Heteroaryl compound, intermediate thereof, and preparation method and use therefor

Abstract

A heteroaryl compound, an intermediate thereof, and a preparation method and use therefor. Specifically disclosed is a compound as represented by formula I, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The compound has good PARG inhibitory activity and has good medicinal prospects.

Description

Heteroaryl compounds, intermediates thereof, preparation methods and applications

[0001] This application claims priority to Chinese Patent Application No. 2023112756108 filed on September 28, 2023, and Chinese Patent Application No. 202311783623.6 filed on December 22, 2023. The entire contents of the aforementioned Chinese patent applications are incorporated herein by reference. Technical Field

[0002] The present 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 damage induces 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 eraser enzymes in the dynamic control of protein ADP-ribosylation. Nature Communication, 2019, 10, 1182.), including an N-terminal disordered domain, a linker domain, a C-terminal catalytic domain, and an ADP-ribose binding domain. The non-conserved disordered domain at the N-terminus is not required for in vitro activity, while the C-terminal ADP-ribose binding domain is highly conserved with other macro-domains and, together with the catalytic domain, forms the minimum structure with complete enzymatic 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, abbreviated as PAR, is composed of adenosine diphosphate-ribose units, with NAD +PARylation is a donor, formed by the catalysis of poly (ADP-ribose) polymerases (PARPs), and can be rapidly degraded by poly (ribosyl) hydrolases. Following DNA damage, many DNA damage response factors recognize PARylation and are recruited to the site of DNA damage through PARylation. However, PARylation needs to be digested promptly so that DNA damage response factors can directly recognize DNA damage and perform repair functions. Otherwise, DNA repair factors will be trapped near DNA damage by PARylation and unable to perform repair functions normally. Therefore, as 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, plays a role in 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 abnormal PARG function 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 that (Maud M et al, Oncogenic activity of poly(ADP-ribose) glycohydrolase. Oncogene, 2019, 38: 2177-2191.) PARG elevation 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 tumorigenesis. Therefore, PARG inhibitors have received increasing attention as potential therapeutic approaches. 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.

[0007] Summary of the Invention

[0008] The technical problem to be solved by the present invention is to overcome the drawback of the limited number of PARG inhibitor compounds in the prior art. 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 efficacy, and promising application prospects.

[0009] The present invention solves the above technical problems through the following technical solutions.

[0010] The present invention provides a compound represented by Formula I, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof;

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

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

[0013] R z Each is independently H, hydroxy, 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 replaced by 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, hydroxy 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, hydroxy 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 replaced by one or more R 2-6 Substituted C1-C6 alkyl, unsubstituted or replaced by 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 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 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;

[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 each independently cyano or halogen; R 2-1-2 is hydrogen or C1-C6 alkyl; R 2-1-3 Each independently represents hydrogen or C1-C6 alkyl; R 2-1-4 are each independently 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 each independently cyano or halogen; R 2-2-2 is hydrogen or C1-C6 alkyl; R 2-2-3 Each independently represents 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 replaced by 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 replaced by one or more R 2-3-9 substituted 5-10 membered heteroaryl; 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; the heteroatoms of the 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0028] R 2-3-1 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R2-3-1-1 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 replaced by 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 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; the heteroatoms of the 5-10 membered heteroaryl group are 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 Each independently is hydrogen, unsubstituted or replaced by 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 are each independently halogen or 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 halogen;

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

[0039] R 2-3-1-3 Each 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 replaced by 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 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;

[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 are each independently carboxyl, halogen, deuterium, oxo or hydroxy;

[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 halogen;

[0050] R 2-3-2-5 Each independently represents halogen, hydroxy, oxo, C1-C6 alkoxy, unsubstituted or substituted by one or more R 2-3-2-5-1 Substituted C1-C6 alkyl; R 2-3-2-5-1 are each independently 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; 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 replaced by 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 independently is hydroxy, 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 Each independently is hydrogen, unsubstituted or replaced by one or more R 2-5-1 substituted 4-10 membered heterocycloalkyl, unsubstituted or replaced by 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 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;

[0056] R 2-5-1 Each independently

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

[0058] R2-5-1-2 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 hydroxy, 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 by one or more R 2-6-1 substituted 4-10 membered heterocycloalkyl or unsubstituted or substituted by one or more R 2-6-2 substituted 5-10 membered heteroaryl; the heteroatoms of the 4-10 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 5-10 membered heteroaryl group 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 independently is 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 by one or more R 2-7-1 substituted 4-10 membered heterocycloalkyl or unsubstituted or substituted by one or more R 2-7-2 substituted 5-10 membered heteroaryl; the heteroatoms of the 4-10 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 5-10 membered heteroaryl group 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 Each is independently halogen, C1-C6 alkyl, R 2-7-1-1 is a C1-C6 alkyl group; R 2-7-1- 2 is a C1-C6 alkyl group;

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

[0069] R 2-8 Each independently represents a C1-C6 alkyl group, or two R 2-8 The atoms to which it is connected 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 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;

[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 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;

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

[0078] L is carbonyl, methylene,

[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 A substituted 6-14 membered aryl 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; and 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 group 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 is independently 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 by one or more R 3a-5 Substituted C1-C6 alkoxy or cyano;

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

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

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

[0091] R 3a-5 Each is independently hydroxy, halogen or C1-C6 alkyl;

[0092] R 4 and R 5 Each is independently H, hydroxy, 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 are each 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] X1 is N;

[0096] X2 is C;

[0097] Z1 is N;

[0098] Z2 is C;

[0099] W is

[0100] R 1 is unsubstituted or replaced by 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;

[0101] R 1-1 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 1-1-1 Substituted C1-C6 alkyl;

[0102] R 1-1-1 Each is independently halogen, hydroxy or C1-C6 alkyl;

[0103] R 1-2 Each is independently hydroxy, cyano, halogen, unsubstituted or substituted with one or more R 1-2-1 Substituted C1-C6 alkyl;

[0104] R 1-2-1 Each is independently halogen, hydroxy or C1-C6 alkyl;

[0105] R 2 is unsubstituted or replaced by one or more R 2-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 2-9 Substituted C3-C6 cycloalkyl or unsubstituted or replaced by one or more R 2-10 Substituted C3-C6 cycloalkenyl; 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;

[0106] 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 replaced by 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;

[0107] R 2-3-1 Each is independently hydroxy, cyano, or halogen;

[0108] R 2-3-2 is hydrogen, C1-C6 alkyl, unsubstituted or replaced by one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl, C1-C6 alkoxy, unsubstituted or substituted by 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;

[0109] R 2-3-3 Each is independently hydrogen, C1-C6 alkyl;

[0110] R 2-3-5 are each independently halogen or deuterium;

[0111] R 2-3-7 Each is independently a C1-C6 alkyl group;

[0112] 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;

[0113] R 2-3-2-2-1 are each independently halogen or hydroxy;

[0114] R2-3-2-2-2 are each independently carboxyl, halogen, deuterium, oxo or hydroxy;

[0115] R 2-3-2-2-3 Each is independently a C1-C6 alkyl group;

[0116] R 2-3-2-5 Each independently represents halogen, hydroxy, oxo, C1-C6 alkoxy, unsubstituted or substituted by one or more R 2-3-2-5-1 Substituted C1-C6 alkyl; R 2-3-2-5-1 are each independently halogen;

[0117] R 2-5 Each independently is unsubstituted or substituted with one or more R 2-5-4 Substituted C1-C6 alkyl;

[0118] R 2-5-4 Each is independently C1-C6 alkoxy, hydroxy, cyano or halogen;

[0119] R 2-9 Each is independently C1-C6 alkoxy, C1-C6 alkyl, hydroxy, cyano or halogen;

[0120] R 2-10 Each is independently C1-C6 alkoxy, C1-C6 alkyl, hydroxy, cyano or halogen;

[0121] L is a carbonyl group;

[0122] R 3 for

[0123] 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 A substituted 6-14 membered aryl 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; and 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;

[0124] 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 group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0125] 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 replaced by one or more R 3-1-1-3 substituted C1-C6 alkyl, 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;

[0126] R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl;

[0127] R 3-1-4 and R 3-1-5 Each is independently hydroxy, halogen or C1-C6 alkyl;

[0128] 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 is independently H or C1-C6 alkyl;

[0129] R 3-1-2-2 and R 3-1-2-3 Each independently is H or C1-C6 alkyl;

[0130] R 3a are each independently hydroxyl, Oxo (C=O), hydroxyl, Halogen, unsubstituted or replaced by one or more R 3a-4 Substituted C1-C6 alkyl, unsubstituted or substituted by one or more R 3a-5 Substituted C1-C6 alkoxy or cyano;

[0131] R 3a-1 and R 3a-2 Each is independently H or C1-C6 alkyl;

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

[0133] R 3a-4 C 6-14 Aryl, hydroxyl, halogen, or C1-C6 alkyl; R 3a-4-1 and R 3a-4-2 Each is independently H or C1-C6 alkyl;

[0134] R 3a-5 is hydroxy, halogen or C1-C6 alkyl;

[0135] R 4 and R 5 Each is independently H.

[0136] In one embodiment, the compound represented by Formula I, its stereoisomers or pharmaceutically acceptable salts thereof;

[0137] X1 is N;

[0138] Z1 is N;

[0139] X2 is C;

[0140] Z2 is C;

[0141] W is

[0142] R 1 is unsubstituted or replaced by 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;

[0143] R 1-1 Each is independently cyano or unsubstituted C1-C6 alkyl;

[0144] R 1-2 Each is independently an unsubstituted C1-C6 alkyl group;

[0145] R 2 is unsubstituted or replaced by one or more R 2-3Substituted 4-12 membered heterocycloalkyl; 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;

[0146] R 2-3 are each independently an unsubstituted C1-C6 alkyl group,

[0147] R 2-3-2 is an unsubstituted C1-C6 alkyl group or is replaced by one or more R 2-3-2-2 substituted C3-C6 cycloalkyl;

[0148] R 2-3-3 Each is independently an unsubstituted C1-C6 alkyl group;

[0149] 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;

[0150] R 2-3-2-2-2 is halogen, hydroxyl or deuterium;

[0151] L is a carbonyl group;

[0152] R 3 for

[0153] 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 group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0154] 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;

[0155] R 3a-1 and R 3a-2 Each one is independent of H;

[0156] R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each is independently H or C1-C6 alkyl;

[0157] R3a-4 C 6-14 Aryl, hydroxy, halogen or -NH2;

[0158] R 4 and R 5 Each is independently H.

[0159] 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"):

[0160] The compound represented by formula I satisfies the following conditions: 1 is unsubstituted or replaced by 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 heteroatoms is 1, 2 or 3.

[0161] 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 ).

[0162] In one embodiment, the compound represented by formula I satisfies the following conditions: L is a carbonyl group, R 3 for

[0163] In one embodiment, the compound represented by formula I satisfies the following conditions: 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 groups;

[0164] Or, R 3-1-1 is 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 substituted 5-12 membered heteroaryl, unsubstituted or replaced by one or more R 3-1-1-4 substituted 5-12 membered heteroaryl;

[0165] 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.

[0166] In one scheme, R z wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0167] 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.

[0168] In one scheme, R z-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0169] In one scheme, R w wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0170] In one scheme, R 1 wherein the C3-C6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group.

[0171] In one scheme, R 1 In the embodiment, the 3-6 membered heterocycloalkyl group is a 4-6 membered heterocycloalkyl group, the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1. For example, the 3-6 membered heterocycloalkyl group is an oxetane group (for example, ).

[0172] In one scheme, R 1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0173] In one scheme, R 1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, sec-butyl or tert-butyl, for example, methyl.

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

[0175] 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.

[0176] In one scheme, R 1-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

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

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

[0179] 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.

[0180] In one scheme, R 2 wherein the 6-10 membered aryl group is a phenyl group or a naphthyl group, for example, a phenyl group.

[0181] In one scheme, R 2 In the embodiment, 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.

[0182] 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 azacyclohexane group (e.g. ) or aza-oxacyclohexane (e.g. For example, the 4-12 membered heterocycloalkyl group is an azacyclopentyl group (e.g. ).

[0183] In one scheme, R 2 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0184] In one scheme, R 2 wherein the C3-C6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group.

[0185] In one scheme, R 2 In the example, the C3-C6 cycloalkenyl group is a C4-C6 cycloalkenyl group, wherein the cycloalkenyl group preferably contains 1 or 2 double bonds.

[0186] In one scheme, R 2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0187] 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.

[0188] In one scheme, R 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.

[0189] In one scheme, R 2-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0190] 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.

[0191] 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.

[0192] In one scheme, R 2-1-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0193] In one scheme, R 2-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0194] 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.

[0195] In one scheme, R 2-2 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0196] In one scheme, R 2-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0197] 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.

[0198] 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.

[0199] 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.

[0200] In one scheme, R 2-2-4 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0201] In one scheme, R 2-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0202] In one scheme, R 2-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, sec-butyl or tert-butyl, for example, methyl.

[0203] In one scheme, R 2-3 In the embodiment, the 3-6 membered heterocycloalkyl groups are each independently a 4-6 membered heterocycloalkyl group, wherein the heteroatom is preferably N, O or S, and the number of heteroatoms is preferably 1 or 2.

[0204] In one scheme, 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.

[0205] In one scheme, R 2-3 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0206] 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.

[0207] In one scheme, R 2-3-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0208] In one scheme, R 2-3-1 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0209] In one scheme, R2-3-1 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0210] In one scheme, R 2-3-2 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, sec-butyl or tert-butyl, for example, methyl or isopropyl.

[0211] In one scheme, R 2-3-2 wherein the C3-C6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group.

[0212] In one scheme, 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.

[0213] In one scheme, R 2-3-2 In the embodiment, the 3-6 membered heterocycloalkyl group is a 4-6 membered heterocycloalkyl group, 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 group is an oxetanyl group, an azetidinyl group, an oxolane group, an azocyclopentane group, an oxhexane group, an azohexane group, a pyrazinyl group, a thiazolidinyl group or an oxabicyclohexane group.

[0214] In one scheme, R 2-3-2 In the embodiment, 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.

[0215] In one scheme, R 2-3-3 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, sec-butyl or tert-butyl, for example, methyl.

[0216] 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.

[0217] In one scheme, R 2-3-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0218] 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.

[0219] 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.

[0220] 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.

[0221] In one scheme, R 2-3-8 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0222] 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.

[0223] In one scheme, R 2-3-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0224] In one scheme, R 2-3-1-2 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0225] 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.

[0226] In one scheme, R 2-3-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0227] In one scheme, R 2-3-2-1 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0228] 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.

[0229] 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.

[0230] In one scheme, R 2-3-2-1-1 wherein the 6-10 membered aryl groups are each independently phenyl or naphthyl.

[0231] 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.

[0232] 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.

[0233] In one scheme, R 2-3-2-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0234] 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.

[0235] In one scheme, R 2-3-2-2 In the embodiment, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, for example, methoxy.

[0236] In one scheme, R 2-3-2-2-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0237] In one scheme, R 2-3-2-2-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0238] 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.

[0239] In one scheme, R 2-3-2-3-1 wherein the 6-10 membered aryl groups are each independently phenyl or naphthyl.

[0240] In one scheme, R 2-3-2-3-1-1 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0241] In one scheme, R 2-3-2-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0242] In one scheme, R 2-3-2-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0243] In one scheme, 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.

[0244] 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.

[0245] In one scheme, R 2-3-2-5-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0246] 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.

[0247] 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.

[0248] In one scheme, R 2-4 In the embodiment, the 4-10 membered heterocycloalkyl groups are each independently a 4-6 membered heterocycloalkyl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0249] 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.

[0250] In one scheme, R 2-4 wherein the 6-10 membered aryl groups are each independently phenyl or naphthyl.

[0251] In one scheme, R 2-4 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0252] 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.

[0253] In one scheme, R 2-4-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0254] In one scheme, R 2-4-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0255] 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.

[0256] In one scheme, R 2-4-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0257] 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.

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

[0259] 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.

[0260] 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.

[0261] 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.

[0262] In one scheme, R 2-5 In the embodiment, the 4-10 membered heterocycloalkyl groups are each independently a 4-6 membered heterocycloalkyl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0263] In one scheme, R 2-5 wherein the 6-10 membered aryl groups are each independently phenyl or naphthyl.

[0264] 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.

[0265] 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.

[0266] 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.

[0267] 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.

[0268] In one scheme, R 2-5-3 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0269] In one scheme, R 2-5-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0270] In one scheme, 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, such as methoxy, ethoxy or isopropoxy.

[0271] 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, 1-butyl, sec-butyl or tert-butyl, for example, methyl, ethyl or isopropyl.

[0272] In one scheme, R 2-6 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0273] 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.

[0274] In one scheme, R 2-6 In the embodiment, the 4-10 membered heterocycloalkyl groups are each independently a 4-6 membered heterocycloalkyl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0275] 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.

[0276] In one scheme, R 2-6-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0277] 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.

[0278] In one scheme, R 2-6-1-1 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl.

[0279] In one scheme, R 2-6-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0280] 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.

[0281] 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.

[0282] In one scheme, R 2-7 In the embodiment, the 4-10 membered heterocycloalkyl groups are each independently a 4-6 membered heterocycloalkyl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0283] 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.

[0284] In one scheme, R 2-7-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0285] 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.

[0286] 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.

[0287] 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.

[0288] In one scheme, R 2-7-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0289] 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.

[0290] 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.

[0291] In one scheme, R 2-8 In the embodiment, the 4-10 membered heterocycloalkyl groups are each independently a 4-6 membered heterocycloalkyl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

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

[0293] In one scheme, R 2-9 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl, for example, methyl.

[0294] In one scheme, R 2-9 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0295] In one scheme, R 2-9 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0296] 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.

[0297] 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.

[0298] In one scheme, R 2-9-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0299] In one scheme, R 2-10 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0300] In one scheme, 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.

[0301] In one scheme, R 2-10 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, 2-butyl or 3-butyl, for example, methyl.

[0302] 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.

[0303] 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.

[0304] 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.

[0305] In one scheme, R 2-11 In the embodiment, the 3-6 membered heterocycloalkyl groups are each independently a 4-6 membered heterocycloalkyl group, wherein the heteroatom is preferably N or O, and the number of heteroatoms is preferably 1 or 2.

[0306] 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.

[0307] 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.

[0308] In one scheme, 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, sec-butyl or tert-butyl, such as methyl or ethyl.

[0309] 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.

[0310] In one scheme, R 3-1 and R 3-1 In, the 4-12 membered heterocycloalkyl is each independently one or more of a monocycle, a bridged ring, a cyclic ring and a spirocycle. The monocycle 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 spirocycle 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., ).

[0311] 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. ).

[0312] In one scheme, R 3-1 and R 3-1 wherein the 6-14 membered aryl groups are each independently phenyl or naphthyl.

[0313] 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, the 4-12 membered heterocycloalkyl is each independently one or more of a monocyclic ring, a bridged ring, a paracyclic ring and a spirocyclic ring. The monocyclic ring may be a 4-6 membered heterocycloalkyl. The paracyclic 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, a bicycloheptanal or a bicyclononanal. 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.

[0314] 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. );

[0315] 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. );

[0316] The 3-membered and 5-membered heterocycloalkyl groups may be cyclopropyl and azetidine groups (e.g., ); the 4-membered and 5-membered heterocycloalkyl groups may be cyclobutyl and azetidine groups (for example, ); The 5-membered and 6-membered heterocycloalkyl groups may be azacyclopentyl and oxanyl, tetrahydrofuryl and pyridinyl, hexahydropyrrolopyrazinyl, hexahydropyrazin and oxazinyl or hexahydroimidazopyrazinyl, for example

[0317] 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 spiro 6-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. ).

[0318] In one scheme, R 3-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0319] In one scheme, R 3-1-1 In, the 4-12 membered heterocycloalkyl is each independently one or more of a monocycle, a bridged ring, a cyclic ring and a spirocycle. The monocycle 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 spirocycle 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 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., ).

[0320] In one scheme, R 3-1-1 In the embodiment, 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. ).

[0321] In one scheme, R 3-1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, sec-butyl or tert-butyl, such as methyl or ethyl.

[0322] In one scheme, R 3-1-1 wherein the 6-14 membered aryl groups are each independently phenyl or naphthyl.

[0323] In one scheme, R 3-1-1 wherein the C1-C6 alkoxy groups are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, for example, methoxy.

[0324] 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.

[0325] In one scheme, R 3-1-1-1 wherein the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine.

[0326] In one scheme, R 3-1-1-2 and R 3-1-1-4 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, sec-butyl or tert-butyl, for example, methyl.

[0327] In one scheme, R 3-1-1-2 and R 3-1-1-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0328] 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.

[0329] In one scheme, 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.

[0330] In one scheme, R 3-1-1-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0331] In one scheme, R 3-1-1-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0332] 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.

[0333] In one scheme, R 3-1-2 and R 3-1-3 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0334] In one scheme, 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, sec-butyl or tert-butyl, for example, methyl.

[0335] In one scheme, R 3-1-4 and R 3-1-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0336] In one scheme, R3-1-4 and R 3-1-5 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-butyl, sec-butyl or tert-butyl, for example, methyl.

[0337] In one scheme, 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.

[0338] In one scheme, R 3-1-2-1 wherein the C3-C6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl.

[0339] In one scheme, 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, sec-butyl or tert-butyl, for example, methyl.

[0340] 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.

[0341] In one scheme, R 3a wherein the halogen is fluorine, chlorine, bromine or iodine, for example fluorine.

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

[0343] In one scheme, R 3a In the embodiment, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy, for example, methoxy.

[0344] 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.

[0345] In one scheme, R 3a-3In the embodiment, 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-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, sec-butyl or tert-butyl, for example, methyl.

[0347] In one scheme, R 3a-4 In the C 6-14 Each aryl group is independently phenyl or naphthyl, for example phenyl.

[0348] In one scheme, R 3a-4 wherein the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine.

[0349] 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.

[0350] 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.

[0351] In one scheme, R 3a-5 wherein the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine.

[0352] 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.

[0353] In one scheme, R 4 and R 5 wherein the halogen is independently fluorine, chlorine, bromine or iodine, for example fluorine.

[0354] 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.

[0355] In one scheme, R 4 and R 5wherein the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 1-butoxy, 2-butoxy or 3-butoxy.

[0356] In one scheme, R 4-1 and R 4-2 wherein the halogen is independently fluorine, chlorine, bromine or iodine.

[0357] In one embodiment, the compound represented by formula I may be a compound represented by formula Ib,

[0358] 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;

[0359] 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;

[0360] m is 0, 1 or 2; k is 0, 1 or 2;

[0361] R 1-2a is hydrogen or R 1-2 ;

[0362] 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.

[0363] In one embodiment, the compound represented by formula I may be a compound represented by formula Ic,

[0364] M is N, O or S;

[0365] i is 0, 1 or 2; j is 0, 1 or 2; i and j are not 0 at the same time;

[0366] L1 is a C1-C6 alkyl group (such as methyl, ethyl or propyl), and L1 is optionally replaced by one or more R L1 replace;

[0367] R L1 are each independently a C1-C6 alkyl group (e.g., methyl);

[0368] 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 3-1-1-2substituted 5-12 membered heteroaryl;

[0369] R 4 、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.

[0370] In one embodiment, the compound represented by Formula I may be a compound represented by Formula Id or Formula Ie.

[0371] 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;

[0372] Ring F is 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 group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0373] 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.

[0374] 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 3-1-2Substituted C3-C6 cycloalkyl (e.g. cyclopropyl, cyclopentyl). In one embodiment, in the compound represented by formula I, when R 3-1 、R 3-2 When forming a 4-12 membered heterocycloalkyl 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., ).

[0375] In one scheme, R 3-1-2 and R 3-1-3 are each independently halogen or hydroxy.

[0376] In one scheme, R 3a Each independently represents hydroxy, halogen, C1-C6 alkyl which is unsubstituted or substituted with one or more hydroxy, or C1-C6 alkyl which is unsubstituted or substituted with 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.

[0377] 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 to which it is connected, the 4-12 membered heterocycloalkyl is surrounded by 2, 3 or 4 R 3a replace;

[0378] R 3a Each is independently halogen, hydroxy, -NH2, C1-C6 alkoxy (eg, methoxy) or cyano.

[0379] In one solution, X1 is N.

[0380] In one solution, Z1 is N.

[0381] In one solution, X2 is C.

[0382] In one solution, Z2 is C.

[0383] In one embodiment, L is a carbonyl group.

[0384] In one embodiment, in the compound represented by formula I, R 1 is unsubstituted or replaced by 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

[0385] In one scheme, R 1-1 Each is independently 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.

[0386] In one scheme, R 1-2 Each is independently an unsubstituted C1-C6 alkyl group.

[0387] In one scheme, R 2 For one or more R 2-3 A substituted 4- to 12-membered heterocycloalkyl group, wherein the heteroatoms of the 4- to 12-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.

[0388] In one scheme, R 2 is unsubstituted or replaced by one or more R 2-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 2-10 Substituted C3-C6 cycloalkenyl; 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, for example, R 2 for

[0389] In one scheme, R 2-3 are each independently an unsubstituted C1-C6 alkyl group, For example, unsubstituted C1-C6 alkyl.

[0390] In one scheme, R 2-3 Each independently is hydroxy, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl,

[0391] In one scheme, R 2-3-1 are each independently a hydroxyl group.

[0392] In one scheme, R 2-3-2 is unsubstituted C1-C6 alkyl, unsubstituted or replaced by one or more R 2-3-2-2 Substituted C3-C6 cycloalkyl, such as R 2-3-2 For one or more R 2-3-2-2Substituted C3-C6 cycloalkyl.

[0393] In one scheme, R 2-3-3 Each is independently an unsubstituted C1-C6 alkyl group.

[0394] In one scheme, R 2-3-2-2 Each is independently a C1-C6 alkoxy group.

[0395] In one scheme, R 2-3-2-2 Each independently represents a C1-C6 alkyl group, unsubstituted or substituted by 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.

[0396] In one scheme, R 2-3-2-2-2 each independently deuterium.

[0397] 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, 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.

[0398] In one scheme, 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, an unsubstituted or substituted group 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.

[0399] In one scheme, R 3-1-1-1 are each independently hydroxy or halogen.

[0400] In one scheme, R 3-1-1-2 Each is independently a C1-C6 alkyl group.

[0401] In one scheme, R 3-1-1-3 Each is independently a C1-C6 alkoxy group or a hydroxy group.

[0402] In one scheme, R 3-1-2 and R 3-1-3 Each independently hydroxyl group, or C1-C6 alkyl.

[0403] In one scheme, R 3-1-4 and R 3-1-5 Each is independently a C1-C6 alkyl group.

[0404] In one scheme, R 3-1-2-1 for or C3-C6 cycloalkyl.

[0405] In one scheme, R 3-1-2-2 and R 3-1-2-3 Each is independently H.

[0406] In one scheme, R 3a are each 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.

[0407] In one scheme, R 3a are independently halogen, hydroxyl, unsubstituted or replaced by one or more R 3a-4 a substituted C1-C6 alkyl group, an unsubstituted C1-C6 alkoxy group or a cyano group.

[0408] In one scheme, R 3a-1 and R 3a-2 Each is independently H.

[0409] In one scheme, R 3a-3 is C1-C6 alkoxy or

[0410] In one scheme, R 3a-4 C 6-14 Aryl, hydroxy, halogen or For example, R 3a-4 C 6-14 aryl or hydroxyl.

[0411] In one scheme, R 3a-4 is hydroxy, halogen or -NH2.

[0412] In one scheme, R 3a-4-1 and R 3a-4-2 Each is independently H.

[0413] The present invention provides a compound represented by Formula I, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof;

[0414] X1 is N;

[0415] X2 is C;

[0416] Z1 is N;

[0417] Z2 is C;

[0418] W is

[0419] R 1 is unsubstituted or replaced by 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;

[0420] R 1-1 are each independently cyano;

[0421] R 1-2 Each is independently a C1-C6 alkyl group;

[0422] R 2 is unsubstituted or replaced by one or more R 2-3 substituted 4-12 membered heterocycloalkyl, unsubstituted or replaced by one or more R 2-10 Substituted C3-C6 cycloalkenyl; 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;

[0423] R 2-3 Each independently is hydroxy, unsubstituted or substituted with one or more R 2-3-1 Substituted C1-C6 alkyl, R2-3-1 are each independently hydroxyl;

[0424] 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;

[0425] R 2-3-3 Each is independently hydrogen or C1-C6 alkyl;

[0426] R 2-3-2-2 Each independently represents halogen, hydroxy, C1-C6 alkyl, unsubstituted or substituted by one or more R 2-3-2-2-2 Substituted C1-C6 alkoxy;

[0427] R 2-3-2-2-2 Each independently is deuterium;

[0428] R 2-5 Each independently is one or more R 2-5-4 Substituted C1-C6 alkyl;

[0429] R 2-5-4 are each independently hydroxyl;

[0430] R 2-10 are each independently hydroxyl;

[0431] L is a carbonyl group;

[0432] R 3 for

[0433] 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 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;

[0434] 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 3aSubstitution; 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;

[0435] 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 replaced by one or more R 3-1-1-3 substituted C1-C6 alkyl, 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 independently is hydroxy 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 is independently C1-C6 alkoxy or hydroxy;

[0436] R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl;

[0437] R 3-1-4 Each is independently a C1-C6 alkyl group;

[0438] R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each is independently H or C1-C6 alkyl;

[0439] R 3-1-2-2 and R 3-1-2-3 Each independently is H;

[0440] 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;

[0441] R 3a-1 and R 3a-2 Each one is independent of H;

[0442] R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R3a-3-2 Each is independently H or C1-C6 alkyl;

[0443] R 3a-4 C 6-14 Aryl, hydroxy, halogen or R 3a-4-1 and R 3a-4-2 Each one is independent of H;

[0444] R 4 and R 5 Each is independently H.

[0445] In a certain embodiment, in the compound represented by formula I;

[0446] X1 is N;

[0447] X2 is C;

[0448] Z1 is N;

[0449] Z2 is C;

[0450] W is

[0451] R 1 is unsubstituted or replaced by 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;

[0452] R 1-1 Each is independently cyano or unsubstituted C1-C6 alkyl;

[0453] R 1-2 Each is independently an unsubstituted C1-C6 alkyl group;

[0454] R 2 is unsubstituted or replaced by one or more R 2-3 Substituted 4-12 membered heterocycloalkyl; 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;

[0455] R 2-3 are each independently an unsubstituted C1-C6 alkyl group,

[0456] R 2-3-2 is an unsubstituted C1-C6 alkyl group or is replaced by one or more R 2-3-2-2 substituted C3-C6 cycloalkyl;

[0457] R2-3-3 Each is independently an unsubstituted C1-C6 alkyl group;

[0458] R 2-3-2-2 Each is independently a C1-C6 alkoxy group;

[0459] L is a carbonyl group;

[0460] R 3 for

[0461] 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;

[0462] 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 group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0463] R 3-1-1 Each is independently hydroxy, 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 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; R 3-1-1-1 Each independently is hydroxy or halogen; R 3-1-1-2 Each is independently a C1-C6 alkyl group;

[0464] R 3-1-2 and R 3-1-3 are independently halogen, hydroxyl, or C1-C6 alkyl;

[0465] R 3-1-4 Each is independently a C1-C6 alkyl group;

[0466] R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each is independently H or C1-C6 alkyl;

[0467] R 3-1-2-2 and R 3-1-2-3 Each independently is H;

[0468] 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;

[0469] R 3a-1 and R 3a-2 Each one is independent of H;

[0470] R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each is independently H or C1-C6 alkyl;

[0471] R 3a-4 C 6-14 Aryl, hydroxy, halogen or -NH2;

[0472] R 4 and R 5 Each is independently H.

[0473] In a certain embodiment, in the compound represented by formula I;

[0474] X1 is N;

[0475] X2 is C;

[0476] Z1 is N;

[0477] Z2 is C;

[0478] W is

[0479] R 1 is unsubstituted or replaced by one or more R 1-1 Substituted C3-C6 cycloalkyl, unsubstituted or replaced by one or more R1-2 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;

[0480] R 1-1 Each is independently an unsubstituted C1-C6 alkyl group;

[0481] R 1-2 Each is independently an unsubstituted C1-C6 alkyl group;

[0482] R 2 is unsubstituted or replaced by one or more R 2-3 Substituted 4-12 membered heterocycloalkyl; 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;

[0483] R 2-3 Each is independently an unsubstituted C1-C6 alkyl group;

[0484] L is a carbonyl group;

[0485] R 3 for

[0486] 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;

[0487] 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 group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0488] R 3-1-1 Each independently represents an unsubstituted C1-C6 alkyl group, an unsubstituted or substituted group with one or more R 3-1-1-1substituted 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; R 3-1-1-1 Each independently is hydroxy or halogen; R 3-1-1-2 Each is independently a C1-C6 alkyl group;

[0489] R 3-1-2 and R 3-1-3 Each independently hydroxyl group, or C1-C6 alkyl;

[0490] R 3-1-4 Each is independently a C1-C6 alkyl group;

[0491] R 3-1-2-1 for or C3-C6 cycloalkyl; R 3-1-2-1a and R 3-1-2-1b Each is independently H or C1-C6 alkyl;

[0492] R 3-1-2-2 and R 3-1-2-3 Each independently is H;

[0493] 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;

[0494] R 3a-1 and R 3a-2 Each one is independent of H;

[0495] R 3a-3 is C1-C6 alkoxy or R 3a-3-1 and R 3a-3-2 Each is independently H or C1-C6 alkyl;

[0496] R 3a-4 C 6-14 aryl or hydroxyl;

[0497] R 4 and R 5 Each is independently H.

[0498] In one scenario, R 1for For example, R 1 for

[0499] In one scheme, W is

[0500] In one scenario, R 2 for For example, R 2 for

[0501] In one scheme, L is

[0502] In one scenario, R 3 for

[0503] In one scenario, R 3 for

[0504] In one embodiment, the compound represented by formula I is any of the following compounds:

[0505] in, refer to

[0506] The present invention also provides a pharmaceutical composition comprising 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.

[0507] The present invention also provides a use of a substance Z in the preparation of a PARG inhibitor and a drug for treating and / or preventing PARG-related diseases. The substance Z is the compound represented by the above formula I, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0508] 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 substance Z, wherein substance Z is the compound represented by the above formula I, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0509] In a preferred embodiment, the PARG-related disease may be breast cancer, such as triple-negative breast cancer, and other PARG-related diseases.

[0510] The present invention also provides a use 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.

[0511] In a preferred embodiment, the breast cancer may be triple-negative breast cancer.

[0512] The present invention provides a compound represented by formula II;

[0513] Among them, R 6 is a C1-C6 alkoxy group (e.g., a methoxy group);

[0514] Y is halogen (e.g., chlorine, bromine or iodine);

[0515] R 7 is H or an amino protecting group (such as p-methoxybenzyl (PMB), benzyl or (trimethylsilyl)ethoxymethyl (SEM));

[0516] R 1-2 、R 5 、R 4 , L are each independently as described in any one of the present invention.

[0517] In one embodiment, the compound represented by formula II is any one of the following compounds:

[0518] The present invention provides a compound represented by formula III;

[0519] in,

[0520] R 8 is an amino protecting group (such as p-methoxybenzyl (PMB), benzyl or (trimethylsilyl)ethoxymethyl (SEM));

[0521] 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.

[0522] In one embodiment, the compound represented by formula III is any one of the following compounds:

[0523] Preferably, the compound represented by formula III is any one of the following compounds:

[0524] Alternatively, the compound represented by formula III is

[0525] in, refer to

[0526] The present invention provides the use of the compounds represented by the above-mentioned formula II and formula III as intermediates for preparing the compound represented by the above-mentioned formula I, its stereoisomers, or pharmaceutically acceptable salts thereof. The use may comprise the following steps: hydrolyzing the compound represented by the above-mentioned formula III in an organic solvent (e.g., dichloromethane) (e.g., trifluoroacetic acid hydrolysis) to obtain the compound represented by the above-mentioned formula I, its stereoisomers, or pharmaceutically acceptable salts thereof.

[0527] Explanation of terms

[0528] The term "a group B which is unsubstituted or substituted by multiple groups A" means that one or more hydrogen atoms in 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 three halogens" means that a C1-C6 alkyl group is substituted by three halogens, and the definitions of the three halogens are independent of each other and do not affect each other, including but not limited to: trifluoromethyl, difluoromethyl, wait.

[0529] A double bond or a single bond.

[0530] The term "plurality" refers to 2 or more, such as 2, 3, 4, 5.

[0531] The term "pharmaceutically acceptable" means relatively non-toxic, safe, and suitable for use by patients.

[0532] 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, and ammonium salts. 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, and methanesulfonates. For details, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition).

[0533] "-" in a group means that the group is attached to the rest of the molecule through that site. For example, CH3-C(=O)- means acetyl.

[0534] The term "halogen" refers to fluorine, chlorine, bromine or iodine. 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 generally multiple substitutions occur on one carbon atom.

[0535] The term "oxo" refers to =0, an oxygen atom replacing two hydrogens on the same carbon atom, ie, a carbonyl replacing a methylene group.

[0536] 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 groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, and n-hexyl.

[0537] The term "alkoxy" refers to a group R X -O-, R X The same definition as the term "alkyl". Alkoxy includes, but is not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, and the like.

[0538] The term "alkenyl" refers to a linear or branched, unsaturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C2 to 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.

[0539] The term "alkynyl" refers to a linear or branched, unsaturated, monovalent hydrocarbon radical having a specified number of carbon atoms (e.g., C2 to C6) and having one or more (e.g., 1, 2, or 3) carbon-carbon sp 3 Triple bond. Alkynyl includes but is not limited to: ethynyl, wait.

[0540] Unless otherwise specified in the present invention, the term "cycloalkyl" refers to a group 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.

[0541] Unless otherwise specified in the present invention, the term "cycloalkenyl" refers to a "cycloalkyl" group having one or more carbon-carbon double bonds, and the definition of "cycloalkyl" is the same as above. For example:

[0542] 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 ) cyclic, unsaturated monovalent hydrocarbon group, which is monocyclic or polycyclic (for example, 2 or 3), in the case of polycyclic, the monocyclics share two atoms and one bond, and (at least one ring / each ring) has aromaticity. 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.

[0543] Unless otherwise specified herein, the term "heterocycloalkyl" refers to a monocyclic, bridged, spirocyclic, or fused ring (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 heteroatom (one or more of N, O, and S). The heterocycloalkyl group may be saturated or unsaturated. The (monocyclic) heterocycloalkyl group is attached to the rest of the molecule via a carbon atom or a heteroatom. Monocyclic heterocycloalkyl groups include, but are not limited to: Spirocyclic heterocycloalkyl groups include but are not limited to: etc. Bridged heterocycloalkyl groups include but are not limited to: Etc. Cycloheterocycloalkyl includes

[0544] 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 monocyclic or polycyclic, with two atoms and one bond shared between the monocyclic rings, and at least one ring having aromatic properties. A heteroaryl group is attached to the rest of the molecule through a carbon atom or a heteroatom; a heteroaryl group is attached to the rest of the molecule through a ring with heteroatoms or a ring without heteroatoms; a heteroaryl group is attached 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.

[0545] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0546] The reagents and raw materials used in the present invention are commercially available.

[0547] The positive effects of the present invention are: (1) the compounds of the present invention have good PARG inhibitory activity, exert good pharmacological effects in vivo, and are more conducive to the pharmacological effects of the compounds; and / or (2) have good selectivity and less toxic side effects. DETAILED DESCRIPTION

[0548] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0549] All compounds of the present invention can be synthesized by different methods by those skilled in the art of organic chemistry. The following describes general synthetic schemes for preparing the compounds of the present invention. These schemes are general and are not meant to limit the possible techniques that a person skilled in the art can use to prepare the compounds disclosed herein. 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 compound or compounds. The preparation and examples described below provide examples of the preparation of the compounds of the present invention by the methods described in the general schemes. The preparation of compounds containing chiral center embodiments can be performed by techniques known to 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.

[0550] The chemical reactions and synthetic techniques described herein are performed in the reagents and corresponding solvents described herein, and the corresponding reaction yields will also be affected by the reagents and solvents used. Furthermore, it should be understood that in the synthetic methods described below, all reaction conditions mentioned, including the choice of solvent, reaction atmosphere, reaction temperature, experimental duration, and reaction feed sequence, should be considered standard operating conditions for the reaction, as readily recognized by those skilled in the art. This is also understood by those skilled in the art of organic synthesis. The functional groups present on various parts of the molecule must be compatible with the reagents used and the reaction itself. Limitations such as incompatibility of some functional groups on various parts of the molecule with the reaction conditions necessitate alternative methods, as will be readily apparent to those skilled in the art. The need to adjust the order of synthetic steps or select a specific synthetic process scheme to obtain the desired compounds of the present invention is readily apparent to those skilled in the art of organic synthesis. It should also be recognized that another key consideration in any synthetic route designed in this field is the tolerance of the appropriate protecting groups used to protect the reactive functional groups present in the compounds described herein. 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)).

[0551] Example

[0552] 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 rather to illustrate how to prepare the relevant compounds. The starting materials and reagents used in these examples, when not prepared by the procedures described herein, are generally commercially available or reported in the relevant chemical literature, or can be prepared by using the procedures described in the chemical literature.

[0553] 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 filtration and removal of the solvent from the filtrate (usually performed under reduced pressure and at a temperature suitable for the stability of the prepared compound). Column chromatography is generally performed using conventional column chromatography or flash column chromatography for column separation and purification, or using a medium pressure chromatograph (Biotage Isola One) pre-packed silica gel column and eluting in a specified solvent or solvent mixture. In some cases, the final product is quickly purified by preparative thin layer chromatography using a 20cm x 20cm x 0.5mm or 20cm x 20cm x 1mm silica gel plate in an appropriate solvent system. Preparative high performance liquid chromatography (HPLC) is performed using a reversed-phase column (Waters Sunfire C18, Waters Xbridge C18, or similar) of a size appropriate to the amount of compound being separated. Elution is typically performed using a gradient of methanol or acetonitrile added to the aqueous phase, with the eluent containing 0.05% or 0.1% formic acid, trifluoroacetic acid, or 10 mM ammonium acetate, at an elution rate that matches the size of the reversed-phase column used and the resolution of the preparation being prepared.

[0554] List of abbreviations

[0555] Example 1: N-cyclopropyl-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0556] Step 1: 8-chloro-6-(chlorosulfonyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester

[0557] To a solution of methyl 6-(benzylsulfanyl)-8-chloroimidazo[3,4-a]pyridine-3-carboxylate (1 g, 3.01 mmol) in dichloromethane (20 mL) was added water (540 mg, 30 mmol) and acetic acid (1.8 g), followed by the slow dropwise addition of sulfonyl chloride (1.62 g, 12.02 mmol). The reaction mixture was stirred at 0°C for 10 minutes. After completion of the reaction, the pH was adjusted to 7-8 with sodium bicarbonate, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford the title compound (crude product, 1 g, 96.77% yield). The crude product was used directly in the next reaction. LC / MS (ESI) (m / z): 309 [M+H] + .

[0558] Step 2: 8-chloro-6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester

[0559] To a solution of methyl 8-chloro-6-(chlorodioxy-λ6-sulfanyl)imidazo[3,4-a]pyridine-3-carboxylate (927 mg, 3 mmol) in dichloromethane (8 mL) was slowly added 3-methyloxetane-3-amine (315 mg, 3.62 mmol) and pyridine (2 mL, 24.73 mmol) under an ice-water bath. The reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was diluted with dichloromethane, washed sequentially 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: 0-60% ethyl acetate) to yield the title compound (white solid, 580 mg, 26.9% yield). LC / MS (ESI) (m / z): 360 [M+H] + .

[0560] Step 3: 8-chloro-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester

[0561] To a solution of methyl 8-chloro-6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate (450 mg, 1.25 mmol) in dichloromethane (20 mL) was slowly added N,N-diisopropylethylamine (323 mg, 2.5 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (250 mg, 1.51 mmol) under an ice-water bath. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was diluted with dichloromethane, washed sequentially 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: 0-30% ethyl acetate) to yield the title compound as a white solid, 410 mg, 91.11% yield. LC / MS (ESI) (m / z): 490 [M+H] + .

[0562] Step 4: 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 methyl ester

[0563] To a solution of methyl 8-chloro-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate (410 mg, 0.84 mmol) and 2S,6S-dimethylmorpholine (96.4 mg, 0.84 mmol) in 1,4-dioxane (10 mL) at room temperature under nitrogen was added Ruphos Pd G3 (70 mg, 0.084 mmol), Ruphos (39 mg, 0.084 mmol), and cesium carbonate (545 mg, 1.67 mmol). The reaction mixture was stirred at 100°C for 1 hour. After completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed sequentially 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: 0-50% ethyl acetate) to give the title compound (white solid, 420 mg, yield 88.3%). LC / MS (ESI) (m / z): 569 [M+H] + .

[0564] 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

[0565] To a solution of methyl 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate (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). The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the pH was adjusted to 6-7 with citric acid and extracted three times with ethyl acetate. The organic phase was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to provide the title compound as a yellow oil (340 mg, 94% yield). LC / MS (ESI) (m / z): 555 [M+H] + .

[0566] Step 6: N-cyclopropyl-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0567] 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 was complete, the reaction solution was diluted with ethyl acetate, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (colorless oil, 50 mg, yield 76%). LC / MS (ESI) (m / z): 594 [M+H] + .

[0568] Step 7: N-cyclopropyl-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0569] To a solution of N-cyclopropyl-8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide (50 mg, 0.088 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (1 mL). The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was isolated by preparative HPLC (C18, 10-50% acetonitrile in H2O and 0.1% FA) to afford the title compound as a white solid, 3.69 mg, 9.2% yield. 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,4 H),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] + .

[0570] The following examples are prepared with reference to the preparation method of Example 1. Starting from appropriate starting materials, the crude product was synthesized according to a similar route. The crude product was subjected to preparative HPLC and freeze-dried to obtain the title compound.

[0571] Example 109: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(3-methyloxetane-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0572] Step 1: 8-(4-isobutyrylpiperazin-1-yl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester

[0573] Under nitrogen, to a solution of methyl 8-chloro-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate (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) were added cesium carbonate (80 mg, 0.25 mmol), Ruphos (11 mg, 0.024 mmol), and Ruphos Pd G3 (10 mg, 0.012 mmol) in sequence. The reaction mixture was purged with nitrogen three times and stirred at 80°C under nitrogen for 2 hours. After completion of the reaction, the reaction mixture 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] + .

[0574] Step 2: 8-(4-isobutyrylpiperazin-1-yl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylic acid

[0575] To a mixed solution of methyl 8-(4-isobutyrylpiperazin-1-yl)-6-(N-(3-methyloxetane-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate (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 mixture was stirred at room temperature for 1 hour. After the reaction was complete, the pH was adjusted to 6-7 with citric acid and extracted three times with ethyl acetate. The organic phase was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound as a yellow solid, 60 mg, 95% yield. LC / MS (ESI) m / z: 596 [M+H] + .

[0576] Step 3: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide

[0577] To a solution of 8-(4-isobutyrylpiperazin-1-yl)-6-(N-(3-methyloxetan-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) was added 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (57.4 mg, 0.15 mmol) and N,N-diisopropylethylamine (39 mg, 0.30 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, 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, 81.3% yield). LC / MS (ESI) m / z: 733 [M+H] + .

[0578] 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

[0579] To a solution of 3-(3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (30 mg, 0.041 mmol) in dichloromethane (1 mL) was slowly added dropwise trifluoroacetic acid (0.5 mL) at 0°C. The reaction mixture 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 / water containing 0.1% FA) to afford the title compound as a yellow solid, 4.66 mg, 18.9% yield. 1H 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] + .

[0580] Example 110: 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

[0581] Step 1: Benzyl ((1S,2S)-2-hydroxycyclopentyl) carbamate

[0582] To a solution of (1S,2S)-2-aminocyclopentan-1-ol (720 mg, 7.2 mmol) in dichloromethane (20 mL) at 0°C was added triethylamine (1.5 g, 15 mmol), followed by the slow dropwise addition of benzyl chloroformate (1.5 g, 12 mmol). The reaction mixture was stirred at 0°C for 2 hours. After completion of the reaction, the reaction mixture was washed sequentially 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: 0-30% ethyl acetate) to yield the title compound (white solid, 1.1 g, 65.9% yield). LC / MS (ESI) (m / z): 236 [M+H] + .

[0583] Step 2: Benzyl ((1S,2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)carbamate

[0584] To a solution of benzyl ((1S,2S)-2-hydroxycyclopentyl)carbamate (1.1 g, 4.7 mmol) in tetrahydrofuran (20 mL) at room temperature were added 3,4-dihydro-2H-pyran (680 mg, 8.0 mmol) and p-toluenesulfonic acid (50 mg). The reaction mixture was stirred at 50°C for 1 hour. After completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed sequentially 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: 0-20% ethyl acetate) to yield the title compound (white solid, 1.3 g, 87.1% yield). LC / MS (ESI) (m / z): 320 [M+H] + .

[0585] Step 3: (1S,2S)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentan-1-amine

[0586] 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) was slowly added 10% palladium on carbon (200 mg) at room temperature. The reaction mixture was stirred at room temperature under a hydrogen atmosphere for 5 hours. After the reaction was complete, the reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure to obtain the title compound (colorless oil, 610 mg, 80.9% yield). LC / MS (ESI) (m / z): 186 [M+H] + .

[0587] Step 4: (1S,2S)-N-(2-((tert-Butyldimethylsilyl)oxy)ethyl)-2-((tetrahydro-2H-pyran-2-yl)oxycyclopentan-1-amine

[0588] 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) at room temperature under nitrogen was added glacial acetic acid (10 mg) and sodium cyanoborohydride (38 mg, 0.6 mmol) in sequence. After the addition, the reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was concentrated under reduced pressure to remove the methanol. The residue was diluted with ethyl acetate, washed sequentially 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: 0-50% ethyl acetate) to obtain the title compound (colorless oil, 35 mg, 37.5% yield). LC / MS (ESI) (m / z): 344 [M+H] + .

[0589] Step 5: 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)

[0590] Cyclopentyl)imidazo[1,5-a]pyridine-3-carboxamide

[0591] 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 solution (2 mL). The reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was diluted with ethyl acetate, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (colorless oil, 30 mg, 39% yield). LC / MS (ESI) (m / z): 880 [M+H] + .

[0592] 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

[0593] 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) was added trifluoroacetic acid (0.5 mL) under an ice-water bath. After addition, the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (C18, 10-50% acetonitrile / water containing 0.1% FA) to afford the title compound as a white solid, 1.15 mg, 6.1% yield. 1 H 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] + .

[0594] Example 111: 8-((2S,6S)-2,6-dimethylmorpholinyl)-N-((1S,2S)-2-hydroxycyclopentyl)-N-(2-methoxyethyl)-6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0595] Step 1: (1S,2S)-N-(2-methoxyethyl)-2-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentan-1-amine

[0596] 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) was added cesium carbonate (35 mg, 0.11 mmol) and 1-bromo-2-methoxyethane (15 mg, 0.11 mmol) under ice-water. The reaction mixture was stirred at 60°C for 3 hours. After the reaction was complete, water was added and the mixture was 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 yield the title compound (yellow oil, 25 mg, 95.3% yield). LC / MS (ESI) (m / z): 244 [M+H] + .

[0597] Step 2: 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

[0598] 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 mixture was stirred at room temperature for 10 minutes. After completion, the mixture 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 yield the title compound (yellow solid, 20 mg, 56.9% yield). LC / MS (ESI) (m / z): 780 [M+H] + .

[0599] Step 3: 8-((2S,6S)-2,6-dimethylmorpholinyl)-N-((1S,2S)-2-hydroxycyclopentyl)-N-(2-methoxyethyl)-6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxamide

[0600] 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 To a solution of 1,000 mg, 0.026 mmol) in dichloromethane (0.5 mL) was added trifluoroacetic acid (0.25 mL). The reaction mixture was stirred at 0°C for 1 hour. After completion, the reaction mixture was added dropwise to a 0°C 5% aqueous sodium bicarbonate solution 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 / H2O containing 0.1% FA) to afford the title compound as a white solid, 2.01 mg, 13.8% yield. 1 H 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] + .

[0601] Example 112: 3-(3-(2-aminoethyl)-3-hydroxypyrrolidine-1-carbonyl)-8-((2S,6S)-2,6-dimethylmorpholinyl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0602] Step 1: tert-Butyl 3-(cyanomethyl)-3-hydroxypyrrolidine-1-carboxylate

[0603] To 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) was slowly added dropwise isopropyl Grignard reagent lithium chloride complex (3.7 mL, 6.0 mmol, 1.6 M in THF) at -78°C. After the addition, the reaction solution was slowly warmed to room temperature and stirred overnight. After the reaction was complete, the mixture was quenched with saturated 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: 30-50% ethyl acetate) to yield the title compound (colorless liquid, 900 mg, 73.8% yield). LC / MS (ESI) (m / z): 227 [M+H] + .

[0604] Step 2: tert-Butyl 3-(2-aminoethyl)-3-hydroxypyrrolidine-1-carboxylate

[0605] Under a nitrogen atmosphere, to a solution of tert-butyl 3-(cyanomethyl)-3-hydroxypyrrolidine-1-carboxylate (900 mg, 4.0 mmol) in methanol (20 mL) was added Raney nickel (200 mg). The reaction solution was purged with nitrogen three times and stirred at room temperature under an atmosphere of hydrogen at 1 atmosphere overnight. After the reaction was complete, the mixture was filtered through celite, and the filtrate was concentrated under reduced pressure to give the title compound (white solid, 550 mg, 54.6% yield). LC / MS (ESI) (m / z): 231 [M+H] + .

[0606] Step 3: tert-Butyl 3-(2-((benzyloxy)carbonyl)amino)ethyl)-3-hydroxypyrrolidine-1-carboxylate

[0607] To a solution of tert-butyl 3-(2-aminoethyl)-3-hydroxypyrrolidine-1-carboxylate (550 mg, 2.4 mmol) in dichloromethane (10 mL) at 0°C was added triethylamine (485 mg, 4.8 mmol) and benzyl chloroformate (450 mg, 2.6 mmol). The reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, water was added and the mixture was 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, 360 mg, 41.1% yield). LC / MS (ESI) (m / z): 365 [M+H] + .

[0608] Step 4: Benzyl (2-(3-hydroxypyrrolidin-3-yl)ethyl)carbamate hydrochloride

[0609] To a bottle containing tert-butyl 3-(2-((benzyloxy)carbonyl)amino)ethyl)-3-hydroxypyrrolidine-1-carboxylate (360 mg, 1.00 mmol) was added dioxane hydrochloride (5 mL, 4 M) at room temperature. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to afford the title compound (white solid, 180 mg, 70.0% yield). LC / MS (ESI) (m / z): 265 [M+H] + .

[0610] Step 5: 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

[0611] 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) was added 1H-benzotriazol-1-yloxytripyrrolidinyl hexafluorophosphate (56 mg, 0.11 mmol) and N,N-diisopropylethylamine (35 mg, 0.27 mmol) at room temperature. The reaction mixture was stirred at room temperature for 3 hours. 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: 80-100% ethyl acetate) to give the title compound (yellow solid, 50 mg, yield 69.4%). LC / MS (ESI) (m / z): 801 [M+H] + .

[0612] Step 6: Benzyl (2-(1-(8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)sulfamoyl)imidazo[1,5-a]pyridine-3-carbonyl)-3-hydroxypyrrolidin-3-yl)ethyl)carbamate

[0613] 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) was added trifluoroacetic acid (0.5 mL) at 0°C. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, 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 as a yellow solid, 30 mg, 71.4% yield. LC / MS (ESI) (m / z): 671 [M+H] + .

[0614] Step 7: 3-(3-(2-aminoethyl)-3-hydroxypyrrolidine-1-carbonyl)-8-((2S,6S)-2,6-dimethylmorpholinyl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0615] Under a nitrogen atmosphere, to a solution of benzyl (2-(1-(8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-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) was added 10% palladium on carbon (10 mg). The reaction mixture was purged with nitrogen three times and then stirred at room temperature under an atmosphere of hydrogen at 1 atmosphere for 1 hour. After completion of the reaction, the reaction mixture 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 afford the title compound as a yellow solid, 3 mg, 12.5% ​​yield. 1H 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] + .

[0616] 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

[0617] 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

[0618] To a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-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 (150 mg, 0.28 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1.5 mL) at 0°C. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (C18, 10-60% acetonitrile / water containing 0.1% FA) to afford the title compound as a yellow solid, 80 mg, 66% yield. The product was then separated by preparative SFC (ChiralPak AS, 250×30 mm ID 5 μm, A for CO and B for MeOH (0.1% 2M NH / MeOH), 40 mL / min) to afford Example 113 (peak 1, retention time: 2.612 min) (yellow solid, 23 mg, 29% yield) and Example 114 (peak 2, retention time: 3.558 min) (yellow solid, 28 mg, 35% yield).

[0619] Example 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] + .

[0620] Example 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] + .

[0621] Example 115: 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

[0622] Step 1: 2-Bromocyclopent-2-en-1-one

[0623] To a solution of cyclopent-2-en-1-one (5 g, 61.0 mmol) in dichloromethane (50 mL) at 0°C was added liquid bromine (9.8 g, 61.0 mmol) and triethylamine (6.2 g, 61.0 mmol). The reaction mixture was stirred at room temperature overnight. After completion, the reaction was quenched with saturated aqueous sodium thiosulfate 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: 10-30% ethyl acetate) to afford the title compound (colorless liquid, 7.5 g, 76.8% yield). 1 H NMR (400MHz, DMSO-d6) δ8.18-7.99(m,1H),2.69-2.62(m,2H),2.49-2.43(m,2H).

[0624] Step 2: 2-Bromocyclopent-2-en-1-ol

[0625] To a solution of 2-bromocyclopent-2-en-1-one (3 g, 18.8 mmol) and cerium trichloride (1.8 g, 7.52 mmol) in methanol (30 mL) at 0°C, sodium borohydride (0.7 g, 18.8 mmol) was added portionwise. The reaction mixture was stirred at room temperature for 2 hours. After completion, the reaction mixture was slowly added dropwise to a saturated aqueous ammonium chloride solution 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 afford the title compound (colorless liquid, 2.5 g, 82.3% yield). 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).

[0626] Step 3: (2-bromocyclopent-2-en-1-yl)oxy)(tert-butyl)dimethylsilane

[0627] To a solution of 2-bromocyclopent-2-en-1-ol (1.5 g, 9.3 mmol) in dichloromethane (20 mL) at 0°C was added imidazole (1.3 g, 18.6 mmol) and tert-butyldimethylsilyl chloride (2.1 g, 14.0 mmol). The reaction mixture was stirred at room temperature overnight. After completion of the reaction, the reaction mixture 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 yield the title compound (colorless liquid, 2.5 g, 97.4% yield). 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).

[0628] Step 4: tert-Butyldimethyl((2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-yl)oxy)silane

[0629] To a solution of (2-bromocyclopent-2-en-1-yl)oxy)(tert-butyl)dimethylsilane (1 g, 3.6 mmol) in anhydrous tetrahydrofuran (10 mL) at -78°C was added n-butyllithium (1.7 mL, 4.3 mmol, 2.5 M in THF) dropwise. The reaction mixture was stirred at -78°C for 1 hour. At this temperature, a solution of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.3 g, 7.2 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was stirred at -78°C for another 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, 47.2% yield). 1 H 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).

[0630] 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

[0631] Under a nitrogen atmosphere, 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) were added Xphos Pd G2 (6 mg, 0.008 mmol) and potassium phosphate (52 mg, 0.25 mmol). The reaction mixture 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 yield the title compound (yellow solid, 56 mg, 87.5% yield). LC / MS (ESI) (m / z): 775 [M+H] + .

[0632] 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

[0633] 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 mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to afford 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 afford the title compound (yellow solid, 3 mg, 15.9% yield). 1H 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] + .

[0634] Example 116: 3-(3-Hydroxy-3-(trifluoromethyl)pyrrolidine-1-carbonyl)-8-(2-hydroxycyclopentyl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0635] Under a 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-en-1-yl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide (20 mg, 0.038 mmol) in methanol (3 mL). The reaction mixture was stirred at room temperature under a hydrogen atmosphere at 1 atmosphere for 1 hour. After the reaction was complete, the reaction mixture was filtered, and the filtrate was purified by preparative HPLC (C18, 10-50% acetonitrile in H2O and 0.1% FA) to afford the title compound as a yellow solid (2 mg, 9.9% yield). 1 H 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] + .

[0636] 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

[0637] Step 1: Benzyl bis(2-hydroxyethyl)carbamate

[0638] To a solution of 2,2'-azadiylbis(ethane-1-ol) (1 g, 9.51 mmol) in acetonitrile (10 mL) was added potassium carbonate (2.6 g, 19.02 mmol) and then benzyl chloroformate (2.4 g, 14.26 mmol) was slowly added dropwise under an ice-water bath. The reaction mixture was stirred at room temperature for 3 hours. After the reaction was complete, the reaction mixture was diluted with ethyl acetate, washed sequentially 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: 0-25% ethyl acetate) to obtain the title compound (colorless oil, 900 mg, 39.5% yield). LC / MS (ESI) (m / z): 240 [M+H] + .

[0639] Step 2: Benzyl bis(2-((tert-butyldimethylsilyl)oxy)ethyl)carbamate

[0640] To a solution of benzyl bis(2-hydroxyethyl)carbamate (900 mg, 3.76 mmol) in dichloromethane (9 mL) was slowly added imidazole (512 mg, 7.52 mmol) and tert-butyldimethylsilyl chloride (1247 mg, 8.27 mmol) under an ice-water bath. The reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was diluted with dichloromethane, washed sequentially 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 oil, 500 mg, 28.4% yield). LC / MS (ESI) (m / z): 468 [M+H] + .

[0641] Step 3: Bis(2-((tert-butyldimethylsilyl)oxy)ethyl)amine

[0642] To a solution of benzyl bis(2-((tert-butyldimethylsilyl)oxy)ethyl)carbamate (500 mg, 1.07 mmol) in methanol (5 mL) at room temperature was added 10% palladium on carbon (50 mg). The reaction solution was purged with nitrogen three times and stirred at room temperature under an atmosphere of hydrogen at 1 atmosphere for 2 hours. After completion of the reaction, the mixture was filtered, and the filtrate was concentrated under reduced pressure to afford the title compound (colorless liquid, 300 mg, 84.1% yield), which was used directly in the next step without purification. LC / MS (ESI) (m / z): 334 [M+H] + .

[0643] Step 4: 8-(bis(2-((tert-butyldimethylsilyl)oxy)ethyl)amino)-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

[0644] Under nitrogen, 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 (107 mg, 0.18 mmol) and bis(2-((tert-butyldimethylsilyl)oxy)ethyl)amine (89 mg, 0.27 mmol) in 1,4-dioxane (3 mL) were added cesium carbonate (117 mg, 0.36 mmol), Ruphos (17 mg, 0.036 mmol), and Ruphos Pd G3 (30 mg, 0.036 mmol) in sequence. The reaction mixture was purged with nitrogen three times and stirred at 80°C under nitrogen for 2 hours. 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: 0-55% ethyl acetate) to afford the title compound (yellow solid, 50 mg, 30.6% yield). LC / MS (ESI) (m / z): 910 [M+H] + .

[0645] Step 5: 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

[0646] Under nitrogen protection, trifluoroacetic acid (0.3 mL) was added to a 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) in dichloromethane (1 mL). The reaction solution was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was added dropwise to a 5% aqueous sodium bicarbonate 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 as a yellow solid (45 mg, 48.9% yield). 1 H 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] + .

[0647] Comparative Example 1: 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(hydroxymethyl)-N-(3-methyloxetane-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0648] Step 1: 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(hydroxymethyl)-N-(3-methyloxetan-3-yl)-N-[(2-(trimethylsilyl)ethoxy)methyl]imidazo[1,5-a]pyridine-6-sulfonamide

[0649] Under nitrogen, lithium aluminum tetrahydride (6.7 mg, 0.18 mmol) was added to a solution of methyl 8-((2S,6S)-2,6-dimethylmorpholinyl)-6-(N-(3-methyloxetan-3-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridine-3-carboxylate (50 mg, 0.088 mmol) in tetrahydrofuran (8 mL). The reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, sodium sulfate decahydrate was added, stirred for half an hour, and then filtered. The filter cake was washed twice with ethyl acetate, and the filtrate was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound (colorless oil, 30 mg, 60% yield). LC / MS (ESI) (m / z): 541 [M+H] + .

[0650] Step 2: 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(hydroxymethyl)-N-(3-methyloxetan-3-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0651] To a solution of 8-((2S,6S)-2,6-dimethylmorpholinyl)-3-(hydroxymethyl)-N-(3-methyloxetan-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). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the residue was isolated by preparative HPLC (C18, 10-50% acetonitrile in 0.1% FA in water) to afford the title compound as a white solid, 3.82 mg, 19.1% yield. 1 H 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] + .

[0652] Effect embodiment

[0653] Experimental methods:

[0654] 1. Biochemical Assay

[0655] 1) Add 20 nL of compound at different concentrations to a 384-well plate using Echo 550 (LABCYTE, #550) (final compound concentrations: 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);

[0656] 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 μM TFMU-ADPr (fluorescein-4-trifluoromethylumbelliferyl-ADP ribose);

[0657] 3) Add reaction buffer I at 10 μL / well to a 384-well plate;

[0658] 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);

[0659] 5) Add 10 μL / well of reaction buffer II to the 384-well plate to start the reaction;

[0660] 6) Incubate at room temperature for 3 minutes to react;

[0661] 7) Place the 384-well plate in a microplate reader and shake for 5 seconds before detecting the signal.

[0662] 8) Analyze the data using GraphPad software and determine the IC50.

[0663] 2. Cell Viability Assay

[0664] 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, 5% CO2 incubator for 24 h to allow complete cell attachment.

[0665] 2) Culture medium (100 μL / well) containing different concentrations of the test compound (final concentrations of the compound: 30,000 nM, 10,000 nM, 3,000 nM, 1,000 nM, 300 nM, 100 nM, 30 nM, 10 nM, 3 nM, 1 nM, 0 nM) was added to the cells and incubated in a 37°C CO2 (5%) incubator for 7 days;

[0666] 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;

[0667] 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;

[0668] 5) Incubate the plate at room temperature for 10 minutes to allow the signal to stabilize, then use a microplate reader (Thermo: Varioskan LUX) to detect and record the luminescence value;

[0669] 6) Analyze the data using GraphPad software and determine the IC 50 .

[0670] 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 in inhibiting the proliferation of the two cell types.

[0671] Data list:

[0672] NT = not tested;

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 Replaced by 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 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; Preferably, 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; 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, The number of atoms 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 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; 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 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; 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 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; 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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