(dba)3 (15.59 mg), and XantPhos (19.69 mg) were added. The mixture was purged with CO gas th...

Claims

a compound represented by the formula (A-I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, T1is selected from N and C(R6); T2is selected from N and C(R7); T3is selected from N and C(R8); X1is selected from the group consisting of null, -0-, -S-, -N(R a )-, -C(=0)-, -C(=S)-, -S(=0)-, -S(=0)2-, -C(R b )2-, and -C(R b )2C(R b )2-; X2is selected from the group consisting of null, -0-, -S-, -N(R a )-, -C(=0)-, -C(=S)-, -S(=0)-, -S(=0)2-, -C(R b )2-, and -C(R b )2C(R b )2-; Z is selected from -C(R a )2-, -C(R b )2-, and -C(=R c )-; L1is selected from the group consisting of null, -O-, -S-, -N(R a )-, C 2-6 alkylene, C 2-6 alkyne, C 1-6 alkylene, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, and 4-10 membered heteroaryl; Ring A is selected from C 3-15 cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 cycloalkenyl, 5-15 membered heterocycloalkenyl, C 6-15 aryl and 5-15 membered heteroaryl; selected from the group consisting of When selected from the group consisting of R1is selected from H, D, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=O)-, C 1-6 alkyl-S(=O)-, C 1-6 alkyl-S(=O)2-, C 1-6 alkyl-O-C(=O)-, C 1-6 alkyl-O-S(=O)-, C 1-6 alkyl-O-S(=O)2-, C 1-6 alkyl-C(=O)-O-, C 1-6 alkyl-S(=O)-O-, C 1-6 alkyl-S(=O)(=NH)-O-, C 1-6 alkyl-S(=O)2-O-, C 1-6 alkyl-NH-C(=O)-, C 1-6 alkyl-NH-S(=O)-, C 1-6 alkyl-NH-S(=O)2-, C 1-6 alkyl-C(=O)-NH-, C 1-6 alkyl-S(=O)-NH-, C 1-6 alkyl-S(=O)2-NH-, C 1-6 alkylNH-S(=O)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-O-, 3-10 membered heterocycloalkyl-O-, C 5-10 cycloalkenyl-O-, 5-10 membered heterocycloalkenyl-O-, C 6-10 aryl-O-, 5-10 membered heteroaryl-O-, C 3-10 cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 cycloalkenyl-S-, 5-10 membered heterocycloalkenyl-S-, C 6-10 aryl-S-, 5-10 membered heteroaryl-S-, C 3-10 cycloalkyl-NH-, 3-10 membered heterocycloalkyl-NH-, C 5-10 cycloalkenyl-NH-, 5-10 membered heterocycloalkenyl-NH-, C 6-10 aryl-NH-, 5-10 membered heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, C 3-10 cycloalkyl-O-CH2-, 3-10 membered heterocycloalkyl-O-CH2-, C 5-10 cycloalkenyl-O-CH2-, 5-10 membered heterocycloalkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 membered heteroaryl-O-CH2-, C 3-10 cycloalkyl-S-CH2-, 3-10 membered heterocycloalkyl-S-CH2-, C 5-10 cycloalkenyl-S-CH2-, 5-10 membered heterocycloalkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 membered heteroaryl-S-CH2-, C 3-10 cycloalkyl-NH-CH2-, 3-10 membered heterocycloalkyl-NH-CH2-, C 5-10 cycloalkenyl-NH-CH2-, 5-10 membered heterocycloalkenyl-NH-CH2-, C 6-10 aryl-NH-CH2-, and 5-10 membered heteroaryl-NH-CH2-, said R1being optionally substituted by one or more R; When selected from the group consisting of When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R; R2, R3, R4, R5are each independently selected from the group consisting of H, D, F, CI, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C(=O)NH-, NHC(=O)-, NHS(=O)-, NHS(=O)2-, C(=O)O-, SC(=O)-, SC(=O)2-, S(=O)C(=O)-, S(=O)2C(=O)-, C(=O)NH-, NHC(=O)-, NHC(=O)NH-, NHC(=O)O-, OC(=O)NH-, SC(=O)NH-, NHS(=O)NH-, NH-, N+H2-, P(=O)(OH)2, P(=O)(OH)O-, P(=O)(O-)2, P(=O)(O-)2OH-, P(=O)(OH)O-, P(=O)(O-)2-, S(=O)NH-, S(=O)2NH-, SO2N(H)C(=O)-, SO2N(H)C(=O)O-, SO2N(H)C(=O)NH-, SO2N(H)C(=O)N(H)-, SO2N(H)- 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=O)-, C 1-6 alkyl-S(=O)-, C 1-6 alkyl-S(=O)2-, C 1-6 alkyl-O-C(=O)-, C 1-6 alkyl-O-S(=O)-, C 1-6 alkyl-O-S(=O)2-, C 1-6 alkyl-C(=O)-O-, C 1-6 alkyl-S(=O)-O-, C 1-6 alkyl-S(=O)2-O-, C 1-6 alkyl-NH-C(=O)-, C 1-6 alkyl-NH-S(=O)-, C 1- 6alkyl-NH-S(=O)2-, C 1-6 alkyl-C(=O)-NH-, C 1-6 alkyl-S(=O)-NH-, C 1-6 alkyl-S(=O)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-O-, 3-10 membered heterocycloalkyl-O-, C 5-10 cycloalkenyl-O-, 5-10 membered heterocycloalkenyl-O-, C 6-10 aryl-O-, 5-10 membered heteroaryl-O-, C 3-10 cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 cycloalkenyl-S-, 5-10 membered heterocycloalkenyl-S-, C 6-10 aryl-S-, 5-10 membered heteroaryl-S-, C 3- 10 cycloalkyl-NH-, 3-10 membered heterocycloalkyl-NH-, C 5-10 cycloalkenyl-NH-, 5-10 membered heterocycloalkenyl-NH-, C 6-10 aryl-NH-, 5-10 membered heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, each of R2, R3, R4, R5is optionally substituted by one or more R; or R2and R3are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; or R3and R4are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; or R4and R5are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 R6, R7, R8are each independently H, halogen, CN, N02, -OR, -SR, -N(R)2, -C(=0)R, -C(=0)OR, -C(=0)N(R)2, -C(=NR)N(R)2, -C(=0)R, -C(=0)OR, -C(= R9is selected from H, D, F, CI, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1- alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl is optionally substituted with one or more R; R 10 selected from H, D, F, CI, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl is optionally substituted with one or more R; or R6is joined together with R1to form a C 5-7 cycloalkyl or 5-10 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-10 membered heterocycloalkyl are optionally substituted with one or more R; or R6and R7are taken together with the nitrogen to which they are attached to form a 5-10 membered heterocycloalkyl group, wherein said 5-10 membered heterocycloalkyl group is optionally substituted with one or more R 10 connected together to form a C 5-7 cycloalkyl or 5-10 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-10 membered heterocycloalkyl are optionally substituted with one or more R alternatively, R6and L1together with the atoms to which they are attached form a 5-6 membered monocyclic heteroaryl and 5-10 membered heterocycloalkenyl; the heteroatoms in the monocyclic heteroaryl and heterocycloalkenyl are independently selected from N, O and S, and the number of heteroatoms is 1, 2 or 3; or, R7and L1together with the atoms to which they are attached form a 5-6 membered monocyclic heteroaryl and 5-10 membered heterocycloalkenyl; the heteroatoms in said monocyclic heteroaryl and heterocycloalkenyl are independently selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3; or, R 10 R2and R3together with the atoms to which they are attached form a 5-10 membered 5-7 cycloalkyl or 5-10 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-10 membered heterocycloalkyl are optionally substituted with one or more R; R a selected from H, C 1-6 alkyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl and 5-10 membered heterocycloalkenyl, said R a optionally substituted with one or more R; R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's; R c selected from O, S, CH2, CH-C 1-6 alkyl, C(C 1-6 alkyl)2, said C 1-6 alkyl is optionally substituted by one or more R; or R9and the substituent R a are linked together to form a 4-10 membered heterocycloalkyl group, which is optionally substituted by one or more R or R9and a substituent on Z are taken together to form a C a joined together to form a C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl, said C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R; or R 10 with the substituents R a together with the carbon atom to which they are attached form a C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl, said C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R or R9and R 10 together with the carbon to which they are attached, form a C 4-10 cycloalkyl or 4-10 membered heterocycloalkyl, said C 4-10 cycloalkyl and 4-10 membered heterocycloalkyl are optionally substituted with one or more R or, two substituents R a connected together to form a C 3-10 cycloalkyl or 4-10 membered heterocycloalkyl, said C 3-10 cycloalkyl and 4-10 membered heterocycloalkyl are optionally substituted with one or more R or any substituent on Z is joined together with any substituent on X1to form a C 3-10 cycloalkyl or 4-10 membered heterocycloalkyl, said C 3-10 cycloalkyl and 4-10 membered heterocycloalkyl are optionally substituted with one or more R; R is selected from the group consisting of D, F, Cl, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, Si(C 1-6 alkyl)3, C 1-6 alkyl, C 1- 6alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=0)-, C 1-6 alkyl-S(=0)-, C 1-6 alkyl-S(=0)2-, C 1-6 alkyl-O-C(=0)-, C 1-6 alkyl-O-S(=0)-, C 1-6 alkyl-O-S(=0)2-, C 1-6 alkyl-C(=0)-O-, C 1-6 alkyl-S(=0)-O-, C 1-6 alkyl-S(=0)(=NH)-O-, C 1-6 alkyl-S(=0)2-O-, C 1-6 alkyl-NH-C(=0)-, C 1-6 alkyl-NH-S(=0)-, C 1-6 alkyl-NH-S(=0)2-, C 1-6 alkyl-C(=0)-NH-, C 1-6 alkyl-S(=0)-NH-, C 1-6 alkyl-S(=0)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C(=0)-, 3-10 membered heterocycloalkyl-C(=0)-, C 5-10 cycloalkenyl-C(=0)-, 5-10 membered heterocycloalkenyl-C(=0)-, C 6-10 aryl-C(=0)- and 5-10 membered heteroaryl-C(=0)-, said R being optionally substituted by one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino or (C 1-6 alk)2amino; n is selected from 0, 1, 2 or 3. the compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of a compound represented by formula (A-II-A) or formula (A-II-B), or a pharmaceutically acceptable salt thereof, wherein, T1is selected from N and C(R6); T2is selected from N and C(R7); T3is selected from N and C(R8); X1is selected from the group consisting of null, -0-, -S-, -N(R a )-, -C(=0)-, -C(=S)-, -S(=0)-, -S(=0)2-, -C(R b )2-, and -C(R b )2C(R b )2-; X2is selected from the group consisting of null, -0-, -S-, -N(R a )-, -C(=0)-, -C(=S)-, -S(=0)-, -S(=0)2-, -C(R b )2-, and -C(R b )2C(R b )2-; Z is selected from -C(R a )2-, -C(R b )2-, and -C(=R c )-; L1is selected from the group consisting of null, -O-, -S-, -N(R a )-, C 2-6 alkylene, C 2-6 alkyne, C 1-6 alkylene, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, and 4-10 membered heteroaryl; Ring A is selected from C 3-15 cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 cycloalkenyl, 5-15 membered heterocycloalkenyl, C 6-15 aryl and 5-15 membered heteroaryl; selected from the group consisting of When selected from the group consisting of R1is selected from H, D, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=O)-, C 1-6 alkyl-S(=O)-, C 1-6 alkyl-S(=O)2-, C 1-6 alkyl-O-C(=O)-, C 1-6 alkyl-O-S(=O)-, C 1-6 alkyl-O-S(=O)2-, C 1-6 alkyl-C(=O)-O-, C 1-6 alkyl-S(=O)-O-, C 1-6 alkyl-S(=O)(=NH)-O-, C 1-6 alkyl-S(=O)2-O-, C 1-6 alkyl-NH-C(=O)-, C 1-6 alkyl-NH-S(=O)-, C 1-6 alkyl-NH-S(=O)2-, C 1-6 alkyl-C(=O)-NH-, C 1-6 alkyl-S(=O)-NH-, C 1-6 alkyl-S(=O)2-NH-, C 1-6 alkylNH-S(=O)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-O-, 3-10 membered heterocycloalkyl-O-, C 5-10 cycloalkenyl-O-, 5-10 membered heterocycloalkenyl-O-, C 6-10 aryl-O-, 5-10 membered heteroaryl-O-, C 3-10 cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 cycloalkenyl-S-, 5-10 membered heterocycloalkenyl-S-, C 6-10 aryl-S-, 5-10 membered heteroaryl-S-, C 3-10 cycloalkyl-NH-, 3-10 membered heterocycloalkyl-NH-, C 5-10 cycloalkenyl-NH-, 5-10 membered heterocycloalkenyl-NH-, C 6-10 aryl-NH-, 5-10 membered heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, C 3-10 cycloalkyl-O-CH2-, 3-10 membered heterocycloalkyl-O-CH2-, C 5-10 cycloalkenyl-O-CH2-, 5-10 membered heterocycloalkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 membered heteroaryl-O-CH2-, C 3-10 cycloalkyl-S-CH2-, 3-10 membered heterocycloalkyl-S-CH2-, C 5-10 cycloalkenyl-S-CH2-, 5-10 membered heterocycloalkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 membered heteroaryl-S-CH2-, C 3-10 cycloalkyl-NH-CH2-, 3-10 membered heterocycloalkyl-NH-CH2-, C 5-10 cycloalkenyl-NH-CH2-, 5-10 membered heterocycloalkenyl-NH-CH2-, C 6-10 aryl-NH-CH2-, and 5-10 membered heteroaryl-NH-CH2-, said R1being optionally substituted by one or more R; When selected from the group consisting of When R1 is selected from C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl and 5-10 membered heterocyclic alkenyl, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2- and 5-10-membered heterocyclic alkenyl-CH2-, wherein R1 is optionally substituted with one or more R; R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1- 6-alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3- 10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, each of R2, R3, R4, R5is optionally substituted with one or more R; or R2and R3are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; or R3and R4are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; or R4and R5are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 R6, R7, R8are each independently H, halogen, CN, N02, -OR, -SR, -N(R)2, -C(=0)R, -C(=0)OR, -C(=0)N(R)2, -C(=NR)N(R)2, -C(=0)R, -C(=0)OR, -C(= R9is selected from H, D, F, CI, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1- alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl is optionally substituted with one or more R; R 10 selected from H, D, F, CI, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl is optionally substituted with one or more R; or R6is joined together with R1to form a C 5-7 cycloalkyl or 5-10 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-10 membered heterocycloalkyl are optionally substituted with one or more R; or R6and R7are taken together with the nitrogen to which they are attached to form a 5-10 membered heterocycloalkyl group, wherein said 5-10 membered heterocycloalkyl group is optionally substituted with one or more R 10 connected together to form a C 5-7 cycloalkyl or 5-10 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-10 membered heterocycloalkyl are optionally substituted with one or more R or R 10 taken together with R2, form a C 5-7 cycloalkyl or 5-10 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-10 membered heterocycloalkyl are optionally substituted with one or more R R a selected from H, C 1-6 alkyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl and 5-10 membered heterocycloalkenyl, said R a is optionally substituted with one or more R R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's; R c O, S, CH2, CH-C 1-6 alkyl, C(C 1-6 alkyl)2, which C 1-6 alkyl is optionally substituted by one or more R; or R9and the substituent R a are linked together to form a 4-10 membered heterocycloalkyl group, which is optionally substituted by one or more R or R9and a substituent on Z are taken together to form a C a connected together to form a C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl, said C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R; or R 10 with the substituents on Z a together form a C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl, said C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R; or R9and R 10 together with the carbon to which they are attached form a C 4-10 cycloalkyl or 4-10 membered heterocycloalkyl, said C 4-10 cycloalkyl and 4-10 membered heterocycloalkyl are optionally substituted with one or more R or, two substituents R a connected together to form a C 3-10 cycloalkyl or 4-10 membered heterocycloalkyl, said C 3-10 cycloalkyl and 4-10 membered heterocycloalkyl are optionally substituted with one or more R or any substituent on Z is joined together with any substituent on X1to form a C 3-10 cycloalkyl or 4-10 membered heterocycloalkyl, said C 3-10 cycloalkyl and 4-10 membered heterocycloalkyl are optionally substituted with one or more R; R is selected from the group consisting of D, F, Cl, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, Si(C 1-6 alkyl)3, C 1-6 alkyl, C 1- 6alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=0)-, C 1-6 alkyl-S(=0)-, C 1-6 alkyl-S(=0)2-, C 1-6 alkyl-O-C(=0)-, C 1-6 alkyl-O-S(=0)-, C 1-6 alkyl-O-S(=0)2-, C 1-6 alkyl-C(=0)-O-, C 1-6 alkyl-S(=0)-O-, C 1-6 alkyl-S(=0)(=NH)-O-, C 1-6 alkyl-S(=0)2-O-, C 1-6 alkyl-NH-C(=0)-, C 1-6 alkyl-NH-S(=0)-, C 1-6 alkyl-NH-S(=0)2-, C 1-6 alkyl-C(=0)-NH-, C 1-6 alkyl-S(=0)-NH-, C 1-6 alkyl-S(=0)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C(=0)-, 3-10 membered heterocycloalkyl-C(=0)-, C 5-10 cycloalkenyl-C(=0)-, 5-10 membered heterocycloalkenyl-C(=0)-, C 6-10 aryl-C(=0)- and 5-10 membered heteroaryl-C(=0)-, said R being optionally substituted by one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino or (C 1-6 alk)2amino; n is selected from 0, 1, 2 or 3. the compound according to claim 1 or 2, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, satisfies one or both of the following conditions, (1) R9is selected from F, Cl, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl is optionally substituted with one or more R; Preferably, R9is selected from C 1-6 alkyl is optionally substituted with one or more R; (2) the 5-6 membered monocyclic heteroaryl and 5-10 membered heterocycloalkenyl groups are wherein #1 and ring A are connected, and #2 and T2are connected. the compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is selected from a compound represented by formula (A-III), formula (A-III-A), or formula (A-III-B), or a pharmaceutically acceptable salt thereof, wherein, X1, X2, Z, L1, ring A, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R are as defined in claim 1 ; R9is selected from F, CI, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3- to 10-membered heterocycloalkyl, which C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3- to 10-membered heterocycloalkyl is optionally substituted with one or more R; Preferably, R9is selected from C 1-6 alkyl is optionally substituted with one or more R. The compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, selected from a compound represented by Formula (A-III-1), Formula (A-III-1-A), or Formula (A-III-1-B), or a pharmaceutically acceptable salt thereof, wherein, X1is selected from the group consisting of null, -0-, -S-, -N(R a )-, -C(=0)-, -C(=S)-, -S(=0)-, -S(=0)2-, -C(R b )2-, and -C(R b )2C(R b )2-; X2is selected from the group consisting of null, -0-, -S-, -N(R a )-, -C(=0)-, -C(=S)-, -S(=0)-, -S(=0)2-, -C(R b )2-, and -C(R b )2C(R b )2-; R a selected from H, C 1-6 alkyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl and 5-10 membered heterocycloalkenyl, said R a is optionally substituted with one or more R R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's; Ring A is selected from C 3-15 cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 cycloalkenyl, 5-15 membered heterocycloalkenyl, C 6-15 aryl and 5-15 membered heteroaryl; selected from the group consisting of R1is selected from H, D, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=O)-, C 1-6 alkyl-S(=O)-, C 1-6 alkyl-S(=O)2-, C 1-6 alkyl-O-C(=O)-, C 1-6 alkyl-O-S(=O)-, C 1-6 alkyl-O-S(=O)2-, C 1-6 alkyl-C(=O)-O-, C 1-6 alkyl-S(=O)-O-, C 1-6 alkyl-S(=O)(=NH)-O-, C 1-6 alkyl-S(=O)2-O-, C 1-6 alkyl-NH-C(=O)-, C 1-6 alkyl-NH-S(=O)-, C 1-6 alkyl-NH-S(=O)2-, C 1-6 alkyl-C(=O)-NH-, C 1-6 alkyl-S(=O)-NH-, C 1-6 alkyl-S(=O)2-NH-, C 1-6 alkylNH-S(=O)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-O-, 3-10 membered heterocycloalkyl-O-, C 5-10 cycloalkenyl-O-, 5-10 membered heterocycloalkenyl-O-, C 6-10 aryl-O-, 5-10 membered heteroaryl-O-, C 3-10 cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 cycloalkenyl-S-, 5-10 membered heterocycloalkenyl-S-, C 6-10 aryl-S-, 5-10 membered heteroaryl-S-, C 3-10 cycloalkyl-NH-, 3-10 membered heterocycloalkyl-NH-, C 5-10 cycloalkenyl-NH-, 5-10 membered heterocycloalkenyl-NH-, C 6-10 aryl-NH-, 5-10 membered heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, C 3-10 cycloalkyl-O-CH2-, 3-10 membered heterocycloalkyl-O-CH2-, C 5-10 cycloalkenyl-O-CH2-, 5-10 membered heterocycloalkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 membered heteroaryl-O-CH2-, C 3-10 cycloalkyl-S-CH2-, 3-10 membered heterocycloalkyl-S-CH2-, C 5-10 cycloalkenyl-S-CH2-, 5-10 membered heterocycloalkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 membered heteroaryl-S-CH2-, C 3-10 cycloalkyl-NH-CH2-, 3-10 membered heterocycloalkyl-NH-CH2-, C 5-10 cycloalkenyl-NH-CH2-, 5-10 membered heterocycloalkenyl-NH-CH2-, C 6-10 aryl-NH-CH2-, and 5-10 membered heteroaryl-NH-CH2-, said R1being optionally substituted by one or more R; R2, R3, R4, R5are each independently selected from the group consisting of H, D, F, CI, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C(=O)NH-, NHC(=O)-, NHC(=O)NH-, NHC(=O)N-, 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=O)-, C 1-6 alkyl-S(=O)-, C 1-6 alkyl-S(=O)2-, C 1-6 alkyl-O-C(=O)-, C 1-6 alkyl-O-S(=O)-, C 1-6 alkyl-O-S(=O)2-, C 1-6 alkyl-C(=O)-O-, C 1-6 alkyl-S(=O)-O-, C 1-6 alkyl-S(=O)2-O-, C 1-6 alkyl-NH-C(=O)-, C 1-6 alkyl-NH-S(=O)-, C 1- 6alkyl-NH-S(=O)2-, C 1-6 alkyl-C(=O)-NH-, C 1-6 alkyl-S(=O)-NH-, C 1-6 alkyl-S(=O)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-O-, 3-10 membered heterocycloalkyl-O-, C 5-10 cycloalkenyl-O-, 5-10 membered heterocycloalkenyl-O-, C 6-10 aryl-O-, 5-10 membered heteroaryl-O-, C 3-10 cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 cycloalkenyl-S-, 5-10 membered heterocycloalkenyl-S-, C 6-10 aryl-S-, 5-10 membered heteroaryl-S-, C 3- 10 cycloalkyl-NH-, 3-10 membered heterocycloalkyl-NH-, C 5-10 cycloalkenyl-NH-, 5-10 membered heterocycloalkenyl-NH-, C 6-10 aryl-NH-, 5-10 membered heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, each of R2, R3, R4, R5is optionally substituted by one or more R; or R2and R3are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 R6, R7, R8are each independently H, halogen, CN, N02, -OR, -SR, -N(R)2, -C(=0)R, -C(=0)OR, -C(=0)N(R)2, -C(=NR)N(R)2, -C(=0)R, -C(=0)OR, -C(= R9is selected from F, Cl, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl optionally substituted with one or more R; R 10 selected from H, D, F, CI, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl is optionally substituted with one or more R; R is selected from the group consisting of D, F, Cl, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, Si(C 1-6 alkyl)3, C 1-6 alkyl, C 1- 6alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=0)-, C 1-6 alkyl-S(=0)-, C 1-6 alkyl-S(=0)2-, C 1-6 alkyl-O-C(=0)-, C 1-6 alkyl-O-S(=0)-, C 1-6 alkyl-O-S(=0)2-, C 1-6 alkyl-C(=0)-O-, C 1-6 alkyl-S(=0)-O-, C 1-6 alkyl-S(=0)(=NH)-O-, C 1-6 alkyl-S(=0)2-O-, C 1-6 alkyl-NH-C(=0)-, C 1-6 alkyl-NH-S(=0)-, C 1-6 alkyl-NH-S(=0)2-, C 1-6 alkyl-C(=0)-NH-, C 1-6 alkyl-S(=0)-NH-, C 1-6 alkyl-S(=0)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C(=0)-, 3-10 membered heterocycloalkyl-C(=0)-, C 5-10 cycloalkenyl-C(=0)-, 5-10 membered heterocycloalkenyl-C(=0)-, C 6-10 aryl-C(=0)- and 5-10 membered heteroaryl-C(=0)-, said R being optionally substituted by one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino or (C 1-6 alk)2amino; n is selected from 0, 1, 2 or 3; Preferably, R9is selected from C 1-6 alkyl is optionally substituted with one or more R. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to claim 1 is selected from a compound represented by formula (A-IV), formula (A-IV-A), formula (A-IV-B), formula (A-V), formula (A-V-A), formula (A-V-B), or formula (A-VI), or a pharmaceutically acceptable salt thereof, wherein, Z, L1, ring A, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R are as defined in claim 1 ; R9is selected from F, CI, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3- to 10-membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3- to 10-membered heterocycloalkyl is optionally substituted with one or more R. The compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, R9and the substituents R on X1 a are linked together to form a 4-10 membered heterocycloalkyl group, which is optionally substituted by one or more R; R9and X1are taken together to form a 4-, 5-, 6-, or 7-membered heterocycloalkyl optionally substituted with one or more R a R9and X1are taken together to form a 4-, 5-, 6-, or 7-membered heterocycloalkyl optionally substituted with one or more R Preferably, the compound is selected from the group consisting of a compound of Formula (A-VII) or Formula (A-VII-A), or a pharmaceutically acceptable salt thereof, T1, T2, T3, X1, X2, Z, L1, ring A, R1, R2, R3, R4, R5, R 10 R is as defined in claim 1. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to claim 1 is selected from a compound represented by formula (A-IX) or formula (A-IX-A), or a pharmaceutically acceptable salt thereof, X1is selected from the group consisting of null, -0-, -S-, -N(R a )-, -C(=0)-, -C(=S)-, -S(=0)-, -S(=0)2-, -C(R b )2-, and -C(R b )2C(R b )2-; X2is selected from the group consisting of null, -0-, -S-, -N(R a )-, -C(=0)-, -C(=S)-, -S(=0)-, -S(=0)2-, -C(R b )2-, and -C(R b )2C(R b )2-; Z is selected from -C(R a )2- -C(R b )2- and -C(=R c )-; R a selected from H, C 1-6 alkyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl and 5-10 membered heterocycloalkenyl, said R a optionally substituted with one or more R; R b The components are independently selected from H, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl and 5-10 heteroaryl, the R b It can be replaced by one or more R's; R c selected from O, S, CH2, CH-C 1-6 alkyl, C(C 1-6 alkyl)2, which C 1-6 alkyl is optionally substituted by one or more R; L1is selected from the group consisting of null, -O-, -S-, -N(R a )-, C 2-6 alkylene, C 2-6 alkyne, C 1-6 alkylene, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, and 4-10 membered heteroaryl; Ring A is selected from C 3-15 cycloalkyl, 3-15 membered heterocycloalkyl, C 5-15 cycloalkenyl, 5-15 membered heterocycloalkenyl, C 6-15 aryl and 5-15 membered heteroaryl; selected from the group consisting of R1is selected from H, D, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=O)-, C 1-6 alkyl-S(=O)-, C 1-6 alkyl-S(=O)2-, C 1-6 alkyl-O-C(=O)-, C 1-6 alkyl-O-S(=O)-, C 1-6 alkyl-O-S(=O)2-, C 1-6 alkyl-C(=O)-O-, C 1-6 alkyl-S(=O)-O-, C 1-6 alkyl-S(=O)(=NH)-O-, C 1-6 alkyl-S(=O)2-O-, C 1-6 alkyl-NH-C(=O)-, C 1-6 alkyl-NH-S(=O)-, C 1-6 alkyl-NH-S(=O)2-, C 1-6 alkyl-C(=O)-NH-, C 1-6 alkyl-S(=O)-NH-, C 1-6 alkyl-S(=O)2-NH-, C 1-6 alkylNH-S(=O)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-O-, 3-10 membered heterocycloalkyl-O-, C 5-10 cycloalkenyl-O-, 5-10 membered heterocycloalkenyl-O-, C 6-10 aryl-O-, 5-10 membered heteroaryl-O-, C 3-10 cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 cycloalkenyl-S-, 5-10 membered heterocycloalkenyl-S-, C 6-10 aryl-S-, 5-10 membered heteroaryl-S-, C 3-10 cycloalkyl-NH-, 3-10 membered heterocycloalkyl-NH-, C 5-10 cycloalkenyl-NH-, 5-10 membered heterocycloalkenyl-NH-, C 6-10 aryl-NH-, 5-10 membered heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, C 3-10 cycloalkyl-O-CH2-, 3-10 membered heterocycloalkyl-O-CH2-, C 5-10 cycloalkenyl-O-CH2-, 5-10 membered heterocycloalkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 membered heteroaryl-O-CH2-, C 3-10 cycloalkyl-S-CH2-, 3-10 membered heterocycloalkyl-S-CH2-, C 5-10 cycloalkenyl-S-CH2-, 5-10 membered heterocycloalkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 membered heteroaryl-S-CH2-, C 3-10 cycloalkyl-NH-CH2-, 3-10 membered heterocycloalkyl-NH-CH2-, C 5-10 cycloalkenyl-NH-CH2-, 5-10 membered heterocycloalkenyl-NH-CH2-, C 6-10 aryl-NH-CH2-, and 5-10 membered heteroaryl-NH-CH2-, said R1being optionally substituted by one or more R; R2, R3, R4, R5are each independently selected from the group consisting of H, D, F, CI, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C(=O)NH-, NHC(=O)-, NHC(=O)NH-, NHC(=O)N-, 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=O)-, C 1-6 alkyl-S(=O)-, C 1-6 alkyl-S(=O)2-, C 1-6 alkyl-O-C(=O)-, C 1-6 alkyl-O-S(=O)-, C 1-6 alkyl-O-S(=O)2-, C 1-6 alkyl-C(=O)-O-, C 1-6 alkyl-S(=O)-O-, C 1-6 alkyl-S(=O)2-O-, C 1-6 alkyl-NH-C(=O)-, C 1-6 alkyl-NH-S(=O)-, C 1- 6alkyl-NH-S(=O)2-, C 1-6 alkyl-C(=O)-NH-, C 1-6 alkyl-S(=O)-NH-, C 1-6 alkyl-S(=O)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-O-, 3-10 membered heterocycloalkyl-O-, C 5-10 cycloalkenyl-O-, 5-10 membered heterocycloalkenyl-O-, C 6-10 aryl-O-, 5-10 membered heteroaryl-O-, C 3-10 cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 cycloalkenyl-S-, 5-10 membered heterocycloalkenyl-S-, C 6-10 aryl-S-, 5-10 membered heteroaryl-S-, C 3- 10 cycloalkyl-NH-, 3-10 membered heterocycloalkyl-NH-, C 5-10 cycloalkenyl-NH-, 5-10 membered heterocycloalkenyl-NH-, C 6-10 aryl-NH-, 5-10 membered heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, each of R2, R3, R4, R5is optionally substituted by one or more R; or R2and R3are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; R6, R7, and R8 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1- 6-alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 1-6 Alkyl-C(=O)-, C 1-6 Alkyl-S(=O)-, C 1-6 Alkyl-S(=O)2-, C 1-6 Alkyl-OC(=O)-, C 1-6 Alkyl-OS(=O)-, C 1-6 Alkyl-OS(=O)2-, C 1-6 Alkyl-C(=O)-O-, C 1-6 Alkyl-S(=O)-O-, C 1-6 Alkyl-S(=O)2-O-, C 1-6 Alkyl-NH-C(=O)-, C 1-6 Alkyl-NH-S(=O)-, C 1-6 Alkyl-NH-S(=O)2-, C 1-6 Alkyl-C(=O)-NH-, C 1-6 Alkyl-S(=O)-NH-, C 1-6 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, C 6-10 Aryl, 5-10 heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10 membered heterocyclic alkenyl-O-, C 6-10 Aryl-O-, 5-10 heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 Cycloalkenyl-S-, 5-10 membered heterocyclic alkenyl-S-, C 6-10 aryl-S-, 5-10 heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, C 6-10 aryl-NH-, 5-10 heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 Cycloalkenyl-CH2-, 5-10 membered heterocyclic alkenyl-CH2-, C 6-10 R6, R7, R8are each independently H, halogen, CN, N02, -OR, -SR, -N(R)2, -C(=0)R, -C(=0)OR, -C(=0)N(R)2, -C(=NR)N(R)2, -C(=0)R, -C(=0)OR, -C(= R 10 selected from H, D, F, CI, Br, I, OH, NH2, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl and 3-10 membered heterocycloalkyl, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl is optionally substituted with one or more R; R is selected from the group consisting of D, F, Cl, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, Si(C 1-6 alkyl)3, C 1-6 alkyl, C 1- 6alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 1-6 alkyl-C(=0)-, C 1-6 alkyl-S(=0)-, C 1-6 alkyl-S(=0)2-, C 1-6 alkyl-O-C(=0)-, C 1-6 alkyl-O-S(=0)-, C 1-6 alkyl-O-S(=0)2-, C 1-6 alkyl-C(=0)-O-, C 1-6 alkyl-S(=0)-O-, C 1-6 alkyl-S(=0)(=NH)-O-, C 1-6 alkyl-S(=0)2-O-, C 1-6 alkyl-NH-C(=0)-, C 1-6 alkyl-NH-S(=0)-, C 1-6 alkyl-NH-S(=0)2-, C 1-6 alkyl-C(=0)-NH-, C 1-6 alkyl-S(=0)-NH-, C 1-6 alkyl-S(=0)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C(=0)-, 3-10 membered heterocycloalkyl-C(=0)-, C 5-10 cycloalkenyl-C(=0)-, 5-10 membered heterocycloalkenyl-C(=0)-, C 6-10 aryl-C(=0)- and 5-10 membered heteroaryl-C(=0)-, said R being optionally substituted with one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino or (C 1-6 alk)2amino; n is selected from 0, 1, 2 or 3. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to claim 1 is selected from a compound represented by formula (A-X) or formula (A-X-A), or a pharmaceutically acceptable salt thereof, X1, X2, Z, L1, ring A, R1, R2, R3, R4, R5, R 10 R is as defined in claim 1. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-9, wherein, R is selected from the group consisting of D, F, Cl, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, Si(C 1-3 alkyl)3, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino, C 1-3 alkyl-C(=0)-, C 1-3 alkyl-S(=0)-, C 1-3 alkyl-S(=0)2-, C 1-3 alkyl-O-C(=0)-, C 1-3 alkyl-O-S(=0)-, C 1-3 alkyl-O-S(=0)2-, C 1-3 alkyl-C(=0)-O-, C 1-3 alkyl-S(=0)-O-, C 1-3 alkyl-S(=0)2-O-, C 1-3 alkyl-NH-C(=0)-, C 1-3 alkyl-NH-S(=0)-, C 1-3 alkyl-NH-S(=0)2-, C 1-3 alkyl-C(=0)-NH-, C 1-3 alkyl-S(=0)-NH-, C 1-3 alkyl-S(=0)2-NH-, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, phenyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl-C(=0)-, 3-6 membered heterocycloalkyl-C(=0)-, C 5-10 cycloalkenyl-C(=0)-, 5-10 membered heterocycloalkenyl-C(=0)-, phenyl-C(=0)- and 5-6 membered heteroaryl-C(=0)-, said R being optionally substituted by one or more D, F, Cl, Br, I, OH, NH2, CN, C 1-6 alkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino or (C 1-3 alk)2amino; Preferably, R is selected from D, F, CI, Br, I, OH, NH2, CN, Si(CH3)3, methyl, ethyl, propyl, isopropyl, CD3, The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein, When selected from the group consisting of R1is selected from H, D, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, C 1-6 alkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino, C 1-3 alkyl-C(=O)-, C 1-3 alkyl-S(=O)-, C 1-3 alkyl-S(=O)2-, C 1- 3alkyl-O-C(=O)-, C 1-3 alkyl-O-S(=O)-, C 1-3 alkyl-O-S(=O)2-, C 1-3 alkyl-C(=O)-O-, C 1-3 alkyl-S(=O)-O-, C 1-3 alkyl-S(=O)(=NH)-O-, C 1-3 alkyl-S(=O)2-O-, C 1-3 alkyl-NH-C(=O)-, C 1-3 alkyl-NH-S(=O)-, C 1-3 alkyl-NH-S(=O)2-, C 1-3 alkyl-C(=O)-NH-, C 1-3 alkyl-S(=O)-NH-, C 1-3 alkyl-S(=O)2-NH-, C 1-3 alkyl-NH-S(=O)2-NH-, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C 5-10 cycloalkenyl, 5-10 membered heterocycloalkenyl, phenyl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-O-, 3-10 membered heterocycloalkyl-O-, C 5-10 cycloalkenyl-O-, 5-10 membered heterocycloalkenyl-O-, C 6-10 aryl-O-, 5-10 membered heteroaryl-O-, C 3-10 cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5-10 cycloalkenyl-S-, 5-10 membered heterocycloalkenyl-S-, C 6-10 aryl-S-, 5-10 membered heteroaryl-S-, C 3-10 cycloalkyl-NH-, 3-10 membered heterocycloalkyl-NH-, C 5-10 cycloalkenyl-NH-, 5-10 membered heterocycloalkenyl-NH-, C 6-10 aryl-NH-, 5-10 membered heteroaryl-NH-, C 3-10 cycloalkyl-CH2-, 3-10 membered heterocycloalkyl-CH2-, C 5-10 cycloalkenyl-CH2-, 5-10 membered heterocycloalkenyl-CH2-, C 6-10 aryl-CH2-, 5-10 membered heteroaryl-CH2-, C 3-10 cycloalkyl-O-CH2-, 3-10 membered heterocycloalkyl-O-CH2-, C 5-10 cycloalkenyl-O-CH2-, 5-10 membered heterocycloalkenyl-O-CH2-, C 6-10 aryl-O-CH2-, 5-10 membered heteroaryl-O-CH2-, C 3- 10 cycloalkyl-S-CH2-, 3-10 membered heterocycloalkyl-S-CH2-, C 5-10 cycloalkenyl-S-CH2-, 5-10 membered heterocycloalkenyl-S-CH2-, C 6-10 aryl-S-CH2-, 5-10 membered heteroaryl-S-CH2-, C 3-10 cycloalkyl-NH-CH2-, 3-10 membered heterocycloalkyl-NH-CH2-, C 5-10 cycloalkenyl-NH-CH2-, 5-10 membered heterocycloalkenyl-NH-CH2-, C 6-10 aryl-NH-CH2-, and 5-10 membered heteroaryl-NH-CH2-, said R1being optionally substituted by one or more R; When selected from the group consisting of R1is selected from C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, C 5-6 cycloalkenyl, 5-6 membered heterocycloalkenyl, C 3-6 cycloalkyl-CH2-, 4-6 membered heterocycloalkyl-CH2-, C 5-6 cycloalkenyl-CH2-, and 5-6 membered heterocycloalkenyl-CH2-; Preferably, when selected from the group consisting of R1is selected from H, D, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, methyl, ethyl, isopropyl, said R1is optionally substituted with one or more R; Preferably, when selected from the group consisting of at the time, R1is selected from The compound according to claim 11, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, When selected from the group consisting of R1is selected from H, D, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, methyl, ethyl, isopropyl, CD3, CF3, When selected from the group consisting of at the time, R1is selected from The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein, R2, R3, R4, and R5 are independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, and C, respectively. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 1-3 Alkyl-C(=O)-, C 1-3 Alkyl-S(=O)-, C 1- 3alkyl-S(=O)2-, C 1-3 Alkyl-OC(=O)-, C 1-3 Alkyl-OS(=O)-, C 1-3 Alkyl-OS(=O)2-, C 1-3 Alkyl-C(=O)-O-, C 1- 3alkyl-S(=O)-O-, C 1-3 Alkyl-S(=O)2-O-, C 1-3 Alkyl-NH-C(=O)-, C 1-3 Alkyl-NH-S(=O)-, C 1-3 Alkyl-NH-S(=O)2-, C 1-3 Alkyl-C(=O)-NH-, C 1-3 Alkyl-S(=O)-NH-, C 1-3 Alkyl-S(=O)2-NH-, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 5-10 Cycloalkenyl, 5-10 membered heterocyclic alkenyl, phenyl, 5-6 membered heteroaryl, C 3-10 Cycloalkyl-O-, 3-10 membered heterocyclic alkyl-O-, C 5-10 Cycloalkenyl-O-, 5-10-membered heterocyclic alkenyl-O-, phenyl-O-, 5-6-membered heteroaryl-O-, C 3-10 Cycloalkyl-S-, 3-10 membered heterocycloalkyl-S-, C 5- 10 Cycloalkenyl-S-, 5-10-membered heterocyclic alkenyl-S-, phenyl-S-, 5-6-membered heteroaryl-S-, C 3-10 Cycloalkyl-NH-, 3-10 membered heterocyclic alkyl-NH-, C 5-10 Cycloalkenyl-NH-, 5-10 membered heterocyclic alkenyl-NH-, phenyl-NH-, 5-6 membered heteroaryl-NH-, C 3-10 Cycloalkyl-CH2-, 3-10 membered heterocyclic alkyl-CH2-, C 5-10 R2, R3, R4, R5are each independently H, halogen, CN, N3, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R, -S(O)2R, -S(O)2N(R)2, -S(O)N(R)2, -S(O)2OR, -OC(O)R, -OC(O)OR, -OC(O)N(R)2, -N(R)2C(O)R, -N(R)2C(O)OR, - Preferably, R2, R3, R4, R5are each independently selected from H, D, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein, R a selected from H and C 1-3 alkyl, said C 1-3 alkyl is optionally substituted with one or more R; preferably, Ra is selected from H, methyl, -CD3, ethyl, propyl and isopropyl. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein, R b selected from H, F, CI, Br, I, OH, NH2, CN, C(=O)OH, C(=O)NH2, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylthio and C 1-3 alkylamino, said R b optionally substituted by one or more R; Preferably, R b is selected from H, F, CI, Br, I, OH, NH2, CN, C(=0)OH, C(=0)NH2, methyl, ethyl, propyl and isopropyl. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to claim 14 or 15, wherein, - X1-X2- is selected from The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein, Ring A is selected from furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, pyridinyl, pyranyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, 2,3-dihydrofuro[3,2-b]pyridinyl, 6,7-dihydro-5H-cyclopenta[b]pyridinyl, 1H-pyrazolo[3,4-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-onyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 3,4-dihydro-2H-pyrazolo[2,3-b][1,4]oxazinyl, pyrazolo[1,5-a]pyrimidinyl, pyrrolo[2,1-f][1,2,4]triazinyl, 3H-[1,2,3]triazolo[4,5-b]pyridinyl, thiazolo[5,4-b]pyridinyl, pyrrolo[1,2-a][1,3,5]triazinyl, 7H-pyrrolo[2,3-c]pyridazinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-onyl, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-onyl, 3,4-dihydro-2H-pyrano[3,2-b]pyridinyl, azetidinyl, pyrrolidinyl, 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazolyl, spiro[3.3]heptanyl, cyclopentanyl, bicyclo[3.1.0]hexanyl, 5a,6,7,7a-tetrahydrocyclobutano[4,5]furo[3,2-b]pyridinyl, 5a,7,8,8a-tetrahydro-6H-cyclopenta[4,5]furo[3,2-b]pyridinyl, 5a,6a-dihydro-6H-cyclopropano[4,5]furo[3,2-b]pyridinyl, 5,5a,6,7,8,8a-hexahydropentano[1,2-b]pyridinyl, 4b,5,5a,6-tetrahydrocyclopropano[3,4]cyclopenta[1,2-b]pyridinyl, 5a,6,7,7a-tetrahydro-5H-cyclobutano[4,5]cyclopenta[1,2-b]pyridinyl, 6a,7,8,8a-tetrahydro-6H-cyclobutano[4,5]pyrano[3,2-b]pyridinyl, 2',3'-dihydrospiro[azetidin-2,4'-pyrano[3,2-b]pyridin]yl, 2',3'-dihydrospiro[aziridin-2,4'-pyrano[3,2-b]pyridin]yl, 7,8-dihydro-6H-pyrano[2,3-b]pyrazinyl, 3,4-dihydro-2H-2,4-methanopyrano[3,2-b]pyridinyl, 6,7-dihydro-5H-cyclopenta[b]pyrazinyl, 6,7-dihydro-5H-cyclopenta[c]pyridazinyl, phenyl, thiazolyl, isothiazolyl, isoxazolyl, 3-azabicyclo[4.2.0] oct-1 (6), 2, 4-trienyl, 6, 7-dihydro-5H-cyclopenta[c]pyridinyl, 1, 3-dihydrofuro[3, 4-c]pyridinyl, 2, 3-dihydrofuro[2, 3-c]pyridinyl, nitroxy pyridyl, nitroxy pyridazinyl, nitroxy pyrimidinyl, and nitroxy pyrazinyl. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to claim 12 or 17, wherein, Structural unit selected from the group consisting of The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein, Ring L1is selected from the group consisting of null, The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to claim 18 or 19, wherein, Structural unit selected from the group consisting of The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1 or 2, wherein, R2and R3are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; or a pharmaceutically acceptable salt thereof, wherein the variables are defined in the description. In some embodiments, the compound of Formula (A-IX), (A-IX-A), or (A-IX-B) is selected from the group consisting of: wherein B ring is C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; T1, T2, T3, X1, X2, Z, L1, ring A, R1, R4, R5, R9, R 10 , R are as defined in claim 1 ; or a pharmaceutically acceptable salt thereof, wherein the variables are as defined in the Summary of Invention section above. In some embodiments, the compound of Formula (A-IX-1), (A-IX-1-A), or (A-IX-1-B), or a pharmaceutically acceptable salt thereof, is a compound of Formula (A-IX-1-A), or a pharmaceutically acceptable salt thereof: wherein B ring is C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; T1, T2, T3, X1, X2, Z, L1, ring A, R1, R4, R5, R6, R7, R8, R9, R 10 , R are as defined in claim 1. The compound according to claim 21, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, R2and R3are joined together to form or R3and R4are joined together to form or R4and R5are joined together to form The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein, R6and R1are joined together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R; or R6and R7are taken together with the nitrogen to which they are attached to form a 5-7 membered heterocycloalkyl group, wherein said heterocycloalkyl group is optionally substituted with one or more R 10 connected together to form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R or R 10 taken together with R2, form a C 5-7 cycloalkyl or 5-7 membered heterocycloalkyl, said C 5-7 cycloalkyl and 5-7 membered heterocycloalkyl are optionally substituted with one or more R or R9and the substituent R a are joined together to form a 4-7 membered heterocycloalkyl group, which is optionally substituted by one or more R. The compound according to claim 23, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, R6and R1are connected together to form an oxolanyl, oxocyclohexanyl, azolanyl, azocyclohexanyl, oxacycloheptanyl or azacycloheptanyl, which is optionally substituted with one or more R; or R6and R7are taken together with the carbon to which they are attached to form an oxolane, oxane, azolane, azane, oxepane, or azepane, optionally substituted with one or more R 10 taken together, form an oxolane, oxane, azolane, azane, oxepane, or azepane, optionally substituted with one or more R or R 10 or R2and R2' taken together with the atoms to which they are attached form an oxolane, oxane, azolane, azane, oxepane, or azepane, optionally substituted with one or more R; or R9and a substituent on X1 a are linked together to form an azetidinyl, azetidinyl, azetidinyl, or azepinyl group, optionally substituted by one or more R; alternatively, any substituent on Z and any substituent on X1are connected together to form an azetidinyl, azolanyl, azocyclohexanyl or azacycloheptanyl, which is optionally substituted with one or more R. The compound, stereoisomer, or pharmaceutically acceptable salt thereof according to any one of claims 1-24, is selected from any one of the following compounds A compound represented by the formula (A-III), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. reacting a compound represented by formula (Int-1) and formula (Int-2) to prepare a compound represented by formula (A-III); wherein R Int-1 selected from hydroxyl, halogen, boronic acid or boronic acid ester, preferably hydroxyl, Cl or R Int-2 selected from hydroxyl, halogen, boronic acid or boronic acid ester, preferably hydroxyl, Cl or X1, X2, Z, L1, ring A, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R are as defined in claim 1. a pharmaceutical composition comprising a compound according to any one of claims 1-25, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. the use of a compound according to any one of claims 1-25, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 27, for the manufacture of a medicament for the treatment of a TNFα-related disease; preferably, the TNFα-related disease is preferably selected from an inflammatory or autoimmune disorder, a neurological or neurodegenerative disorder, a pain or nociceptive disorder, a cardiovascular disorder, a metabolic disorder, an ocular disorder or an oncological disorder; preferably, the TNFα-related disease is preferably selected from rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, psoriasis, Crohn's disease, ulcerative colitis, psoriasis, spondylarthritis, plaque psoriasis, septic shock, ankylosing spondylitis, juvenile idiopathic arthritis, hidradenitis suppurativa, uveitis, systemic lupus erythematosus (lupus), axial spondyloarthritis, polymyositis, pemphigus, multiple sclerosis, neuromyelitis optica, primary biliary cholangitis, autoimmune hepatitis, lupus nephritis, Goodpasture's syndrome, autoimmune oophoritis or autoimmune orchitis.

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