Heteroaryl compound as well as intermediate, preparation method and application thereof

Abstract

The invention discloses a heteroaryl compound as well as an intermediate, a preparation method and application thereof. Specifically disclosed are a compound represented by formula I, and a stereoisomer or a pharmaceutically acceptable salt thereof. The compound disclosed by the invention has relatively good PARG inhibitory activity and has a good medicinal prospect. # imgabs0 #

Description

[0001] This application claims the priority of Chinese Patent Application No. 2023112756108 filed on September 28, 2023 and Chinese Patent Application No. 202311783623.6 filed on December 22, 2023. This application cites the full text of the above Chinese patent application. Technical Field

[0002] The invention relates to a heteroaryl compound, an intermediate thereof, a preparation method and application. Background Art

[0003] PARG is the first poly(ADP-ribose) hydrolase to be identified and encoded by a single gene (Mirella et al. Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments. Experimental Cell Research, 2004, 297(2):521-532.), which can hydrolyze the O-glycosidic bonds between ADP-ribose subunits. PARG is composed of four domains (Meyer B et al. Clustered DNA damageinduces pan-nuclear H2AX phosphorylation mediated by ATM and DNA-PK. Nucleic Acids Res, 2003, 41: 6109-6118.; O'Sullivan J. et al. Emerging roles of eraserenzymes in the dynamic control of protein ADP-ribosylation. Nature Communication, 2019, 10, 1182.), including the N-terminal disordered domain, the linker domain, the C-terminal catalytic domain and the ADP-ribose binding domain. The unconserved disordered domain at the N-terminus is not necessary for in vitro activity, while the ADP-ribose binding domain at the C-terminus is highly conserved with other Macro-domains and together with the catalytic domain forms the minimum structure with complete enzyme activity in vitro (Slade D et al. The structure and catalytic mechanism of a poly(ADP-ribose)glycohydrolase. Nature, 2011, 477: 616-620.).

[0004] Poly ADP-ribosylation (PARylation) is a unique post-translational modification that plays an important role in maintaining genome stability in different signaling pathways, especially in DNA damage repair. Poly ADP-ribose, referred to as PAR, is composed of adenosine diphosphate-ribose units, with NAD +It is a donor, catalyzed by poly ADP-ribose polymerase (PARPs), and can be rapidly degraded by polyribosyl hydrolases. After DNA damage, many DNA damage response factors recognize PARylation and are recruited to the vicinity of DNA damage sites through PARylation. However, PARylation needs to be digested in time so that DNA damage response factors can directly recognize DNA damage and play a repair function. Otherwise, DNA repair factors will be trapped near DNA damage by PARylation and cannot play a normal repair role. Therefore, dePARylation is a direct downstream step of PARylation in DNA repair. Inhibiting this process will affect PARylation-dependent DNA damage repair and selectively kill tumor cells with DNA repair defects.

[0005] PARG, as the most important poly(ADP-ribose) hydrolase, exerts its effect on about 90% of PAR in cells (Laetitia D et al. Poly(ADP-ribose) glycohydrolase(PARG)and its therapeutic potential. Front Biosci, 2009, 14(5):1619-1626.), and plays a role in multiple cellular processes such as DNA damage repair, DNA replication, chromatin regulation, transcription and cell apoptosis. The imbalance of intracellular PAR levels caused by PARG dysfunction will affect the transformation and invasion of cancer cells (Rack JD et al. Macrodomain:structure, function, evolution, and catalytic activities. Annu Rev Biochem. 2016, 85:431-454; Marques M et al. Oncogenic activity of poly(ADP-ribose) glycohydrolase. Oncogene, 2019, 38:2177-2191).

[0006] PARG has been shown to be associated with a variety of diseases. Data show (Maud M et al, Oncogenic activity of poly(ADP-ribose)glycohydrolase. Oncogene, 2019, 38: 2177-2191.) that elevated PARG is associated with poor prognosis in HER2+ patients. PARG and HER2 synergistically promote the growth of breast cancer cells, and inhibition of PARG significantly affects the growth and migration of breast cancer. In addition, studies have shown (Mincheng Y et al. PARG inhibition limits HCC progression and potentiates the efficacy of immune checkpoint therapy. Hepatic and Biliary Cancer, 2022, S0168-8278 (22) 00072-1.) that high PARG expression is closely associated with poor prognosis in liver cancer, and hepatocyte-specific PARG functional loss affects tumor occurrence. Therefore, PARG inhibitors have received increasing attention as potential therapeutics. There are many PARG inhibitors currently under development, and all are in the preclinical research stage. Therefore, it is of great research significance to develop small molecule drugs that can target and inhibit PARG activity and provide patients with safer and more effective PARG inhibitors. Summary of the invention

[0007] The technical problem to be solved by the present invention is to overcome the defect of the prior art that there are few types of PARG inhibitor compounds. To this end, the present invention provides a heteroaryl compound, an intermediate thereof, a preparation method and an application thereof. The compound of the present invention has good PARG inhibitory activity, good drug efficacy and good application prospects.

[0008] The present invention solves the above technical problems through the following technical solutions.

[0009] The present invention provides a compound represented by formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

[0010]

[0011] X1 and X2 are each independently C or N;

[0012] Z1 and Z2 are CR independently Z , NH or N;

[0013] R z Each is independently H, hydroxyl, cyano, halogen, unsubstituted or substituted with one or more R Z-1 Substituted C1-C6 alkyl;

[0014] R Z-1 are each independently halogen or hydroxy;

[0015] W is

[0016] R w is hydrogen or C1-C6 alkyl;

[0017] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0018] R 1-1 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl;

[0019] R 1-1-1 Each is independently halogen, hydroxyl or C1-C6 alkyl;

[0020] R 1-2 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 1-2-1 Substituted C1-C6 alkyl;

[0021] R 1-2-1 Each is independently halogen, hydroxyl or C1-C6 alkyl;

[0022] R 2 is hydrogen, unsubstituted or replaced by one or more R 2-1 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 2 -2 substituted 5-10 membered heteroaryl, unsubstituted or replaced by one or more R 2-3 Substituted 4-12 membered heterocycloalkyl, unsubstituted or substituted with one or more R 2-6 Substituted C1-C6 alkyl, unsubstituted or substituted with one or more R 2-9 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 2-10 Substituted C3-C6 cycloalkenyl, The heteroatoms of the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0023] R 2-1 Each is independently cyano, halogen, unsubstituted or substituted with one or more R 2-1-1 Substituted C1-C6 alkyl, or unsubstituted or replaced by one or more R 2-1-4 Substituted C1-C6 alkoxy;

[0024] R 2-1-1 are independently cyano or halogen; R 2-1-2 is hydrogen or C1-C6 alkyl; R 2-1-3 Each is independently hydrogen or C1-C6 alkyl; R 2-1-4 are each independently a halogen;

[0025] R 2-2 Each is independently cyano, halogen, unsubstituted or substituted with one or more R 2-2-1 Substituted C1-C6 alkyl, C1-C6 alkoxy or

[0026] R 2-2-1 are independently cyano or halogen; R 2-2-2 is hydrogen or C1-C6 alkyl; R 2-2-3 Each is independently hydrogen or C1-C6 alkyl; R 2-2-4 Each is independently a C1-C6 alkyl group or a C3-C6 cycloalkyl group;

[0027] R 2-3 Each is independently cyano, oxo (C=O), hydroxyl, halogen, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-4 substituted 3-6 membered heterocycloalkyl, unsubstituted or replaced by one or more R 2-3-5 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-3-6 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 2-3-7 Substituted amino groups, unsubstituted or substituted with one or more R 2-3-9 substituted 5-10 membered heteroaryl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatom of the 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0028] R 2-3-1Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 2-3-1-1 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-3-1-2 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 2-3-1-3 Substituted amino groups;

[0029] R 2-3-2 is hydrogen, unsubstituted or replaced by one or more R 2-3-2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl, unsubstituted or substituted with one or more R 2-3-2-4 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-3-2-5 substituted 3-6 membered heterocycloalkyl, unsubstituted or replaced by one or more R 2-3-2-6 substituted 5-10 membered heteroaryl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatom of the 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0030] R 2-3-3 are independently hydrogen, unsubstituted or substituted with one or more R 2-3-3-1 Substituted C1-C6 alkyl;

[0031] R 2-3-4 Each is independently C1-C6 alkyl or oxo;

[0032] R 2-3-5 each independently a halogen or a deuterium;

[0033] R 2-3-6 Each is independently a C1-C6 alkyl group;

[0034] R 2-3-7 Each is independently a C1-C6 alkyl group;

[0035] R 2-3-8 Each is independently a C1-C6 alkyl group or a C3-C6 cycloalkyl group;

[0036] R 2-3-9 Each is independently a C1-C6 alkyl group;

[0037] R 2-3-1-1 are each independently a halogen;

[0038] R 2-3-1-2 Each is independently a C1-C6 alkoxy group;

[0039] R 2-3-1-3Each is independently a C1-C6 alkyl group;

[0040] R 2-3-2-1 Each is independently halogen, carboxyl, hydroxyl, oxo, C1-C6 alkoxy, unsubstituted or substituted with one or more R 2-3-2-1-2 Substituted amino, unsubstituted or replaced by one or more R 2-3-2-1-3 Substituted 5-10 membered heteroaryl; the heteroatom of the 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0041] R 2-3-2-1-1 Each is independently a C1-C6 alkyl group or a 6-10 membered aryl group;

[0042] R 2-3-2-1-2 Each is independently a C1-C6 alkyl group;

[0043] R 2-3-2-1-3 Each is independently a C1-C6 alkyl group;

[0044] R 2-3-2-2 Each independently represents halogen, hydroxy, unsubstituted or substituted with one or more R 2-3-2-2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-3-2-2-3 Substituted amino groups;

[0045] R 2-3-2-2-1 are each independently halogen or hydroxy;

[0046] R 2-3-2-2-2 Each is independently carboxyl, halogen, deuterium, oxo or hydroxyl;

[0047] R 2-3-2-2-3 Each is independently a C1-C6 alkyl group;

[0048] R 2-3-2-3 are each independently hydrogen or R 2-3-2-3-1 Each independently is unsubstituted or substituted with one or more R 2-3-2-3-1-1 Substituted 6-10 membered aryl; R 2-3-2-3-1-1 Each is independently a C1-C6 alkoxy group;

[0049] R 2-3-2-4 are each independently a halogen;

[0050] R 2-3-2-5 Each independently represents halogen, hydroxy, oxo, C1-C6 alkoxy, unsubstituted or substituted with one or more R 2 -3-2-5-1 Substituted C1-C6 alkyl; R2-3-2-5-1 are each independently a halogen;

[0051] R 2-3-2-6 Each is independently a C1-C6 alkyl group;

[0052] R 2-3-3-1 Each independently is unsubstituted or substituted with one or more R 2-3-3-1-1 Substituted amino group; R 2-3-3-1-1 Each is independently a C1-C6 alkyl group;

[0053] R 2-4 Each is unsubstituted or substituted with one or more R 2-4-1 substituted 4-10 membered heterocycloalkyl, unsubstituted or replaced by one or more R 2-4-2 substituted 5-10 membered heteroaryl, unsubstituted or replaced by one or more R 2-4-3 Substituted 6-10 membered aryl or unsubstituted or with one or more R 2-4-4 Substituted C3-C6 cycloalkyl; the heteroatoms of the 4-10 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0054] R 2-4-1 Each is independently hydroxyl, halogen, C1-C6 alkyl, R 2-4-2 Each is independently hydroxy, halogen or C1-C6 alkyl; R 2-4-3 Each is independently hydroxy, halogen or C1-C6 alkyl; R 2-4-4 Each is independently hydroxy, halogen or C1-C6 alkyl; R 2-4-1-1 is a C1-C6 alkyl group; R 2-4-1-2 Each is independently a C1-C6 alkyl group;

[0055] R 2-5 are independently hydrogen, unsubstituted or substituted with one or more R 2-5-1 Substituted 4-10 membered heterocycloalkyl, unsubstituted or substituted with one or more R 2-5-3 substituted 6-10 membered aryl, unsubstituted or replaced by one or more R 2-5-4 Substituted C1-C6 alkyl; the heteroatom of the 4-10 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0056] R 2-5-1 Each independently

[0057] R 2-5-1-1is hydrogen or C1-C6 alkyl;

[0058] R 2-5-1-2 Each is independently hydrogen or C1-C6 alkyl;

[0059] R 2-5-2 Each is independently a C1-C6 alkyl group;

[0060] R 2-5-3 Each is independently a C1-C6 alkoxy group;

[0061] R 2-5-4 Each independently is hydroxyl, halogen, C1-C6 alkoxy or

[0062] R 2-5-4-1 Each is independently hydrogen or C1-C6 alkyl;

[0063] R 2-6 Each independently represents halogen, C1-C6 alkyl, unsubstituted or substituted with one or more R 2-6-1 substituted 4-10 membered heterocycloalkyl or unsubstituted or with one or more R 2-6-2 substituted 5-10 membered heteroaryl; the heteroatoms of the 4-10 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0064] R 2-6-1 Each is independently halogen, C1-C6 alkyl or R 2-6-1-1 is a C1-C6 alkyl group;

[0065] R 2-6-2 Each is independently halogen or C1-C6 alkyl;

[0066] R 2-7 is C1-C6 alkyl, unsubstituted or substituted with one or more R 2-7-1 substituted 4-10 membered heterocycloalkyl or unsubstituted or with one or more R 2-7-2 substituted 5-10 membered heteroaryl; the heteroatoms of the 4-10 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0067] R 2-7-1 are independently halogen, C1-C6 alkyl, R 2-7-1-1 is a C1-C6 alkyl group; R 2-7-1-2is a C1-C6 alkyl group;

[0068] R 2-7-2 Each is independently halogen or C1-C6 alkyl;

[0069] R 2-8 Each independently is a C1-C6 alkyl group, or two R 2-8 The atoms to which it is attached are unsubstituted or replaced by one or more R 2-8-1 Substituted 4-10 membered heterocycloalkyl; the heteroatom of the 4-10 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0070] R 2-8-1 Each independently R 2-8-1-1 is hydrogen or C1-C6 alkyl;

[0071] R 2-9 Each independently represents hydroxyl, cyano, amino, unsubstituted or substituted with one or more R 2-9-2 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-9-1 Substituted 5-10 membered heteroaryl; the heteroatom of the 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0072] R 2-9-1 Each is independently a C1-C6 alkyl group;

[0073] R 2-9-2 are each independently hydroxy or halogen;

[0074] R 2-10 Each independently is unsubstituted or substituted with one or more R 2-10-1 Substituted 5-10 membered heteroaryl; the heteroatom of the 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0075] R 2-10-1 Each is independently a C1-C6 alkyl group;

[0076] R 2-11 Each independently is unsubstituted or substituted with one or more R 2-11-1 substituted 5-10 membered heteroaryl, unsubstituted or replaced by one or more R 2-11-2 substituted 3-6 membered heterocycloalkyl; the heteroatoms of the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 3-6 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0077] R2-11-1 Each is independently C1-C6 alkyl; R 2-11-2 Each is independently a C1-C6 alkyl group;

[0078] L is a carbonyl group, a methylene group,

[0079] R 3 for

[0080] R 3-1 and R 3-2 Each independently represents H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-5 The substituted 6-14-membered aryl group, the heteroatoms of the 4-12-membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12-membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0081] Or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0082] R 3-1-1 Each independently represents halogen, hydroxy, unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-1-3 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-1-4 substituted 6-14 membered aryl, unsubstituted or replaced by one or more R 3-1-1-5 The substituted C1-C6 alkoxy group, the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1-1Each is independently C1-C6 alkyl, hydroxyl or halogen; R 3-1-1-2 and R 3-1-1-4 Each is independently C1-C6 alkyl, hydroxyl or halogen; R 3-1-1-3 Each is independently C1-C6 alkyl, hydroxyl or halogen; R 3-1-1-5 Each is independently C1-C6 alkyl, hydroxyl or halogen;

[0083] R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl;

[0084] R 3-1-4 and R 3-1-5 Each is independently hydroxy, halogen or C1-C6 alkyl;

[0085] R 3-1-2-1 is hydroxyl, C1-C6 alkoxy, or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl;

[0086] R 3-1-2-2 and R 3-1-2-3 Each independently is H or C1-C6 alkyl;

[0087] R 3a Each independently Oxo (C=O), hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted or substituted with one or more R 3a-5 Substituted C1-C6 alkoxy or cyano;

[0088] R 3a-1 and R 3a-2 Each independently is H or C1-C6 alkyl;

[0089] R 3a-3 is hydroxyl, C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl;

[0090] R 3a-4 Each independently is C 6-14 Aryl, hydroxyl, halogen, C1-C6 alkyl or R 3a-4-1 and R 3a-4-2 Each independently is H or C1-C6 alkyl;

[0091] R3a-5 Each is independently hydroxy, halogen or C1-C6 alkyl;

[0092] R 4 and R 5 Each is independently H, hydroxyl, amino, cyano, halogen, unsubstituted or substituted with one or more R 4-1 Substituted C1-C6 alkyl or unsubstituted or with one or more R 4-2 Substituted C1-C6 alkoxy;

[0093] R 4-1 and R 4-2 Each is independently hydroxy, cyano or halogen.

[0094] The present invention provides a compound represented by formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

[0095]

[0096] X1 is N;

[0097] X2 is C;

[0098] Z1 is N;

[0099] Z2 is C;

[0100] W is

[0101] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0102] R 1-1 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl;

[0103] R 1-1-1 Each is independently halogen, hydroxyl or C1-C6 alkyl;

[0104] R 1-2 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 1-2-1 Substituted C1-C6 alkyl;

[0105] R 1-2-1 Each is independently halogen, hydroxyl or C1-C6 alkyl;

[0106] R2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl, unsubstituted or substituted with one or more R 2-9 Substituted C3-C6 cycloalkyl or unsubstituted or with one or more R 2-10 Substituted C3-C6 cycloalkenyl; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0107] R 2-3 Each is independently cyano, oxo (C=O), hydroxyl, halogen, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-5 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-3-7 Substituted amino groups;

[0108] R 2-3-1 Each is independently hydroxyl, cyano, or halogen;

[0109] R 2-3-2 is hydrogen, C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl, C1-C6 alkoxy, unsubstituted or substituted with one or more R 2-3-2-5 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0110] R 2-3-3 Each is independently hydrogen, C1-C6 alkyl;

[0111] R 2-3-5 each independently a halogen or a deuterium;

[0112] R 2-3-7 Each is independently a C1-C6 alkyl group;

[0113] R 2-3-2-2 Each independently represents halogen, hydroxy, unsubstituted or substituted with one or more R 2-3-2-2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-3-2-2-3 Substituted amino groups;

[0114] R 2-3-2-2-1 are each independently halogen or hydroxy;

[0115] R 2-3-2-2-2Each is independently carboxyl, halogen, deuterium, oxo or hydroxyl;

[0116] R 2-3-2-2-3 Each is independently a C1-C6 alkyl group;

[0117] R 2-3-2-5 Each independently represents halogen, hydroxy, oxo, C1-C6 alkoxy, unsubstituted or substituted with one or more R 2 -3-2-5-1 Substituted C1-C6 alkyl; R 2-3-2-5-1 are each independently a halogen;

[0118] R 2-5 Each independently is unsubstituted or substituted with one or more R 2-5-4 Substituted C1-C6 alkyl;

[0119] R 2-5-4 Each is independently C1-C6 alkoxy, hydroxy, cyano or halogen;

[0120] R 2-9 Each is independently C1-C6 alkoxy, C1-C6 alkyl, hydroxy, cyano or halogen;

[0121] R 2-10 Each is independently C1-C6 alkoxy, C1-C6 alkyl, hydroxy, cyano or halogen;

[0122] L is a carbonyl group;

[0123] R 3 for

[0124] R 3-1 and R 3-2 Each independently represents H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-5 The substituted 6-14-membered aryl group, the heteroatoms of the 4-12-membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12-membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0125] Or, R 3-1 , R 3-2and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0126] R 3-1-1 Each independently is unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 3-1-1-3 The heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1-1 Each is independently C1-C6 alkyl, hydroxyl or halogen; R 3-1-1-2 Each is independently C1-C6 alkyl, hydroxyl or halogen; R 3-1-1-3 Each is independently C1-C6 alkyl, C1-C6 alkoxy, hydroxyl or halogen;

[0127] R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl;

[0128] R 3-1-4 and R 3-1-5 Each is independently hydroxy, halogen or C1-C6 alkyl;

[0129] R 3-1-2-1 is hydroxyl, C1-C6 alkoxy, or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl;

[0130] R 3-1-2-2 and R 3-1-2-3 Each independently is H or C1-C6 alkyl;

[0131] R 3a are independently hydroxyl, Oxo (C=O), hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted or substituted with one or more R 3a-5 Substituted C1-C6 alkoxy or cyano;

[0132] R 3a-1 and R 3a-2 Each independently is H or C1-C6 alkyl;

[0133] R 3a-3 is hydroxyl, C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl;

[0134] R 3a-4 C 6-14 Aryl, hydroxyl, halogen, or C1-C6 alkyl; R 3a-4-1 and R 3a-4-2 Each independently is H or C1-C6 alkyl;

[0135] R 3a-5 is hydroxy, halogen or C1-C6 alkyl;

[0136] R 4 and R 5 Each is independently H.

[0137] In one embodiment, the compound represented by formula I, its stereoisomer or a pharmaceutically acceptable salt thereof;

[0138]

[0139] X1 is N;

[0140] Z1 is N;

[0141] X2 is C;

[0142] Z2 is C;

[0143] W is

[0144] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0145] R 1-1 Each is independently cyano or unsubstituted C1-C6 alkyl;

[0146] R 1-2 Each is independently an unsubstituted C1-C6 alkyl group;

[0147] R 2is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl; the heteroatom of the 4-12 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0148] R 2-3 are each independently an unsubstituted C1-C6 alkyl,

[0149] R 2-3-2 is unsubstituted C1-C6 alkyl or is replaced by one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl;

[0150] R 2-3-3 Each is independently an unsubstituted C1-C6 alkyl group;

[0151] R 2-3-2-2 Each independently is unsubstituted or substituted with one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy;

[0152] R 2-3-2-2-2 is halogen, hydroxyl or deuterium;

[0153] L is a carbonyl group;

[0154] R 3 for

[0155] R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0156] R 3a are independently halogen, hydroxyl, Oxo (C=O), hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano;

[0157] R 3a-1 and R 3a-2 Each is independent of H;

[0158] R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl;

[0159] R 3a-4 C 6-14 Aryl, hydroxy, halogen or -NH2;

[0160] R 4 and R 5 Each is independently H.

[0161] In a certain embodiment, in the compound represented by Formula I, its stereoisomers or pharmaceutically acceptable salts thereof; the definitions of certain groups may be as described below, and the definitions of other groups may be as described in any of the above embodiments (hereinafter referred to as "a certain embodiment"):

[0162] The compound represented by formula I satisfies the following conditions: 1 is unsubstituted or substituted with one or more R 1-2 A substituted 3-6 membered heterocycloalkyl group (for example, the 3-6 membered heterocycloalkyl group is an oxetanyl group); the heteroatoms of the 3-6 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of the heteroatoms is 1, 2 or 3.

[0163] In one embodiment, the compound represented by formula I satisfies the following conditions: X1 is N; X2 is C; Y1 is N; Y2 is C( for ).

[0164] In one embodiment, the compound represented by formula I satisfies the following conditions: L is a carbonyl group, R 3 for

[0165] In one embodiment, the compound represented by formula I satisfies the following conditions: R 3-1 and R 3-2 At least one (e.g., 1 or 2) is unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-5 Substituted 6-14 membered aryl;

[0166] Or, R 3-1-1 is unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-1-4 substituted 5-12 membered heteroaryl;

[0167] Or, R 3-1, R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a replace.

[0168] In one scheme, R z wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0169] In one scheme, R z wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0170] In one scheme, R z-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0171] In one scheme, R w In the above, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0172] In one scheme, R 1 In the above, the C3-C6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl.

[0173] In one scheme, R 1 In the embodiment, the 3-6 membered heterocycloalkyl is a 4-6 membered heterocycloalkyl, the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1. For example, the 3-6 membered heterocycloalkyl is an oxetane (for example, ).

[0174] In one scheme, R 1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0175] In one scheme, R 1-1 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0176] In one scheme, R 1-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0177] In one scheme, R 1-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0178] In one scheme, R 1-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0179] In one scheme, R 1-2 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0180] In one scheme, R 1-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0181] In one scheme, R 1-2-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0182] In one scheme, R 2 In the above, the 6-10 membered aryl group is phenyl or naphthyl, for example phenyl.

[0183] In one scheme, R 2 In the above, the 5-10 membered heteroaryl group is a 5- or 6-membered heteroaryl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0184] In one scheme, R 2 In the embodiment, the 4-12 membered heterocycloalkyl group is a 4-6 membered heterocycloalkyl group, wherein the heteroatoms are preferably selected from one or both of N and O, and the number of heteroatoms is preferably 2. For example, the 4-12 membered heterocycloalkyl group is an azacyclohexyl group (e.g. ) or aza-oxacyclohexane (e.g. For example, the 4-12 membered heterocycloalkyl group is an azocyclopentyl group (e.g. ).

[0185] In one scheme, R 2 In the above, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0186] In one scheme, R 2 In the above, the C3-C6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0187] In one scheme, R 2 In the above, the C3-C6 cycloalkenyl group is a C4-C6 cycloalkenyl group, wherein the cycloalkenyl group preferably contains 1 or 2 double bonds.

[0188] In one scheme, R 2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0189] In one scheme, R 2-1wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0190] In one scheme, R 2-1 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0191] In one scheme, R 2-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0192] In one scheme, R 2-1-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0193] In one scheme, R 2-1-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0194] In one scheme, R 2-1-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0195] In one scheme, R 2-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0196] In one scheme, R 2-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0197] In one scheme, R 2-2 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0198] In one scheme, R 2-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0199] In one scheme, R 2-2-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0200] In one scheme, R 2-2-3wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0201] In one scheme, R 2-2-4 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0202] In one scheme, R 2-2-4 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0203] In one scheme, R 2-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0204] In one scheme, R 2-3 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0205] In one scheme, R 2-3 In the above, the 3-6 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, wherein the heteroatom is preferably N, O or S, and the number of heteroatoms is preferably 1 or 2.

[0206] In one scheme, R 2-3 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0207] In one scheme, R 2-3 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0208] In one scheme, R 2-3 In the above, the 5-10 membered heteroaryl groups are each independently a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0209] In one scheme, R 2-3-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0210] In one scheme, R 2-3-1 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0211] In one scheme, R2-3-1 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0212] In one scheme, R 2-3-2 In the above, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl or isopropyl.

[0213] In one scheme, R 2-3-2 In the above, the C3-C6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl.

[0214] In one scheme, R 2-3-2 In the above, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0215] In one scheme, R 2-3-2 In the above, the 3-6 membered heterocycloalkyl is a 4-6 membered heterocycloalkyl, wherein the heteroatom is preferably N, O or S, and the number of heteroatoms is preferably 1 or 2. For example, the 3-6 membered heterocycloalkyl is oxetanyl, azetidinyl, oxolanyl, azocyclopentanyl, oxhexanyl, azohexanyl, pyrazinyl, thiazolidinyl or oxabicyclohexanyl.

[0216] In one scheme, R 2-3-2 In the above, the 5-10 membered heteroaryl group is a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0217] In one scheme, R 2-3-3 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0218] In one scheme, R 2-3-4 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0219] In one scheme, R 2-3-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0220] In one scheme, R 2-3-6 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0221] In one scheme, R2-3-7 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0222] In one scheme, R 2-3-8 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0223] In one scheme, R 2-3-8 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0224] In one scheme, R 2-3-9 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0225] In one scheme, R 2-3-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0226] In one scheme, R 2-3-1-2 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0227] In one scheme, R 2-3-1-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0228] In one scheme, R 2-3-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0229] In one scheme, R 2-3-2-1 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0230] In one scheme, R 2-3-2-1 In the above, the 5-10 membered heteroaryl groups are each independently a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0231] In one scheme, R 2-3-2-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0232] In one scheme, R 2-3-2-1-1 wherein the 6-10 membered aryl groups are each independently phenyl or naphthyl.

[0233] In one scheme, R 2-3-2-1-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0234] In one scheme, R 2-3-2-1-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0235] In one scheme, R 2-3-2-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0236] In one scheme, R 2-3-2-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0237] In one scheme, R 2-3-2-2 In the above, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, for example, methoxy.

[0238] In one scheme, R 2-3-2-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0239] In one scheme, R 2-3-2-2-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0240] In one scheme, R 2-3-2-2-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0241] In one scheme, R 2-3-2-3-1 wherein the 6-10 membered aryl groups are each independently phenyl or naphthyl.

[0242] In one scheme, R 2-3-2-3-1-1 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0243] In one scheme, R 2-3-2-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0244] In one scheme, R 2-3-2-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0245] In one scheme, R 2-3-2-5 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0246] In one scheme, R 2-3-2-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0247] In one scheme, R 2-3-2-5-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0248] In one scheme, R 2-3-2-6 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0249] In one scheme, R 2-3-3-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0250] In one scheme, R 2-4 In the above, the 4-10 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0251] In one scheme, R 2-4 In the above, the 5-10 membered heteroaryl groups are each independently a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0252] In one scheme, R 2-4 wherein the 6-10 membered aryl groups are each independently phenyl or naphthyl.

[0253] In one scheme, R 2-4 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0254] In one scheme, R 2-4-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0255] In one scheme, R 2-4-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0256] In one scheme, R 2-4-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0257] In one scheme, R 2-4-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0258] In one scheme, R 2-4-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0259] In one scheme, R 2-4-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0260] In one scheme, R 2-4-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0261] In one scheme, R 2-4-4 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0262] In one scheme, R 2-4-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0263] In one scheme, R 2-4-1-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0264] In one scheme, R 2-5 In the above, the 4-10 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0265] In one scheme, R 2-5 wherein the 6-10 membered aryl groups are each independently phenyl or naphthyl.

[0266] In one scheme, R 2-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0267] In one scheme, R 2-5-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0268] In one scheme, R 2-5-1-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0269] In one scheme, R 2-5-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0270] In one scheme, R 2-5-3 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0271] In one scheme, R 2-5-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0272] In one scheme, R 2-5-4 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, for example, methoxy, ethoxy or isopropoxy.

[0273] In one scheme, R 2-5-4-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prime-butyl, sec-butyl or tert-butyl, such as methyl, ethyl or isopropyl.

[0274] In one scheme, R 2-6 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0275] In one scheme, R 2-6 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0276] In one scheme, R 2-6 In the above, the 4-10 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0277] In one scheme, R 2-6In the above, the 5-10 membered heteroaryl groups are each independently a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0278] In one scheme, R 2-6-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0279] In one scheme, R 2-6-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0280] In one scheme, R 2-6-1-1 In the above, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0281] In one scheme, R 2-6-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0282] In one scheme, R 2-6-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0283] In one scheme, R 2-7 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0284] In one scheme, R 2-7 In the above, the 4-10 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0285] In one scheme, R 2-7 In the above, the 5-10 membered heteroaryl groups are each independently a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0286] In one scheme, R 2-7-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0287] In one scheme, R 2-7-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0288] In one scheme, R 2-7-1-1wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0289] In one scheme, R 2-7-1-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0290] In one scheme, R 2-7-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0291] In one scheme, R 2-7-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0292] In one scheme, R 2-8 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0293] In one scheme, R 2-8 In the above, the 4-10 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0294] In one scheme, R 2-8-1-1 In the above, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0295] In one scheme, R 2-9 In the above, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl, for example, methyl.

[0296] In one scheme, R 2-9 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0297] In one scheme, R 2-9 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0298] In one scheme, R 2-9 In the above, the 5-10 membered heteroaryl groups are each independently a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0299] In one scheme, R 2-9-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0300] In one scheme, R 2-9-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0301] In one scheme, R 2-10 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0302] In one scheme, R 2-10 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0303] In one scheme, R 2-10 In the above, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl, for example, methyl.

[0304] In one scheme, R 2-10 In the above, the 5-10 membered heteroaryl groups are each independently a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0305] In one scheme, R 2-10-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0306] In one scheme, R 2-11 In the above, the 5-10 membered heteroaryl groups are each independently a 5-membered heteroaryl group or a 6-membered heteroaryl group, wherein the heteroatom is preferably N and / or S, and the number of heteroatoms is preferably 1 or 2.

[0307] In one scheme, R 2-11 In the above, the 3-6 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0308] In one scheme, R 2-11-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0309] In one scheme, R 2-11-2wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0310] In one scheme, R 3-1 and R 3-1 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, such as methyl or ethyl.

[0311] In one scheme, R 3-1 and R 3-1 In the C3-C 12 The cycloalkyl groups are each independently C3-C6 cycloalkyl groups, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0312] In one scheme, R 3-1 and R 3-1 In, the 4-12 membered heterocycloalkyl is independently one or more of a monocyclic ring, a bridged ring, a cyclic ring and a spirocyclic ring. The monocyclic ring may be a 4-6 membered heterocycloalkyl. The cyclic ring may be a 3-membered 5-membered heterocycloalkyl, a 4-membered 5-membered heterocycloalkyl, a 5-membered 6-membered heterocycloalkyl, a 4-membered 6-membered heterocycloalkyl or a 5-membered 5-membered heterocycloalkyl. The spirocyclic ring may be a 3-ring spiro-5-ring, a 4-ring spiro-6-ring, a 4-ring spiro-5-ring, a 5-ring spiro-5-ring, a 4-ring spiro-4-ring, a 5-ring spiro-6-ring or a 3-ring spiro-6-ring. The bridged ring may be a bicyclooctanal or a bicycloheptane. The heteroatoms of the 4-12 membered heterocycloalkyl are preferably selected from N and / or O, and the number of heteroatoms is preferably 1 or 2. For example, the 4-6 membered heterocycloalkyl is an oxetane (for example, ), azacyclopentyl (e.g., ), azacyclohexane (e.g., ) or oxacyclohexane (e.g., ).

[0313] In one scheme, R 3-1 and R 3-1 In the above, the 5-12 membered heteroaryl groups are each independently a 5-membered or 6-membered heteroaryl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2. For example, the 5-12 membered heteroaryl groups are each independently a pyrazolyl group (e.g. ).

[0314] In one scheme, R 3-1 and R 3-1 wherein the 6-14 membered aryl groups are each independently phenyl or naphthyl.

[0315] In one scheme, R 3-1 and R 3-1 In the case of R 3-1 , R3-2 When forming a 4-12 membered heterocycloalkyl with the N atom connected thereto, wherein the 4-12 membered heterocycloalkyl is independently one or more of a monocyclic, a bridged ring, a cyclic and a spirocyclic ring. The monocyclic ring may be a 4-6 membered heterocycloalkyl. The cyclic ring may be a 3-membered and 5-membered heterocycloalkyl, a 4-membered and 5-membered heterocycloalkyl, a 5-membered and 6-membered heterocycloalkyl, a 4-membered and 6-membered heterocycloalkyl or a 5-membered and 5-membered heterocycloalkyl. The spirocyclic ring may be a 3-ring spiro-5-ring, a 4-ring spiro-6-ring, a 4-ring spiro-5-ring, a 5-ring spiro-5-ring, a 4-ring spiro-4-ring, a 5-ring spiro-6-ring or a 3-ring spiro-6-ring. The bridged ring may be a bicyclooctane, a bicycloheptane or a bicyclononane. The heteroatoms of the 4-12 membered heterocycloalkyl are preferably selected from N and / or O, and the number of heteroatoms is preferably 1 or 2.

[0316] The bicyclooctanes may be bicyclo[3.2.1]octanes (e.g. ); the bicycloheptaalkane may be bicyclo[3.1.1]heptaalkane (e.g. ) or bicyclo[2.2.1]heptaalkane (e.g. );

[0317] The 4-6 membered heterocycloalkyl group may be an azetidinyl group (e.g., ), azacyclopentyl (e.g., ), azacyclohexane (e.g., ), tetrahydropyridinyl, piperazinyl or morpholinyl (e.g. );

[0318] The 3-membered and 5-membered heterocycloalkyl groups may be cyclopropylazacyclopentyl groups (e.g., ); the 4-membered and 5-membered heterocycloalkyl group may be a cyclobutyl and azacyclopentyl group (for example, ); the 5-membered and 6-membered heterocycloalkyl group may be an azacyclopentyl and oxacyclohexyl group, a tetrahydrofuran and pyridinyl group, a hexahydropyrrolopyrazinyl group, a hexahydropyrazin and oxazinyl group or a hexahydroimidazopyrazinyl group, for example

[0319] The 3-ring spiro-5-ring may be an azaspiroheptane alkyl group (e.g., ); the 4-ring spiro-5-ring may be an azaspiro-octanyl group (e.g. ), diazaspirooctane (e.g. ); the 5-ring spiro-5-ring may be oxazaspironanyl (e.g. ); the 4-ring spiro6-ring may be an azaspironanyl group (e.g. ), diazaspironanyl (e.g. ) or dioxazaspironanyl; the 5-ring spiro-6-ring may be azacyclohexane spiroazacyclopentane alkyl (e.g. ).

[0320] In one scheme, R 3-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0321] In one scheme, R 3-1-1 In, the 4-12 membered heterocycloalkyl is independently one or more of a monocyclic ring, a bridged ring, a cyclic ring and a spirocyclic ring. The monocyclic ring may be a 4-6 membered heterocycloalkyl. The cyclic ring may be a 3-membered 5-membered heterocycloalkyl, a 4-membered 5-membered heterocycloalkyl, a 5-membered 6-membered heterocycloalkyl, a 4-membered 6-membered heterocycloalkyl or a 5-membered 5-membered heterocycloalkyl. The spirocyclic ring may be a 3-ring spiro-5-ring, a 4-ring spiro-6-ring, a 4-ring spiro-5-ring, a 5-ring spiro-5-ring, a 4-ring spiro-4-ring, a 5-ring spiro-6-ring or a 3-ring spiro-6-ring. The bridged ring may be a bicyclooctane, a bicycloheptane or a bicyclononane. The heteroatoms of the 4-12 membered heterocycloalkyl are selected from N and / or O, and the number of heteroatoms is preferably 1 or 2. For example, the 4-6 membered heterocycloalkyl is an oxetane (for example, ), azacyclopentyl (e.g., ), azacyclohexane (e.g., ) or oxacyclohexane (e.g., ).

[0322] In one scheme, R 3-1-1 In the above, the 5-12 membered heteroaryl groups are each independently a 5-membered or 6-membered heteroaryl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 2. For example, the 5-12 membered heteroaryl groups are each independently a pyridyl group (e.g. ) or pyrazolyl (e.g. ).

[0323] In one scheme, R 3-1-1 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, such as methyl or ethyl.

[0324] In one scheme, R 3-1-1 wherein the 6-14 membered aryl groups are each independently phenyl or naphthyl.

[0325] In one scheme, R 3-1-1 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, for example, methoxy.

[0326] In one scheme, R 3-1-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0327] In one scheme, R 3-1-1-1 In the above, the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine.

[0328] In one scheme, R 3-1-1-2 and R 3-1-1-4 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0329] In one scheme, R 3-1-1-2 and R 3-1-1-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0330] In one scheme, R 3-1-1-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0331] In one scheme, R 3-1-1-3 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0332] In one scheme, R 3-1-1-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0333] In one scheme, R 3-1-1-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0334] In one scheme, R 3-1-1-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0335] In one scheme, R 3-1-2 and R 3-1-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0336] In one scheme, R 3-1-2 and R 3-1-3 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0337] In one scheme, R 3-1-4 and R 3-1-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0338] In one scheme, R 3-1-4and R 3-1-5 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0339] In one scheme, R 3-1-2-1 In the above, the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0340] In one scheme, R 3-1-2-1 In the above, the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl.

[0341] In one scheme, R 3-1-2-1a and R 3-1-2-1b In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0342] In one scheme, R 3-1-2-2 and R 3-1-2-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0343] In one scheme, R 3a In the above, the halogen is fluorine, chlorine, bromine or iodine, for example fluorine.

[0344] In one scheme, R 3a In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, such as methyl or ethyl.

[0345] In one scheme, R 3a In the above, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, for example, methoxy.

[0346] In one scheme, R 3a-1 and R 3a-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0347] In one scheme, R 3a-3 In the above, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, for example, methoxy.

[0348] In one scheme, R 3a-3-1 and R 3a-3-2 In the above, the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, prim-butyl, sec-butyl or tert-butyl, for example, methyl.

[0349] In one scheme, R 3a-4 In the C 6-14 Each aryl group is independently phenyl or naphthyl, for example phenyl.

[0350] In one scheme, R 3a-4 In the above, the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine.

[0351] In one scheme, R 3a-4 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0352] In one scheme, R 3a-4-1 and R 3a-4-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0353] In one scheme, R 3a-5 In the above, the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine.

[0354] In one scheme, R 3a-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0355] In one scheme, R 4 and R 5 In the above, the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine.

[0356] In one scheme, R 4 and R 5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0357] In one scheme, R 4 and R 5 In the above, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0358] In one scheme, R4-1 and R 4-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0359] In one embodiment, the compound represented by formula I may be a compound represented by formula Ib,

[0360]

[0361] Ring D is a 3-6 membered heterocycloalkyl group; the heteroatoms of the 3-6 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0362] Ring C is a 4-12 membered heterocycloalkyl group; the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0363] m is 0, 1 or 2; k is 0, 1 or 2;

[0364] R 1-2a is hydrogen or R 1-2 ;

[0365] X1, X2, Z1, Z2, R 4 , R 5 , R 3-1 , R 3-2 , L, R 2-3 and R 1-2 The definition of is as described in any one of the present invention.

[0366] In one embodiment, the compound represented by formula I may be a compound represented by formula Ic,

[0367]

[0368] M is N, O or S;

[0369] i is 0, 1 or 2; j is 0, 1 or 2; i and j are not 0 at the same time;

[0370] L1 is a C1-C6 alkyl group (e.g., methyl, ethyl or propyl), and L1 is optionally substituted by one or more R L1 replace;

[0371] R L1 Each is independently a C1-C6 alkyl group (e.g., methyl);

[0372] Ring A is unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl;

[0373] R4 , R 5 , R 3-1-1-1 , R 3-1-1-2 , R 1-2a , R 1-2 , R 2-3 , k, ring C, m, and L are as defined in any one of the present invention.

[0374] In one embodiment, the compound represented by Formula I may be a compound represented by Formula Id or Formula Ie.

[0375]

[0376] Ring E is unsubstituted or substituted with one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0377] Ring F is a 4-12 membered heterocycloalkyl group, which is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0378] M, i, j, R 4 , R 5 , R 3-1-2 , R 3-1-3 , R 3-1-4 , R 3a , R 1-2a , R 1-2 , R 2-3 , k, ring C, m, and L are as defined in any one of the present invention.

[0379] In one embodiment, in the compound represented by formula I, R 3-1 and R 3-2 Each independently represents H, unsubstituted or substituted with one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, preferably, R 3-1 and R 3-2 Each independently is unsubstituted or substituted with one or more R 3-1-2In one embodiment, in the compound represented by formula I, when R 3-1 , R 3-2 When the 4-12-membered heterocycloalkyl is formed with the N atom connected thereto, the 4-12-membered heterocycloalkyl is a 4-6-membered (e.g., 5-membered) heterocycloalkyl or a 7-9-membered spirocyclic heterocycloalkyl, wherein in the 4-6-membered (e.g., 5-membered) heterocycloalkyl, the heteroatom is preferably N, and the number of heteroatoms is preferably 1; in the 7-9-membered spirocyclic heterocycloalkyl, the heteroatom is preferably N and O, and the number of heteroatoms is preferably 2 or 3, or the 7-9-membered polycyclic heterocycloalkyl is preferably a dispiro[2.4]nitrogen heterocycle (e.g., ).

[0380] In one scheme, R 3-1-2 and R 3-1-3 Each is independently halogen or hydroxy.

[0381] In one scheme, R 3a Each of them is independently hydroxyl, halogen, C1-C6 alkyl which is unsubstituted or substituted by one or more hydroxyl groups, or C1-C6 alkyl which is unsubstituted or substituted by one or more R 3a-5 Substituted C1-C6 alkoxy or cyano, such as hydroxy, halogen, unsubstituted or substituted by one or more R 3a-5 Substituted C1-C6 alkoxy or cyano.

[0382] In one embodiment, in the compound represented by formula I, when R 3-1 , R 3-2 When the 4-12 membered heterocycloalkyl is formed with the N atom connected thereto, the 4-12 membered heterocycloalkyl is surrounded by 2, 3 or 4 R 3a replace;

[0383] R 3a Each is independently halogen, hydroxy, -NH2, C1-C6 alkoxy (eg, methoxy) or cyano.

[0384] In one embodiment, X1 is N.

[0385] In one solution, Z1 is N.

[0386] In one solution, X2 is C.

[0387] In one solution, Z2 is C.

[0388] In one embodiment, L is a carbonyl group.

[0389] In one embodiment, in the compound represented by formula I, R 1 is unsubstituted or substituted with one or more R 1-2substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, for example, R 1 for

[0390] In one scheme, R 1-1 Each independently is cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, for example, unsubstituted C1-C6 alkyl, another example is cyano.

[0391] In one scheme, R 1-2 Each is independently an unsubstituted C1-C6 alkyl group.

[0392] In one scheme, R 2 For one or more R 2-3 The substituted 4-12 membered heterocycloalkyl group has a heteroatom selected from one or more of N, O and S, and the number of the heteroatoms is 1, 2 or 3.

[0393] In one scheme, R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl, unsubstituted or substituted with one or more R 2-10 The heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, for example, R 2 for

[0394] In one scheme, R 2-3 are each independently an unsubstituted C1-C6 alkyl group, For example, unsubstituted C1-C6 alkyl.

[0395] In one scheme, R 2-3 Each independently is hydroxyl, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl,

[0396] In one scheme, R 2-3-1 are each independently hydroxyl.

[0397] In one scheme, R 2-3-2 is unsubstituted C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl, such as R 2-3-2 For one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl.

[0398] In one scheme, R 2-3-3 Each is independently an unsubstituted C1-C6 alkyl group.

[0399] In one scheme, R 2-3-2-2 Each is independently a C1-C6 alkoxy group.

[0400] In one scheme, R 2-3-2-2 Each independently is C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy, preferably unsubstituted or substituted by one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy.

[0401] In one scheme, R 2-3-2-2-2 Each independently is deuterium.

[0402] In one scheme, R 3-1 and R 3-2 Each independently represents H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 The substituted 5-12 membered heteroaryl group, the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3.

[0403] In one scheme, R 3-1-1 Each independently is hydroxyl, unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 Substituted 5-12 membered heteroaryl, unsubstituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, for example, R 3-1-1 Each independently represents an unsubstituted C1-C6 alkyl group, unsubstituted or substituted with one or more R 3 -1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl; wherein the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3.

[0404] In one scheme, R 3-1-1-1 Each is independently hydroxy or halogen.

[0405] In one scheme, R 3-1-1-2 Each is independently a C1-C6 alkyl group.

[0406] In one scheme, R 3-1-1-3 Each is independently a C1-C6 alkoxy group or a hydroxy group.

[0407] In one scheme, R 3-1-2 and R 3-1-3 Each independently hydroxyl group, Or C1-C6 alkyl.

[0408] In one scheme, R 3-1-4 and R 3-1-5 Each is independently a C1-C6 alkyl group.

[0409] In one scheme, R 3-1-2-1 for Or C3-C6 cycloalkyl.

[0410] In one scheme, R 3-1-2-2 and R 3-1-2-3 Each is independently H.

[0411] In one scheme, R 3a are independently hydroxyl, Oxo (C=O), Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano, for example, R 3a Each independently Oxo (C=O), hydroxyl, halogen, C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano.

[0412] In one scheme, R 3a are independently halogen, hydroxyl, unsubstituted or substituted with one or more R 3a-4 substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano.

[0413] In one scheme, R 3a-1 and R 3a-2 Each is independent of H.

[0414] In one scheme, R 3a-3 is C1-C6 alkoxy or

[0415] In one scheme, R3a-4 C 6-14 Aryl, hydroxyl, halogen or For example, R 3a-4 C 6-14 Aryl or hydroxy.

[0416] In one scheme, R 3a-4 It is hydroxy, halogen or -NH2.

[0417] In one scheme, R 3a-4-1 and R 3a-4-2 Each is independent of H.

[0418] The present invention provides a compound represented by formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

[0419]

[0420] X1 is N;

[0421] X2 is C;

[0422] Z1 is N;

[0423] Z2 is C;

[0424] W is

[0425] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0426] R 1-1 are each independently cyano;

[0427] R 1-2 Each is independently a C1-C6 alkyl group;

[0428] R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl, unsubstituted or substituted with one or more R 2-10 Substituted C3-C6 cycloalkenyl; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0429] R 2-3 Each independently is hydroxyl, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl,

[0430] R 2-3-1 are each independently hydroxyl;

[0431] R 2-3-2 is C1-C6 alkyl or unsubstituted or substituted by one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl;

[0432] R 2-3-3 Each is independently hydrogen or C1-C6 alkyl;

[0433] R 2-3-2-2 Each independently represents halogen, hydroxyl, C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy;

[0434] R 2-3-2-2-2 Each independently is deuterium;

[0435] R 2-5 Each independently is one or more R 2-5-4 Substituted C1-C6 alkyl;

[0436] R 2-5-4 are each independently hydroxyl;

[0437] R 2-10 are each independently hydroxyl;

[0438] L is a carbonyl group;

[0439] R 3 for

[0440] R 3-1 and R 3-2 Each independently represents H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl or unsubstituted or with one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0441] Or, R 3-1 , R 3-2and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0442] R 3-1-1 Each independently is unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 3-1-1-3 The heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1-1 Each is independently hydroxyl or halogen; R 3-1-1-2 and R 3-1-1-4 Each is independently C1-C6 alkyl; R 3-1-1-3 Each independently is a C1-C6 alkoxy group or a hydroxyl group;

[0443] R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl;

[0444] R 3-1-4 Each is independently a C1-C6 alkyl group;

[0445] R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl;

[0446] R 3-1-2-2 and R 3-1-2-3 Each independently is H;

[0447] R 3a are each independently hydroxyl, Oxo (C=O), Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, C1-C6 alkoxy or cyano;

[0448] R 3a-1 and R 3a-2 Each is independent of H;

[0449] R 3a-3is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl;

[0450] R 3a-4 C 6-14 Aryl, hydroxyl, halogen or R 3a-4-1 and R 3a-4-2 Each is independent of H;

[0451] R 4 and R 5 Each is independently H.

[0452] In one embodiment, in the compound represented by formula I;

[0453] X1 is N;

[0454] X2 is C;

[0455] Z1 is N;

[0456] Z2 is C;

[0457] W is

[0458] R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0459] R 1-1 Each is independently cyano or unsubstituted C1-C6 alkyl;

[0460] R 1-2 Each is independently an unsubstituted C1-C6 alkyl group;

[0461] R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl; the heteroatom of the 4-12 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0462] R 2-3 are each independently an unsubstituted C1-C6 alkyl,

[0463] R 2-3-2 is unsubstituted C1-C6 alkyl or is replaced by one or more R 2-3-2-2Substituted C3-C6 cycloalkyl;

[0464] R 2-3-3 Each is independently an unsubstituted C1-C6 alkyl group;

[0465] R 2-3-2-2 Each is independently a C1-C6 alkoxy group;

[0466] L is a carbonyl group;

[0467] R 3 for

[0468] R 3-1 and R 3-2 Each independently represents H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0469] Or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0470] R 3-1-1 Each is independently hydroxyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 The heteroatoms of the 4-12-membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12-membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1-1 Each is independently hydroxyl or halogen; R 3-1-1-2 Each independently is a C1-C6 alkyl group;

[0471] R3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl;

[0472] R 3-1-4 Each is independently a C1-C6 alkyl group;

[0473] R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl;

[0474] R 3-1-2-2 and R 3-1-2-3 Each independently is H;

[0475] R 3a are independently halogen, hydroxyl, Oxo (C=O), hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano;

[0476] R 3a-1 and R 3a-2 Each is independent of H;

[0477] R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl;

[0478] R 3a-4 C 6-14 Aryl, hydroxy, halogen or -NH2;

[0479] R 4 and R 5 Each is independently H.

[0480] In one embodiment, in the compound represented by formula I;

[0481] X1 is N;

[0482] X2 is C;

[0483] Z1 is N;

[0484] Z2 is C;

[0485] W is

[0486] R 1 is unsubstituted or substituted with one or more R1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0487] R 1-1 Each is independently an unsubstituted C1-C6 alkyl group;

[0488] R 1-2 Each is independently an unsubstituted C1-C6 alkyl group;

[0489] R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl; the heteroatom of the 4-12 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0490] R 2-3 Each is independently an unsubstituted C1-C6 alkyl;

[0491] L is a carbonyl group;

[0492] R 3 for

[0493] R 3-1 and R 3-2 Each independently represents H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0494] Or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0495] R 3-1-1Each independently represents an unsubstituted C1-C6 alkyl group, unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 The heteroatoms of the 4-12-membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12-membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1-1 Each is independently hydroxyl or halogen; R 3-1-1-2 Each independently is a C1-C6 alkyl group;

[0496] R 3-1-2 and R 3-1-3 Each independently hydroxyl group, or C1-C6 alkyl;

[0497] R 3-1-4 Each is independently a C1-C6 alkyl group;

[0498] R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl;

[0499] R 3-1-2-2 and R 3-1-2-3 Each independently is H;

[0500] R 3a Each independently Oxo (C=O), hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano;

[0501] R 3a-1 and R 3a-2 Each is independent of H;

[0502] R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl;

[0503] R 3a-4 C 6-14 Aryl or hydroxyl;

[0504] R 4 and R 5 Each is independently H.

[0505] In one scenario, R 1 for For example, R 1 for

[0506] In one scheme, W is

[0507] In one scenario, R 2 for For example, R 2 for

[0508] In one scheme, L is

[0509] In one scenario, R 3 for

[0510]

[0511] In one scenario, R 3 for

[0512]

[0513] In one embodiment, the compound represented by formula I is any of the following compounds:

[0514]

[0515]

[0516]

[0517]

[0518]

[0519]

[0520] in, refer to

[0521] The present invention also provides a pharmaceutical composition, which comprises a substance Z and a pharmaceutical excipient, wherein the substance Z is the compound represented by the above formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

[0522] The present invention also provides an application of a substance Z in the preparation of a PARG inhibitor and a drug for treating and / or preventing PARG-related diseases, wherein the substance Z is the compound represented by the above formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

[0523] The present invention also provides a method for treating and / or preventing PARG-related diseases, which comprises administering to a patient an effective amount of a substance Z, wherein the substance Z is a compound represented by the above formula I, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0524] In a preferred embodiment, the PARG-related disease may be breast cancer, such as triple-negative breast cancer, and other PARG-related diseases.

[0525] The present invention also provides an application of a substance Z in the preparation of a drug for treating and / or preventing breast cancer, wherein the substance Z is the compound represented by the above formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

[0526] In a preferred embodiment, the breast cancer may be triple-negative breast cancer.

[0527] The present invention provides a compound represented by formula II;

[0528]

[0529] Among them, R 6 is a C1-C6 alkoxy group (e.g., a methoxy group);

[0530] Y is halogen (e.g., chlorine, bromine or iodine);

[0531] R 7 is H or an amino protecting group (such as p-methoxybenzyl (PMB), benzyl or (trimethylsilyl)ethoxymethyl (SEM));

[0532] R 1-2 , R 5 , R 4 , L are each independently as described in any one of the present invention.

[0533] In one embodiment, the compound represented by formula II is any of the following compounds:

[0534]

[0535] The present invention provides a compound represented by formula III;

[0536]

[0537] in,

[0538] R8 is an amino protecting group (such as p-methoxybenzyl (PMB), benzyl or (trimethylsilyl)ethoxymethyl (SEM));

[0539] R 1 ,w,R 2 , X1, X2, Z1, Z2, R 3 , R 5 , R 4 , L are each independently as described in any one of the present invention.

[0540] In one embodiment, the compound represented by formula III is any of the following compounds:

[0541] Preferably, the compound represented by formula III is any of the following compounds:

[0542]

[0543]

[0544] Alternatively, the compound represented by formula III is

[0545]

[0546]

[0547]

[0548] in, refer to

[0549] The present invention provides an application of the compounds represented by the above formula II and formula III as intermediates for preparing the compound represented by the formula I, its stereoisomers or pharmaceutically acceptable salts thereof. The application may include the following steps: in an organic solvent (such as dichloromethane), the compound represented by the formula III is subjected to a hydrolysis reaction (such as trifluoroacetic acid hydrolysis) to obtain the compound represented by the formula I, its stereoisomers or pharmaceutically acceptable salts thereof.

[0550] Explanation of terms

[0551] The term "a group B which is unsubstituted or substituted by multiple groups A" means that one or more hydrogen atoms in the group B are independently replaced by a group A or B is unsubstituted. When multiple groups A appear at the same time, unless otherwise specified, their definitions are independent of each other and do not affect each other. For example, "a C1-C6 alkyl group substituted by 3 halogens" means that a C1-C6 alkyl group will be substituted by 3 halogens, and the definitions of the 3 halogens are independent of each other and do not affect each other, including but not limited to: trifluoromethyl, difluoromethyl, wait.

[0552] A double bond or a single bond.

[0553] The term "plurality" refers to 2 or more, for example, 2, 3, 4, 5.

[0554] The term "pharmaceutically acceptable" means relatively non-toxic, safe, and suitable for use by patients.

[0555] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When the compound contains a relatively acidic functional group, a base addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, sodium salts, potassium salts, calcium salts, aluminum salts, magnesium salts, bismuth salts, ammonium salts, and the like. When the compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochlorides, sulfates, formates, methanesulfonates, and the like. For details, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition).

[0556] "-" in a group means that the group is attached to the rest of the molecule through this site. For example, CH3-C(=O)- means acetyl.

[0557] The term "halogen" refers to fluorine, chlorine, bromine or iodine. The halogen substitution in the present invention includes, but is not limited to, substitution by one halogen, substitution by two halogens, substitution by three halogens, and usually multiple substitutions occur on one carbon atom.

[0558] The term "oxo" refers to =0, an oxygen atom replacing two hydrogens on the same carbon atom, ie, replacing a methylene group with a carbonyl group.

[0559] The term "alkyl" refers to a linear or branched, saturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C1-C6). Alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, etc.

[0560] The term "alkoxy" refers to a group R X -O-, R XThe same definition as the term "alkyl". Alkoxy includes, but is not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, and the like.

[0561] The term "alkenyl" refers to a linear or branched, unsaturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C2-C6) and having one or more (e.g., 1, 2, or 3) carbon-carbon sp 2 Double bond. Alkenyl groups include but are not limited to: vinyl, wait.

[0562] The term "alkynyl" refers to a linear or branched, unsaturated, monovalent hydrocarbon radical having a specified number of carbon atoms (e.g., C2-C6) and having one or more (e.g., 1, 2, or 3) carbon-carbon sp 3 triple bond. Alkynyl groups include but are not limited to: ethynyl, wait.

[0563] Unless otherwise specified in the present invention, the term "cycloalkyl" refers to a cycloalkyl having a specified number of carbon atoms (e.g., C3 to C 10 , C3-C6), cyclic, saturated, monovalent hydrocarbon groups include but are not limited to: wait.

[0564] Unless otherwise specified in the present invention, the term "cycloalkenyl" refers to a "cycloalkyl" having one or more carbon-carbon double bonds, and the definition of "cycloalkyl" is the same as above. For example:

[0565] Unless otherwise specified in the present invention, the term "aryl" refers to a group having a specified number of carbon atoms (e.g., C6 to C 14 or C6~C 10 ) is a cyclic, unsaturated, monovalent hydrocarbon group, which is a single ring or multiple rings (for example, 2 or 3). When it is a multiple ring, the single rings share two atoms and a bond, and (at least one ring / each ring) is aromatic. The aryl group is connected to the rest of the molecule through an aromatic ring or a non-aromatic ring. Aryl groups include, but are not limited to: phenyl, naphthyl, wait.

[0566] Unless otherwise specified in the present invention, the term "heterocycloalkyl" refers to a monocyclic, bridged, spirocyclic, or cyclic (preferably monocyclic) ring having a specified number of ring atoms (e.g., 4-12 or 4-10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatoms (one or more of N, O, and S). The heterocycloalkyl group may be saturated or unsaturated. (Monocyclic) heterocycloalkyl groups are connected to the rest of the molecule via carbon atoms or heteroatoms. Monocyclic heterocycloalkyl groups include, but are not limited to: Spirocyclic heterocycloalkyl groups include, but are not limited to:

[0567] etc. Bridged heterocycloalkyl groups include but are not limited to: Etc. Cyclic heterocycloalkyl includes

[0568] Unless otherwise specified in the present invention, the term "heteroaryl" refers to a cyclic, unsaturated, monovalent group having a specified number of ring atoms (e.g., 5-10 or 5-6 members), a specified number of heteroatoms (e.g., 1, 2, or 3), a specified type of heteroatom (one or more of N, O, and S), which is a monocyclic or polycyclic ring, with two atoms and a bond shared between the monocyclic rings, and at least one ring having aromatic properties. The heteroaryl group is connected to the rest of the molecule through a carbon atom or a heteroatom; the heteroaryl group is connected to the rest of the molecule through a ring with heteroatoms or a ring without heteroatoms; the heteroaryl group is connected to the rest of the molecule through a ring with aromatic properties or a ring without aromatic properties. Heteroaryl groups include, but are not limited to: wait.

[0569] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0570] The reagents and raw materials used in the present invention are commercially available.

[0571] The positive effects of the present invention are: (1) the compounds of the present invention have good PARG inhibitory activity, exert good efficacy in vivo, and are more conducive to the efficacy of the compounds; and / or (2) have good selectivity and less toxic side effects. DETAILED DESCRIPTION

[0572] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0573] All compounds of the present invention can be synthesized by different methods by those skilled in the art of organic chemistry. The following describes a general synthetic scheme for preparing the compounds of the present invention. These schemes are general, but are not meant to limit the possible techniques that a person skilled in the art can use to prepare the compounds disclosed herein. The different methods for preparing the compounds of the present invention will be apparent to those skilled in the art. In addition, the various steps in the synthesis can be performed in an alternating order to obtain the desired one or more compounds. The preparation and examples described below give examples of the preparation of the compounds of the present invention by the methods described in the general scheme. The preparation of compounds containing chiral center embodiments can be performed by techniques mastered by those skilled in the art. For example, chiral compounds can be prepared by chiral separation of racemic products by HPLC; alternatively, the example compounds can be prepared by known methods to obtain chiral compounds.

[0574] The chemical reactions and synthesis techniques described herein are carried out in the reagents and corresponding solvents described herein, and the corresponding reaction yields are also affected by the reagents and solvents used. In addition, it should be understood that in the synthetic method described below, all the reaction conditions mentioned, including the choice of solvent, reaction atmosphere, reaction temperature, experimental duration and reaction feeding order, should be regarded as the operating condition standard of the reaction, which should be easily recognized by those skilled in the art. At the same time, it is also understandable to those skilled in the art in the field of organic synthesis. The functional groups present on each part of the molecule must be compatible with the reagents used and the reaction itself. For such restrictions that some functional groups present on each part of the molecule are incompatible with the reaction conditions, alternative methods must be used, which will be obvious to those skilled in the art. It is obvious that it is necessary to judge to adjust the order of the synthetic steps, or to select a specific synthetic process scheme to obtain the desired compound of the present invention. This is understandable and easily recognized by those skilled in the art in the field of organic synthesis. It should also be recognized that another major consideration for any synthetic route designed in this field is the reasonable selection of protecting groups for protecting the tolerance of reactive functional groups present in the compounds described in the present invention. For details, please refer to the work of Greene et al., an authority in the field of chemistry (Protective Groups in Organic Synthesis, Third Edition, Wiley and Sons (1999)).

[0575] Example

[0576] The preparation of the compounds and the intermediates used in the preparation of the compounds can be prepared using the procedures shown in the following examples and related procedures. The methods and conditions used in these examples and the actual compounds prepared in these examples are not meant to be limiting, but are meant to illustrate how to prepare the related compounds. The starting materials and reagents used in these examples, when not prepared by the procedures described herein, are generally available on the market, or reported in the relevant chemical literature, or can be prepared by using the procedures described in the chemical literature.

[0577] In the examples given herein, the term "drying and concentrating" generally refers to adding anhydrous sodium sulfate or magnesium sulfate drying solution to an organic solvent, followed by filtering and removing the solvent from the filtrate (generally under reduced pressure and at a temperature suitable for the stability of the prepared compound). Column chromatography generally uses conventional column chromatography or flash column chromatography for column separation and purification, or uses a medium pressure chromatograph (Biotage Isola One) pre-packed with silica gel columns and eluted in a specified solvent or solvent mixture. In some cases, the final product is quickly purified by preparative thin layer chromatography using 20cm x 20cm x 0.5mm or 20cm x 20cm x1mm silica gel plates in an appropriate solvent system. Preparative high performance liquid chromatography (HPLC) is performed using a reverse phase column (Waters Sunfire C18, Waters Xbridge C18 or similar reverse phase column) of a size appropriate to the amount of compound to be separated, typically using a gradient of methanol or acetonitrile concentration added to the aqueous phase, with the eluent containing 0.05% or 0.1% formic acid, trifluoroacetic acid or 10 mM ammonium acetate, with an elution rate matched to the size of the reverse phase column used and the resolution of the preparation.

[0578] List of abbreviations

[0579]

[0580] Example 1: N-cyclopropyl-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane- 3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0581]

[0582] Step 1: 8-Chloro-6-(chlorosulfonyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester

[0583] At 0°C, water (540 mg, 30 mmol) and acetic acid (1.8 g) were added to a solution of methyl 6-(benzylsulfanyl)-8-chloroimidazo[3,4-a]pyridine-3-carboxylate (1 g, 3.01 mmol) in dichloromethane (20 mL), and then sulfonyl chloride (1.62 g, 12.02 mmol) was slowly added dropwise. The reaction solution was stirred at 0°C for 10 minutes. After the reaction was complete, the reaction solution was adjusted to pH = 7-8 with sodium bicarbonate, washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (crude product, 1 g, yield 96.77%), which was directly used in the next step. LC / MS(ESI)(m / z): 309[M+H] + .

[0584] Step 2: 8-chloro-6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-yl Methyl carboxylate

[0585] In an ice-water bath, 3-methyloxetane-3-amine (315 mg, 3.62 mmol) and pyridine (2 mL, 24.73 mmol) were slowly added to a solution of 8-chloro-6-(chlorodioxy-λ6-sulfanyl)imidazo[3,4-a]pyridine-3-carboxylic acid methyl ester (927 mg, 3 mmol) in dichloromethane (8 mL), and the reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was diluted with dichloromethane, washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-60% ethyl acetate) to obtain the title compound (white solid, 580 mg, yield 26.9%). LC / MS(ESI)(m / z):360[M+H] + .

[0586] Step 3: 8-Chloro-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy) Methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate

[0587] In an ice-water bath, N,N-diisopropylethylamine (323 mg, 2.5 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (250 mg, 1.51 mmol) were slowly added to a solution of 8-chloro-6-(N-(3-methyloxetane-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester (450 mg, 1.25 mmol) in dichloromethane (20 mL) under ice-water bath, and the reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was diluted with dichloromethane, washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to obtain the title compound (white solid, 410 mg, yield 91.11%). LC / MS(ESI)(m / z):490[M+H] +.

[0588] Step 4: 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N- Methyl ((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate

[0589] Under nitrogen protection at room temperature, Ruphos Pd G3 (70 mg, 0.084 mmol), Ruphos (39 mg, 0.084 mmol) and cesium carbonate (545 mg, 1.67 mmol) were added to a solution of 8-chloro-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester (410 mg, 0.84 mmol) and 2S,6S-dimethylmorpholine (96.4 mg, 0.84 mmol) in 1,4-dioxane (10 mL) in sequence, and the reaction solution was stirred at 100°C for 1 hour. After the reaction was complete, the reaction solution was diluted with ethyl acetate, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to give the title compound (white solid, 420 mg, yield 88.3%). LC / MS (ESI) (m / z): 569 [M+H] + .

[0590] Step 5: 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N- ((2-(Trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid

[0591] To a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester (370 mg, 0.65 mmol) in tetrahydrofuran (3 mL), methanol (1 mL) and water (1 mL) was added lithium hydroxide (54.6 mg, 1.3 mmol) at room temperature, and the reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was adjusted to pH = 6-7 with citric acid and extracted three times with ethyl acetate. The organic phase was washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (yellow oil, 340 mg, yield 94%). LC / MS(ESI)(m / z):555[M+H] + .

[0592] Step 6: N-cyclopropyl-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane-3- 1-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0593] To a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid (60 mg, 0.11 mmol) and cyclopropylamine (9.50, 0.17 mmol) in N,N-dimethylformamide (5 mL) were added 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (63.3 mg, 0.17 mmol) and N,N-diisopropylethylamine (28.7 mg, 0.22 mmol) at room temperature, and the reaction solution was stirred at room temperature for 1 hour. After the reaction is complete, the reaction solution is diluted with ethyl acetate, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (colorless oil, 50 mg, yield 76%). LC / MS (ESI) (m / z): 594 [M+H] + .

[0594] Step 7: N-cyclopropyl-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane-3- (amino)sulfonyl)imidazo[1,5-a]pyridine-3-carboxamide

[0595] At room temperature, trifluoroacetic acid (1 mL) was added to N-cyclopropyl-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide (50 mg, 0.088 mmol) in dichloromethane (2 mL), and the reaction solution was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure, and the residue was separated by preparative HPLC (C18, 10-50% acetonitrile in H2O and 0.1% FA) to give the title compound (white solid, 3.69 mg, yield 9.2%). 1 H NMR (400MHz, DMSO-d6) δ9.58(s,1H),8.79(d,J=4.6Hz,1H),8.59(s,1H),7.62(s,1H),6.55(s,1H),4.61(t,J=6.8Hz,2H),4.20-4.14(m,4H), 3.26-3.20(m,2H),3.08-3.01(m,2H),2.93-2.87(m,1H),1.47(s,3H),1.30(d,J=6.4Hz,6H),0.72-0.67(m,4H).LC / MS(ESI)(m / z):464[M+H] + .

[0596] The following examples are prepared by referring to Example 1, starting from appropriate starting materials, and following a similar route. The crude product was purified by preparative HPLC and freeze-dried to give the title compound.

[0597]

[0598]

[0599]

[0600]

[0601]

[0602]

[0603]

[0604]

[0605]

[0606]

[0607]

[0608]

[0609]

[0610]

[0611]

[0612]

[0613]

[0614]

[0615]

[0616]

[0617]

[0618]

[0619]

[0620]

[0621]

[0622]

[0623]

[0624]

[0625]

[0626]

[0627]

[0628]

[0629] Example 109: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(4-isobutyrylpiperazine-1- yl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0630]

[0631] Step 1: 8-(4-isobutyrylpiperazin-1-yl)-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylpiperazin-1-yl)- Methylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate

[0632] Under nitrogen protection, cesium carbonate (80 mg, 0.25 mmol), Ruphos (11 mg, 0.024 mmol) and Ruphos Pd G3 (10 mg, 0.012 mmol) were added to a solution of 8-chloro-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester (60 mg, 0.12 mmol) and 2-methyl-1-(piperazin-1-yl)propan-1-one (38.26 mg, 0.25 mmol) in 1,4-dioxane (1.2 mL) in sequence. The reaction solution was replaced with nitrogen three times and stirred at 80°C for 2 hours under nitrogen protection. After the reaction was complete, the reaction solution was cooled to room temperature, diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to give the title compound (yellow solid, 63 mg, yield 84.4%). LC / MS (ESI) m / z: 610 [M+H] + .

[0633] Step 2: 8-(4-isobutyrylpiperazin-1-yl)-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylpiperazin-1-yl)- (methylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid

[0634] To a mixed solution of 8-(4-isobutyrylpiperazin-1-yl)-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester (65 mg, 0.11 mmol) in tetrahydrofuran (1 mL) and water (0.25 mL) was added lithium hydroxide (9 mg, 0.21 mmol) at room temperature. The reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was adjusted to pH = 6-7 with citric acid and extracted three times with ethyl acetate. The organic phase was washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (yellow solid, 60 mg, yield 95%). LC / MS(ESI)m / z:596[M+H] + .

[0635] Step 3: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(4-isobutyrylpiperazin-1-yl)-N- (3-Methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine- 6-Sulfonamide

[0636] At room temperature, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (57.4 mg, 0.15 mmol) and N,N-diisopropylethylamine (39 mg, 0.30 mmol) were added to a solution of 8-(4-isobutyrylpiperazin-1-yl)-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid (60 mg, 0.10 mmol) and 3-(trifluoromethyl)pyrrolidin-3-ol (11.65 mg, 0.10 mmol) in N,N-dimethylformamide (1 mL) at room temperature. The reaction solution was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to give the title compound (yellow solid, 60 mg, yield 81.3%). LC / MS (ESI) m / z: 733 [M+H] + .

[0637] Step 4: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(4-isobutyrylpiperazin-1-yl)-N- (3-Methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0638] Trifluoroacetic acid (0.5 mL) was slowly added dropwise to a solution of 3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (30 mg, 0.041 mmol) in dichloromethane (1 mL) at 0°C. The reaction solution was stirred at room temperature for 30 minutes. The mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (C18, 10-50% acetonitrile / aqueous solution containing 0.1% FA) to give the title compound (yellow solid, 4.66 mg, yield 18.9%). 1 H NMR(400MHz,CD3OD)δ9.67-9.58(m,1H),7.76(d,J=3.9Hz,1H),6.68(s,1H),4.84-4.83 (m,1H),4.77-4.73(m,2H),4.60-4.40(m,1H),4.40-4.31(m,1H),4.30-4.27(m,2H),4.0 3-3.92(m,1H),3.89-3.85(m,4H),3.40-3.32(m,4H),3.06-2.99(m,1H),2.39-2.26(m, 1H),2.20-2.10(m,1H),1.60(s,3H),1.14(d,J=6.7Hz,6H).LC / MS(ESI)(m / z):603[M+H] + .

[0639] Example 110: 8-((2S,6S)-2,6-dimethylmorpholinyl)-N-((1S,2S)-2-hydroxycyclopentyl)-N-(2- 6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0640]

[0641] Step 1: Benzyl ((1S,2S)-2-hydroxycyclopentyl) carbamate

[0642] At 0°C, triethylamine (1.5 g, 15 mmol) was added to a solution of (1S, 2S)-2-aminocyclopentan-1-ol (720 mg, 7.2 mmol) in dichloromethane (20 mL), and then benzyl chloroformate (1.5 g, 12 mmol) was slowly added dropwise. The reaction solution was stirred at 0°C for 2 hours. After the reaction was complete, the reaction solution was washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to give the title compound (white solid, 1.1 g, yield 65.9%). LC / MS (ESI) (m / z): 236 [M+H] + .

[0643] Step 2: Benzyl ((1S,2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)carbamate

[0644] At room temperature, 3,4-dihydro-2H-pyran (680 mg, 8.0 mmol) and p-toluenesulfonic acid (50 mg) were added to a solution of benzyl ((1S, 2S)-2-hydroxycyclopentyl) carbamate (1.1 g, 4.7 mmol) in tetrahydrofuran (20 mL). The reaction solution was stirred at 50°C for 1 hour. After the reaction was complete, the reaction solution was diluted with ethyl acetate, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-20% ethyl acetate) to give the title compound (white solid, 1.3 g, yield 87.1%). LC / MS (ESI) (m / z): 320 [M+H] + .

[0645] Step 3: (1S,2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentan-1-amine

[0646] At room temperature, slowly add 10% palladium on carbon (200 mg) to a solution of benzyl ((1S, 2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)carbamate (1.3 g, 4.0 mmol) in methanol (20 mL). The reaction solution was stirred at room temperature for 5 hours under a hydrogen atmosphere. After the reaction was complete, the reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure to obtain the title compound (colorless oil, 610 mg, yield 80.9%). LC / MS (ESI) (m / z): 186 [M+H] + .

[0647] Step 4: (1S,2S)-N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-2-((tetrahydro-2H-pyrrolidone)- pyran-2-yl)oxycyclopentan-1-amine

[0648] Under nitrogen protection at room temperature, to a solution of (1S, 2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentan-1-amine (50 mg, 0.3 mmol) and 2-(tert-butyldimethylsilyloxy)acetaldehyde (50 mg, 0.3 mmol) in methanol (0.5 mL), glacial acetic acid (10 mg) and sodium cyanoborohydride (38 mg, 0.6 mmol) were added in sequence. After the addition, the reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated under reduced pressure to remove methanol. The residue was diluted with ethyl acetate, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to obtain the title compound (colorless oil, 35 mg, yield 37.5%). LC / MS(ESI)(m / z):344[M+H] + .

[0649] Step 5: N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-8-((2S,6S)-2,6-dimethylmorpholine ((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)- NN-((1S,2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)

[0650] Cyclopentyl)imidazo[1,5-a]pyridine-3-carboxamide

[0651] To a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid (30 mg, 0.6 mmol) and (1S,2S)-N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-2-((tetrahydro-2H-pyran-2-yl)oxycyclopentan-1-amine (30 mg, 0.1 mmol) was added at room temperature. 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (40 mg, 0.1 mmol) and N,N-diisopropylethylamine (30 mg, 0.23 mmol) were added to the amide (2 mL) solution. The reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was diluted with ethyl acetate, washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (colorless oil, 30 mg, yield 39%). LC / MS (ESI) (m / z): 880 [M+H] + .

[0652] Step 6: 8-((2S,6S)-2,6-dimethylmorpholinyl)-N-((1S,2S)-2-hydroxycyclopentyl)-N-(2-hydroxyethyl)- 6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0653] Under ice-water bath, trifluoroacetic acid (0.5 mL) was added to a solution of N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)-NN-((1S,2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)imidazo[1,5-a]pyridine-3-carboxamide (30 mg, 0.03 mmol) in dichloromethane (1 mL). After addition, the reaction solution was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by preparative HPLC (C18, 10-50% acetonitrile / containing 0.1% FA aqueous solution) to give the title compound (white solid, 1.15 mg, yield 6.1%). 1H NMR(400MHz,CD3OD)δ8.97(s,1H),7.60(s,1H),6.58(s,1H),4.77-4.74(m ,2H),4.31-4.23(m,4H),4.08-3.96(m,1H),3.92-3.65(m,3H),3.37-3.34 (m,2H),3.29-3.26(m,2H),3.14-3.07(m,2H),2.23-1.93(m,4H),1.92-1. 65(m,2H),1.60(s,3H),1.39(d,J=6.4Hz,6H).LC / MS(ESI)(m / z):552[M+H] + .

[0654] Example 111: 8-((2S,6S)-2,6-dimethylmorpholinyl)-N-((1S,2S)-2-hydroxycyclopentyl)-N-(2- 6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0655]

[0656] Step 1: (1S,2S)-N-(2-methoxyethyl)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentan-1-amine

[0657] In an ice-water bath, cesium carbonate (35 mg, 0.11 mmol) and 1-bromo-2-methoxyethane (15 mg, 0.11 mmol) were added to a solution of (1S,2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentan-1-amine (20 mg, 0.11 mmol) in anhydrous N,N-dimethylformamide (1 mL). The reaction solution was stirred at 60 degrees Celsius for 3 hours. After the reaction was complete, water was added and extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to give the title compound (yellow oil, 25 mg, yield 95.3%). LC / MS(ESI)(m / z):244[M+H] + .

[0658] Step 2: 8-((2S,6S)-2,6-dimethylmorpholinyl)-N-(2-methoxyethyl)-6-(N-(3-methyloxazoline) Cyclobutan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)-N(((1S,2S)-2-((tetrahydro- 2H-pyran-2-yl)oxy)cyclopentyl)imidazo[1,5-a]pyridine-3-carboxamide

[0659] To a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid (25 mg, 0.045 mmol) in N,N-dimethylformamide (1 mL) at 0°C were added N,N-diisopropylethylamine (12 mg, 0.09 mmol), (1S,2S)-N-(2-methoxyethyl)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentan-1-amine (11 mg, 0.045 mmol) and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (26 mg, 0.068 mmol). The reaction solution was stirred at room temperature for 10 minutes. After the reaction was complete, it was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to obtain the title compound (yellow solid, 20 mg, yield 56.9%). LC / MS (ESI) (m / z): 780 [M+H] + .

[0660] Step 3: 8-((2S,6S)-2,6-dimethylmorpholinyl)-N-((1S,2S)-2-hydroxycyclopentyl)-N-(2-methoxy 6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0661] At 0°C, 8-((2S,6S)-2,6-dimethylmorpholinyl)-N-(2-methoxyethyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)-N(((1S,2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)imidazo[1,5-a]pyridine-3-carboxamide (2 Trifluoroacetic acid (0.25 mL) was added to a solution of 2-(2-hydroxy-1-nitropropene)-2-nitropropene ( ... 1H NMR (400MHz, DMSO-d6) δ8.90 (s, 1H), 8.58 (s, 1H), 7.66 (d, J = 13.0Hz, 1H), 6.51 ( s,1H),4.89-4.36(m,3H),4.19-4.14(m,4H),4.08-3.90(m,2H),3.80-3.61(m,4H ),3.32-3.28(m,2H),3.24-3.20(m,2H),3.10-3.03(m,3H),2.10-1.90(m,2H),1. 86-1.55(m,4H),1.47(s,3H),1.31(d,J=6.4Hz,6H).LC / MS(ESI)(m / z):566[M+H] + .

[0662] Example 112: 3-(3-(2-aminoethyl)-3-hydroxypyrrolidine-1-carbonyl)-8-((2S,6S)-2,6-dimethylpyrrolidine methylmorpholinyl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0663]

[0664] Step 1: tert-Butyl 3-(cyanomethyl)-3-hydroxypyrrolidine-1-carboxylate

[0665] At -78 ° C, slowly drip isopropyl Grignard reagent lithium chloride complex (3.7 mL, 6.0 mmol, 1.6 M in THF) into a solution of tert-butyl 3-oxopyrrolidine-1-carboxylate (1 g, 5.4 mmol) and 2-iodoacetonitrile (1 g, 6.0 mmol) in anhydrous tetrahydrofuran (20 mL). After the addition, the reaction solution is slowly warmed to room temperature and stirred overnight. After the reaction is complete, saturated ammonium chloride is quenched and extracted with ethyl acetate. The organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 30-50% ethyl acetate) to obtain the title compound (colorless liquid, 900 mg, yield 73.8%). LC / MS (ESI) (m / z): 227 [M+H] + .

[0666] Step 2: tert-Butyl 3-(2-aminoethyl)-3-hydroxypyrrolidine-1-carboxylate

[0667] Under nitrogen atmosphere, add Raney nickel (200 mg) to a solution of tert-butyl 3-(cyanomethyl)-3-hydroxypyrrolidine-1-carboxylate (900 mg, 4.0 mmol) in methanol (20 mL). The reaction solution was replaced with nitrogen three times, and stirred at room temperature under an atmospheric pressure of hydrogen to react overnight. After the reaction was complete, it was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure to obtain the title compound (white solid, 550 mg, yield 54.6%). LC / MS (ESI) (m / z): 231 [M+H] + .

[0668] Step 3: tert-Butyl 3-(2-((Benzyloxy)carbonyl)amino)ethyl)-3-hydroxypyrrolidine-1-carboxylate

[0669] At 0°C, triethylamine (485mg, 4.8mmol) and benzyl chloroformate (450mg, 2.6mmol) were added to a solution of tert-butyl 3-(2-aminoethyl)-3-hydroxypyrrolidine-1-carboxylate (550mg, 2.4mmol) in dichloromethane (10mL). The reaction solution was stirred at room temperature for 2 hours. After the reaction was complete, water was added and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 50-80% ethyl acetate) to obtain the title compound (yellow liquid, 360mg, yield 41.1%). LC / MS(ESI)(m / z): 365[M+H] + .

[0670] Step 4: Benzyl (2-(3-hydroxypyrrolidin-3-yl)ethyl)carbamate hydrochloride

[0671] At room temperature, dioxane hydrochloride (5 mL, 4 M) was added to a bottle containing tert-butyl 3-(2-((benzyloxy)carbonyl)amino)ethyl)-3-hydroxypyrrolidine-1-carboxylate (360 mg, 1.00 mmol). The reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated under reduced pressure to obtain the title compound (white solid, 180 mg, yield 70.0%). LC / MS (ESI) (m / z): 265 [M+H] + .

[0672] Step 5: Benzyl (2-(1-(8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane- 3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carbonyl)-3- (2-Hydroxypyrrolidin-3-yl)ethyl)carbamate

[0673] At room temperature, 1H-benzotriazol-1-yloxytripyrrolidinyl hexafluorophosphate (56 mg, 0.11 mmol) and N,N-diisopropylethylamine (35 mg, 0.27 mmol) were added to a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid (50 mg, 0.09 mmol) and benzyl(2-(3-hydroxypyrrolidin-3-yl)ethyl)carbamate hydrochloride (36 mg, 0.135 mmol) in N,N-dimethylformamide (1 mL) at room temperature. The reaction solution was stirred at room temperature for 3 hours. After the reaction was complete, water was added and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 80-100% ethyl acetate) to give the title compound (yellow solid, 50 mg, yield 69.4%). LC / MS (ESI) (m / z): 801 [M+H] + .

[0674] Step 6: Benzyl (2-(1-(8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane- (3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carbonyl)-3-hydroxypyrrolidin-3-yl)ethyl)carbamate

[0675] To a solution of benzyl (2-(1-(8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carbonyl)-3-hydroxypyrrolidin-3-yl)ethyl)carbamate (50 mg, 0.063 mmol) in dichloromethane (1 mL) at 0°C was added trifluoroacetic acid (0.5 mL). The reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was concentrated to dryness. The residue was dissolved in methanol (2 mL), and aqueous ammonia (0.5 mL) was added. The mixture was stirred at room temperature for 30 minutes and concentrated under reduced pressure to give the title compound (yellow solid, 30 mg, yield 71.4%). LC / MS(ESI)(m / z): 671[M+H] + .

[0676] Step 7: 3-(3-(2-aminoethyl)-3-hydroxypyrrolidine-1-carbonyl)-8-((2S,6S)-2,6-dimethylpyrrolidine lino)-N-(3-methyloxetane-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0677] Under nitrogen atmosphere, 10% palladium on carbon (10 mg) was added to a solution of benzyl (2-(1-(8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carbonyl)-3-hydroxypyrrolidin-3-yl)ethyl)carbamate (30 mg, 0.045 mmol) in methanol (3 mL) under nitrogen atmosphere. After nitrogen replacement three times, the reaction solution was stirred at room temperature under an atmospheric pressure of hydrogen atmosphere for 1 hour. After the reaction was complete, the reaction solution was filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (C18, 10-80% acetonitrile / H2O solution containing 0.1% FA) to give the title compound (yellow solid, 3 mg, yield 12.5%). 1 H NMR(400MHz,CD3OD)δ9.58(d,J=4.5Hz,1H),7.64(d,J=8.5Hz,1H),6.64(s,1H),4.7 7-4.73(m,2H),4.44-4.30(m,1H),4.29-4.24(m,4H),4.08-3.93(m,1H),3.92-3.77 (m,2H),3.67-3.47(m,1H),3.28-3.26(m,1H),3.21-3.14(m,2H),3.13-3.08(m,2H) ,2.11-1.97(m,4H),1.60(s,3H),1.39(d,J=6.4Hz,6H).LC / MS(ESI)(m / z):537[M+H] + .

[0678] Example 113 and Example 114: 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-((S * )-3-hydroxy-3- (Trifluoromethyl)pyrrolidine-1-carbonyl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide and 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-((R*)-3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-N- (3-Methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0679]

[0680] Step 1: 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-((S)-3-hydroxy-3-(trifluoromethyl)pyrrolidine- 1-Carbonyl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0681] Trifluoroacetic acid (1.5 mL) was added to a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-N-(3-methyloxetane-3-yl)-N((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (150 mg, 0.28 mmol) in dichloromethane (3 mL) at 0°C. The reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC (C18, 10-60% acetonitrile / aqueous solution containing 0.1% FA) to give the title compound (yellow solid, 80 mg, yield 66%). Subsequently, the compound of Example 113 (peak 1, retention time: 2.612 min) (yellow solid, 23 mg, yield 29%) and the compound of Example 114 (peak 2, retention time: 3.558 min) (yellow solid, 28 mg, yield 35%) were separated by preparative SFC (ChiralPak AS, 250×30 mm ID 5 μm, A for CO2 and B for MeOH (0.1% 2M NH3 / MeOH), 40 mL / min).

[0682] Embodiment 113 : 1 H NMR (400MHz, DMSO-d6) δ9.52-9.42 (m, 1H), 8.58 (s, 1H), 7.73 (d, J = 7.5Hz, 1H),6.66-6.49(m,2H),4.64-4.57(m,2H),4.49-4.30(m,1H),4.25-4.12( m,5H),3.98-3.71(m,2H),3.24-3.16(m,2H),3.09-3.02(m,2H),2.34-2.0 7(m,2H),1.45(s,3H),1.31(d,J=6.4Hz,6H).LC / MS(ESI)(m / z):562[M+H] + .

[0683] Embodiment 114 : 1H NMR (400MHz, DMSO-d6) δ9.56-9.42 (m, 1H), 8.58 (s, 1H), 7.75 (d, J = 7.1Hz, 1H),6.63-6.53(m,2H),4.65-4.57(m,2H),4.47-4.32(m,1H),4.25-4.12( m,5H),3.98-3.72(m,2H),3.25-3.17(m,2H),3.10-3.02(m,2H),2.35-2.0 7(m,2H),1.47(s,3H),1.31(d,J=6.4Hz,6H).LC / MS(ESI)(m / z):562[M+H] + .

[0684] Example 115: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(5-hydroxycyclopent-1-ene-1- yl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0685]

[0686] Step 1: 2-Bromocyclopent-2-en-1-one

[0687] At 0°C, add liquid bromine (9.8g, 61.0mmol) and triethylamine (6.2g, 61.0mmol) to a solution of cyclopent-2-en-1-one (5g, 61.0mmol) in dichloromethane (50mL). The reaction solution was stirred at room temperature overnight. After the reaction was complete, saturated sodium thiosulfate aqueous solution was added to quench, and dichloromethane was extracted. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10-30% ethyl acetate) to obtain the title compound (colorless liquid, 7.5g, yield 76.8%). 1 H NMR (400MHz, DMSO-d6) δ8.18-7.99(m,1H),2.69-2.62(m,2H),2.49-2.43(m,2H).

[0688] Step 2: 2-Bromocyclopent-2-en-1-ol

[0689] At 0°C, sodium borohydride (0.7 g, 18.8 mmol) was added in batches to a solution of 2-bromocyclopent-2-ene-1-one (3 g, 18.8 mmol) and cerium trichloride (1.8 g, 7.52 mmol) in methanol (30 mL). The reaction solution was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was slowly added dropwise to a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 20-30% ethyl acetate) to obtain the title compound (colorless liquid, 2.5 g, yield 82.3%).1 H NMR (400MHz, DMSO-d6) δ6.04 (s, 1H), 5.28 (d, J = 7.0Hz, 1H), 4.54-4.42 (m, 1H), 2.40-2.11 (m, 3H), 1.70-1.60 (m, 1H).

[0690] Step 3: (2-bromocyclopent-2-en-1-yl)oxy)(tert-butyl)dimethylsilane

[0691] At 0°C, imidazole (1.3 g, 18.6 mmol) and tert-butyldimethylsilyl chloride (2.1 g, 14.0 mmol) were added to a solution of 2-bromocyclopent-2-ene-1-ol (1.5 g, 9.3 mmol) in dichloromethane (20 mL). The reaction solution was stirred at room temperature overnight. After the reaction was complete, the reaction solution was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-15% ethyl acetate) to obtain the title compound (colorless liquid, 2.5 g, yield 97.4%). 1 H NMR(400MHz,DMSO-d6)δ6.13-6.00(m,1H),4.77-4.63(m,1H),2.41-2.26(m,2H ),2.23-2.15(m,1H),1.72-1.62(m,1H),0.89(s,9H),0.10(s,3H),0.08(s,3H).

[0692] Step 4: tert-Butyldimethyl (2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopentane-2-yl) 1-Alkenyl)oxy)silane

[0693] At -78°C, n-butyl lithium (1.7 mL, 4.3 mmol, 2.5 M in THF) was added dropwise to a solution of (2-bromocyclopent-2-en-1-yl)oxy)(tert-butyl)dimethylsilane (1 g, 3.6 mmol) in anhydrous tetrahydrofuran (10 mL). The reaction solution was stirred at -78°C for 1 hour. At this temperature, a solution of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborane (1.3 g, 7.2 mmol) in tetrahydrofuran (5 mL) was added. The reaction solution was stirred at -78°C for 2 hours. After the reaction was complete, saturated aqueous ammonium chloride was added to quench the reaction, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10-20% ethyl acetate) to give the title compound (colorless liquid, 550 mg, yield 47.2%). 1H NMR(400MHz,DMSO-d6)δ6.45-6.36(m,1H),4.88-4.78(m,1H),2.42-2.33(m,1H),2.22-2.12(m ,1H),2.08-1.97(m,1H),1.53-1.43(m,1H),1.13(s,12H),0.79(s,9H),0.01(d,J=3.2Hz,6H).

[0694] Step 5: 8-(5-(((tert-butyldimethylsilyl)oxy)cyclopent-1-en-1-yl)-3-(3-hydroxy-3- (trifluoromethyl)pyrrolidine-1-carbonyl)-N-(3-methyloxetan-3-yl)-N((2-(trimethylsilyl)ethoxy) Methyl)imidazo[1,5-a]pyridine-6-sulfonamide

[0695] Under nitrogen atmosphere, Xphos Pd G2 (6 mg, 0.008 mmol) and potassium phosphate (52 mg, 0.25 mmol) were added to a solution of 8-chloro-3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (50 mg, 0.082 mmol) and tert-butyldimethyl((2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-yl)oxy)silane (50 mg, 0.164 mmol) in 1,4-dioxane (5 mL) and water (1 mL). The reaction solution was stirred at 90°C under nitrogen overnight. After the reaction was complete, water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 50-80% ethyl acetate) to give the title compound (yellow solid, 56 mg, yield 87.5%). LC / MS (ESI) (m / z): 775 [M+H] + .

[0696] Step 6: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(5-hydroxycyclopent-1-en-1-yl)- N-(3-Methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0697] To a solution of 8-(5-(((tert-butyldimethylsilyl)oxy)cyclopent-1-en-1-yl)-3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-N-(3-methyloxetan-3-yl)-N((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (56 mg, 0.072 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.5 ml) at 0°C. The reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated under reduced pressure to obtain the title compound (yellow oil, 40 mg, crude product). 20 mg of the crude product was further purified by preparative HPLC (C18, 10-80% acetonitrile / H2O solution containing 0.1% FA) to obtain the title compound (yellow solid, 3 mg, yield 15.9%). 1 H NMR(400MHz,DMSO-d6))δ9.83-9.77(m,1H),8.70(s,1H),8.01(d,J=7.5Hz,1H),7 .54(d,J=2.1Hz,1H),6.78(s,1H),6.60(d,J=21.6Hz,1H),5.14(s,2H),4.68-4.55 (m,2H),4.50-4.34(m,1H),4.29-4.10(m,3H),3.95-3.73(m,2H),2.77-2.66(m,1H ),2.46-1.99(m,4H),1.87-1.76(m,1H),1.50(s,3H).LC / MS(ESI)(m / z):531[M+H] + .

[0698] Example 116: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(2-hydroxycyclopentyl)-N-(3- methyloxetane-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0699]

[0700] Under nitrogen atmosphere, 10% palladium on carbon (10 mg) was added to a solution of 3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(5-hydroxycyclopent-1-ene-1-yl)-N-(3-methyloxetane-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide (20 mg, 0.038 mmol) in methanol (3 mL). The reaction solution was stirred at room temperature under an atmosphere of hydrogen for 1 hour. After the reaction was complete, the reaction solution was filtered and the filtrate was purified by preparative HPLC (C18, 10-50% acetonitrile in H2O and 0.1% FA) to give the title compound (yellow solid, 2 mg, yield 9.9%). 1H NMR(400MHz,CD3OD)δ9.90-9.80(m,1H),7.89-7.80(m,1H),7.89-7.80(m,1H), 4.78-4.71(m,2H),4.59-4.55(m,1H),4.45-4.25(m,4H),4.04-3.83(m,2H),3.4 4-3.34(m,1H),2.41-2.25(m,2H),2.21-2.10(m,2H),2.08-1.94(m,2H),1.94- 1.87(m,1H),1.83-1.74(m,1H),1.63-1.58(m,3H).LC / MS(ESI)(m / z):533[M+H] + .

[0701] Example 117: 8-(bis(2-hydroxyethyl)amino)-3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)- N-(3-Methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0702]

[0703] Step 1: Benzyl bis(2-hydroxyethyl)carbamate

[0704] Under an ice-water bath, potassium carbonate (2.6 g, 19.02 mmol) was added to a solution of 2,2'-azadiylbis(ethane-1-ol) (1 g, 9.51 mmol) in acetonitrile (10 mL), and then benzyl chloroformate (2.4 g, 14.26 mmol) was slowly added dropwise. The reaction solution was stirred at room temperature for 3 hours. After the reaction was complete, the reaction solution was diluted with ethyl acetate, washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-25% ethyl acetate) to obtain the title compound (colorless oil, 900 mg, yield 39.5%). LC / MS (ESI) (m / z): 240 [M+H] + .

[0705] Step 2: Benzyl bis(2-((tert-butyldimethylsilyl)oxy)ethyl)carbamate

[0706] In an ice-water bath, imidazole (512 mg, 7.52 mmol) and tert-butyldimethylsilyl chloride (1247 mg, 8.27 mmol) were slowly added to a solution of benzyl bis(2-hydroxyethyl)carbamate (900 mg, 3.76 mmol) in dichloromethane (9 mL), and the reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was diluted with dichloromethane, washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-15% ethyl acetate) to obtain the title compound (colorless oil, 500 mg, yield 28.4%). LC / MS(ESI)(m / z):468[M+H] + .

[0707] Step 3: Bis(2-((tert-butyldimethylsilyl)oxy)ethyl)amine

[0708] At room temperature, add 10% palladium on carbon (50 mg) to a solution of benzyl bis(2-((tert-butyldimethylsilyl)oxy)ethyl)carbamate (500 mg, 1.07 mmol) in methanol (5 mL). The reaction solution was replaced with nitrogen three times and stirred at room temperature for 2 hours under an atmosphere of hydrogen at an atmospheric pressure. After the reaction was completed, the filtrate was filtered and concentrated under reduced pressure to obtain the title compound (colorless liquid, 300 mg, yield 84.1%), which was used directly in the next step without purification. LC / MS(ESI)(m / z):334[M+H] + .

[0709] Step 4: 8-(bis(2-((tert-butyldimethylsilyl)oxy)ethyl)amino)-3-(3-hydroxy-3-(tris) ((2-(trimethylsilyl)ethoxy)methyl)pyrrolidine-1-carbonyl)-N-(3-methyloxetan-3-yl)- yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0710] Under nitrogen protection, cesium carbonate (117 mg, 0.36 mmol), Ruphos (17 mg, 0.036 mmol) and Ruphos Pd G3 (30 mg, 0.036 mmol) were added to a solution of 8-chloro-3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (107 mg, 0.18 mmol) and bis(2-((tert-butyldimethylsilyl)oxy)ethyl)amine (89 mg, 0.27 mmol) in 1,4-dioxane (3 mL) in sequence. The reaction solution was replaced with nitrogen three times and stirred at 80°C for 2 hours under nitrogen. After the reaction was complete, water was added and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-55% ethyl acetate) to give the title compound (yellow solid, 50 mg, yield 30.6%). LC / MS (ESI) (m / z): 910 [M+H] + .

[0711] Step 5: 8-(bis(2-hydroxyethyl)amino)-3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-N-(3- methyloxetane-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0712] Under nitrogen protection, trifluoroacetic acid (0.3 mL) was added to a dichloromethane (1 mL) solution of 8-(bis(2-((tert-butyldimethylsilyl)oxy)ethyl)amino)-3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-N-(3-methyloxetane-3-yl)-N((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (50 mg, 0.055 mmol). The reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was dropped into a 5% sodium bicarbonate aqueous solution cooled in an ice-water bath and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative HPLC (C18, 10-50% acetonitrile / water solution containing 0.1% FA) to give the title compound (yellow solid, 45 mg, 48.9% yield). 1H NMR (400MHz, CD3OD) δ9.54-9.41(m,1H),7.91(s,1H),6.58(s,1H),4.79-4.74(m,3H),4.37-4.32(m,1H),4.28-4.26(m,2 H),3.83-3.80(m,4H),3.73-3.69(m,4H),3.36-3.33(m,2H),2.21-2.12(m,2H),1.60(s,3H).LC / MS(ESI)(m / z):552[M+H] + .

[0713] Comparative Example 1: 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(hydroxymethyl)-N-(3-methyloxetane alkyl-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0714]

[0715] Step 1: 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(hydroxymethyl)-N-(3-methyloxetane-3-yl)- 2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide

[0716] Under nitrogen protection, lithium aluminum tetrahydride (6.7 mg, 0.18 mmol) was added to a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester (50 mg, 0.088 mmol) in tetrahydrofuran (8 mL), and the reaction solution was stirred at room temperature for 2 hours. After the reaction was complete, sodium sulfate decahydrate was added to the reaction solution and stirred for half an hour, then filtered, the filter cake was washed twice with ethyl acetate, the filtrate was washed with water and saturated brine in turn, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (colorless oil, 30 mg, yield 60%). LC / MS(ESI)(m / z):541[M+H] + .

[0717] Step 2: 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(hydroxymethyl)-N-(3-methyloxetane-3-yl)- yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0718] To a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(hydroxymethyl)-N-(3-methyloxetane-3-yl)-N-[(2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (30 mg, 0.055 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.5 mL) at room temperature, and the reaction solution was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was separated by preparative HPLC (C18, 10-50% acetonitrile in 0.1% FA aqueous solution) to give the title compound (white solid, 3.82 mg, yield 19.1%). 1H NMR (400MHz, DMSO-d6) δ8.47(s,1H),8.36(s,1H),7.40(s,1H),6.32(s,1H),5.65-5.59(m,1H),4.87(d,J=5.3Hz,2H),4.63-4.57 (m,2H),4.19-4.12(m,4H),3.21-3.15(m,2H),3.07-3.00(m,2H),1.47(s,3H),1.30(d,J=6.4Hz,6H).LC / MS(ESI)(m / z):411[M+H] + .

[0719] Effect Example

[0720] Experimental methods:

[0721] 1. Biochemical Assay

[0722] 1) Add 20 nL of compounds of different concentrations into a 384-well plate using Echo 550 (LABCYTE, #550) (final concentrations of compounds: 1000 nM, 300 nM, 100 nM, 30 nM, 10 nM, 3 nM, 1 nM, 0.3 nM, 0.1 nM, 0.03 nM, 0 nM);

[0723] 2) Prepare reaction buffer I: 50 mM Tris (2-amino-2-hydroxymethyl-1,3-propanediol, Sigma, #T1503) pH 7.4, 0.015% Triton X-100 (4-(1,1,3,3-tetramethylbutyl)phenyl-polyethylene glycol, Sigma, #T8787), 0.1% BSA (bovine serum albumin, Sigma, #A1933), 5 mM KCl, 66.2 uM TFMU-ADPr (fluorescein-4-trifluoromethylumbelliferyl-ADP ribose);

[0724] 3) Add reaction buffer I at 10 μL / well into a 384-well plate;

[0725] 4) Prepare reaction buffer II: 50 mM Tris PH 7.4, 0.015% Triton X-100, 0.1% BSA, 5 mM KCl, 4 nM PARG (poly ADP-ribose hydrolase);

[0726] 5) Add reaction buffer II at 10 μL / well into the 384-well plate to start the reaction;

[0727] 6) Incubate at room temperature for 3 min to react;

[0728] 7) Place the 384-well plate in the microplate reader and shake for 5 seconds before detecting the signal;

[0729] 8) Analyze the data using GraphPad software and determine the IC50.

[0730] 2. Cell Viability Assay

[0731] 1) Cells were plated in 384-well cell culture plates. HCC1806 (Nanjing Kebai, ATCC cell bank, 100 cells / well) and MDA-MB-231 (ATCC cell bank, 120 cells / well) were incubated in a 37°C CO2 (5%) incubator for 24 h to allow the cells to fully adhere to the plate.

[0732] 2) Add culture medium (100 μL / well) containing different concentrations of the test compound (final concentration of the compound is: 30000 nM, 10000 nM, 3000 nM, 1000 nM, 300 nM, 100 nM, 30 nM, 10 nM, 3 nM, 1 nM, 0 nM) to the cells and incubate in a CO2 (5%) incubator at 37°C for 7 days;

[0733] 3) Place the culture plate containing cells at room temperature for 30 minutes to allow the plate and its contents to equilibrate to room temperature;

[0734] 4) Add CellTiter-Glo (Promega: V9101) reagent equal to the volume of cell culture medium to each well of cells and mix the contents on an orbital shaker for 2 minutes to induce cell lysis;

[0735] 5) The plate was incubated at room temperature for 10 minutes to allow the signal value to stabilize, and then the luminescence value was detected by a microplate reader (Thermo: VarioskanLUX);

[0736] 6) Analyze the data using GraphPad software and determine the IC 50 .

[0737] The test showed that the example compounds of the present application had a strong inhibitory effect on the proliferation of HCC1806 cells, and a weak inhibitory effect on the proliferation of MDA-MB-231 cells, indicating that the example compounds of the present application had good selectivity for the inhibitory effect on the proliferation of the two types of cells.

[0738] Data list:

[0739] NT = not tested;

[0740]

[0741]

[0742]

Claims

1. A compound of formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof; X1 is N; X2 is C; Z1 is N; Z2 is C; W is R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 1-1 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl; R 1-1-1 Each is independently halogen, hydroxyl or C1-C6 alkyl; R 1-2 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 1-2-1 Substituted C1-C6 alkyl; R 1-2-1 Each is independently halogen, hydroxyl or C1-C6 alkyl; R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl, unsubstituted or substituted with one or more R 2-9 Substituted C3-C6 cycloalkyl or unsubstituted or with one or more R 2-10 Substituted C3-C6 cycloalkenyl; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 2-3 Each is independently cyano, oxo, hydroxyl, halogen, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-5 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-3-7 Substituted amino groups; R 2-3-1 are each independently hydroxy, cyano or halogen; R 2-3-2 is hydrogen, C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl, C1-C6 alkoxy, unsubstituted or substituted with one or more R 2-3-2-5 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 2-3-3 Each is independently hydrogen or C1-C6 alkyl; R 2-3-5 each independently a halogen or a deuterium; R 2-3-7 Each is independently a C1-C6 alkyl group; R 2-3-2-2 Each independently represents halogen, hydroxy, unsubstituted or substituted with one or more R 2-3-2-2-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 2-3-2-2-3 Substituted amino groups; R 2-3-2-2-1 are each independently halogen or hydroxy; R 2-3-2-2-2 Each is independently carboxyl, halogen, deuterium, oxo or hydroxyl; R 2-3-2-2-3 Each is independently a C1-C6 alkyl group; R 2-3-2-5 Each independently represents halogen, hydroxy, oxo, C1-C6 alkoxy, unsubstituted or substituted with one or more R 2-3-2-5-1 Substituted C1-C6 alkyl; R 2-3-2-5-1 are each independently a halogen; R 2-5 Each independently is unsubstituted or substituted with one or more R 2-5-4 Substituted C1-C6 alkyl; R 2-5-4 Each is independently C1-C6 alkoxy, hydroxy, cyano or halogen; R 2-9 Each is independently C1-C6 alkoxy, C1-C6 alkyl, hydroxy, cyano or halogen; R 2-10 Each is independently C1-C6 alkoxy, C1-C6 alkyl, hydroxy, cyano or halogen; L is a carbonyl group; R 3 for R 3-1 and R 3-2 Each independently represents H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-5 The substituted 6-14-membered aryl group, the heteroatoms of the 4-12-membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12-membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Or, R 3-1 , R 3-2 Together with the N atom connected thereto, it forms a 4-12 membered heterocycloalkyl group, wherein 4-12 membered heterocycloalkyl is optionally substituted by 1 or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1 Each independently is unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 3-1-1-3 The heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3 -1-1-1 Each is independently C1-C6 alkyl, hydroxyl or halogen; R 3-1-1-2 Each is independently C1-C6 alkyl, hydroxyl or halogen; R 3 -1-1-3 Each is independently C1-C6 alkyl, C1-C6 alkoxy, hydroxyl or halogen; R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl; R 3-1-4 and R 3-1-5 Each is independently hydroxy, halogen or C1-C6 alkyl; R 3-1-2-1 is hydroxyl, C1-C6 alkoxy, or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl; R 3-1-2-2 and R 3-1-2-3 Each independently is H or C1-C6 alkyl; R 3a are independently hydroxyl, Oxo, hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted or substituted with one or more R 3a-5 Substituted C1-C6 alkoxy or cyano; R 3a-1 and R 3a-2 Each independently is H or C1-C6 alkyl; R 3a-3 is hydroxyl, C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl; R 3a-4 C 6-14 Aryl, hydroxyl, halogen, or C1-C6 alkyl; R 3a-4-1 and R 3a-4-2 Each independently is H or C1-C6 alkyl; R 3a-5 is hydroxy, halogen or C1-C6 alkyl; R 4 and R 5 Each is independently H.

2. The compound of formula I according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: It meets one or more of the following conditions: (1)R 1 wherein the C3-C6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl; (2)R 1 In the embodiment, the 3-6 membered heterocycloalkyl is a 4-6 membered heterocycloalkyl, the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1, for example, the 3-6 membered heterocycloalkyl is an oxetane, for example, the 3-6 membered heterocycloalkyl is (3)R 1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (4)R 1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (5)R 1-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (6)R 1-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (7)R 1-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (8)R 1-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (9)R 1-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (10)R 1-2-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (11)R 2 In the embodiment, the 4-12 membered heterocycloalkyl group is a 4-6 membered heterocycloalkyl group, wherein the heteroatom is preferably N and / or O, and the number of heteroatoms is preferably 2. For example, the 4-12 membered heterocycloalkyl group is an azocyclopentane group, an azocyclohexane group, an azooxane group, and the azocyclohexane group is, for example, The aza-oxacyclohexane group is, for example, For example, the azacyclopentyl group is (12)R 2 wherein the C3-C6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (13)R 2 In the above, the C3-C6 cycloalkenyl group is a C4-C6 cycloalkenyl group, wherein the cycloalkenyl group preferably contains 1 or 2 double bonds; (14)R 2-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (15)R 2-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (16)R 2-3 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy; (17)R 2-3-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (18)R 2-3-2 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, such as methyl or isopropyl; (19)R 2-3-2 wherein the C3-C6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl; (20)R 2-3-2 wherein the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy; (21)R 2-3-2 In the above, the 3-6 membered heterocycloalkyl is a 4-6 membered heterocycloalkyl, wherein the heteroatom is preferably N, O or S, and the number of heteroatoms is preferably 1 or 2, for example, the 3-6 membered heterocycloalkyl is oxetanyl, azetidinyl, oxolanyl, azocyclopentanyl, oxhexanyl, azohexanyl, pyrazinyl, thiazolidinyl or oxabicyclohexanyl; (22)R 2-3-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (23)R 2-3-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (24)R 2-3-7 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (25)R 2-3-2-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (26)R 2-3-2-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (27)R 2-3-2-2 wherein the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, such as methoxy; (28)R 2-3-2-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (29)R 2-3-2-2-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (30)R 2-3-2-2-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (31)R 2-3-2-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (32)R 2-3-2-5 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy; (33)R 2-3-2-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (34)R 2-3-2-5-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (35)R 2-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (36)R 2-5-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (37)R 2-5-4 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy; (38)R 2-9 and R 2-10 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (39)R 2-9 and R 2-10 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (40)R 2-9 and R 2-10 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy; (41)R 3-1 and R 3-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, such as methyl or ethyl; (42)R 3-1 and R 3-1 In the C3-C 12 The cycloalkyl groups are each independently C3-C6 cycloalkyl groups, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (43)R 3-1 and R 3-1 wherein the 4-12 membered heterocycloalkyl groups are each independently one or more of a monocyclic ring, a bridged ring, a cyclic ring and a spirocyclic ring; the monocyclic ring may be a 4-6 membered heterocycloalkyl group; the cyclic ring may be a 3-membered 5-membered heterocycloalkyl group, a 4-membered 5-membered heterocycloalkyl group, a 5-membered 6-membered heterocycloalkyl group, a 4-membered 6-membered heterocycloalkyl group or a 5-membered 5-membered heterocycloalkyl group; the spirocyclic ring may be a 3-ring spiro-5-ring, a 4-ring spiro-6-ring, a 4-ring spiro-5-ring, a 5-ring spiro-5-ring, a 4-ring spiro-4-ring, a 5-ring spiro-6-ring or a 3-ring spiro-6-ring; the bridged ring may be a bicyclooctanalkanes or a bicycloheptanalkanes; the heteroatoms of the 4-12 membered heterocycloalkyl groups are selected from N and / or O, and the number of heteroatoms is preferably 1 or 2; the 4-6 membered heterocycloalkyl groups are, for example, oxetane, azacyclopentane, azacyclohexane or oxetane, and for example (44)R 3-1 and R 3-1 In the above, the 5-12 membered heteroaryl groups are each independently a 5-membered or 6-membered heteroaryl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2; for example, the 5-12 membered heteroaryl groups are each independently a pyrazolyl group, and the pyrazolyl group is, for example, (45)R 3-1 and R 3-1 wherein the 6-14 membered aryl groups are each independently phenyl or naphthyl; (46)R 3-1 and R 3-1 In the case of R 3-1 , R 3-2 When forming a 4-12 membered heterocycloalkyl with the N atom connected thereto, wherein the 4-12 membered heterocycloalkyl is independently one or more of a monocyclic, a bridged ring, a cyclic and a spirocyclic ring; the monocyclic ring may be a 4-6 membered heterocycloalkyl; the cyclic ring may be a 3-membered and 5-membered heterocycloalkyl, a 4-membered and 5-membered heterocycloalkyl, a 5-membered and 6-membered heterocycloalkyl, a 4-membered and 6-membered heterocycloalkyl or a 5-membered and 5-membered heterocycloalkyl; the spirocyclic ring may be a 3-ring spiro-5-ring, a 4-ring spiro-6-ring, a 4-ring spiro-5-ring, a 5-ring spiro-5-ring, a 4-ring spiro-4-ring, a 5-ring spiro-6-ring or a 3-ring spiro-6-ring; the bridged ring may be a bicyclooctane, a bicycloheptane or a bicyclononane; the heteroatoms of the 4-12 membered heterocycloalkyl are preferably selected from N and / or O, and the number of heteroatoms is preferably 1 or 2; Preferably, the bicyclooctanes may be bicyclo[3.2.1]octanes, for example The bicycloheptaalkane may be bicyclo[3.1.1]heptaalkane or bicyclo[2.2.1]heptaalkane, for example Preferably, the 4-6 membered heterocycloalkyl group may be azetidinyl, azopentyl, azohexyl, tetrahydropyridyl, piperazinyl or morpholinyl, for example Preferably, the 3-membered and 5-membered heterocycloalkyl groups may be cyclopropyl and azetidinyl groups, for example The 4-membered and 5-membered heterocycloalkyl groups may be cyclobutyl and azetyl groups, for example The 5-membered and 6-membered heterocycloalkyl groups may be azacyclopentyl and oxanyl groups, tetrahydrofuran and pyridyl groups, hexahydropyrrolopyrazinyl groups, hexahydropyrazinooxazinyl groups or hexahydroimidazopyrazinyl groups, for example Preferably, the 3-ring spiro-5-ring may be an azaspiroheptane alkyl group, for example The 4-ring spiro-5-ring may be an azaspiro-octanyl group or a diazaspiro-octanyl group, for example The 5-ring spiro-5-ring may be an oxazaspironanyl group, for example The 4-ring spiro6-ring may be an azaspironanyl group, a diazaspironanyl group or a dioxaazaspironanyl group, for example The 5-ring spiro-6-ring may be an azacyclohexane spiro azacyclopentane group, for example (47)R 3-1-1 wherein the 4-12 membered heterocycloalkyl is independently one or more of a monocyclic, a bridged ring, a paracyclic and a spirocyclic ring; the monocyclic ring may be a 4-6 membered heterocycloalkyl; the paracyclic ring may be a 3-membered and 5-membered heterocycloalkyl, a 4-membered and 5-membered heterocycloalkyl, a 5-membered and 6-membered heterocycloalkyl, a 4-membered and 6-membered heterocycloalkyl or a 5-membered and 5-membered heterocycloalkyl; the spirocyclic ring may be a 3-ring spiro-5-ring, a 4-ring spiro-6-ring, a 4-ring spiro-5-ring, a 5-ring spiro-5-ring, a 4-ring spiro-4-ring, a 5-ring spiro-6-ring or a 3-ring spiro-6-ring; the bridged ring may be a bicyclooctanalkanes, a bicycloheptanalkanes or a bicyclononanalkanes; the heteroatoms of the 4-12 membered heterocycloalkyl are preferably selected from N and / or O, and the number of heteroatoms is preferably 1 or 2; the 4-6 membered heterocycloalkyl is, for example, an oxetane, an azocyclopentane, an azocyclohexane or an oxetane, and for example (48)R 3-1-1 In the above, the 5-12 membered heteroaryl groups are each independently a 5-membered or 6-membered heteroaryl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 2, and the 5-12 membered heteroaryl groups are each independently, for example, pyridyl or pyrazolyl, and for example (49)R 3-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, such as methyl or ethyl; (50)R 3-1-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (51)R 3-1-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine; (52)R 3-1-1-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (53)R 3-1-1-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (54)R 3-1-1-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (55)R 3-1-1-3 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy; (56)R 3-1-1-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (57)R 3-1-2 and R 3-1-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (58)R 3-1-2 and R 3-1-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (59)R 3-1-4 and R 3-1-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine; (60)R 3-1-4 and R 3-1-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (61)R 3-1-2-1 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy; (62)R 3-1-2-1 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl; (63)R 3-1-2-1a and R 3-1-2-1b wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (64)R 3-1-2-2 and R 3-1-2-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (65)R 3a wherein the halogen is fluorine, chlorine, bromine or iodine, for example fluorine; (66)R 3a wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, such as methyl or ethyl; (67)R 3a wherein the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, such as methoxy; (68)R 3a-1 and R 3a-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (69)R 3a-3 wherein the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, such as methoxy; (70)R 3a-3-1 and R 3a-3-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or t-butyl, for example, methyl; (71)R 3a-4 In the C 6-14 Aryl is each independently phenyl or naphthyl, for example phenyl; (72)R 3a-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine; (73)R 3a-4 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (74)R 3a-4-1 and R 3a-4-2 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl; (75)R 3a-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine; (76)R 3a-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

3. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound represented by formula I satisfies one or more of the following conditions: (1)R 1 is unsubstituted or substituted with one or more R 1-2 A substituted 3-6 membered heterocycloalkyl group; the heteroatom of the 3-6 membered heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. For example, the 3-6 membered heterocycloalkyl group is an oxetane group; (2) X1 is N; X2 is C; Y1 is N; Y2 is C; (3)R 3-1 and R 3-2 At least one of them is unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-5 Substituted 6-14 membered aryl; Or, R 3-1-1 is unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-1-4 substituted 5-12 membered heteroaryl; Or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a replace; and (4) L is a carbonyl group, R 3 for 4. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound represented by formula I satisfies one or more of the following conditions: (1) In the compound represented by formula I, R 3-1 and R 3-2 Each is independently H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Preferably, R 3-1 and R 3-2 Each is independently H, unsubstituted or substituted with one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl; or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12-membered heterocycloalkyl group, wherein the 4-12-membered heterocycloalkyl group is a 4-6-membered heterocycloalkyl group or a 7-9-membered spirocyclic heterocycloalkyl group, wherein The heteroatom is preferably N, and the number of heteroatoms is preferably 1; preferably, in the 7-9 membered spiro heterocycloalkyl, the heteroatoms are preferably N and O, and the number of heteroatoms is preferably 2 or 3, or, the 7-9 membered spiro heterocycloalkyl is a dispiro[2.4] nitrogen heterocycle; More preferably, R 3-1 and R 3-2 Each independently is unsubstituted or substituted with one or more R 3-1-2 substituted C3-C6 cycloalkyl, such as cyclopropane or cyclopentane; or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is supported by 2, 3 or 4 R 3a replace; (2)R 3-1-2 and R 3-1-3 Each independently is halogen or hydroxy; (3)R 3a Each of them is independently hydroxyl, halogen, C1-C6 alkyl which is unsubstituted or substituted by one or more hydroxyl groups, or C1-C6 alkyl which is unsubstituted or substituted by one or more R 3a-5 Substituted C1-C6 alkoxy or cyano, such as hydroxy, halogen, unsubstituted or substituted by one or more R 3a-5 substituted C1-C6 alkoxy or cyano; preferably, R 3a Each is independently halogen, hydroxy, -NH2, C1-C6 alkoxy or cyano; (4)R 1-1 Each independently is cyano, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl, for example, unsubstituted C1-C6 alkyl; (5)R 1-2 Each is independently an unsubstituted C1-C6 alkyl; (6)R 2 For one or more R 2-3 A substituted 4-12 membered heterocycloalkyl group, wherein the heteroatom of the 4-12 membered heterocycloalkyl group is selected from one or more of N, O and S, and the number of the heteroatoms is 1, 2 or 3; (7)R 2-3 are each independently an unsubstituted C1-C6 alkyl group, For example, unsubstituted C1-C6 alkyl; (8)R 2-3-2 is unsubstituted C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl; (9)R 2-3-3 Each is independently an unsubstituted C1-C6 alkyl group; (10)R 2-3-2-2 Each is independently a C1-C6 alkoxy group; (11)R 3-1-1 Each independently is hydroxy, unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 Substituted 5-12 membered heteroaryl, unsubstituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, for example, R 3-1-1 Each independently represents an unsubstituted C1-C6 alkyl group, unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 Substituted 5-12 membered heteroaryl; wherein the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; (12)R 3-1-1-1 are each independently hydroxy or halogen; (13)R 3-1-1-2 and R 3-1-1-4 Each is independently a C1-C6 alkyl group; (14)R 3-1-2 and R 3-1-3 Each independently hydroxyl group, or C1-C6 alkyl; (15)R 3-1-4 and R 3-1-5 Each is independently a C1-C6 alkyl group; (16)R 3-1-2-1 for or C3-C6 cycloalkyl; (17)R 3-1-2-2 and R 3-1-2-3 Each independently is H; (18)R 3a are independently hydroxyl, Oxo, hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano, for example, R 3a Each independently Oxo, hydroxyl, Halogen, C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano; (19)R 3a-1 and R 3a-2 Each is independent of H; (20)R 3a-3 is C1-C6 alkoxy or (21)R 3a-4 C 6-14 Aryl, hydroxyl, halogen or For example, R 3a-4 C 6-14 Aryl or hydroxyl; (22)R 3a-4-1 and R 3a-4-2 Each is independent of H; (23)R 4 and R 5 Each independently is H; and (24) L is a carbonyl group.

5. The compound of formula I according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: It meets one or more of the following conditions: (1)R 1 is unsubstituted or substituted with one or more R 1-2 substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, for example, R 1 for (2)R 1-1 are each independently cyano; (3)R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl, unsubstituted or substituted with one or more R 2-10 substituted C3-C6 cycloalkenyl; the heteroatom of the 4-12 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, for example, R 2 for (4)R 2-3 Each independently is hydroxy, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl, (5)R 2-3-1 are each independently hydroxyl; (6)R 2-3-2 For one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl; (7)R 2-3-2-2 Each independently is C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy, preferably unsubstituted or substituted by one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy; (8)R 2-3-2-2-2 Each independently is deuterium; (9)R 3-1-1-3 Each is independently a C1-C6 alkoxy group or a hydroxy group; (10)R 3a are independently halogen, hydroxyl, unsubstituted or substituted with one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano; (11)R 3a-4 It is hydroxy, halogen or -NH2.

6. The compound of formula I according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is any of the following: Solution 1: X1 is N; X2 is C; Z1 is N; Z2 is C; W is R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 1-1 Each is independently cyano or unsubstituted C1-C6 alkyl; R 1-2 Each is independently an unsubstituted C1-C6 alkyl group; R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl; the heteroatom of the 4-12 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 2-3 are each independently an unsubstituted C1-C6 alkyl, R 2-3-2 is unsubstituted C1-C6 alkyl or is replaced by one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl; R 2-3-3 Each is independently an unsubstituted C1-C6 alkyl group; R 2-3-2-2 Each independently is unsubstituted or substituted with one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy; R 2-3-2-2-2 is halogen, hydroxyl or deuterium; L is a carbonyl group; R 3 for R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3a are independently halogen, hydroxyl, Oxo, hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano; R 3a-1 and R 3a-2 Each is independent of H; R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl; R 3a-4 C 6-14 Aryl, hydroxy, halogen or -NH2; R 4 and R 5 Each independently is H; Option 2: X1 is N; X2 is C; Z1 is N; Z2 is C; W is R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 1-1 are each independently cyano; R 1-2 Each is independently a C1-C6 alkyl group; R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl, unsubstituted or substituted with one or more R 2-10 Substituted C3-C6 cycloalkenyl; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 2-3 Each independently is hydroxy, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl, R 2-3-1 are each independently hydroxyl; R 2-3-2 is C1-C6 alkyl or unsubstituted or substituted by one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl; R 2-3-3 Each is independently hydrogen or C1-C6 alkyl; R 2-3-2-2 Each independently represents halogen, hydroxyl, C1-C6 alkyl, unsubstituted or substituted with one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy; R 2-3-2-2-2 Each independently is deuterium; R 2-5 Each independently is one or more R 2-5-4 Substituted C1-C6 alkyl; R 2-5-4 are each independently hydroxyl; R 2-10 are each independently hydroxyl; L is a carbonyl group; R 3 for R 3-1 and R 3-2 Each is independently H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl or unsubstituted or with one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1 Each independently is unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl or unsubstituted or with one or more R 3-1-1-3 The heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3 -1-1-1 Each is independently hydroxyl or halogen; R 3-1-1-2 and R 3-1-1-4 Each is independently C1-C6 alkyl; R 3-1-1-3 Each independently is a C1-C6 alkoxy group or a hydroxyl group; R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl; R 3-1-4 Each is independently a C1-C6 alkyl group; R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl; R 3-1-2-2 and R 3-1-2-3 Each independently is H; R 3a are independently hydroxyl, Oxo group, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, C1-C6 alkoxy or cyano; R 3a-1 and R 3a-2 Each is independent of H; R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl; R 3a-4 C 6-14 Aryl, hydroxyl, halogen or R 3a-4-1 and R 3a-4-2 Each is independent of H; R 4 and R 5 Each independently is H; Option 3: X1 is N; X2 is C; Z1 is N; Z2 is C; W is R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 1-1 Each is independently cyano or unsubstituted C1-C6 alkyl; R 1-2 Each is independently an unsubstituted C1-C6 alkyl group; R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl; the heteroatom of the 4-12 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 2-3 are each independently an unsubstituted C1-C6 alkyl, R 2-3-2 is unsubstituted C1-C6 alkyl or is replaced by one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl; R 2-3-3 Each is independently an unsubstituted C1-C6 alkyl group; R 2-3-2-2 Each is independently a C1-C6 alkoxy group; L is a carbonyl group; R 3 for R 3-1 and R 3-2 Each is independently H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1 Each is independently hydroxyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, unsubstituted or replaced by one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 The heteroatoms of the 4-12-membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12-membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3 -1-1-1 Each is independently hydroxyl or halogen; R 3-1-1-2 Each independently is a C1-C6 alkyl group; R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl; R 3-1-4 Each is independently a C1-C6 alkyl group; R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl; R 3-1-2-2 and R 3-1-2-3 Each independently is H; R 3a are independently halogen, hydroxyl, Oxo, hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano; R 3a-1 and R 3a-2 Each is independent of H; R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl; R 3a-4 C 6-14 Aryl, hydroxy, halogen or -NH2; R 4 and R 5 Each independently is H; Option 4: In the compound represented by formula I; X1 is N; X2 is C; Z1 is N; Z2 is C; W is R 1 is unsubstituted or substituted with one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R 1-2 Substituted 3-6 membered heterocycloalkyl; the heteroatom of the 3-6 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 1-1 Each is independently an unsubstituted C1-C6 alkyl group; R 1-2 Each is independently an unsubstituted C1-C6 alkyl group; R 2 is unsubstituted or substituted with one or more R 2-3 Substituted 4-12 membered heterocycloalkyl; the heteroatom of the 4-12 membered heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 2-3 Each is independently an unsubstituted C1-C6 alkyl; L is a carbonyl group; R 3 for R 3-1 and R 3-2 Each is independently H, unsubstituted or substituted with one or more R 3-1-1 Substituted C1-C6 alkyl, unsubstituted or replaced by one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Or, R 3-1 , R 3-2 and the N atom connected thereto form a 4-12 membered heterocycloalkyl group, wherein the 4-12 membered heterocycloalkyl group is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1 Each independently represents an unsubstituted C1-C6 alkyl group, unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 The heteroatoms of the 4-12-membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12-membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3-1-1-1 Each is independently hydroxyl or halogen; R 3-1-1-2 Each independently is a C1-C6 alkyl group; R 3-1-2 and R 3-1-3 Each independently hydroxyl group, or C1-C6 alkyl; R 3-1-4 Each is independently a C1-C6 alkyl group; R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each independently is H or C1-C6 alkyl; R 3-1-2-2 and R 3-1-2-3 Each independently is H; R 3a Each independently Oxo, hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy or cyano; R 3a-1 and R 3a-2 Each is independent of H; R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each independently is H or C1-C6 alkyl; R 3a-4 C 6-14 Aryl or hydroxyl; R 4 and R 5 Each is independently H.

7. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound represented by formula I is a compound represented by formula Ib, Ring D is a 3-6 membered heterocycloalkyl group; the heteroatoms of the 3-6 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Ring C is a 4-12 membered heterocycloalkyl group; the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; m is 0, 1 or 2; k is 0, 1 or 2; R 1-2a is hydrogen or R 1-2 ; Among them, X1, X2, Z1, Z2, R 4 , R 5 , R 3-1 , R 3-2 , L, R 2-3 and R 1-2 As described in claim 1.

8. The compound of formula (I) according to claim 7, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound represented by Formula I is a compound represented by Formula Ic, a compound represented by Formula Id, or a compound represented by Formula Ie; in, M is each independently N, O or S; i is independently 0, 1 or 2; j is independently 0, 1 or 2; i and j are not 0 at the same time; L1 is a C1-C6 alkyl group, L1 is optionally substituted by one or more R L1 replace; R L1 Each is independently a C1-C6 alkyl group; Ring A is unsubstituted or substituted with one or more R 3-1-1-1 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-1-2 substituted 5-12 membered heteroaryl; Ring E is unsubstituted or substituted with one or more R 3-1-2 Substituted C3-C 12 Cycloalkyl, unsubstituted or substituted with one or more R 3-1-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 3-1-4 A substituted 5-12 membered heteroaryl group, wherein the heteroatoms of the 4-12 membered heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; the heteroatoms of the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Ring F is a 4-12 membered heterocycloalkyl group, which is optionally substituted by one or more R 3a Substitution; the heteroatoms of the 4-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 4 , R 5 , R 3-1-1-1 , R 3-1-1-2 , R 1-2a , R 3-1-2 , R 3-1-3 , R 3-1-4 , R 3a , R 1-2 , R 2-3 , k, ring C, m, and L are each independently as described in claim 7.

9. The compound of formula I according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound represented by formula I satisfies any of the following conditions: (1)R 1 for (2)W is (3)R 2 for (4) L is (5)R 3 for 10. The compound of formula I according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound represented by formula I is any of the following compounds: in, refer to 11. A pharmaceutical composition comprising a substance Z and a pharmaceutical excipient, wherein the substance Z is a compound of formula I according to any one of claims 1 to 10, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

12. Use of a substance Z in the preparation of a PARG inhibitor and a drug for treating and / or preventing PARG-related diseases, wherein the substance Z is a compound of formula I as described in any one of claims 1 to 10, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 11; the PARG-related disease may be breast cancer, such as triple-negative breast cancer.

13. Use of a substance Z in the preparation of a drug for treating and / or preventing breast cancer, wherein the substance Z is a compound of formula I as described in any one of claims 1 to 10, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 11, and the breast cancer may be triple-negative breast cancer.

14. A compound of formula II or a compound of formula III; in, R 6 is a C1-C6 alkoxy group; Y is halogen; R 7 is H or an amino protecting group, such as p-methoxybenzyl, benzyl or (trimethylsilyl)ethoxymethyl; R 8 is an amino protecting group, for example p-methoxybenzyl, benzyl or (trimethylsilyl)ethoxymethyl; R 1 ,w,R 2 , X1, X2, Z1, Z2, R 3 , R 1-2 , R 5 , R 4 , L are each independently as described in any one of claims 1 to 10; Preferably, the compound represented by formula II is any of the following compounds: Preferably, the compound represented by formula III is any of the following compounds: Alternatively, the compound represented by formula III is in, refer to

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