1H-pyrazolo[4,3-c]pyridine compounds, their components, and their uses

Abstract

This invention relates to compounds of formula (A), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvates thereof, pharmaceutical compositions thereof, and their use in the treatment and / or prevention of diseases mediated by wild-type and / or mutant BTK kinases.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and specifically relates to highly selective compounds that inhibit Bruton's tyrosine kinase (BTK) and its drug resistance mutations, pharmaceutical compositions containing them, as well as their preparation methods and uses. Prior Technology

[0002] Bruton's tyrosine kinase (Btk) belongs to the Tec family of cytoplasmic tyrosine kinases, the second largest family of non-receptor kinases in humans. It is expressed in all cell lineages of the hematopoietic system (except T cells) and is localized in bone marrow, spleen, and lymph node tissues. Inactivating mutations in the gene encoding Btk result in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (XID) in mice. Both diseases are characterized by significant defects in B cell development and function, highlighting the crucial role of Btk in B cell development and function. Furthermore, constitutive initiation of Btk in B cells leads to the accumulation of autoreactive plasma cells. Preclinical studies have shown that Btk-deficient mice are resistant to developing collagen-induced arthritis. In addition, clinical studies of Rituxan (a CD20 antibody that depletes mature B cells) have revealed the critical role of B cells in many inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Furthermore, the aberrant activation of Btk plays an important role in the pathogenesis of B-cell lymphoma, suggesting that Btk inhibition may be used to treat hematologic malignancies.

[0003] The covalent Btk inhibitor ibrutinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), and chronic graft-versus-host disease (cGVHD). Despite its excellent efficacy and generally good tolerability, adverse events such as bleeding, rash, and diarrhea have been reported.

[0004] These ibrutinib-related adverse reactions are believed to be primarily related to off-target effects of ibrutinib, which have been shown to be associated with inhibition of EGFR and Tec. Targeting EGFR induces significant skin toxicity and gastrointestinal adverse reactions because the EGFR signaling cascade is relevant to the biology of the skin and gastrointestinal systems. Both Btk and Tec belong to the Tec family of kinases. Platelets express Btk and Tec, which serve downstream of glycoprotein VI (GPVI) signaling. Tec compensates for the absence of Btk in downstream GPVI signaling in murine platelets. Inhibition of Tec kinase by ibrutinib interferes with platelet aggregation and may contribute to the observed bleeding. Therefore, BTK inhibitors with high Btk inhibition and low EGFR and Tec inhibition are needed to reduce or avoid bleeding, rash, and diarrhea.

[0005] Ibrutinib also irreversibly binds to interleukin-2-induced tyrosine kinase (ITK). ITK plays a crucial role in the function of FcR-stimulated neutral killer (NK) cells, primarily through antibody-dependent NK cell-mediated cytotoxicity (ADCC). ADCC is currently the standard of care for B-cell malignancies, so there is a desire for a Btk inhibitor with high Btk inhibition and low ITK inhibition.

[0006] Covalent (irreversible) BTK inhibitors specifically target the cysteine ​​residue C481 within the BTK group. Primary and secondary resistance have emerged after treatment with ibrutinib. Mutations in BTK groups such as C481S, C481Y, C481R, and C481F have been shown to significantly interfere with drug binding. It is predicted that the observed incidence of resistance will increase over time with continued clinical use.

[0007] Non-covalent (reversible) BTK inhibitors do not require binding to the C481 residue of BTK to effectively inhibit wild-type and mutant BTK with the C481 residue replaced. However, existing literature reports that non-covalent BTK inhibitors can also induce acquired resistance mutations, such as V416L, A428D, M437R, T474I, and L528W mutations. Therefore, it is necessary to develop new BTK inhibitors. Summary of the Invention

[0008] This invention provides a novel 1H-pyrazolo[4,3-c]pyridine compound and compositions containing the compound, as well as their uses, which exhibit better inhibitory activity against BTK, C481 mutant BTK, and V416L, A428D, M437R, T474I, or L528W mutant BTK kinases. Compared with EGFR, TEC, and ITK kinases, it has higher selectivity and better pharmacodynamic and / or pharmacokinetic properties, and can treat BTK kinase-mediated diseases or conditions.

[0009] To address this, the present invention adopts the following technical solution: In one aspect, the present invention relates to compounds of formula (A), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof: (A) in, Ring A is a benzene ring or a 5-6 membered heteroaromatic ring; X1 is N, CD, or CH; X2 is either N or CR2; R1 is H, D, halogen, -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -NRbRc, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRbRc, -ORa, -OC(O)Ra, -OC(O)NRbRc, -NRaS(O)2Rb, -S(O)2NRbRc, -S(O)Ra, -S(O)2Ra, -P(=O)RbRc, -OP(=O)RbRc, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C2-6 alkyne, C3-6 cycloalkyl ... The 3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted with one or more R groups; Each of Ra, Rb, and Rc is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Rb and Rc together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R; R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R'; R3 and R4 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rs and Rt are independently H, D, halogen, -ORa, -NRbRc, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; m can be 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; Each R is independent of: 1)H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, -C1-6 alkyl-C3-6 cycloalkyl, -C1-6 alkyl-3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) Two Rs on the same atom or two adjacent atoms, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12-membered heterocyclic group, a C6-10 aryl, or a 5-10-membered heteroaryl, wherein said group is optionally substituted by one or more R''s; Each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C 6-10 aryl or 5-10 heteroaryl, or two R' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each R”' is independently substituted with H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl is optionally substituted with one or more D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl. Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0010] In another aspect, the present invention relates to compounds of formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof: (I) in, X1 is N, CD, or CH; X2 is either N or CR2; R1 is H, D, halogen, -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -NRbRc, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRbRc, -ORa, -OC(O)Ra, -OC(O)NRbRc, -NRaS(O)2Rb, -S(O)2NRbRc, -S(O)Ra, -S(O)2Ra, -P(=O)RbRc, -OP(=O)RbRc, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C2-6 alkyne, C3-6 cycloalkyl ... The 3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted with one or more R groups; Each of Ra, Rb, and Rc is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Rb and Rc together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R; R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R'; R3 and R4 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rs and Rt are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; m can be 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; Each R is independent of: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) Two Rs on the same atom or two adjacent atoms, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12-membered heterocyclic group, a C6-10 aryl, or a 5-10-membered heteroaryl, wherein said group is optionally substituted by one or more R''s; Each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C 6-10 aryl or 5-10 heteroaryl, or two R' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0011] In another aspect, the present invention relates to a pharmaceutical composition comprising the compound of the present invention, or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof, and a pharmaceutically acceptable excipient, and optionally, other therapeutic agents.

[0012] In another aspect, this invention relates to the use of the compounds of the invention, or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvates, or pharmaceutical compositions of the invention, in the preparation of medicaments for treating and / or preventing diseases mediated by wild-type and / or mutant BTK kinases; preferably, the mutant BTK kinase is selected from BTK C481S, BTK C481F, BTK C481Y, BTK C481R, BTK C481T, BTK C481G or BTK C481W; preferably, the mutant BTK kinase is BTK C481S; preferably, the mutant BTK kinase is BTK V416L, BTK A428D, BTK M437R, BTK T474I or BTK L528W; preferably, the mutant BTK kinase is BTK T474I or BTK L528W.

[0013] In another aspect, the present invention relates to a method for treating and / or preventing diseases mediated by wild-type and / or mutant BTK kinases in a subject, the method comprising administering to the subject a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention; preferably, the mutant BTK kinase is selected from BTK C481S, BTK C481F, BTK C481Y, BTK C481R, BTK C481T, BTK C481G, or BTK C481W; preferably, the mutant BTK kinase is BTK C481S; preferably, the mutant BTK kinase is BTK V416L, BTK A428D, BTK M437R, BTK T474I, or BTK L528W; preferably, the mutant BTK kinase is BTK T474I or BTK L528W.

[0014] In another aspect, the present invention relates to the compounds of the present invention, or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvates, or pharmaceutical compositions of the present invention, for the treatment and / or prevention of diseases mediated by wild-type and / or mutant BTK kinases; preferably, the mutant BTK kinase is selected from BTK C481S, BTK C481F, BTK C481Y, BTK C481R, BTK C481T, BTK C481G or BTK C481W; preferably, the mutant BTK kinase is BTK C481S; preferably, the mutant BTK kinase is BTK V416L, BTK A428D, BTK M437R, BTK T474I or BTK L528W; preferably, the mutant BTK kinase is BTK T474I or BTK L528W.

[0015] More specifically, the BTK-mediated diseases described in this invention are selected from: allergic diseases, autoimmune diseases, inflammatory diseases, or cancer.

[0016] More specifically, the BTK-mediated diseases described in this invention are B-cell proliferative disorders, selected from chronic lymphocytic lymphoma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, acute lymphocytic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic myeloid monoglobulin leukemia, chronic neutrophilic leukemia, acute undifferentiated leukemia, anaplastic large cell lymphoma, prolymphocytic leukemia, juvenile myelomonocytic leukemia, adult T-cell leukemia, acute myeloid leukemia with trilineage myelodysplastic syndrome, mixed phenotype leukemia, myelodysplastic syndrome, myeloproliferative disorders, marginal zone lymphoma, or Waldenström macroglobulinemia.

[0017] More specifically, the BTK-mediated disease described in this invention is multiple myeloma (MM).

[0018] Other objects and advantages of the present invention will become apparent to those skilled in the art from the following detailed description, embodiments, and claims.

[0019] definition Chemical definition The definitions of specific functional groups and chemical terms are described in more detail below.

[0020] When listing numerical ranges, each value and subranges within that range are included. For example, “C1-6 alkyl” includes C1, C2, C3, C4, C5, C6, C1-6, C1-5, C1-4, C1-3, C1-2, C2-6, C2-5, C2-4, C2-3, C3-6, C3-5, C3-4, C4-6, C4-5, and C5-6 alkyl.

[0021] "C1-6 alkyl" refers to a straight-chain or branched saturated hydrocarbon group having 1 to 6 carbon atoms, also referred to herein as "lower alkyl". In some embodiments, C1-4 alkyl is preferred; in some embodiments, C1-3 alkyl is preferred. Examples of the alkyl group include, but are not limited to: methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3-pentyl (C5), pentyl (C5), neopentyl (C5), 3-methyl-2-butyl (C5), tert-pentyl (C5), and n-hexyl (C6). Regardless of whether the alkyl group is modified with "substituted", each alkyl group is optionally substituted independently, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, with suitable substituents defined below.

[0022] "C1-6 alkyl" refers to a divalent group formed by removing one hydrogen atom from a "C1-6 alkyl" group.

[0023] "Halogen" or "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), and iodine (I). In some embodiments, the halogen group is F, Cl, or Br. In some embodiments, the halogen group is F or Cl. In some embodiments, the halogen group is F. Therefore, "C1-6 haloalkyl" and "C1-3 haloalkyl" refer to the aforementioned "C1-6 alkyl" and "C1-3 alkyl" respectively, which are substituted with one or more halogen groups. In some embodiments, C1-4 haloalkyl is preferred, and more preferably C1-2 haloalkyl. Exemplary haloalkyl groups include, but are not limited to: -CF3, -CH2F, -CHF2, -CHFCH2F, -CH2CHF2, -CF2CF3, -CCl3, -CH2Cl, -CHCl2, 2,2,2-trifluoro-1,1-dimethyl-ethyl, etc.

[0024] "C2-6 alkenyl" refers to a straight-chain or branched hydrocarbon group having 2 to 6 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, or 3 carbon-carbon double bonds). The one or more carbon-carbon double bonds can be internal (e.g., in 2-butenyl) or terminal (e.g., in 1-butenyl). In some embodiments, C2-4 alkenyl is preferred. Examples of the alkenyl group include, but are not limited to: vinyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-propen-2-yl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), pentenyl (C5), pentadienyl (C5), hexenyl (C6), and so on. Regardless of whether the alkenyl group is preceded by "substituted," each alkenyl group is optionally substituted independently, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, with suitable substituents defined below. In some embodiments, the alkenyl group is an unsubstituted C2-6 alkenyl group. In some embodiments, the alkenyl group is a substituted C2-6 alkenyl group.

[0025] "C2-6 ynyl" refers to a straight-chain or branched hydrocarbon group having 2 to 6 carbon atoms, one or more carbon-carbon triple bonds (e.g., 1, 2, or 3 carbon-carbon triple bonds), and optionally one or more carbon-carbon double bonds (e.g., 1, 2, or 3 carbon-carbon double bonds). In some embodiments, C2-4 ynyl is preferred. In some embodiments, the ynyl group does not contain any double bonds. One or more carbon triple bonds may be internal (e.g., in 2-butynyl) or terminal (e.g., in 1-butynyl). Examples of the ynyl group include, but are not limited to: ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), pentyynyl (C5), 3-methylbut-1-ynyl (C5), hexynyl (C6), and so on. Regardless of whether the alkynyl group is preceded by "substituted", each alkynyl group is optionally substituted independently, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, with suitable substituents defined below. In some embodiments, the alkynyl group is a substituted C2-6 alkynyl group.

[0026] "C3-10 cycloalkyl" refers to a non-aromatic cyclic hydrocarbon group having 3 to 10 ring carbon atoms and zero heteroatoms. In some embodiments, C3-8 cycloalkyl is preferred, C3-6 cycloalkyl is more preferred, and further preferred are C4-6 cycloalkyl and C5-6 cycloalkyl. Cycloalkyl also includes cyclic systems in which the aforementioned cycloalkyl ring is fused with one or more aryl or heteroaryl groups, wherein the connecting point is on the cycloalkyl ring, and in such cases, the number of carbons continues to indicate the number of carbons in the cycloalkyl system. Exemplary cycloalkyl groups include, but are not limited to: cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptanetrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptyl (C7), bicyclo[2.2.2]octyl (C8), cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C10), cyclodecenyl (C10), octahydro-1H-indenyl (C9), decahydronaphthyl (C10), spiro[4.5]decyl (C9), cyclo[4.5]decyl (C9), cyclo[2. ... 10), etc. Regardless of whether the cycloalkyl group is modified with "substituted", each of the cycloalkyl groups is independently optionally substituted, for example, 1 to 5 substituents, 1 to 3 substituents or 1 substituent, with suitable substituents defined as follows.

[0027] "3-12-membered heterocyclic group" refers to a group having a cyclic carbon atom and 1 to 4 cyclic heteroatoms, comprising a 3- to 12-membered non-aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon. In heterocyclic groups containing one or more nitrogen atoms, the linkage may be a carbon or nitrogen atom, provided the valence allows. In some embodiments, 3-10-membered heterocyclic groups are preferred, which are 3- to 10-membered non-aromatic ring systems having a cyclic carbon atom and 1 to 4 cyclic heteroatoms; in some embodiments, 5-10-membered heterocyclic groups are preferred, which are 5- to 10-membered non-aromatic ring systems having a cyclic carbon atom and 1 to 4 cyclic heteroatoms; in some embodiments, 3-7-membered heterocyclic groups are preferred, which are 3- to 7-membered non-aromatic ring systems having a cyclic carbon atom and 1 to 3 cyclic heteroatoms, especially 3- to 7-membered monocyclic non-aromatic ring systems (also called 3-7-membered monocyclic heterocyclic groups); in some embodiments, 4- A 7-membered heterocyclic group is preferred, which is a 4- to 7-membered non-aromatic ring system having a ring carbon atom and 1 to 3 ring heteroatoms; in some embodiments, a 3- to 6-membered heterocyclic group is preferred, which is a 3- to 6-membered non-aromatic ring system having a ring carbon atom and 1 to 3 ring heteroatoms; in some embodiments, a 4- to 6-membered heterocyclic group is preferred, which is a 4- to 6-membered non-aromatic ring system having a ring carbon atom and 1 to 3 ring heteroatoms; further preferably, a 5- to 6-membered heterocyclic group (e.g., a 5-membered or 6-membered heterocyclic group) is a 5- or 6-membered non-aromatic ring system having a ring carbon atom and 1 to 3 ring heteroatoms. The heterocyclic group also includes a ring system in which the aforementioned heterocyclic ring is fused and helicaled with one or more cycloalkyl, heterocyclic, aryl, or heteroaryl groups, wherein the connection point is on the heterocyclic ring; and in such cases, the number of ring members continues to represent the number of ring members in the heterocyclic ring system. Therefore, this application also includes "6-12 fused bicyclic heterocycles" and "8-10 fused bicyclic heterocycles," which represent heterocyclic groups in which two rings are fused together by sharing two adjacent atoms, having a total of 6-12 ring atoms and 8-10 ring atoms, respectively. This application also includes "7-10 spirocyclic heterocycles," which represent heterocyclic groups in which two rings are helically linked together by sharing one atom, having a total of 7-10 ring atoms. Regardless of whether the heterocyclic group is modified with "substituted," each of the heterocyclic groups may be independently and optionally substituted, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, with suitable substituents defined below.

[0028] Exemplary 3-membered heterocyclic groups containing one heteroatom include, but are not limited to: azircyclopropane, oxacyclopropane, and thiorenyl. Exemplary 4-membered heterocyclic groups containing one heteroatom include, but are not limited to: azircyclobutane, oxacyclobutane, and thiorenyl. Exemplary 5-membered heterocyclic groups containing one heteroatom include, but are not limited to: tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclic groups containing two heteroatoms include, but are not limited to: dioxacyclopentane, oxasμLfuranyl, dithiophenyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclic groups containing three heteroatoms include, but are not limited to: triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclic groups containing one heteroatom include, but are not limited to: piracetamyl, tetrahydropyranyl, dihydropyridyl, and thianyl. Exemplary 6-membered heterocyclic groups containing two heteroatoms include, but are not limited to: piracetamyl, morpholinyl, dithianyl, and dioxane. Exemplary 6-membered heterocyclic groups containing three heteroatoms include, but are not limited to: triazinanyl. Exemplary 7-membered heterocyclic groups containing one heteroatom include, but are not limited to: azirheptanyl, oxetaneheptyl, and thionylheptyl. Exemplary 8-membered heterocyclic groups containing one heteroatom include, but are not limited to: azirheptanyl, oxetaneheptyl, and thionylheptyl. Exemplary 5-membered heterocyclic groups fused with a C6 aryl ring (also referred to herein as 5,6-bicyclic heterocyclic groups) include, but are not limited to: dihydroindolyl, isodihydroindolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, benzoxazolinone, etc. Exemplary 6-membered heterocyclic groups fused with a C 6 aryl ring (also referring to 6,6-bicyclic heterocyclic groups herein) include, but are not limited to: tetrahydroquinolinyl, tetrahydroisoquinolinyl, etc.

[0029] "C 6-10 aryl" refers to a group ("C 6-10 aryl") having a monocyclic or polycyclic (e.g., bicyclic) 4n+2 aromatic ring system (e.g., having 6 or 10 shared π electrons arranged in a ring) providing 6-10 ring carbon atoms and zero heteroatoms in the aromatic ring system. In some embodiments, the aryl group has six ring carbon atoms ("C 6 aryl"; e.g., phenyl). In some embodiments, the aryl group has ten ring carbon atoms ("C 10 aryl"; e.g., naphthyl, e.g., 1-naphthyl and 2-naphthyl). "C 6-10 aryl" also includes ring systems in which the aforementioned aryl ring is fused with one or more carbocyclic or heterocyclic groups, wherein the atomic group or connecting point is on the aryl ring, in which case the number of carbon atoms continues to represent the number of carbon atoms in the aryl ring system. Regardless of whether the aryl group is modified with "substituted", each aryl group is independently and optionally substituted, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, with appropriate substituents defined as follows.

[0030] "5-10-membered heteroaryl" refers to a group comprising a 5- to 10-membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 shared π electrons arranged in a ring) having a cyclic carbon atom and 1-4 cyclic heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, preferred 5- to 6-membered heteroaryl (e.g., 5-membered or 6-membered heteroaryl) is a group comprising a 5- or 6-membered monocyclic 4n+2 aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms (e.g., having 6 shared π electrons arranged in a ring), wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In heteroaryl containing one or more nitrogen atoms, the bonding point can be a carbon or nitrogen atom, provided the valence allows. A heteroaryl bicyclic system may include one or more heteroatoms in one or both rings. The heteroaryl group also includes a ring system in which the aforementioned heteroaryl ring is fused with one or more carbocyclic or heterocyclic groups, and the connection point is on the heteroaryl ring, in which case the number of carbon atoms continues to represent the number of carbon atoms in the heteroaryl ring system. Regardless of whether the heteroaryl group is preceded by the word "substituted", each of the heteroaryl groups is optionally substituted independently, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, with suitable substituents defined as follows.

[0031] Exemplary 5-membered heteroaryl groups containing one heteroatom include, but are not limited to: pyrrole, furanyl, and thiophene. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, but are not limited to: imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, but are not limited to: triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, but are not limited to: tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, but are not limited to: pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, but are not limited to: pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing three or four heteroatoms include, but are not limited to: triazinyl and tetraazinyl, respectively. Exemplary 7-membered heteroaryl groups containing one heteroatom include, but are not limited to: azirheptatrienyl, oxacycloheptatrienyl, and thioheptatrienyl. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to: indolyl, isoindolyl, indazole, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzoimidazolyl, benzoxazolyl, benzoisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzoisothiazolyl, benzothiadiazolyl, indazinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to: naphthidyl, pteridinyl, quinolinyl, isoquinolinyl, zolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl.

[0032] Exemplary substituents on carbon atoms include, but are not limited to: halogens, -CN, -NO₂, -N₃, -SO₂H, -SO₃H, -OH, -OR aa, -ON(R bb)₂, -N(R bb)₂, -N(R bb)₃ +X⁻, -N(OR cc)R bb, -SH, -SR aa, -SSR cc, -C(=O)R aa, -CO₂⁻, -CHO, -C(OR cc)₂, -CO₂R aa, -OC(=O)R aa, -OCO₂R aa, -C(=O)N(R bb)₂, -OC(=O)N(R bb)₂, -NR bbC(=O)R aa, -NR bbCO₂R aa, -NR bbC(=O)N(R bb)₂, -C(=NR bb)R aa, -C(=NR bb)OR aa, -OC(=NR bb)R aa, -OC(=NR bb)OR aa, -C(=NR bb)N(R bb) 2, -OC(=NR bb)N(R bb) 2, -NR bbC(=NR bb)N(R bb) 2, -C(=O)NR bbSO 2R aa, -NR bbSO 2R aa, -SO 2N(R bb) 2, -SO 2R aa, -SO 2OR aa, -OSO 2R aa, -S(=O)R aa, -OS(=O)R aa, -Si(R aa) 3, -OSi(R aa) 3, -C(=S)N(R bb) 2, -C(=O)SR aa, -C(=S)SR aa, -SC(=S)SR aa, -SC(=O)SR aa, -OC(=O)SR aa, -SC(=O)OR aa, -SC(=O)R aa, -P(=O) 2R aa, -OP(=O) 2R aa, -P(=O)(R aa) 2, -OP(=O)(R aa) 2, -OP(=O)(OR cc) 2, -P(=O) 2N(R bb) 2. -OP(=O) 2N(R bb) 2. -P(=O)(NR bb) 2. -OP(=O)(NR bb) 2. -NR bbP(=O)(OR cc) 2. -NR bbP(=O)(NR bb) 2. -P(R cc) 2. -P(R cc) 3. -OP(R cc) 2. -OP(R cc) 3. -B(R aa) 2. -B(OR cc) 2. -BR aa(OR cc), alkyl, haloalkyl, alkenyl, ynyl, carbocyclic, heterocyclic, aryl, and heteroaryl, wherein,Each alkyl, alkenyl, ynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently substituted by 0, 1, 2, 3, 4, or 5 Rdd groups; Alternatively, the two hydrogen atoms on the carbon atom may be substituted with =O, =S, =NN(R bb) 2, =NNR bbC(=O)R aa, =NNR bbC(=O)OR aa, =NNR bbS(=O) 2R aa, =NR bb, or =NOR cc; Each of the Raa groups is independently selected from alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl groups, or two Raa groups are combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently substituted by 0, 1, 2, 3, 4, or 5 Rdd groups; Each of Rbb is independently selected from: hydrogen, -OH, -ORaa, -N(Rcc)2, -CN, -C(=O)Raa, -C(=O)N(Rcc)2, -CO2Raa, -SO2Rcc, -C(=NRcc)ORaa, -C(=NRcc)N(Rcc)2, -SO2Rcc, -SO2ORcc, -SORaa, -C(=S)N(Rcc)2, -C(=O)SRcc, -C(=S)SRcc, -P(=O)2Raa, -P(=O)(Raa)2, -P(=O)2N(Rcc)2, -P(=O)(NRcc)2 2. Alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl groups, or two R bb groups combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently substituted by 0, 1, 2, 3, 4, or 5 R dd groups; Each of the Rcc groups is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl groups, or two Rcc groups are combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently substituted by 0, 1, 2, 3, 4, or 5 Rdd groups; Each of Rdd is independently selected from: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -ORee, -ON(Rff)2, -N(Rff)3 +X-, -N(ORee)Rff, -SH, -SRee, -SSRee, -C(=O)Ree, -CO2H, -CO2Ree, -OC(=O)Ree, -OCO2Ree, -C(=O)N(Rff)2, -OC(=O)N(Rff)2, -NRffC(=O)Ree, -NRffCO2Ree, -NRffC(=O)N(Rff)2, -C(=NRff)ORee, -OC(=NRff)Ree ee, -OC(=NR ff)OR ee, -C(=NR ff)N(R ff) 2, -OC(=NR ff)N(R ff) 2, -NR ffC(=NR ff)N(R ff) 2, -NR ffSO 2R ee, -SO 2N(R ff) 2, -SO 2R ee, -SO 2OR ee, -OSO 2R ee, -S(=O)R ee, -Si(R ee) 3, -OSi(R ee) 3, -C(=S)N(R ff) 2, -C(=O)SR ee, -C(=S)SR ee, -SC(=S)SR ee, -P(=O) 2R ee, -P(=O)(R ee) 2, -OP(=O)(R ee) 2. -OP(=O)(OR ee) 2. Alkyl, haloalkyl, alkenyl, ynyl, carbocyclic, heterocyclic, aryl, heteroaryl, wherein each alkyl, alkenyl, ynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently substituted by 0, 1, 2, 3, 4, or 5 Rgg groups, or two geminal Rdd substituents may combine to form =O or =S; Each of Ree is independently selected from alkyl, haloalkyl, alkenyl, ynyl, carbocyclic, aryl, heterocyclic, and heteroaryl groups, wherein each alkyl, alkenyl, ynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently substituted by 0, 1, 2, 3, 4, or 5 Rgg groups; Each of Rff groups is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl groups, or two Rff groups are combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently substituted by 0, 1, 2, 3, 4, or 5 Rgg groups; Each of Rgg independently represents: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OC1-6alkyl, -ON(C1-6alkyl)2, -N(C1-6alkyl)2 +X-, -NH(C1-6alkyl)2 +X-, -NH3 +X-, -N(OC1-6alkyl)(C1-6alkyl), -N(OH)(C1-6alkyl), -NH(OH), -SH, -SC1-6alkyl, -SS(C1-6alkyl), -C(=O)(C1-6alkyl), -CO2H, -CO2alkyl(C1-6alkyl), -OC(=O)(C1-6alkyl), -OCO2alkyl(C1-6alkyl). -C(=O)NH 2, -C(=O)N(C 1-6 alkyl) 2, -OC(=O)NH(C 1-6 alkyl), -NHC(=O)(C 1-6 alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -NHCO 2(C 1-6 alkyl), -NHC(=O)N(C 1-6 alkyl) 2, -NHC(=O)NH(C 1-6 alkyl), -NHC(=O)NH 2, -C(=NH)O(C 1-6 alkyl), -OC(=NH)(C 1-6 alkyl), -OC(=NH)OC 1-6 alkyl, -C(=NH)N(C 1-6 alkyl) 2, -C(=NH)NH(C 1-6 alkyl), -C(=NH)NH 2, -OC(=NH)N(C 1-6 alkyl) 2. -OC(NH)NH (C 1-6 alkyl), -OC(NH)NH 2, -NHC(NH)N (C 1-6 alkyl) 2, -NHC(=NH)NH 2, -NHSO 2 (C 1-6 alkyl), -SO 2N (C 1-6 alkyl) 2, -SO 2NH (C 1-6 alkyl), -SO 2NH 2, -SO 2C 1-6 alkyl, -SO 2OC 1-6 alkyl, -OSO 2C 1-6 alkyl, -SOC 1-6 alkyl, -Si (C 1-6 alkyl) 3, -OSi (C 1-6 alkyl) 3, -C(=S)N (C 1-6 alkyl) 2, C(=S)NH (C 1-6 alkyl), C(=S)NH 2, -C(=O)S (C 1-6 alkyl), -C(=S)SC 1-6 alkyl, -SC(=S)SC 1-6 alkyl, -P(=O) 2(C 1-6 alkyl), -P(=O)(C 1-6 alkyl) 2, -OP(=O)(C 1-6 alkyl) 2, -OP(=O)(OC 1-6 alkyl) 2, C 1-6 alkyl, C 1-6 haloalkyl, C 2-C 6 alkenyl, C2-C 6-alkynyl, C 3-C 7-carbocyclic, C 6-C 10-aryl, C 3-C 7-heterocyclic, C 5-C 10-heteroaryl; or two geminal R gg substituents may combine to form =O or =S; wherein, X- is a counterion.

[0033] Exemplary substituents on the nitrogen atom include, but are not limited to: hydrogen, -OH, -OR aa, -N(R cc) 2, -CN, -C(=O)R aa, -C(=O)N(R cc) 2, -CO 2R aa, -SO 2R aa, -C(=NR bb)R aa, -C(=NR cc)OR aa, -C(=NR cc)N(R cc) 2, -SO 2N(R cc) 2, -SO 2R cc, -SO 2OR cc, -SOR aa, -C(=S)N(R cc) 2, -C(=O)SR cc, -C(=S)SR cc, -P(=O) 2R aa, -P(=O)(R aa) 2, -P(=O) 2N(R cc) 2, -P(=O)(NR cc) 2. Alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl groups, or two Rcc groups attached to a nitrogen atom, combine to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently substituted by 0, 1, 2, 3, 4, or 5 Rdd groups, and wherein Raaa, Rbb, Rcc, and Rdd are as described above.

[0034] "Deuterated" or "D-substituted" refers to the substitution of one or more hydrogen atoms in a compound or group by deuterium; deuteration can be monosubstituted, disubstituted, polysubstituted, or total substituted. The terms "one or more deuterated" and "one or more deuterated" are used interchangeably.

[0035] "Non-deuterated compounds" refer to compounds containing a proportion of deuterium atoms that is no higher than the content of natural deuterium isotopes (0.015%).

[0036] The content of deuterium isotopes at the deuterated position is at least 0.015% greater than the content of natural deuterium isotopes, preferably greater than 30%, more preferably greater than 50%, more preferably greater than 75%, more preferably greater than 95%, and more preferably greater than 99%.

[0037] The term "pharmaceutically acceptable salt" refers to those salts that, within the bounds of reliable medical judgment, are suitable for contact with the tissues of humans and lower animals without excessive toxicity, irritation, allergic reactions, etc., and in proportion to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66:1-19. Pharmaceutically acceptable salts of the compounds of this invention include salts derived from suitable inorganic and organic acids and inorganic and organic alkalis. Examples of pharmaceutically acceptable, non-toxic acid addition salts are salts formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or salts formed with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid. Salts formed using methods conventional in the art are also included, such as ion exchange methods. Other pharmaceutically acceptable salts include: adipic acid salts, alginate salts, ascorbate salts, aspartate salts, benzenesulfonate salts, benzoate salts, bisulfate salts, borate salts, butyrate salts, camphorate salts, camphor sulfonate salts, citrate salts, cyclopentylpropionate salts, diglucuronate salts, dodecyl sulfate salts, ethanesulfonate salts, formate salts, fumarate salts, gluconate salts, glyceryl phosphate salts, glucuronate salts, hemisulfate salts, heptarate salts, hexanoate salts, hydroiodate salts, 2-hydroxy-ethanesulfonate salts, lactobionate salts, lactate salts, laurate salts, lauryl sulfate salts, malate salts, maleate salts, malonate salts, methanesulfonate salts, 2-naphthalenesulfonate salts, nicotinate salts, nitrate salts, oleate salts, oxalate salts, palmitate salts, dihydroxynaphthalate salts, pectinate salts, persulfate salts, 3-phenylpropionate salts, phosphate salts, picrate salts, p-pentanoate salts, propionate salts, stearate salts, succinate salts, sulfate salts, tartrate salts, thiocyanate salts, p-toluenesulfonate salts, undecanoate salts, valerate salts, etc. Pharmaceutically acceptable salts derived from suitable alkalis include alkali metals, alkaline earth metals, ammonium, and N+(C1-4 alkyl)4 salts. Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and so on. Other pharmaceutically acceptable salts, if appropriate, include non-toxic ammonium salts, quaternary ammonium salts, and amine cations that form with counterions such as halide, hydroxide, carboxyl, sulfate, phosphate, nitrate, lower alkyl sulfonates, and aryl sulfonates.

[0038] The term "subject" in the administration includes, but is not limited to: humans (i.e., men or women of any age group, e.g., pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults, or older adults)) and / or non-human animals, such as mammals, e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. The terms "human," "patient," and "subject" are used interchangeably herein.

[0039] The terms “disease,” “disorder,” and “symptom” are used interchangeably in this article.

[0040] Unless otherwise stated, the term “treatment” as used herein includes effects that occur when a subject has a specific disease, disorder, or condition, which reduce the severity of the disease, disorder, or condition, or delay or slow the development of the disease, disorder, or condition (“therapeutic treatment”), and also includes effects that occur before a subject begins to have a specific disease, disorder, or condition (“preventive treatment”).

[0041] The term "combination" and related terms refer to the simultaneous or sequential administration of the therapeutic agents of the present invention. For example, the compounds of the present invention may be administered simultaneously or sequentially with another therapeutic agent in separate unit dosage forms, or simultaneously with another therapeutic agent in a single unit dosage form. Simple Explanation of the Diagram

[0042] none. Implementation

[0043] compound

[0044] In this document, “compound of the present invention” refers to a compound of formula (I) (including subsets thereof), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0045] In one embodiment, the invention relates to a compound of formula (A), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate, or solvate thereof: (A) in, Ring A is a benzene ring or a 5-6 membered heteroaromatic ring; X1 is N, CD, or CH; X2 is either N or CR2; R1 is H, D, halogen, -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -NRbRc, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRbRc, -ORa, -OC(O)Ra, -OC(O)NRbRc, -NRaS(O)2Rb, -S(O)2NRbRc, -S(O)Ra, -S(O)2Ra, -P(=O)RbRc, -OP(=O)RbRc, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C2-6 alkyne, C3-6 cycloalkyl ... The 3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted with one or more R groups; Each of Ra, Rb, and Rc is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Rb and Rc together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R; R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R'; R3 and R4 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rs and Rt are independently H, D, halogen, -ORa, -NRbRc, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; m can be 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; Each R is independent of: 1)H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, -C1-6 alkyl-C3-6 cycloalkyl, -C1-6 alkyl-3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) Two Rs on the same atom or two adjacent atoms, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12-membered heterocyclic group, a C6-10 aryl, or a 5-10-membered heteroaryl, wherein said group is optionally substituted by one or more R''s; Each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C 6-10 aryl or 5-10 heteroaryl, or two R' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each R”' is independently substituted with H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl is optionally substituted with one or more D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl. Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0046] In another embodiment, the invention relates to compounds of formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof: (I) in, X1 is N, CD, or CH; X2 is either N or CR2; R1 is H, D, halogen, -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -NRbRc, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRbRc, -ORa, -OC(O)Ra, -OC(O)NRbRc, -NRaS(O)2Rb, -S(O)2NRbRc, -S(O)Ra, -S(O)2Ra, -P(=O)RbRc, -OP(=O)RbRc, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C2-6 alkyne, C3-6 cycloalkyl ... The 3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted with one or more R groups; Each of Ra, Rb, and Rc is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Rb and Rc together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R; R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R'; R3 and R4 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rs and Rt are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; m can be 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; Each R is independent of: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) Two Rs on the same atom or two adjacent atoms, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12-membered heterocyclic group, a C6-10 aryl, or a 5-10-membered heteroaryl, wherein said group is optionally substituted by one or more R''s; Each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C 6-10 aryl or 5-10 heteroaryl, or two R' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0047] Ring A In one embodiment, ring A is a benzene ring; in another embodiment, ring A is a 5-6 membered heteroaromatic ring, such as a 6-membered heteroaromatic ring, such as a pyridine ring.

[0048] X 1 In one implementation, X1 is N; in another implementation, X1 is CH; in yet another implementation, X1 is CD.

[0049] X 2 and R 2 In one implementation, X2 is N; in another implementation, X2 is CR2. In one specific embodiment, X2 is CR2, and R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted by one or more R'; in another specific embodiment, X2 is CR2, and R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the ... 1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C6-10 aryl, or 5-10-membered heteroaryl are optionally substituted by one or more R'; in another specific embodiment, X2 is CR2, and wherein R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered monocyclic heterocyclic, 6-12-membered fused bicyclic heterocyclic, 7-10-membered spirocyclic heterocyclic, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered monocyclic heterocyclic, 6-12-membered fused bicyclic heterocyclic, 7-10-membered spirocyclic heterocyclic, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R'; in another specific embodiment, X 2 is CR 2, and wherein R 2 is H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered monocyclic heterocyclic group, C6-10 aryl or 5-10 membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered monocyclic heterocyclic group, C6-10 aryl and 5-10 membered heteroaryl are optionally substituted by one or more R'. In a more specific embodiment, X2 is CR2, and wherein R2 is H, D, halogen, methyl, -CHF2, ethyl, isopropyl, , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or The aforementioned groups are optionally substituted with one or more D atoms until complete deuteration; preferably H, D, halogen, methyl, -CHF2, ethyl, isopropyl, , , , , , , , , , , , , , , , , or The aforementioned groups are optionally replaced by one or more D atoms until complete deuteration; preferably H, D, methyl, or -CHF2. , , , , , , , , , , , or The aforementioned groups are optionally substituted by one or more D groups until fully deuterated; preferably H, D, methyl, -CHF2, , , , The aforementioned groups are optionally substituted by one or more D groups until fully deuterated; preferably H, D, -CHF2, or The above-mentioned groups are optionally substituted by one or more D groups until fully deuterated; preferably H; preferably -CHF2; preferably... The aforementioned groups are optionally replaced by one or more D groups until fully deuterated.

[0050] R 1 In one embodiment, R1 is H, D, halogen, -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -NRbRc, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRbRc, -ORa, -OC(O)Ra, -OC(O)NRbRc, -NRaS(O)2Rb, -S(O)2NRbRc, -S(O)Ra, -S(O)2Ra, -P(=O)RbRc, -OP(=O)RbRc, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, 1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more R; in another embodiment, R1 is H, D, halogen, -C(O)NRbRc, C6-10 aryl, or 5-10 heteroaryl, wherein the C6-10 aryl and 5-10 heteroaryl are optionally substituted with one or more R; in another embodiment, R1 is H; in another embodiment, R1 is C6-10 aryl or 5-10 heteroaryl, wherein the C6-10 aryl and 5-10 heteroaryl are optionally substituted with one or more R; in another embodiment, R1 is 5-10 heteroaryl, wherein the 5-10 heteroaryl is optionally substituted with one or more R. In another embodiment, R1 is a 5- or 6-membered heteroaryl group, wherein the 5- or 6-membered heteroaryl group is optionally substituted by one or more R groups. In one specific implementation scheme, R1 is 1) H; or 2) Where Y1 is N or CR; or 3) ;or 4) Where Y2 is O or S; or 5) Where Y3 is N, CH, or CD; or 6) , or Where Y5 and Y6 are independently N or C and at least one of Y5 and Y6 is N, and W1, W2 or W3 are independently N or CR. This indicates a single or double bond, provided that the double ring containing Y3, Y4, Y5, Y6, W1, W2, and W3 is an aromatic ring; or 7) , or Where Y7 and Y8 are independently N or C and at least one of Y7 and Y8 is N, Y9 is N, CH or CD, and W4, W5 and W6 are independently N or CR. It indicates a single or double bond, provided that the double ring containing Y3, Y7, Y8, Y9, W4, W5, and W6 is an aromatic ring. In another specific implementation, R1 is 1) H; or 2) Where Y1 and Y2 are independently N or CR; or 3) ;or 4) Where Y3 is O or S; or 5) , or , where Z1, Z2, Z3 and Z4 are independently N or CR. In one specific implementation scheme, R1 represents H, D, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or In which the aforementioned clusters are replaced by one or more Rs; preferably, 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , or The above-mentioned groups are optionally replaced by one or more R; preferably, , , , , , , , , , , , , , , , , , , or The above-mentioned groups are optionally replaced by one or more R; preferably H.

[0051] R3 and R4 In one embodiment, R3 and R4 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; in another embodiment, R3 and R4 are independently H, D, or halogen; in another embodiment, R3 and R4 are independently H, D, or F; in another embodiment, R3 and R4 are independently H or D; in another embodiment, R3 and R4 are independently H; in yet another embodiment, R3 and R4 are independently D.

[0052] R5 and R6 In one embodiment, R5 is a halogen; in another embodiment, R5 is F. In one embodiment, R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; in another embodiment, R6 is a C1-3 alkyl or C1-3 haloalkyl, wherein the C1-3 alkyl and C1-3 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; in another embodiment, R6 is methyl, CD3, ethyl, isopropyl, CHF2, CH2F, or CF3; in another embodiment, R6 is methyl, CF3, or CD3. In yet another embodiment, R6 is methyl or CD3.

[0053] R s and m In one embodiment, Rs is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; in another embodiment, Rs is H, D, halogen, C1-3 alkyl, or C1-3 haloalkyl, wherein the C1-3 alkyl and C1-3 haloalkyl are optionally substituted with one or more D until fully deuterated; in another embodiment, Rs is H, D, or halogen; in another embodiment, Rs is H, D, or F; in another embodiment, Rs is -ORa or -NRbRc; in another embodiment, Rs is -ORa. In one implementation, m is 0, 1, 2, or 3; in another implementation, m is 0, 1, or 2; in another implementation, m is 0 or 1; in another implementation, m is 0; in another implementation, m is 1; in another implementation, m is 2; in another implementation, m is 3. In one embodiment, m is 1, and Rs is H, D, F, methyl, CD3, or CF3; in another embodiment, m is 1, and Rs is H, D, F, methyl, or CD3; in yet another embodiment, m is 1, and Rs is H, D, or F; in yet another embodiment, m is 1, and Rs is methyl or CD3.

[0054] R t and n In one embodiment, Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; in another embodiment, Rt is H, D, halogen, C1-3 alkyl, or C1-3 haloalkyl, wherein the C1-3 alkyl and C1-3 haloalkyl are optionally substituted with one or more D until fully deuterated; in another embodiment, Rt is H, D, halogen, or C1-3 alkyl, wherein the C1-3 alkyl is optionally substituted with one or more D until fully deuterated; in another embodiment, Rt is H, D, or halogen; in another embodiment, Rt is H, D, or F; in another embodiment, Rt is -ORa or -NRbRc; in another embodiment, Rt is -ORa. In one implementation, n is 0, 1, 2, 3, or 4; in another implementation, n is 0, 1, 2, or 3; in another implementation, n is 0, 1, or 2; in another implementation, n is 0 or 1; in another implementation, n is 0; in another implementation, n is 1; in another implementation, n is 2; in another implementation, n is 3; in another implementation, n is 4. In one embodiment, n is 1, and Rt is H, D, F, methyl, CD3, or CF3; in another embodiment, n is 1, and Rt is H, D, F, methyl, or CD3; in yet another embodiment, n is 1, and Rt is H, D, or F; in yet another embodiment, n is 1, and Rt is methyl or CD3.

[0055] R In one implementation, each R is independently for 1)H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, -C1-6 alkyl-C3-6 cycloalkyl, -C1-6 alkyl-3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) Two Rs on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, a 3-12 heterocyclic group, a C6-10 aryl or a 5-10 heteroaryl group, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1) H, D, halogens, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR dC(O)R e, -OR d, -S(O) 2R d or -P(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein said group is optionally substituted by one or more R''; or 3) Two Rs on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, a 3-12 heterocyclic group, a C6-10 aryl or a 5-10 heteroaryl group, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1) H, D, halogens, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR dC(O)R e, -OR d, -S(O) 2R d or -P(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein said group is optionally substituted by one or more R''; or 3) Two Rs on two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, a 3-7 member monocyclic heterocyclic group, a 6-12 member fused bicyclic heterocyclic group, a 7-10 member spirocyclic heterocyclic group, a C6-10 aryl group, or a 5-10 member heteroaryl group, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1)H, D, halogen, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR dC(O)R e, -OR d, -S(O) 2R d; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein said group is optionally substituted by one or more R''; or 3) Two Rs on two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, a C6-10 aryl or a 5-10 membered heteroaryl, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1)H, D, halogen, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR dC(O)R e, -OR d, -S(O) 2R d; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein said group is optionally substituted by one or more R''; or 3) Two Rs on two adjacent atoms together with the atoms they are attached to form a 3-7 member monocyclic heterocyclic group, a 6-12 member fused bicyclic heterocyclic group, or a 5-10 member heteroaryl group, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1) H, D, or halogens; or 2) C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, or 5-6 membered heterocyclic group, wherein said group is optionally substituted by one or more R''; or 3) Two Rs on two adjacent atoms together with the atoms they are attached to form a 5-10 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1) H, D, or halogens; or 2) C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, or 5-6 membered heterocyclic group, wherein said group is optionally substituted by one or more R''; or 3) Two Rs on two adjacent atoms together with the atoms they are attached to form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1) H, D, or halogens; or 2) C1-6 alkyl, C1-6 haloalkyl, or 5-6 membered heterocyclic group, wherein said group is optionally substituted by one or more R''; or 3) Two Rs on two adjacent atoms together with the atoms they are attached to form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1) H, D, or halogens; or 2) C1-6 alkyl or C1-6 haloalkyl, wherein the group is optionally substituted by one or more R''; or 3) Two Rs on two adjacent atoms together with the atoms they are attached to form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the group is optionally substituted by one or more R's. In another implementation, each R is independently for 1) H or D; or 2) Me, CHF2, CH2CF3, or pirimidinyl, wherein said group is optionally substituted by one or more R's; or 3) Two Rs on two adjacent atoms together with the atoms they are attached to form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the group is optionally substituted by one or more R's.

[0056] R' In one embodiment, each R' is independently H, D, halogen, oxo, -C(O)Rd, -C(O)ORd, -C(O)NR eRf, -NR eRf, -NR dC(O)Re, -NR dC(O)ORe, -NR dC(O)NR eRf, -ORd, -OC(O)Rd, -OC(O)NR eRf, -NR dS(O)2Re, -S(O)2NR eRf, -S(O)Rd, -S(O)2Rd, -P(=O)R eRf, -OP(=O)R eRf, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R' on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''. In another embodiment, each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl or 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R''s. In another embodiment, each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, or -C(O)NR eR f. In another implementation, each R' is independently H, D, or a halogen. In another implementation, each R' is independently H or D.

[0057] Ra, Rb, and Rc In one embodiment, each Ra, Rb, and Rc is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rb and Rc together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted by one or more Rs. In another embodiment, each Ra, Rb, and Rc is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl are optionally substituted with one or more R. In another embodiment, each Ra, Rb, and Rc is independently an H or C3-6 cycloalkyl group, wherein the C3-6 cycloalkyl group is optionally substituted with one or more R groups.

[0058] Rd, Re and Rf In one embodiment, each Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted by one or more R''s. In another embodiment, each Rd, Re, and Rf is independently H, C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, or C6-10 aryl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, and C6-10 aryl groups are optionally substituted by one or more R''. In another embodiment, each Rd, Re, and Rf is independently H, a C1-6 alkyl, a C3-6 cycloalkyl, or a 3-7 membered heterocyclic group, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”.

[0059] R” In one embodiment, each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more Ds until fully deuterated. In another embodiment, each R” is independently H, D, -C(O)ORg, -C(O)NRhRj, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl or 3-7 heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl or 3-7 heterocyclic group; wherein the C1-6 alkyl and 3-7 heterocyclic groups are optionally substituted by one or more D until fully deuterated. In another implementation, R” is replaced by one or more R”'.

[0060] R”' In one embodiment, each R”' is independently H; in one embodiment, each R”' is independently D; in one embodiment, each R”' is independently halogen; in one embodiment, each R”' is independently C1-6 alkyl; in one embodiment, each R”' is independently C1-6 haloalkyl; in one embodiment, each R”' is independently C3-6 cycloalkyl; in one embodiment, each R”' is independently 3-7-membered heterocyclic; in one embodiment, each R”' is independently C6-10 aryl; in one embodiment, each R”' is independently substituted with 5-10-membered heteroaryl; in one embodiment, each R”' is substituted by one or more D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C6-10 aryl, or 5-10-membered heteroaryl.

[0061] Rg, Rh, and Rj In one embodiment, H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached, form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more Ds until fully deuterated. In another embodiment, each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more Ds until fully deuterated. In another embodiment, each Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated. Any technical solution or any combination thereof in any of the above specific embodiments can be combined with any technical solution or any combination thereof in other specific embodiments. For example, any technical solution or any combination thereof of X1, X2 and R2, R1, R3 and R4, R5 and R6, Rs and m, Rt and n, R, R', R”, Rd, Re and Rf, Rg, Rh and Rj. This invention aims to include combinations of all these technical solutions; due to space limitations, they will not be listed one by one.

[0062] In a more specific embodiment, the present invention relates to compounds of formula (A) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof: (A) in, Ring A is a benzene ring or a 5-6 membered heteroaromatic ring; X1 is N, CD, or CH; X2 is either N or CR2; R1 is H, D, halogen, -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -NRbRc, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRbRc, -ORa, -OC(O)Ra, -OC(O)NRbRc, -NRaS(O)2Rb, -S(O)2NRbRc, -S(O)Ra, -S(O)2Ra, -P(=O)RbRc, -OP(=O)RbRc, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C2-6 alkyne, C3-6 cycloalkyl ... The 3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted with one or more R groups; Each of Ra, Rb, and Rc is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Rb and Rc together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R; R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R'; R3 and R4 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rs and Rt are independently H, D, halogen, -ORa, -NRbRc, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; m can be 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; Each R is independent of: 1)H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, -C1-6 alkyl-C3-6 cycloalkyl, -C1-6 alkyl-3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) Two Rs on the same atom or two adjacent atoms, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12-membered heterocyclic group, a C6-10 aryl, or a 5-10-membered heteroaryl, wherein said group is optionally substituted by one or more R''s; Each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C 6-10 aryl or 5-10 heteroaryl, or two R' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each R”' is independently substituted with H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl is optionally substituted with one or more D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl. Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0063] In a more specific embodiment, the present invention relates to compounds of formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof: (I) in, X1 is N, CD, or CH; X2 is either N or CR2; R1 is H, D, halogen, -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -NRbRc, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRbRc, -ORa, -OC(O)Ra, -OC(O)NRbRc, -NRaS(O)2Rb, -S(O)2NRbRc, -S(O)Ra, -S(O)2Ra, -P(=O)RbRc, -OP(=O)RbRc, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C2-6 alkyne, C3-6 cycloalkyl ... The 3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted with one or more R groups; Each of Ra, Rb, and Rc is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Rb and Rc together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R; R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R'; R3 and R4 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rs and Rt are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; m can be 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; Each R is independent of: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) Two Rs on the same atom or two adjacent atoms, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12-membered heterocyclic group, a C6-10 aryl, or a 5-10-membered heteroaryl, wherein said group is optionally substituted by one or more R''s; Each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C 6-10 aryl or 5-10 heteroaryl, or two R' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated. In a more specific embodiment, the present invention relates to compounds of formula (I) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein R1 is an H, D, C6-10 aryl or a 5-10 heteroaryl, wherein the C6-10 aryl and the 5-10 heteroaryl are optionally substituted by one or more R; Preferably, R1 is H, D, , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , or The aforementioned groups are optionally substituted with one or more R groups; Preferably, R1 is , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or The aforementioned groups are optionally substituted with one or more R groups; Preferably, R1 is , , , , , , , , , , , , , , , , , , or The aforementioned groups are optionally substituted with one or more R groups; Preferably, R1 is H. In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I) above, or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, wherein R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered monocyclic heterocyclic group, 6-12 membered fused bicyclic heterocyclic group, 7-10 membered spirocyclic heterocyclic group, C6-10 aryl group, or 5-10 membered heteroaryl group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered monocyclic heterocyclic group, 6-12 membered fused bicyclic heterocyclic group, 7-10 membered spirocyclic heterocyclic group, C6-10 aryl group, and 5-10 membered heteroaryl group are optionally substituted by one or more R'; Preferably, R2 is H, D, halogen, methyl, -CHF2, ethyl, isopropyl, , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or In this process, the aforementioned groups are arbitrarily replaced by one or more D atoms until complete deuteration occurs; Preferably, R2 is H, D, halogen, methyl, -CHF2, ethyl, isopropyl, , , , , , , , , , , , , , , , , or The aforementioned groups are optionally substituted by one or more D groups until complete deuteration; Preferably, R2 is H, D, methyl, or -CHF2. , , , , , , , , , , , or The aforementioned groups are optionally substituted by one or more D groups until complete deuteration; Preferably, R2 is H, D, -CHF2 or The aforementioned groups are optionally substituted by one or more D groups until complete deuteration; Preferably, R2 is H or D; Preferably, R2 is -CHF2 or The aforementioned groups are optionally substituted by one or more D groups until complete deuteration; Preferably, R2 is The aforementioned groups are optionally replaced by one or more D groups until fully deuterated.

[0064] In a more specific embodiment, the present invention relates to the compound of formula (A) or formula (I) above, or its tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvates, wherein R 5 is F.

[0065] In a more specific embodiment, the present invention relates to the compound of formula (A) or formula (I) above, or its tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvates, wherein R6 is methyl or -CD3.

[0066] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, which are compounds of formula (II): (II) in, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y1 is either N or CR12; R10, R11, and R12 are independent of: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) R11 and R12, together with the atoms they are attached to, form a C3-6 cycloalkyl group, which is optionally substituted by one or more R's; or 4) R10 and R11 or R11 and R12, together with the atoms they are attached to, form a 3-12 membered heterocyclic group or a 5-10 membered heteroaryl group, wherein said group is optionally substituted by one or more R''; or 5) R11 and R12, together with the atoms they are attached to, form a C6-10 aryl group, which may optionally be substituted by one or more R''s; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated. In a more specific embodiment, the present invention relates to compounds of formula (II) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y1 is either N or CR12; R10 is H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; R11 and R12 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Alternatively, R11 and R12, together with the atoms they are attached to, form a C3-6 cycloalkyl group, which is optionally substituted with one or more R's; or R10 and R11 or R11 and R12, together with the atoms they are attached to, form a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, or a 5-10 membered heteroaryl group, wherein said group is optionally substituted by one or more R's; or R11 and R12, together with the atoms they are attached to, form a C6-10 aryl group, which may optionally be substituted by one or more R''s. Each R” is independently a D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated. In a more specific embodiment, the present invention relates to compounds of formula (II) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H. R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y1 is either N or CR12; R10 is H, a C1-6 alkyl, or a C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R''; preferably, R10 is H, a C1-3 alkyl, or a C1-3 haloalkyl, wherein the C1-3 alkyl and C1-3 haloalkyl are optionally substituted by one or more D'', up to complete deuteration; R11 and R12 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms up to complete deuteration; preferably, R11 and R12 are independently H or D. Alternatively, R11 and R12, together with the atoms they are attached to, form a C3-6 cycloalkyl group, optionally substituted with one or more R''s; more preferably, R11 and R12, together with the atoms they are attached to, form a cyclohexyl group, optionally substituted with one or more R''s; or R10 and R11, or R11 and R12, together with the atoms they are attached to, form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted by one or more R''; preferably, R10 and R11, or R11 and R12, together with the atoms they are attached to, form a 6 membered heterocyclic group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; or R10 and R11, or R11 and R12, together with the atoms they are attached to, form a 6-12 fused bicyclic heterocycle, optionally substituted by one or more R''; preferably, R10 and R11, or R11 and R12, together with the atoms they are attached to, form an 8-10 fused bicyclic heterocycle having one or two ring heteroatoms selected from N, optionally substituted by one or more R''; or R11 and R12, together with the atoms they are attached to, form a C6-10 aryl group, which is optionally substituted by one or more R''; preferably, R11 and R12, together with the atoms they are attached to, form a phenyl group, which is optionally substituted by one or more R''; or R10 and R11 or R11 and R12, together with the atoms they are attached to, form a 5-10 membered heteroaryl group, which is optionally substituted by one or more R''; preferably, R10 and R11 or R11 and R12, together with the atoms they are attached to, form a 5- or 6-membered heteroaryl group having one or two cyclic heteroatoms selected from N, wherein said group is optionally substituted by one or more R''; Each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated.

[0067] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, which are compounds of formula (II-1): (II-1) in, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y1 is N, CH, or CD; R10 and R11, together with the atoms they are attached to, form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted by one or more R''; preferably, R10 and R11, together with the atoms they are attached to, form a 6 membered heterocyclic group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; or R10 and R11, together with the atoms they are attached to, form a 6-12 member fused bicyclic heterocycle, optionally substituted by one or more R''; preferably, R10 and R11, together with the atoms they are attached to, form an 8-10 member fused bicyclic heterocycle having one or two ring heteroatoms selected from N, optionally substituted by one or more R''; or R10 and R11, together with the atoms they are attached to, form a 5-10 membered heteroaryl group, which is optionally substituted by one or more R''; preferably, R10 and R11, together with the atoms they are attached to, form a 6 membered heteroaryl group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; Each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated. In a more specific embodiment, the present invention relates to compounds of formula (II-1) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, R 5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y1 is N, CH, or CD; R10 and R11, together with the atoms they are attached to, form the following groups: , , , , , , , , , or The group is optionally substituted with one or more D atoms until fully deuterated; Preferably, R10 and R11, together with the atoms they are attached to, form the following groups: , , , , or The group thereon is optionally replaced by one or more D atoms, up to complete deuteration.

[0068] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, which are compounds of formula (III): (III) in, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R13, R14, and R15 are independent of: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) R13 and R14 or R13 and R15 together with the atoms they are attached to form a 3-12 membered heterocyclic group or a 5-10 membered heteroaryl group, wherein said group is optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0069] In a more specific embodiment, the present invention relates to compounds of formula (III) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R 13 is H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; R14 and R15 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms up to complete deuteration; Alternatively, R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, or a 5-10 membered heteroaryl group, wherein said group is optionally substituted by one or more R''s. Each R” is independently a D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated.

[0070] In a more specific embodiment, the present invention relates to compounds of formula (III) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H. R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; R13 is H, a C1-6 alkyl, a C1-6 haloalkyl, or a 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R13 is H, a C1-3 alkyl, C1-3 haloalkyl, or a 6 membered heterocyclic group having one or two ring heteroatoms selected from N, wherein the C1-3 alkyl, C1-3 haloalkyl, and 6 membered heterocyclic group are optionally substituted by one or more R”; R14 and R15 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms up to complete deuteration; preferably, R14 and R15 are independently H or D. Alternatively, R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted by one or more R''; preferably, R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 6 membered heterocyclic group having one or two ring heteroatoms selected from N, which is optionally substituted by one or more R''; or R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 6-12 fused bicyclic heterocycle, optionally substituted by one or more R''; preferably, R13 and R14 or R13 and R15, together with the atoms they are attached to, form an 8-10 fused bicyclic heterocycle having one or two ring heteroatoms selected from N, optionally substituted by one or more R''; or R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 5-10 membered heteroaryl group, which is optionally substituted by one or more R''; preferably, R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 6 membered heteroaryl group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; Each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated.

[0071] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, which are compounds of formula (III-1): (III-1) in, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted by one or more R''; preferably, R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 6 membered heterocyclic group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; or R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 6-12 fused bicyclic heterocycle, optionally substituted by one or more R''; preferably, R13 and R14 or R13 and R15, together with the atoms they are attached to, form an 8-10 fused bicyclic heterocycle having one or two ring heteroatoms selected from N, optionally substituted by one or more R''; or R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 5-10 membered heteroaryl group, which is optionally substituted by one or more R''; preferably, R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 6 membered heteroaryl group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; Each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated.

[0072] In a more specific embodiment, the present invention relates to the compound of formula (III-1) above, or its tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvates, wherein, R 5 is F; R6 is methyl or -CD3; Rt is H, D, or F; R13 and R14 or R13 and R15 together with the atoms they are bonded to form The group thereon is optionally replaced by one or more D atoms, up to complete deuteration.

[0073] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, which are compounds of formula (IV): (IV) in, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y2 is either O or S; R16 and R17 are independent for 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) R16 and R17, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12 membered heterocyclic group, a C6-10 aryl group, or a 5-10 membered heteroaryl group, wherein said group is optionally substituted by one or more R's; or Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0074] In a more specific embodiment, the present invention relates to compounds of formula (IV) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y2 is either O or S; R16 and R17 are independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic groups, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic groups are optionally substituted by one or more R''. Alternatively, R16 and R17, together with the atoms they are attached to, form a C3-6 cycloalkyl group, which may optionally be substituted with one or more R's; or R16 and R17, together with the atoms they are attached to, form 3-7 membered monocyclic heterocyclic groups, which are optionally substituted by one or more R's; or R16 and R17, together with the atoms they are attached to, form a 6-12 member fused bicyclic heterocycle, which is optionally substituted by one or more R's; or R16 and R17, together with the atoms they are attached to, form a C6-10 aryl group, which may optionally be substituted by one or more R's; or R16 and R17, together with the atoms they are attached to, form 5-10 heteroaryl groups, which may optionally be substituted by one or more R''. Each R” is independently a D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated.

[0075] In a more specific embodiment, the present invention relates to compounds of formula (IV) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H. R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y2 is either O or S; R16 and R17 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R''; preferably, R10 is H, D, C1-3 alkyl, or C1-3 haloalkyl, wherein the C1-3 alkyl and C1-3 haloalkyl are optionally substituted by one or more D', up to complete deuteration; Alternatively, R16 and R17, together with the atoms they are attached to, form a C3-6 cycloalkyl group, optionally substituted with one or more R''s; more preferably, R16 and R17, together with the atoms they are attached to, form a cyclohexyl group, optionally substituted with one or more R''s; or R16 and R17, together with the atoms they are attached to, form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form a 6 membered heterocyclic group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a 6-12 member fused bicyclic heterocycle, optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form an 8-10 member fused bicyclic heterocycle having one or two ring heteroatoms selected from N, optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a C6-10 aryl group, which is optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form a phenyl group, which is optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a 5-10 membered heteroaryl group, which is optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form a 6 membered heteroaryl group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; Each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated.

[0076] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, which are compounds of formula (IV-1): (IV-1) in, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y2 is either O or S; R16 and R17, together with the atoms they are attached to, form a C3-6 cycloalkyl group, which is optionally substituted by one or more R''s; preferably, R16 and R17, together with the atoms they are attached to, form a cyclohexyl group, which is optionally substituted by one or more R''s; or R16 and R17, together with the atoms they are attached to, form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form a 6 membered heterocyclic group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a 6-12 member fused bicyclic heterocycle, optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form an 8-10 member fused bicyclic heterocycle having one or two ring heteroatoms selected from N, optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a C6-10 aryl group, which is optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form a phenyl group, which is optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a 5-10 membered heteroaryl group, which is optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form a 6 membered heteroaryl group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; Each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated.

[0077] In a more specific embodiment, the present invention relates to the compound of formula (IV-1) above, or its tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvates, wherein, R 5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y2 is either O or S; R16 and R17, together with the atoms they are attached to, form the following groups: , or The group thereon is optionally replaced by one or more D atoms, up to complete deuteration.

[0078] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, which are compounds of formula (V): (V) in, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Y1 is either N or CR12; preferably, Y1 is N. Y2 is N or CR 13; R10 is H, C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, or 5-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, and 5-6 membered heterocyclic group are optionally substituted by one or more R"; R11, R12, and R13 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Alternatively, R10 and R11, together with the atoms they are attached to, form a 5-10 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-10 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; Wherein R” is H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -OR g, -OC(O)R g, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, or 4-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, and 4-6 membered heterocyclic group are optionally substituted with one or more D, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0079] In a more specific embodiment, the present invention relates to compounds of formula (V) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is CR2; R2 is H, D, or -CH(CH3)(CF3); R 5 is F; R 6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Y1 is either N or CR12; preferably, Y1 is N. Y2 is N or CR 13; R10 is H, Me, CHF2, CH2CF3, or pirimidinyl, which may optionally be substituted by one or more R''. R 11 is H, D, or Me; R12 and R13 are independently H or D; Alternatively, R10 and R11, together with the atoms they are attached to, form a 5-10 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-10 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; Where R” is Me, Et, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh or oxocyclic butyl; Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl.

[0080] In a more specific embodiment, the present invention relates to compounds of formula (V) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Y1 is either N or CR12; preferably, Y1 is N. Y2 is N or CR 13; R10 is H, C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, or 5-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, and 5-6 membered heterocyclic group are optionally substituted by one or more R"; R11, R12, and R13 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Alternatively, R10 and R11, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; Wherein R” is H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -OR g, -OC(O)R g, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, or 4-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, and 4-6 membered heterocyclic group are optionally substituted with one or more D, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0081] In a more specific embodiment, the present invention relates to compounds of formula (V) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Y1 is either N or CR12; preferably, Y1 is N. Y2 is N or CR 13; R10 is H, C1-6 alkyl, C1-6 haloalkyl, or 5-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 5-6 membered heterocyclic group are optionally substituted by one or more R"; R 11 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R12 and R13 are independently H, D, or halogens; Alternatively, R10 and R11, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; Wherein R” is H, D, halogen, -C(O)ORg, -C(O)NRhRj, C1-6 alkyl, C1-6 haloalkyl, or 4-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 4-6 membered heterocyclic group are optionally substituted with one or more D, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds until fully deuterated.

[0082] In a more specific embodiment, the present invention relates to compounds of formula (V) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is CR2; R2 is H, D, or -CH(CH3)(CF3); R 5 is F; R 6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Y1 is either N or CR12; preferably, Y1 is N. Y2 is N or CR 13; R10 is H, Me, CHF2, CH2CF3, or pirimidinyl, which may optionally be substituted by one or more R''. R 11 is H, D, or Me; R12 and R13 are independently H or D; Alternatively, R10 and R11, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; Where R” is Me, Et, -C(O)ORg, -C(O)NRhRj, or oxocyclic butyl; Each of Rg, Rh and Rj is independently H, D, C1-6 alkyl or C1-6 haloalkyl.

[0083] In a more specific embodiment, the present invention relates to compounds of formula (V) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Y1 is either N or CR12; preferably, Y1 is N. Y2 is N or CR 13; R10, R11, R12, and R13 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Alternatively, R10 and R11, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; Wherein R” is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated.

[0084] In a more specific embodiment, the present invention relates to compounds of formula (V) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Y1 is either N or CR12; preferably, Y1 is N. Y2 is N or CR 13; R 10 is H, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; R 11 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R12 and R13 are independently H, D, or halogens; Alternatively, R10 and R11, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; Wherein R” is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated.

[0085] In a more specific embodiment, the present invention relates to compounds of formula (V) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is CR2; R2 is H, D, or -CH(CH3)(CF3); R 5 is F; R 6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Y1 is either N or CR12; preferably, Y1 is N. Y2 is N or CR 13; R10 is H, Me, CHF2, or CH2CF3; R 11 is H, D, or Me; R12 and R13 are independently H or D; Alternatively, R10 and R11, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12, together with the atoms they are attached to, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by one or more R”; Where R” represents Me or Et.

[0086] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, which are compounds of formula (VI): (VI) in, X2 is either N or CR2; preferably, X2 is CR2. R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; R 10 is H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R12 and R13 are independently H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated.

[0087] In a more specific embodiment, the present invention relates to compounds of formula (VI) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is CR2; R2 is H, D, or -CH(CH3)(CF3); R 5 is F; R 6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; R10 is H, Me, CHF2, or CH2CF3; R12 and R13 are independently H or D.

[0088] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, which are compounds of formula (VII): (VII) in, X2 is either N or CR2; preferably, X2 is CR2. R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Y3 is either O or S; R10 and R11 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Alternatively, R10 and R11, together with the atoms they are attached to, form a C5-8 cycloalkyl, a 5-6 heterocyclic group, a C6-10 aryl group, or a 5-6 heteroaryl group, wherein the C5-8 cycloalkyl, 5-6 heterocyclic group, C6-10 aryl group, and 5-6 heteroaryl group are optionally substituted by one or more R''. Wherein R” is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated.

[0089] In a more specific embodiment, the present invention relates to compounds of formula (VII) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is CR2; R2 can be H, D, halogen, or -CH(CH3)(CF3); R 5 is F; R 6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Y3 is either O or S; R10 is H, Me, CHF2, or CH2CF3; R 11 is H or D; Alternatively, R10 and R11, together with the atoms they are attached to, form a C5-8 cycloalkyl, a 5-6 heterocyclic group, a C6-10 aryl group, or a 5-6 heteroaryl group, wherein the C5-8 cycloalkyl, 5-6 heterocyclic group, C6-10 aryl group, and 5-6 heteroaryl group are optionally substituted by one or more R''. Where R” represents Me or Et.

[0090] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, which are compounds of formula (VIII), (VIII-1), or (VIII-2): (VIII) (VIII-1) or (VIII-2) in, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, R2 is H or D. R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Z1 is N or CR 20; Z2 is N or CR 21; Z3 is N or CR 22; Z 4 is N or CR 23; R20, R22, and R23 are independently H, D, halogen, -OC(O)Rd, -NRdC(O)Re, -C(O)NReRf, -C(O)ORd, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated, and R20, R22, and R23 are independently optionally substituted with one or more R''. R 21 is H, D, halogen, -OR d, -NR eR f, -C(O)R d, -OC(O)R d, -NR dC(O)R e, -C(O)NR eR f, -C(O)OR d, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, and 4-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated, and R 21 is optionally substituted with one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-8 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-8 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted by one or more Ds up to complete deuteration, and are optionally substituted by one or more R''s. Wherein R” is H, D, halogen, -OR g, -NR hR j, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein R” is optionally substituted by one or more D, halogen, C1-6 alkyl, or C1-6 haloalkyl groups; Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0091] In a more specific embodiment, the present invention relates to compounds of formula (VIII), (VIII-1), or (VIII-2), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, wherein, X2 is CR2; R2 is H, D, F, Me, CHF2, CF3, or -CH(CH3)(CF3); preferably, R2 is H or D; R 5 is F; R 6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Z1 is N or CR 20; Z2 is N or CR 21; Z3 is N or CR 22; Z 4 is N or CR 23; R 20 is H or D; R21 is a H, D, F, Cl, Me, CHF2, CF3, CH2CF3, -C(OH)(CH3)2, -ORd, -NRdC(O)Re, -S(O)Rd, -S(O)2Rd, -P(=O)ReRf, or a 4-7 membered heterocyclic group, which may optionally be substituted by one or more R”. R 22 is H, D, -NR dC(O)R e or -C(O)NR eR f, which may optionally be replaced by one or more R”; R 23 is H or D; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, and 4-7 membered heterocyclic group is optionally substituted by one or more R”; Wherein R” is Me, Et, -ORg, -NRhRj or a 4-7 membered heterocyclic group, wherein R” is optionally substituted by one or more D, halogen, C1-6 alkyl or C1-6 haloalkyl groups; Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl.

[0092] In a more specific embodiment, the present invention relates to compounds of formula (VIII), (VIII-1), or (VIII-2), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, R2 is H or D. R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Z1 is N or CR 20; Z2 is N or CR 21; Z3 is N or CR 22; Z 4 is N or CR 23; R20, R22, and R23 are independently H, D, halogen, -OC(O)Rd, -NRdC(O)Re, -C(O)NReRf, -C(O)ORd, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated, and R20, R22, and R23 are independently optionally substituted with one or more R''. R 21 is H, D, halogen, -OR d, -NR eR f, -OC(O)R d, -NR dC(O)R e, -C(O)NR eR f, -C(O)OR d, -S(O)R d, -S(O)2R d, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, and 4-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated, and R 21 is optionally substituted with one or more R''; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-8 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-8 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted by one or more Ds up to complete deuteration, and are optionally substituted by one or more R''s. Wherein R” is H, D, halogen, -OR g, -NR hR j, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein R” is optionally substituted by one or more D, halogen, C1-6 alkyl, or C1-6 haloalkyl groups; Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0093] In a more specific embodiment, the present invention relates to compounds of formula (VIII), (VIII-1), or (VIII-2), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, wherein, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, R2 is H or D. R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3, or 4; Z1 is N or CR 20; Z2 is N or CR 21; Z3 is N or CR 22; Z 4 is N or CR 23; R20 and R23 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R 21 is H, D, halogen, -OR d, -NR dC(O)Re, -S(O)R d, -S(O) 2R d, C1-6 alkyl, C1-6 haloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 4-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated, and R 21 is optionally substituted with one or more R''; R 22 is H, D, -NR dC(O)R e or -C(O)NR eR f, which may optionally be replaced by one or more R”; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, and 4-7 membered heterocyclic group is optionally substituted by one or more R”; Wherein R” is H, D, halogen, -OR g, -NR hR j, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein R” is optionally substituted by one or more D, halogen, C1-6 alkyl, or C1-6 haloalkyl groups; Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more Ds up to complete deuteration.

[0094] In a more specific embodiment, the present invention relates to compounds of formula (VIII), (VIII-1), or (VIII-2), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, wherein, X2 is CR2; R2 is H, D, Me, CHF2 or -CH(CH3)(CF3); preferably, R2 is H or D; R 5 is F; R 6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Z1 is N or CR 20; Z2 is N or CR 21; Z3 is N or CR 22; Z 4 is N or CR 23; R 20 is H or D; R21 is an H, D, F, Cl, Me, CHF2, CF3, CH2CF3, -C(OH)(CH3)2, -ORd, -NRdC(O)Re, -S(O)Rd, -S(O)2Rd, or a 4-7 membered heterocyclic group, optionally substituted by one or more R”; R 22 is H, D, -NR dC(O)R e or -C(O)NR eR f, which may optionally be replaced by one or more R”; R 23 is H or D; Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, and 4-7 membered heterocyclic group is optionally substituted by one or more R”; Wherein R” is Me, Et, -ORg, -NRhRj or a 4-7 membered heterocyclic group, wherein R” is optionally substituted by one or more D, halogen, C1-6 alkyl or C1-6 haloalkyl groups; Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl.

[0095] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, which are compounds of formula (IX): (IX) in, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y 3 is N or CR 111; R18, R19, R110, and R111 are independent of: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12 membered heterocyclic group, a C6-10 aryl, or a 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R's; or Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the N atom to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more D atoms until fully deuterated.

[0096] In a more specific embodiment, the present invention relates to compounds of formula (IX) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y 3 is N or CR 111; R18 is H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; R 110 is H, D, halogen, -NR dC(O)Re, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R19 and R111 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Alternatively, R 18 and R 19, or R 18 and R 110, or R 110 and R 111, together with the atoms they are attached to, form a C 3-6 cycloalkyl, a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, a C 6-10 aryl, or a 5-10 membered heteroaryl, wherein said groups are optionally substituted by one or more R's; or Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0097] In a more specific embodiment, the present invention relates to compounds of formula (IX) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H. R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y 3 is N or CR 111; R 18 is H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R 18 is halogen, -C(O)NR eR f, -OR d, -S(O) 2R d, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; R 110 is H, D, halogen, -NR dC(O)Re, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, R 19 is H or D; R19 and R111 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms up to complete deuteration; preferably, R110 is H or D; Alternatively, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 3-7 member monocyclic heterocyclic group, optionally substituted with one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5- or 6-membered heterocyclic group having one or two cyclic heteroatoms selected from N, O, and S, wherein the group is optionally substituted with one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5-membered heterocyclic group having one or two cyclic heteroatoms selected from N, wherein the group is optionally substituted with one or more R''; or R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 6-12 fused bicyclic heterocycle, optionally substituted by one or more R''s; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form an 8-10 fused bicyclic heterocycle having 1-3 cyclic heteroatoms selected from N, O, and S, optionally substituted by one or more R''s; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form an 8-10 fused bicyclic heterocycle having 1 or 2 cyclic heteroatoms selected from N, optionally substituted by one or more R''s; or R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5-10 membered heteroaryl group, optionally substituted by one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5 or 6 membered heteroaryl group having 1-3 cyclic heteroatoms selected from N, O, and S, optionally substituted by one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5 membered heteroaryl group having 1-3 cyclic heteroatoms selected from N, O, and S, wherein said group is optionally substituted by one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R''... 111, together with the atoms they are attached to, form a 5-membered heteroaryl group having one or two selected from N-ring heteroatoms, wherein said group is optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0098] In a more specific embodiment, the present invention relates to compounds of formula (IX) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X 2 is CH; R 5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y 3 is N or CR 111; R 18 and R 19, or R 18 and R 110, or R 110 and R 111, together with the atoms they are attached to, form a 5-membered heteroaryl group having one or two N-ring heteroatoms, wherein said group is optionally substituted by one or more R''. Each R” is independently a D, halogen, C1-6 alkyl or C1-6 haloalkyl, or two R” on the same atom or two adjacent atoms together with the atoms to which they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl and 3-7 membered heterocyclic group are optionally substituted by one or more D until fully deuterated.

[0099] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, which are compounds of formula (IX-1): (IX-1) in, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y3 is N, CH, or CD; preferably, Y3 is N or CH. R 18 is H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R 18 is halogen, -C(O)NR eR f, -OR d, -S(O) 2R d, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0100] In a more specific embodiment, the present invention relates to compounds of formula (IX-1), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, R 5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y 3 is N or CH; R 18 is H, F, Cl, -CH 3, -CHF 2, -CF 3, -OCF 3, , , , , , , , , , , , , , , , , , , The group is optionally substituted with one or more D atoms until fully deuterated; Preferably, R 18 is F, Cl, -CH 3, -CHF 2, -CF 3, -OCF 3, , , , , , , , , , , , , , , , , The group is optionally substituted with one or more D atoms until fully deuterated; Preferably, R 18 is -CH 3, , , , , , , , , , , , or The group thereon is optionally replaced by one or more D atoms, up to complete deuteration.

[0101] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, which are compounds of formula (X): (X) in, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y3 represents N, CH, or CD; Y4 represents N, CH, or CD; Y5 and Y6 are independently N or C, and at least one of Y5 and Y6 is N; W1 is N or CR 112; W2 is N or CR 113; W 3 is N or CR 114; Indicates a single or double bond; This is predicated on the fact that the double ring containing Y3, Y4, Y5, Y6, W1, W2, and W3 is an aromatic ring; R112, R113, and R114 are independent of: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) R 112 and R 113 or R 113 and R 114, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12 membered heterocyclic group, a C6-10 aryl group, or a 5-10 membered heteroaryl group, wherein said group is optionally substituted by one or more R's; or Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0102] In a more specific embodiment, the present invention relates to compounds of formula (X) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y3 represents N, CH, or CD; Y4 represents N, CH, or CD; Y5 and Y6 are independently N or C, and at least one of Y5 and Y6 is N; W1 is N or CR 112; W2 is N or CR 113; W 3 is N or CR 114; Indicates a single or double bond; This is predicated on the fact that the double ring containing Y3, Y4, Y5, Y6, W1, W2, and W3 is an aromatic ring; R112, R113, and R114 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R''. Alternatively, R 112 and R 113 or R 113 and R 114, together with the atoms they are attached to, form a C 3-6 cycloalkyl, a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, a C 6-10 aryl, or a 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R''s. Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0103] In a more specific embodiment, the present invention relates to compounds of formula (X) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H. R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y3 is N, CH, or CD; preferably, Y3 is N or CH. Y4 is N, CH, or CD; preferably, Y4 is N or CH. Y5 and Y6 are independently N or C, and at least one of Y5 and Y6 is N; W1 is N or CR 112; W2 is N or CR 113; W 3 is N or CR 114; Indicates a single or double bond; This is predicated on the fact that the double ring containing Y3, Y4, Y5, Y6, W1, W2, and W3 is an aromatic ring; R112, R113, and R114 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R112, R113, and R114 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R”; Alternatively, R 112 and R 113 or R 113 and R 114, together with the atoms they are attached to, form a 3-7 membered heterocyclic group, which is optionally substituted by one or more R''; preferably, R 112 and R 113 or R 113 and R 114, together with the atoms they are attached to, form a 5- or 6-membered heterocyclic group having one or two independent cyclic heteroatoms selected from N, O, and S, which is optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0104] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, which are compounds of formula (X-1) or (X-2): (X-1) or (X-2) in, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y3 is N, CH, or CD; preferably, Y3 is N or CH. Y4 is N, CH, or CD; preferably, Y4 is N or CH. W1 is N or CR 112; W2 is N or CR 113; W 3 is N or CR 114; R112, R113, and R114 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R112, R113, and R114 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R”; Alternatively, R 112 and R 113 or R 113 and R 114, together with the atoms they are attached to, form a 3-7 membered heterocyclic group, which is optionally substituted by one or more R''; preferably, R 112 and R 113 or R 113 and R 114, together with the atoms they are attached to, form a 5- or 6-membered heterocyclic group having one or two independent cyclic heteroatoms selected from N, O, and S, wherein said group is optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0105] In a more specific embodiment, the present invention relates to compounds of formula (X-1) or (X-2), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, wherein, R 5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y 3 is N or CH; Y4 is either N or CH; W1 is N or CR 112; W2 is N or CR 113; W 3 is N or CR 114; R112, R113, and R114 are H; Alternatively, R 112 and R 113 or R 113 and R 114, together with the atoms they are attached to, form the following groups: or The group thereon is optionally replaced by one or more D atoms, up to complete deuteration.

[0106] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, which are compounds of formula (XI): (XI) in, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y3 represents N, CH, or CD; Y7 and Y8 are independently N or C, and at least one of Y7 and Y8 is N; Y 9 represents N, CH, or CD; W 4 is N or CR 115; W 5 is N or CR 116; W 6 is N or CR 117; Indicates a single or double bond; This is predicated on the fact that the bicyclic ring containing Y3, Y7, Y8, Y9, W4, W5, and W6 is an aromatic ring; R 115, R 116 and R 117 are independent of: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R"; or 3) R 115 and R 116 or R 116 and R 117, together with the atoms they are attached to, form a C3-6 cycloalkyl, a 3-12 membered heterocyclic group, a C6-10 aryl group, or a 5-10 membered heteroaryl group, wherein said group is optionally substituted by one or more R's; or Each of Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or a 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''. Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's, up to complete deuteration; Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10 heteroaryl, or Rh and Rj together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds until fully deuterated.

[0107] In a more specific embodiment, the present invention relates to compounds of formula (XI) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D, up to complete deuteration; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Y3 represents N, CH, or CD; Y7 and Y8 are independently N or C, and at least one of Y7 and Y8 is N; Y 9 represents N, CH, or CD; W 4 is N or CR 115; W 5 is N or CR 116; W 6 is N or CR 117; Indicates a single or double bond; This is predicated on the fact that the bicyclic ring containing Y3, Y7, Y8, Y9, W4, W5, and W6 is an aromatic ring; R115, R116, and R117 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R''. Alternatively, R 115 and R 116 or R 116 and R 117, together with the atoms to which they are attached, form a C 3-6 cycloalkyl, a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, a C 6-10 aryl, or a 5-10 membered heteroaryl, wherein said group is optionally substituted by one or more R''s. Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0108] In a more specific embodiment, the present invention relates to compounds of formula (XI) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein, X2 is either N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H. R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y3 is N, CH, or CD; preferably, Y3 is N or CH. Y7 and Y8 are independently N or C, and at least one of Y7 and Y8 is N; Y9 is N, CH, or CD; preferably, Y4 is N or CH; W 4 is N or CR 115; W 5 is N or CR 116; W 6 is N or CR 117; Indicates a single or double bond; This is predicated on the fact that the bicyclic ring containing Y3, Y7, Y8, Y9, W4, W5, and W6 is an aromatic ring; R115, R116, and R117 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R115, R116, and R117 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R”; Alternatively, R 115 and R 116 or R 116 and R 117, together with the atoms they are attached to, form a 3-7 membered heterocyclic group, which is optionally substituted by one or more R''; more preferably, R 115 and R 116 or R 116 and R 117, together with the atoms they are attached to, form a 5- or 6-membered heterocyclic group, wherein said group is optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0109] In a more specific embodiment, the present invention relates to compounds of formula (A) or formula (I), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, which are compounds of formula (XI-1) or (XI-2): (XI-1) or (XI-2) in, X2 is either N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H. R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y3 is N, CH, or CD; preferably, Y3 is N or CH. Y9 is N, CH, or CD; preferably, Y9 is N or CH. W 4 is N or CR 115; W 5 is N or CR 116; W 6 is N or CR 117; R115, R116, and R117 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R115, R116, and R117 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R”; Alternatively, R 115 and R 116 or R 116 and R 117, together with the atoms they are attached to, form a 3-7 membered heterocyclic group, which is optionally substituted by one or more R''; preferably, R 115 and R 116 or R 116 and R 117, together with the atoms they are attached to, form a 5- or 6-membered heterocyclic group having one or two independent cyclic heteroatoms selected from N, O, and S, wherein said group is optionally substituted by one or more R''; Each of Rd, Re, and Rf is independently H, a C1-6 alkyl, a C1-6 haloalkyl, or a C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R"; Each R” is independently a D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more Ds until fully deuterated; Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated.

[0110] In a more specific embodiment, the present invention relates to compounds of formula (XI-1) or (XI-2), or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates, wherein, X2 is either N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H. R 5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y 3 is N or CH; Y 9 represents N or CH; W 4 is N or CR 115; W 5 is N or CR 116; W 6 is N or CR 117; R115, R116, and R117 are H; Alternatively, R 115 and R 116 or R 116 and R 117, together with the atoms they are attached to, form the following groups: or The group thereon is optionally replaced by one or more D atoms, up to complete deuteration.

[0111] In a more specific embodiment, the present invention relates to compounds of formula (I) above, or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein said compounds are selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , or .

[0112] The compounds of this invention may include one or more asymmetric centers and therefore may exist in a variety of stereoisomeric forms, such as enantiomers and / or diastereomers. For example, the compounds of this invention may be individual enantiomers, diastereomers, or geometric isomers (e.g., cis and trans isomers), or may be in the form of mixtures of stereoisomers, including racemic mixtures and mixtures rich in one or more stereoisomers. The isomers can be separated from the mixture by methods known to those skilled in the art, including chiral high-performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferably, the isomers can be prepared by asymmetric synthesis.

[0113] "Tautomers" refer to compounds in which one functional group changes its structure to become another functional group isomer, and can rapidly interconvert to each other, becoming two isomers in dynamic equilibrium. These two isomers are called tautomers.

[0114] Those skilled in the art will understand that organic compounds can form complexes with solvents, react in the solvent, or precipitate or crystallize out of the solvent. These complexes are called "solvates." When the solvent is water, the complex is called a "hydrate." This invention covers all solvates of the compounds of this invention.

[0115] The term "solvent" refers to a compound or its salt that is bound to a solvent and formed by a solvent decomposition reaction. This physical association may include hydrogen bonding. Common solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, etc. The compounds described herein can be prepared, for example, in crystalline form and can be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include stoichiometric and non-stoichiometric solvates. In some cases, the solvate will be separable, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. "Solvent" includes solvates in solution and separable solvates. Representative solvates include hydrates, ethanolates, and methanolates.

[0116] The term "hydrate" refers to a compound that is bound to water. Typically, it is determined by the ratio of the number of water molecules contained in the hydrate to the number of molecules of the compound in the hydrate. Therefore, a hydrate of a compound can be represented, for example, by the general formula R‧x‧H₂O, where R is the compound and x is a number greater than 0. A given compound can form more than one type of hydrate, including, for example, monohydrates (x is 1), lower hydrates (x is a number greater than 0 and less than 1, e.g., hemihydrates (R‧0.5‧H₂O)), and polyhydrates (x is a number greater than 1, e.g., dihydrates (R‧2‧H₂O) and hexahydrates (R‧6‧H₂O)).

[0117] The compounds of this invention can be in amorphous or crystalline forms (crystalline or polymorphic). Furthermore, the compounds of this invention can exist in one or more crystalline forms. Therefore, this invention encompasses all amorphous or crystalline forms of the compounds of this invention within its scope. The term "polymorph" refers to the crystalline form of a compound (or its salts, hydrates, or solvates) with a specific crystal packing arrangement. All polymorphs have the same elemental composition. Different crystalline forms typically have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal shapes, photoelectric properties, stability, and solubility. Recrystallization solvents, crystallization rates, storage temperatures, and other factors can lead to the dominance of one crystalline form. Various polymorphs of the compounds can be prepared by crystallization under different conditions.

[0118] This invention also includes isotopically labeled compounds equivalent to those described in formula (I), but with one or more atoms replaced by atoms of different atomic qualities or mass numbers than those commonly found in nature. Examples of isotopes that can be introduced into the compounds of this invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as 2H, 3H, 13C, 11C, 14C, 15N, 18O, 17O, 31P, 32P, 35S, 18F, and 36Cl, respectively. Compounds of this invention containing the above-mentioned isotopes and / or other isotopes, their prodrugs, and pharmaceutically acceptable salts of said compounds or said prodrugs are all within the scope of this invention. Certain isotopically labeled compounds of this invention, such as those incorporating radioactive isotopes (e.g., 3H and 14C), can be used for drug and / or substrate tissue distribution assays. Tritium (3H) and carbon-14 (14C) isotopes are preferred because they are easy to prepare and detect. Furthermore, substitution with heavier isotopes, such as deuterium (2H), may be preferred in some cases due to their greater metabolic stability, which can provide therapeutic benefits, such as prolonged in vivo half-life or reduced dosage requirements. Isotopically labeled compounds of formula (I) of the present invention and their prodrugs can generally be prepared by replacing non-isotopically labeled reagents with readily available isotopically labeled reagents when performing the procedures described below and / or the processes disclosed in the examples and preparation examples.

[0119] Furthermore, prodrugs (also known as precursor drugs or predrugs) are also included in the context of this invention. As used herein, the term "prodrug" refers to a compound that is converted in vivo, for example, by hydrolysis in the blood, into its active form having a medical effect. Pharmaceutically acceptable prodrugs are described in T. Higuchi and V. Stella, Prodrugs as Novel Delivery Systems, ACS Symposium Series Vol. 14, Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, and D. Fleisher, S. Ramon and H. Barbra, “Improved oral drug delivery: solubility limitations overcome by the use of prodrugs”, Advanced Drug Delivery Reviews (1996) 19(2) 115-130, each of which is incorporated herein by reference.

[0120] A prodrug is any covalently bonded compound of the present invention that, when administered to a patient, releases the parent compound in vivo. Prodrugs are typically prepared by modifying functional groups in such a manner that the modification can be performed by conventional means or by in vivo cleavage to produce the parent compound. Prodrugs include, for example, compounds of the present invention in which a hydroxyl, amino, or thiol group is bonded to any group, which, when administered to a patient, can cleave to form a hydroxyl, amino, or thiol group. Thus, representative examples of prodrugs include (but are not limited to) acetate / acetylamine, formate / acetylamine, and benzoate / acetylamine derivatives of formula (I) with hydroxyl, thiol, and amino functional groups. Additionally, in the case of carboxylic acids (-COOH), esters, such as methyl esters, ethyl esters, etc., can be used. The ester itself can be active and / or hydrolyzable under in vivo conditions. Suitable pharmaceutically acceptable in vivo hydrolyzable ester groups include those groups that readily decompose in the body to release the parent acid or its salt.

[0121] Drug components, formulations and reagent kits

[0122] In another aspect, the present invention provides pharmaceutical compositions comprising the compounds of the present invention (also referred to as the "active component") and pharmaceutically acceptable excipients. In some embodiments, the pharmaceutical composition comprises an effective amount of the active component. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the active component. In some embodiments, the pharmaceutical composition comprises a preventatively effective amount of the active component.

[0123] Pharmaceutically acceptable excipients used in this invention refer to non-toxic carriers, adjuvants, or mediators that do not impair the pharmacological activity of the compounds formulated together. Pharmaceutically acceptable carriers, adjuvants, or mediators that may be used in the compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins (such as human serum albumin), buffering substances (such as phosphates), glycine, sorbic acid, potassium sorbate, mixtures of saturated vegetable fatty acid metaglycerides, water, salts or electrolytes (such as protamine sulfate), disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, silicone, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol, and lanolin.

[0124] The present invention also includes a kit (e.g., a pharmaceutical package). The provided kit may include the compounds of the present invention, other therapeutic agents, and first and second containers (e.g., vials, ampoules, bottles, syringes, and / or dispersible packaging or other suitable containers) containing the compounds of the present invention and other therapeutic agents. In some embodiments, the provided kit may optionally include a third container containing pharmaceutical excipients for diluting or suspending the compounds of the present invention and / or other therapeutic agents. In some embodiments, the compounds of the present invention and other therapeutic agents provided in the first and second containers are combined to form a unit dosage form.

[0125] The pharmaceutical compositions provided by this invention can be administered via a variety of routes, including but not limited to: oral administration, parenteral administration, inhalation administration, topical administration, rectal administration, nasal administration, oral administration, vaginal administration, administration via implantation, or other routes of administration. For example, parenteral administration as used herein includes subcutaneous administration, intradermal administration, intravenous administration, intramuscular administration, intra-articular administration, intra-arterial administration, intra-synovial administration, intrasternal administration, intramenstrual administration, intralesional administration, and intracranial injection or infusion techniques.

[0126] Typically, an effective amount of the compound described herein is administered. The amount of compound actually administered may be determined by the physician based on relevant circumstances, including the condition being treated, the chosen route of administration, the actual compound administered, the individual patient's age, weight and response, the severity of the patient's symptoms, etc.

[0127] When used to prevent the conditions described in this invention, the compounds provided herein are administered to subjects at risk of developing the conditions, typically based on a physician's advice and under physician supervision, at the dosage levels described above. Subjects at risk of developing a specific condition generally include subjects with a family history of the condition, or those identified through genetic testing or screening as particularly susceptible to developing the condition.

[0128] The pharmaceutical composition provided herein can also be administered long-term (“long-term administration”). Long-term administration means administering the compound or its pharmaceutical composition over a prolonged period, such as 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, etc., or may be administered indefinitely, such as for the remainder of the subject's life. In some embodiments, long-term administration is intended to provide a constant level of said compound in the blood over a prolonged period, such as within a therapeutic window.

[0129] Various administration methods can be used to further deliver the pharmaceutical composition of the present invention. For example, in some embodiments, the pharmaceutical composition can be administered by bolus injection, for instance, to rapidly increase the concentration of the compound in the blood to an effective level. The bolus dose depends on the target systemic level of the active ingredient; for example, an intramuscular or subcutaneous bolus dose results in a slow release of the active ingredient, while a bolus dose delivered directly to a vein (e.g., via IV infusion) allows for a more rapid delivery, causing the concentration of the active ingredient in the blood to rapidly increase to an effective level. In other embodiments, the pharmaceutical composition can be administered in the form of a continuous infusion, for example, via IV infusion, thereby providing a steady-state concentration of the active ingredient in the subject's body. Furthermore, in other embodiments, a bolus dose of the pharmaceutical composition can be administered first, followed by a continuous infusion.

[0130] Oral formulations may be in the form of bulk liquid solutions, suspensions, or bulk powders. However, more commonly, for the purpose of precise dosing, the formulations are provided in unit dose form. The term "unit dosage form" refers to a physically discrete unit suitable as a unit dose for human patients and other mammals, each unit containing a predetermined quantity of active substance and suitable pharmaceutical excipients suitable for producing the desired therapeutic effect. Typical unit dose forms include pre-filled, pre-measured ampoules or syringes for liquid formulations, or pills, tablets, capsules, etc., in the case of solid formulations. In such formulations, the compound is typically a smaller component (about 0.1 to about 50% by weight, or preferably about 1 to about 40% by weight), with the remainder being various carriers or excipients and processing aids useful for forming the desired dosage form.

[0131] For oral dosage, a typical regimen is one to five oral doses daily, particularly two to four oral doses, typically three oral doses. Using these dosage regimens, each dose provides approximately 0.01 to approximately 20 mg / kg of the compound of the invention, with preferred doses each providing approximately 0.1 to approximately 10 mg / kg, particularly approximately 1 to approximately 5 mg / kg.

[0132] To provide blood levels similar to or lower than those achieved with an injection dose, a transdermal dose is typically selected, in amounts ranging from about 0.01 to about 20% of body weight, preferably from about 0.1 to about 20% of body weight, preferably from about 0.1 to about 10% of body weight, and even more preferably from about 0.5 to about 15% of body weight.

[0133] From approximately 1 to approximately 120 hours, especially 24 to 96 hours, the injection dose level ranges from approximately 0.1 mg / kg / hour to at least 10 mg / kg / hour. To obtain an adequate steady-state level, a preload bolus of approximately 0.1 mg / kg to approximately 10 mg / kg or more may also be administered. For human patients weighing 40 to 80 kg, the maximum total dose should not exceed approximately 2 g / day.

[0134] Liquid forms suitable for oral administration may include suitable aqueous or non-aqueous carriers, as well as buffers, suspending and dispersing agents, colorants, flavoring agents, etc. Solid forms may include, for example, any of the following components, or compounds with similar properties: binders, such as microcrystalline cellulose, tragacanth gum, or gelatin; excipients, such as starch or lactose; disintegrants, such as alginic acid, Primogel, or corn starch; lubricants, such as magnesium stearate; glidants, such as colloidal silica; sweeteners, such as sucrose or saccharin; or flavoring agents, such as peppermint, methyl salicylate, or orange flavorings.

[0135] Injectable compositions are typically based on injectable sterile saline or phosphate-buffered saline, or other injectable excipients known in the art. As previously described, in such compositions, the active compound is typically a small component, often about 0.05 to 10% by weight, with the remainder being injectable excipients, etc.

[0136] Transdermal compositions are typically formulated as topical ointments or creams containing an active ingredient. When formulated as an ointment, the active ingredient is typically combined with a paraffin-based or water-miscible ointment base. Alternatively, the active ingredient may be formulated as a cream with, for example, an oil-in-water emulsion base. Such transdermal formulations are well known in the art and generally include other components to enhance stable skin penetration of the active ingredient or formulation. All such known transdermal formulations and components are included within the scope of this invention.

[0137] The compounds of this invention can also be administered via transdermal devices. Therefore, transdermal drug delivery can be achieved using reservoirs, porous membranes, or patches with various solid matrices.

[0138] The above-described components for oral, injectable, or topical administration are merely representative. Other materials and processing techniques are described in Part 8 of Remington's Pharmaceutical Sciences, 17th edition, 1985, Mack Publishing Company, Easton, Pennsylvania, which is incorporated herein by reference.

[0139] The compounds of this invention can also be administered in a sustained-release form or from a sustained-release drug delivery system. Descriptions of representative sustained-release materials can be found at Remington's Pharmaceutical Sciences.

[0140] This invention also relates to pharmaceutically acceptable formulations of the compounds of the invention. In one embodiment, the formulation comprises water. In another embodiment, the formulation comprises a cyclodextrin derivative. The most common cyclodextrins are α-, β-, and γ-cyclodextrins, respectively, composed of 6, 7, and 8 α-1,4-linked glucose units, optionally including one or more substituents on the linked sugar moieties, including but not limited to: methylated, hydroxyalkylated, acetylated, and sulfonyl ether substituted groups. In some embodiments, the cyclodextrin is a sulfonyl ether β-cyclodextrin, for example, sulfobutyl ether β-cyclodextrin, also known as Captisol. See, for example, US 5,376,645. In some embodiments, the formulation comprises hexapropyl-β-cyclodextrin (e.g., 10-50% in water).

[0141] Indications

[0142] On the other hand, the use of compounds of formula (I) disclosed herein (including all individual embodiments and subsets thereof) or their tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvents is provided as a medicament.

[0143] The compounds of this invention exhibit potent and selective BTK inhibition. For example, the compounds of this invention exhibit nanomolar potency against wild-type BTK and BTK kinases encoded by BTK genes including BTK kinase inhibitor resistance mutations (including, for example, BTK C481S, BTK T474I, or BTK L528W).

[0144] In some embodiments, the compounds of the present invention selectively target BTK kinases. For example, the compounds of the present invention can selectively target BTK kinases relative to another kinase or non-kinase target. In some embodiments, the compounds of the present invention can selectively target BTK kinases relative to one or more kinases selected from BRK, CSK, ERBB4, FYN, MEK1, MEK2, TEC, TXK, YES1, BMX, BLK, EGFR, ITK, SRC, JAK1, JAK2, and JAK3. In other embodiments, the compounds of the present invention can selectively target BTK kinases relative to one or more kinases selected from TEC, EGFR, and ITK. In still other embodiments, the compounds of the present invention can selectively target BTK kinases relative to one or more kinases selected from TEC and EGFR. In some embodiments, the compounds of the present invention exhibit at least 30-fold selectivity for BTK kinases relative to another kinase. For example, the compounds of the present invention exhibit at least 40-fold selectivity, at least 50-fold selectivity, at least 60-fold selectivity, at least 70-fold selectivity, at least 80-fold selectivity, at least 90-fold selectivity, at least 100-fold selectivity, at least 200-fold selectivity, at least 300-fold selectivity, at least 400-fold selectivity, at least 500-fold selectivity, at least 600-fold selectivity, at least 700-fold selectivity, at least 800-fold selectivity, at least 900-fold selectivity, or at least 1000-fold selectivity, relative to another kinase. In some embodiments, the compounds of the present invention exhibit at least 100-fold selectivity to BTK kinase relative to another kinase. In some embodiments, the selectivity to BTK kinase relative to another kinase is measured in a cellular assay (e.g., the cellular assay provided herein).

[0145] In some embodiments, the compounds of the present invention can be used to treat BTK kinase-mediated diseases mediated by covalently bonded BTK kinase inhibitor resistance mutations. In more specific embodiments, the covalently bonded BTK kinase inhibitor resistance mutations are C481S, C481F, C481Y, C481R, C481T, C481G, and C481W.

[0146] In some embodiments, the compounds of the present invention can be used to treat BTK kinase-mediated diseases resistant to non-covalent BTK kinase inhibitor mutations. In more specific embodiments, non-covalent BTK kinase inhibitor resistance mutations are V416L, A428D, M437R, T474I, and L528W.

[0147] In some embodiments, BTK kinase inhibitor resistance mutations are one or more point mutations in the BTK gene. In some embodiments, one or more point mutations in the BTK gene result in the translation of a BTK protein with one or more amino acid substitutions at one or more of the following amino acid positions: 117, 316, 416, 428, 437, 474, 481, 528, 560, 562, and 601. In some embodiments, one or more point mutations in the BTK gene result in the translation of a BTK protein with one or more of the following amino acid substitutions: T117P, T316A, V416L, A428D, M437R, T474I, T474M, T474S, C481S, C481F, C481T, C481G, C481R, L528W, P560L, R562W, R562G, and F601L.

[0148] The compounds of this invention can be used to treat diseases and conditions treated with BTK kinase inhibitors, such as BTK-related diseases and conditions, such as proliferative diseases, such as cancer, including hematologic cancers and solid tumors, and inflammatory conditions, immune diseases, or fibrosis.

[0149] In some embodiments of any of the methods or uses described herein, the cancer (e.g., BTK-related cancer) is a hematologic cancer. In some embodiments of any of the methods or uses described herein, the cancer (e.g., BTK-related cancer) is a solid tumor. In some embodiments of any of the methods or uses described herein, the cancer (e.g., BTK-related cancer) is a B-cell malignancy. In some embodiments of any of the methods or uses described herein, the cancer (e.g., BTK-related cancer) is Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma (e.g., splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma), Burkitt lymphoma, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), primary central nervous system lymphoma, small lymphocytic lymphoma, chronic lymphocytic lymphoma, acute lymphoblastic leukemia, B-cell prolymphocytic leukemia, precursor B-cell lymphoblastic leukemia, hairy cell leukemia, acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, plasmacytoma, plasmacytoma, bone cancer, bone metastases, breast cancer, gastric-esophageal cancer, pancreatic cancer, ovarian cancer, prostate cancer, lung cancer, colon cancer, head and neck cancer, or glioma.

[0150] In some implementations, the hematologic malignancy is selected from leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, or myeloma, such as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic lymphoma (CLL), chronic myeloid leukemia (CML), chronic myeloid monoglobulin leukemia (CMML), chronic neutrophilic leukemia (CNL), acute undifferentiated leukemia (AML), anaplastic large cell lymphoma (ALCL), prolymphocytic leukemia (PML), juvenile myelomonocytic leukemia (JMML), adult T-cell leukemia (ALL), and myeloproliferative disorders with trilineage myeloproliferative abnormalities. Common hematologic malignancies include acute myeloid leukemia (AML / TMDS), mixed phenotype leukemia (MLL), myelodysplastic syndromes (MDS), myeloproliferative disorders (MPD), diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma (e.g., splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma), Burkitt lymphoma, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), primary central nervous system lymphoma, small lymphoglobulin lymphoma, precursor B-cell lymphoblastic leukemia, hairy cell leukemia, mucosa-associated lymphoid tissue lymphoma, plasma cell myeloma, plasmacytoma, and multiple myeloma. Other examples of hematologic malignancies include myelodysplastic disorders (MPDs) such as polycythemia vera (PV), essential thrombocytopenic purpura (ET), and idiopathic primary myelofibrosis (IMF / IPF / PMF). In some implementations, hematologic cancers are mantle cell lymphoma, chronic lymphocytic lymphoma, small lymphocytic lymphoma, Waldenström macroglobulinemia, or marginal zone lymphoma.

[0151] In some implementation schemes, solid tumors are selected from bone cancer, bone metastases, breast cancer, gastric-esophageal cancer, pancreatic cancer, ovarian cancer, prostate cancer, lung cancer, colon cancer, and head and neck cancer.

[0152] In some implementation schemes, the immune disease is selected from arthritis, multiple sclerosis, osteoporosis, irritable bowel syndrome, inflammatory bowel disease, Crohn's disease, lupus, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, Still's disease, juvenile arthritis, diabetes, myasthenia gravis, Hashimoto's thyroiditis, Auder's thyroiditis, Graves' disease, Sjögren's syndrome, Guillain-Barré syndrome, acute disseminated encephalomyelitis, Addison's disease, oculoclonus syndrome, and obsessive-compulsive disorder. Spondylitis, antiphospholipid syndrome, aplastic anemia, autoimmune hepatitis, celiac disease, Goodpassuia syndrome, idiopathic thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Leter syndrome, Goyan's arteritis, warm autoimmune hemolytic anemia, Wegener's granulomatosis, psoriasis, alopecia areata, Bechtel's disease, chronic fatigue, autonomic nervous system disorders, endometriosis, interstitial cystitis, neurogenic myotonia. Scleroderma and vulvar pain, asthma, appendicitis, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, colitis, conjunctivitis, colitis, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, hepatitis, inflammatory bowel disease, suppurative inflammation, laryngitis, mastitis, meningitis, myelitis, myocarditis, myositis, nephritis Inflammation, oophoritis, orchitis, osteitis, otitis, pancreatitis, mumps, pericarditis, peritonitis, pharyngitis, pleurisy, phlebitis, pneumonia, lung disease, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendinitis, tonsillitis, uveitis, vaginitis, vasculitis, vulvitis, graft-versus-host disease, transplantation, blood transfusion, allergic reactions, hypersensitivity reactions, type I hypersensitivity reactions, allergic conjunctivitis, allergic rhinitis, and atopic dermatitis.

[0153] In some implementations, inflammatory diseases are selected from arthritis, asthma, appendicitis, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, colitis, conjunctivitis, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, hepatitis, hidradenitis suppurativa, laryngitis, mastitis, meningitis, osteomyelitis, myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleurisy, phlebitis, pneumonia, pulmonary disease, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendinitis, tonsillitis, uveitis, vaginitis, vasculitis, and vulvitis.

[0154] In some implementation schemes, autoimmune diseases are selected from lupus and Sjögren's syndrome, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, Still's disease, juvenile arthritis, diabetes, myasthenia gravis, Hashimoto's thyroiditis, Odd's thyroiditis, Graves' disease, Sjögren's syndrome, Guillain-Barré syndrome, acute disseminated encephalomyelitis, Addison's disease, oculoclonus-myoclonus syndrome, ankylosing spondylitis, antiphospholipid syndrome, aplastic anemia, autoimmune hepatitis, celiac disease, Goodpassuia syndrome, idiopathic thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Lightell's syndrome, Goyan's arteritis, hemolytic anemia, Wegener's granulomatosis, psoriasis, alopecia areata, Behçet's disease, chronic fatigue, autonomic dysfunction, endometriosis, interstitial cystitis, neurogenic myotonia, scleroderma, and vulvar pain.

[0155] In some implementations, xenoimmune diseases are selected from graft-versus-host disease, transplantation, blood transfusion, allergy, hypersensitivity, type I hypersensitivity, allergic conjunctivitis, allergic rhinitis, and atopic dermatitis.

[0156] In some implementations, fibrosis is selected from pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), common interstitial pneumonia (UIP), interstitial lung disease, cryptogenic fibrotic alveolitis (CFA), obliterative bronchiolitis, bronchiectasis, fatty liver disease, steatosis (e.g., nonalcoholic steatohepatitis (NASH), cholestatic liver disease (e.g., primary biliary cirrhosis (PBC)), cirrhosis, alcoholic liver fibrosis, bile duct injury, bile fibrosis, cholestasis, or bile duct lesions.

[0157] In the treatment methods of this invention, "effective amount" is intended to refer to an amount or dose sufficient to produce the desired therapeutic benefit in an individual requiring the treatment. The effective amount or dose of the compounds of this invention can be determined by conventional methods (e.g., modeling, dose escalation, or clinical trials) and by conventional factors (e.g., the pattern or route of drug delivery, the pharmacokinetics of the agent, the severity and course of the infection, the individual's health status and weight, and the judgment of the treating physician). Exemplary doses are in the range of about 0.1 mg to 1 g per day, or about 1 mg to 50 mg per day, or about 50 mg to 250 mg per day, or about 250 mg to 1 g per day. The total dose can be a single or separate dose unit (e.g., BID, TID, QID).

[0158] After a patient's condition improves, the dosage can be adjusted for prophylactic or maintenance therapy. For example, the dosage or frequency of administration, or both, can be reduced to maintain the desired therapeutic or preventative effect, depending on the symptoms. Of course, treatment can be discontinued if symptoms have improved to an appropriate level. However, if any symptom recurs, the patient may require long-term intermittent treatment. Patients may also require long-term, slow-release therapy.

[0159] Drug combination

[0160] The compounds of the present invention described herein may be combined with one or more other active ingredients in pharmaceutical compositions or methods to treat the diseases and conditions described herein. Other additional active ingredients include other therapeutic agents or pharmaceuticals that mitigate adverse effects of therapeutic agents against the intended disease target. Such combinations may be used to increase efficacy, improve other disease symptoms, reduce one or more adverse effects, or reduce the required dosage of the compounds of the present invention. Additional active ingredients may be formulated into pharmaceutical compositions separate from the compounds of the present invention or may be included with the compounds of the present invention in a single pharmaceutical composition. Additional active ingredients may be administered concurrently with, before, or after the administration of the compounds of the present invention.

[0161] Combination agents include additional active ingredients that are known or observed to be effective in treating the diseases and conditions described herein, including those that are effective against another target associated with the disease. For example, the compositions and formulations of the present invention, as well as the methods of treatment, may further comprise other drugs or medicines, such as other active agents that can be used to treat or alleviate the target disease or related symptoms or conditions. For cancer indications, other agents include (but are not limited to) kinase inhibitors, such as EGFR inhibitors (e.g., erlotinib, gefitinib); Raf inhibitors (e.g., vemurafenib); VEGFR inhibitors (e.g., sunitinib); standard chemotherapeutic agents, such as alkylating agents, antimetabolites, antitumor antibiotics, topoisomerase inhibitors, platinum drugs, mitotic inhibitors, antibodies, hormone therapy, or corticosteroids. For pain indications, suitable combination agents include anti-inflammatory agents, such as NSAIDs. The pharmaceutical compositions of the present invention may additionally comprise one or more of the active agents described, and the methods of treatment may additionally comprise an effective amount of one or more of the active agents described.

[0162] [Example]

[0163] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, parts and percentages are parts by weight and weight percentages.

[0164] Typically, in the preparation process, each reaction is carried out in an inert solvent at room temperature to reflux temperature (e.g., 0 °C to 100 °C, preferably 0 °C to 80 °C). The reaction time is usually 0.1–60 hours, preferably 0.5–24 hours.

[0165] The abbreviations used in this article have the following meanings:

[0166] [Table 1] DCM dichloromethane STAB Sodium triacetylated borohydride DMF N,N-Dimethylformamide HATU 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate KHMDS bis(trimethylsilyl)aminopotassium Xphos 2-Dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl THF Tetrahydrofuran Pd(OAc) 2 Palladium acetate MTBE Methyl tert-butyl ether NBS N-bromosuccinimide LDA Diisopropylaminolithium T 3P 1-Propylphosphine CDI N,N'-Carbonyldiimidazole TsOH p-Toluenesulfonic acid NMP N-Methylpyrrolidone Pd(PPh 3) 4 Tetra(triphenylphosphine)palladium TFA Trifluoroacetic acid NIS N-Iodosuccinimide DMSO dimethyl sulfoxide EDCI 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide B 2Pin 2 Pinaryl diboronate HOBT 1-Hydroxybenzotriazole Pd(dppf)Cl 2 [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride DCE 1,2-Dichloroethane LiHMDS Lithium bis(trimethylsilyl)amine m-CPBA m-chloroperoxybenzoic acid DIPEA N,N-Diisopropylethylamine Oxone Potassium persulfate complex salt Pd 2(dba) 3 Tris(dibenzylacetone)dipalladium BocNHNH 2 tert-butyl hydrazine carbamate Xantphos 4,5-Bisdiphenylphosphine-9,9-Dimethyloxanthracene Pd(t-Bu 3P) 2 Di(tert-tert-butylphosphine)palladium Tol Toluene DME Ethylene glycol dimethyl ether TPP Triphenylphosphine DIAD Diisopropyl azodicarbonate DMP Des Martin Oxidizer TBAF Tetra-n-butylammonium fluoride MsCl Methyl sulfonate

[0167] [, Synthesis of related intermediate compounds , ]

[0168] [, intermediate , ] [, A-1 ((5- , ] [, fluorine , ] [, -2- , ] [, Methoxybenzoyl , ] [, ) , ] [, amino , ] [, ) , ] [, Preparation of potassium methyltrifluoroborate , ] [, The following synthetic route was adopted. , ] [, , ] Step 1: Synthesis of compound 5-fluoro-2-methoxybenzyl chloride Add 26 g (150 mmol) of 5-fluoro-2-methoxybenzoic acid and 300 mL of anhydrous dichloromethane to a 100 mL three-necked flask equipped with a magnetic stirrer. Stir until dissolved, cool in an ice-water bath, and add 38 g (300 mmol) of oxaliplatin and 1.1 g (15 mmol) of anhydrous N,N-dimethylformamide dropwise under a nitrogen atmosphere. After the addition is complete, remove the ice bath and stir the mixture overnight at room temperature. Remove the solvent and unreacted oxaliplatin by vacuum distillation, and set aside for later use. Step 2 Synthesis of Intermediate A-1 Add 36.3 g (165 mmol) of bromomethylborate pinacol ester and 300 mL of anhydrous tetrahydrofuran to a 1000 mL three-necked flask equipped with a magnetic stirrer. Cool to -78 °C under a nitrogen atmosphere. Add 165 mL (1 M) of a tetrahydrofuran solution of bis(trimethylsilyl)amino potassium and stir for 30 minutes. Heat to room temperature and stir for 30 minutes. Add 21.1 g (660 mmol) of anhydrous methanol and stir at room temperature for 1 hour. Filter out the insoluble solids. Evaporate the solvent from the filtrate at no more than 30 °C. Add 200 mL of anhydrous tetrahydrofuran and evaporate the solvent. Repeat twice. Dissolve the residue in 200 mL of anhydrous tetrahydrofuran. Slowly add 200 mL of a tetrahydrofuran solution of 5-fluoro-2-methoxybenzoyl chloride. After the addition is complete, stir at room temperature under a nitrogen atmosphere overnight. The solvent was removed by evaporation, and the residue was dissolved in methanol (300 mL). Potassium hydrogen fluoride aqueous solution (64 g, 825 mmol, 200 mL) was added, and the mixture was stirred overnight at room temperature. The solvent was removed by vacuum evaporation, and toluene (100 mL) was azeotropically refluxed twice to remove water. The residue was washed with methyl tert-butyl ether, filtered, and the filter cake was washed with hot methanol / acetone (1 / 3, 1000 mL) solution. The filtrate was concentrated to dryness, and methyl tert-butyl ether was added to slurry the mixture, precipitating a solid. The solid was filtered, and the filter cake was dried to give 31 g of a white solid, with a yield of 70.7%. 1H NMR (400 MHz, DMSO- D 6) δ (ppm): 7.75 (br s, 1H), 7.65-7.62 (m, 1H), 7.30-7.25 (m, 1H), 7.17-7.14 (m, 1H), 3.87 (s, 3H), 2.13-2.10 (m, 2H).

[0169] [, intermediate , ] [, A-2 (Z)-3- , ] [, amino , ] [, -3-(4- , ] [, Bromophenyl , ] [, ) , ] [, Preparation of acrylonitrile , ] [, The following synthetic route was adopted. , ] 4-Bromobenzonitrile (50 g, 274.7 mmol) and anhydrous tetrahydrofuran (500 mL) were added to a 1000 mL three-necked flask equipped with a magnetic stirrer. The mixture was stirred until dissolved, evacuated to a vacuum and purged with nitrogen three times, and the temperature was lowered to -78 ºC. Diisopropylaminolithium (206 mL, 412.0 mmol) was added dropwise, and the reaction was maintained at -78 ºC for 4 hours. Anhydrous acetonitrile (17.3 g, 412.0 mmol) was then added dropwise. After the addition was complete, the reaction was stirred at room temperature under a nitrogen atmosphere for 12 hours. The reaction was quenched with water (500 mL), extracted with ethyl acetate (500 mL × 2), and the organic phases were combined. The mixture was washed with saturated brine (500 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 42.6 g of a white solid, yield 70.0%. LC-MS (APCI): m / z = 223.0 (M+1)+.

[0170] [, intermediate , ] [, A-3 2-(4- , ] [, Bromophenyl , ] [, )-4- , ] [, Oxygenation , ] [, -6-(1,1,1- , ] [, Trifluoropropane , ] [, -2- , ] [, base , ] [, )-1,4- , ] [, dihydropyridine , ] [, -3- , ] [, Preparation of nitriles , ] [, Using the following synthetic route , ] [, , ] Step 1: Synthesis of ethyl 5,5,5-trifluoro-4-methyl-3-oxovalerate N,N'-carbonyldiimidazole (68.5 g, 422.3 mmol), anhydrous tetrahydrofuran (600 mL), and 3,3,3-trifluoro-2-methylpropionic acid (50 g, 351.9 mmol) were added to a 1000 mL three-necked flask equipped with a magnetic stirrer. The mixture was stirred until dissolved and stirred at room temperature under a nitrogen atmosphere for 4 hours. Anhydrous magnesium chloride (33.5 g, 351.9 mmol) and potassium 3-ethoxy-3-oxopropionate (89.8 g, 527.8 mmol) were added, and the mixture was stirred at room temperature under a nitrogen atmosphere for 12 hours. The pH of the reaction mixture was adjusted to approximately 3 by adding hydrochloric acid (1 M) dropwise. The mixture was extracted with ethyl acetate (500 mL × 2), and the organic phases were combined. The mixture was washed with saturated brine (500 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 44.8 g of a white solid, with a yield of 60.0%. LC-MS (APCI): m / z = 213.0 (M+1) +. Step 2 Synthesis of intermediate A-3 Intermediate A-2 (42.6 g, 200.9 mmol), ethyl 5,5,5-trifluoro-4-methyl-3-oxovalerate (22.3 g, 100.4 mmol), and N-methylpyrrolidone (60 mL) were added to a 500 mL three-necked flask equipped with a magnetic stirrer. The mixture was stirred at 250 ºC for 1 h under a nitrogen atmosphere. After cooling to room temperature, the mixture was extracted with water (200 mL) and ethyl acetate (200 mL × 2). The organic phases were combined, washed with saturated brine (500 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 14.9 g of white solid, yield 40.0%. LC-MS (APCI): m / z = 371.0 (M+1) +.

[0171] [, intermediate , ] [, A-4 (4-((5- , ] [, fluorine , ] [, -2- , ] [, Methoxybenzamide , ] [, ) , ] [, methyl , ] [, ), ] [, Phenyl , ] [, ) , ] [, Preparation of boric acid , ] [, The following synthetic route was adopted. , ] Tetrahydrofuran (120 mL), 4-aminomethylphenyl borate (12 g, 64.1 mmol), and 5-fluoro-2-methoxybenzoic acid (10.9 g, 64.1 mmol) were added to a 500 mL single-necked flask equipped with a magnetic stirrer and a condenser. The mixture was stirred until dissolved. Then, an ethyl acetate solution of 1-propylphosphonic anhydride (75.5 mL, 128.3 mmol, 1.7 M) and N,N-diisopropylethylamine (33 g, 256 mmol) were added while stirring. The mixture was evacuated and purged with nitrogen three times. The temperature was raised to 70 °C and the mixture was stirred and kept at this temperature overnight. Cool to room temperature, concentrate under reduced pressure, add water (120 mL) and dichloromethane (200 mL), separate the organic phase, extract the aqueous phase with dichloromethane (200 mL × 2), combine the organic phases, dry with anhydrous sodium sulfate, filter, concentrate the filtrate to dryness, add dichloromethane (100 mL), stir for 60 minutes, filter, wash the filter cake with a small amount of dichloromethane, and then dry under vacuum to give 17.6 g of white solid, yield 90.7%.

[0172] [, intermediate , ] [, A-5 4-( , ] [, benzyloxy , ] [, )-2- , ] [, Preparation of chloronicotinamide , ] [, The following synthetic route was adopted. , ] [, , ] Under an ice-water bath, 2,4-dichloronicotinonitrile (21.7 g, 125.4 mmol), benzyl alcohol (13.55 g, 125.4 mmol), and anhydrous tetrahydrofuran (200 mL) were added to a 1 L three-necked flask equipped with a magnetic stirrer. The mixture was stirred until homogeneous under nitrogen protection. Sodium hydride (6 g, 150 mmol, 60%, 0.5 g each time) was added slowly in batches over 30 minutes. After the addition was complete, the reaction was continued under an ice-water bath for 30 minutes, then the ice-water bath was removed, and the reaction was continued for 1 hour. The reaction was quenched with water (100 mL), and the tetrahydrofuran was removed by rotary evaporation. A large amount of solid precipitated from the system. The solid was filtered, and the filter cake was washed with water. The washed solid was dissolved in dichloromethane (200 mL), washed with water (100 mL), washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 28.1 g of a pale yellow oil. Ethyl acetate (50 mL) was added with stirring, and the mixture was heated in an oil bath to dissolve completely. Petroleum ether (120 mL) was then slowly added. The mixture was slowly cooled to room temperature, and a large amount of white solid precipitated. The mixture was filtered, and the filter cake was washed with petroleum ether and dried under vacuum to give 22.1 g of white solid, yield 72%. LC-MS (APCI): m / z = 245.0 (M+1)+.

[0173] [, intermediate , ] [, A-6 2- , ] [, bromine , ] [, -6- , ] [, fluorine , ] [, -4-(1- , ] [, Trifluoromethyl , ] [, - , ] [, vinyl , ] [, ) , ] [, Preparation of benzonitrile , ] [, The following synthetic route was adopted. , ] [, , ] Step 1: Synthesis of compound 2-fluoro-4-(1-trifluoromethyl-vinyl)benzonitrile 4-Bromo-2-fluorobenzonitrile (5 g, 25 mmol), ethylene glycol dimethyl ether (100 mL), 1-(trifluoromethyl)ethyleneborate hexanol ester (8.325 g, 37.5 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (910 mg, 1.25 mmol), cesium carbonate (24.4 g, 75 mmol), and water (25 mL) were added to a container. The mixture was purged with nitrogen three times and heated to 110 °C overnight. The reaction solution was cooled to room temperature, and water (100 mL) was added. The mixture was extracted with ethyl acetate (150 mL × 3). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by silica gel column chromatography to obtain 4.5 g of a pale yellow oil, with a yield of 83%. 1H NMR (400 MHz, DMSO- D 6) δ (ppm): 8.05-8.01 (t, J = 8.0 Hz, 1H), 7.70 (d, J = 10.8 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 6.42 (t, J = 2.8 Hz, 1H), 6.33 (s, 1H). Step 2 Synthesis of Intermediate A-6 2-Fluoro-4-(1-trifluoromethyl-vinyl)benzonitrile (4.5 g, 20.93 mmol), p-toluenesulfonic acid monohydrate (4.38 g, 23.02 mmol), N-bromosuccinimide (4.1 g, 23.02 mmol), palladium acetate (235 mg, 1.05 mmol), and 1,2-dichloroethane (80 mL) were added to a container, and the mixture was heated to 70 °C and reacted overnight. The reaction solution was cooled to room temperature, water (100 mL) was added, and the mixture was extracted with ethyl acetate (200 mL × 3). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by silica gel column chromatography to give 2.0 g of a pale yellow solid, yield 32%. LC-MS (APCI): m / z = 294.0 (M+1)+.

[0174] [, intermediate , ] [, A-7 2-(4- , ] [, Bromophenyl , ] [, )-4- , ] [, hydroxyl , ] [, -6- , ] [, Oxygenation , ] [, -1,6- , ] [, dihydropyridine , ] [, -3- , ] [, Preparation of nitriles , ] [, The following synthetic route was adopted. , ] Diethyl malonate (2.16 g, 13.5 mmol), intermediate A-2 (2.0 g, 9 mmol), and N-methylpyrrolidone (10 mL) were added to a 20 mL microwave-safe tube equipped with a magnetic stirrer. The tube was sealed and microwaved to 250 °C for 10 min. The reaction was repeated twice. The reaction solution was cooled to room temperature, and the reaction was quenched with saturated brine (50 mL). The mixture was extracted with ethyl acetate (50 mL × 2), and the organic phases were combined, concentrated, and filtered through a silica gel column to give 2.0 g of white solid, yield 25.9%. LC-MS (APCI): m / z = 291.0 (M+1)+.

[0175] [, intermediate , ] [, A-8 3-(3- , ] [, amino , ] [, -4-(4- , ] [, Bromophenyl , ] [, )-1H- , ] [, Pyrazol , ] [, [4,3-c] , ] [, Pyridine , ] [, -6- , ] [, base , ] [, ), ] [, Guadrine , ] [, -1- , ] [, Preparation of benzyl carboxylate , ] [, The following synthetic route was adopted. , ] [, , ] Step 1: Synthesis of compound 3-(3-ethoxy-3-oxopropionic)piperidine-1-carboxylic acid benzyl ester 1-((benzyloxy)carbonyl)piperidine-3-carboxylic acid (5 g, 19.0 mmol) and tetrahydrofuran (75 mL) were added to a 250 mL three-necked flask equipped with a magnetic stirrer and stirred until dissolved. N,N'-carbonyldiimidazole (3.70 g, 22.8 mmol) was added, and the mixture was stirred at room temperature under a nitrogen atmosphere for 4 hours. Magnesium chloride (1.81 g, 19.0 mmol) and potassium 3-ethoxy-3-oxopropionate (4.85 g, 28.5 mmol) were added, and the mixture was stirred at room temperature under a nitrogen atmosphere for 12 hours. The pH was adjusted to approximately 3 with 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate (50 mL × 2). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 4.56 g of a white solid, yield 72.0%. LC-MS (APCI): m / z = 334.0 (M+1)+. Step 2: Synthesis of compound 3-(6-(4-bromophenyl)-5-cyano-4-hydroxypyridin-2-yl)piperidine-1-carboxylic acid benzyl ester 3-(3-ethoxy-3-oxopropionic acid)piperidine-1-carboxylic acid benzyl ester (4.5 g, 13.51 mmol), intermediate A-2 (1 g, 4.504 mmol), and N-methylpyrrolidone (5 mL) were added to a 20 mL microwave-safe tube. The mixture was stirred at 250 °C for 1 hour under a nitrogen atmosphere. The reaction was quenched with water (50 mL), extracted with ethyl acetate (50 mL × 2), and the organic phases were combined. The mixture was washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 1.03 g of white solid, yield 46.6%. LC-MS (APCI): m / z = 492.0 (M+1)+. Step 3: Synthesis of compound 3-(6-(4-bromophenyl)-4-chloro-5-cyanopyridin-2-yl)piperidine-1-carboxylic acid benzyl ester 1.03 g (2.098 mmol) of 3-(6-(4-bromophenyl)-5-cyano-4-hydroxypyridin-2-yl)piperidine-1-carboxylic acid benzyl ester and 5 mL of phosphorus oxychloride were added to a 25 mL single-necked flask equipped with a magnetic stirrer and a condenser. The mixture was stirred at 90 °C for 2 hours under a nitrogen atmosphere. After cooling in an ice-water bath, the pH was adjusted to approximately 9 by adding saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate (50 mL × 2), and the organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 573 mg of white solid, yield 53.6%. LC-MS (APCI): m / z = 510.0 (M+1)+. Step 4: Synthesis of intermediate A-8 Benzyl 3-(6-(4-bromophenyl)-4-chloro-5-cyanopyridin-2-yl)piperidine-1-carboxylate (573 mg, 1.126 mmol), hydrazine hydrate (281.8 mg, 5.63 mmol), and N,N-dimethylformamide (3 mL) were added to a 25 mL sealed tube. The mixture was stirred at 110 °C for 1.5 h under a nitrogen atmosphere. After cooling in an ice-water bath, the pH was adjusted to alkaline by adding saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate (30 mL × 2), and the organic phases were combined. The mixture was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 500 mg of white solid, with a yield of 87.9%. LC-MS (APCI): m / z = 506.0 (M+1)+.

[0176] [, intermediate , ] [, A-9 4-(3- , ] [, amino , ] [, -4-(4- , ] [, Bromophenyl , ] [, )-1H- , ] [, Pyrazol , ] [, [4,3-c] , ] [, Pyridine , ] [, -6- , ] [, base , ] [, ) , ] [, Guadrine , ] [, -1- , ] [, Preparation of benzyl carboxylate , ] [, The following synthetic route was adopted. , ] [, , ] [, , ] Step 1: Synthesis of compound 4-(3-ethoxy-3-oxopropionic)piperidine-1-carboxylic acid benzyl ester [, , ] 1-((benzyloxy)carbonyl)piperidine-4-carboxylic acid (10 g, 38 mmol), anhydrous tetrahydrofuran (200 mL), and N,N'-carbonyldiimidazole (7.4 g, 45.6 mmol) were added to a container. The mixture was heated to 70 °C and reacted for 1 hour. After cooling to room temperature, potassium 3-ethoxy-3-oxopropionate (5.93 g, 38 mmol) and anhydrous magnesium chloride (3.62 g, 38 mmol) were added, and the mixture was heated to 70 °C and stirred overnight. After the reaction solution cooled, it was quenched with 1 N hydrochloric acid. The solution was diluted with water (100 mL), extracted with ethyl acetate (200 mL × 3), washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, concentrated, and the residue was separated by silica gel column chromatography to obtain 10.5 g of a transparent oily liquid, with a yield of 82.1%. LC-MS (APCI): m / z = 334.0 (M+1) +. Step 2: Synthesis of compound 4-(6-(4-bromophenyl)-5-cyano-4-hydroxypyridin-2-yl)piperidine-1-carboxylic acid benzyl ester 4-(3-ethoxy-3-oxopropionic acid)piperidine-1-carboxylic acid benzyl ester (1.5 g, 4.5 mmol), intermediate A-2 (500 mg, 2.25 mmol), and N-methylpyrrolidone (15 mL) were added to a container, and the mixture was microwaved at 250 °C for 10 min. The reaction solution was cooled to room temperature, and water (100 mL) was added. The mixture was extracted with ethyl acetate (100 mL × 3). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by silica gel column chromatography to give 700 mg of a light brown solid, yield 63%. LC-MS (APCI): m / z = 494.1 (M+1) +. Step 3: Synthesis of compound 4-(6-(4-bromophenyl)-4-chloro-5-cyanopyridin-2-yl)piperidine-1-carboxylic acid benzyl ester 3.9 g (7.91 mmol) of 4-(6-(4-bromophenyl)-5-cyano-4-hydroxypyridin-2-yl)piperidine-1-carboxylic acid benzyl ester and 30 mL of phosphorus oxychloride were added to a container. The mixture was heated to 80 °C for 2 hours. The reaction solution was concentrated, quenched with warm water, and the pH was adjusted to neutral with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate (200 mL × 3). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was separated by silica gel column chromatography to give 2.5 g of brown solid, yield 61%. LC-MS (APCI): m / z = 510.1 (M+1)+. Step 4: Synthesis of Intermediate A-9 Benzyl 4-(6-(4-bromophenyl)-4-chloro-5-cyanopyridin-2-yl)piperidine-1-carboxylate (2.5 g, 4.9 mmol), N,N-dimethylformamide (25 mL), and hydrazine hydrate (1.25 g, 24.51 mmol) were added to a container, and the mixture was heated to 110 °C and reacted for 1.5 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (150 mL × 3), washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by silica gel column chromatography to give 1.5 g of a pale yellow solid, yield 60%. LC-MS (APCI): m / z = 506.0 (M+1)+.

[0177] [, intermediate , ] [, A-10 , ] [, compound , ] [, 6- , ] [, bromine , ] [, -3',6'- , ] [, Dihydrogen , ] [, -[3,4'- , ] [, Bipyridine , ] [, ]-1'(2'H)- , ] [, Preparation of tert-butyl formate , ] A-10 [, The following synthetic route was adopted. , ] To a 500 mL single-necked flask equipped with a magnetic stirrer and a condenser, add 15.0 g (53.2 mmol) of 2-bromo-5-iodopyridine, 18 g (18.5 mmol) of N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester, 100 mL (100 mL) of 1,4-dioxane, and 25 mL of water. Stir until dissolved. Then add 22 g (133 mmol) of tripotassium phosphate and 3.8 g (5.32 mmol) of [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride. Evacuate the mixture and purge it with nitrogen three times. Slowly raise the temperature to 100 °C under a nitrogen atmosphere and stir for 12 hours. Cool to room temperature, filter off insoluble solids, wash with ethyl acetate (20 mL), remove organic solvent by vacuum distillation, add ethyl acetate (150 mL), separate the organic phase, extract the aqueous phase with ethyl acetate (30 mL), combine the organic phases, wash with saturated brine (50 mL), dry to anhydrous sodium sulfate, filter, concentrate the filtrate to dryness and pass through a silica gel column to give 15.1 g of white solid, yield 83.8%. LC-MS (APCI): m / z = 339.0 (M+1)+.

[0178] [, intermediate , ] [, A-11 , ] [, compound , ] [, 4-(6- , ] [, Bromopyridine , ] [, -3- , ] [, base , ] [, ) , ] [, Pyrazine , ] [, -1- , ] [, Preparation of tert-butyl formate , ] A-11 [, The following synthetic route was adopted. , ] To a 500 mL three-necked flask equipped with a magnetic stirrer and a condenser, add 1-(tert-butyloxycarbonyl)piperazine (20.00 g, 106.38 mmol), 2-bromo-5-iodopyridine (36.24 g, 127.66 mmol), tris(dibenzylideneacetone)palladium (2.43 g, 2.66 mmol), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (3.08 g, 5.32 mmol), sodium tert-butoxide (30.64 g, 319.14 mmol), and toluene (200 mL). Evacuate the mixture and purge it with nitrogen three times. Stir to disperse the mixture and react it overnight at 60 °C. The reaction was quenched by adding saturated brine (200 mL) after cooling to room temperature. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (200 mL × 2). The organic phases were combined, washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 30.50 g of white solid, yield 84.1%. LC-MS (APCI): m / z = 342.1 (M+1) +.

[0179] [, intermediate , ] [, A-12 , ] [, compound , ] [, 4-((6- , ] [, Bromopyridine , ] [, -3- , ] [, base , ] [, ) , ] [, methyl , ] [, ) , ] [, Pyrazine , ] [, -1- , ] [, Preparation of tert-butyl formate , ] A-12 [, The following synthetic route was adopted. , ] Step 1: Synthesis of compound (6-bromopyridin-3-yl)methanesulfonate methyl ester 6-Bromo-3-hydroxymethylpyridine (5.0 g, 26.88 mmol), triethylamine (8.15 g, 80.64 mmol), and dichloromethane (60 mL) were added sequentially to a container and stirred until dissolved. Methylsulfonyl chloride (6.16 g, 53.76 mmol) was added dropwise under an ice-water bath. After the addition was complete, the mixture was stirred at room temperature for 2 hours under a nitrogen atmosphere. The reaction was quenched with water (50 mL), and the organic phase was separated. The aqueous phase was extracted with dichloromethane (100 mL × 2). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a yellow oil, which was used directly in the next reaction. Step 2 Synthesis of intermediate A-12 To a container, methyl (6-bromopyridin-3-yl)methanesulfonate (approximately 26.88 mmol), acetonitrile (60 mL), 1-(tert-butyloxycarbonyl)piperazine (3.22 g, 32.26 mmol), and N,N-diisopropylethylamine (10.4 g, 80.64 mmol) obtained in the previous step were added sequentially. The mixture was stirred until dissolved, heated to 70 °C, and stirred for 2 hours. After cooling to room temperature, the solvent was removed by vacuum distillation. Water (50 mL) and ethyl acetate (50 mL) were added, and the mixture was stirred for 2 minutes. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (30 mL × 2). The organic phases were combined, washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and filtered through a column to obtain 4.3 g of a white solid, with a yield of 45.1%. LC-MS (APCI): m / z = 356.1 (M+1)+.

[0180] [, intermediate , ] [, A-13 , ] [, compound , ] [, 4-(( , ] [, Methylsulfonylurea , ] [, ) , ] [, Oxygen , ] [, ) , ] [, Guadrine , ] [, -1- , ] [, Preparation of tert-butyl formate , ] [, , ] A-13 [, , ] [, The following synthetic route was adopted. , ] [, , ] [, , ] N-tert-Butoxycarbonyl-4-hydroxyguanidine (4.0 g, 20 mmol), triethylamine (4.0 g, 39.5 mmol), and dichloromethane (40 mL) were added sequentially to the container. The container was cooled to 0 °C in an ice bath, and methanesulfonyl chloride (3.0 g, 26.2 mmol) was added dropwise. After the addition was complete, the container was allowed to warm to room temperature and stirred at room temperature for 2 hours. The reaction was quenched with water and extracted with dichloromethane (100 mL × 3). The organic phase was washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, concentrated, and used directly in subsequent reactions. [, , ]

[0181] [, intermediate , ] [, B-1 4-(4- , ] [, Bromophenyl , ] [,)-6-(1,1,1- , ] [, Trifluoropropane , ] [, -2- , ] [, base , ] [, )-1H- , ] [, Pyrazol , ] [, [4,3-c] , ] [, Pyridine , ] [, -3- , ] [, Preparation of amines , ] [, The following synthetic route was adopted. , ] Step 1: Synthesis of compound 2-(4-bromophenyl)-4-chloro-6-(1,1,1-trifluoroprop-2-yl)nicotinonitrile Intermediate A-3 (500 mg, 1.351 mmol) and phosphorus oxychloride (2 mL) were added to a 25 mL single-necked flask equipped with a magnetic stirrer and a condenser. The mixture was stirred at 90 ºC for 1 hour under a nitrogen atmosphere. After cooling to room temperature, the pH was adjusted to approximately 9 with saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate (30 mL × 2), and the organic phases were combined. The mixture was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 311 mg of a white solid, with a yield of 60%. LC-MS (APCI): m / z = 389.0 (M+1)+. Step 4: Synthesis of Intermediate B-1 2-(4-bromophenyl)-4-chloro-6-(1,1,1-trifluoroprop-2-yl)nicotinonitrile (311 mg, 0.801 mmol), hydrazine hydrate (200.6 mg, 4.008 mmol), and N,N-dimethylformamide (3 mL) were added to a 25 mL sealed tube. The mixture was stirred at 110 ºC for 1.5 h under nitrogen atmosphere. After cooling to room temperature, saturated brine (10 mL) was added, followed by extraction with ethyl acetate (30 mL × 2). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 240 mg of white solid, yield 78%. LC-MS (APCI): m / z = 385.0 (M+1)+.

[0182] [, intermediate , ] [, B-2 N-(4-(3- , ] [, cyano , ] [, -4- , ] [, Hydroxypyridine , ] [, -2- , ] [, base , ] [, ) , ] [, benzyl , ] [, )-5- , ] [, fluorine , ] [, -2- , ] [, Preparation of methoxybenzamide , ] [, The following synthetic route was adopted. , ] [, ① , ] [, , ] Step 1: Synthesis of compound N-(4-(3-cyano-4-methoxypyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzylamine 2-Chloro-4-methoxynicotinonitrile (5.0 g, 27.8 mmol), intermediate A-4 (11.0 g, 12 mmol), tetrakis(triphenylphosphine)palladium (0.35 g, 0.3 mmol), potassium carbonate (10.3 g, 74.6 mmol), and 1,4-dioxane (50 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer and a condenser. The mixture was evacuated and purged with nitrogen three times. The temperature was raised to 80 °C under nitrogen atmosphere and stirred for 12 hours. After cooling to room temperature, ethyl acetate (100 mL) was added, filtered, concentrated, and passed through a silica gel column to give 6.0 g of white solid, yield 50.1%. LC-MS (APCI): m / z = 392.14 (M+1)+. Step 2 Synthesis of intermediate B-2 N-(4-(3-cyano-4-methoxypyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzylamine (6.0 g, 8.0 mmol) and N,N-dimethylmethoxyamine (60 mL) were added to a 250 mL single-necked flask equipped with a magnetic stirrer and a condenser. The mixture was stirred until dissolved, and then p-toluenesulfonic acid (27.0 g, 69 mmol) and lithium chloride (6.5 g, 154 mmol) were added. The mixture was evacuated and purged with nitrogen three times. The temperature was raised to 180 °C, and the reaction was allowed to proceed for 30 minutes. After cooling to room temperature, the reaction mixture was poured into a stirred ice-water solution (400 mL), resulting in the precipitation of a large amount of white solid. The solid was filtered, washed with ice-water, and the filter cake was dissolved in dichloromethane (100 mL). The solution was dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to obtain 4.0 g of white solid, with a yield of 72%. LC-MS (APCI): m / z = 378.12 (M+1) +. 1H NMR (400 MHz, DMSO- D 6) δ (ppm): 12.39 (s, 1H), 8.95 (t, J = 6.0 Hz, 1H), 7.80 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.54-7.51 (m, 3H), 7.38-7.33 (m, 1H), 7.22-7.18 (m, 1H), 6.35 (br s, 1H), 4.86 (br s, 2H), 4.60 (d, J = 6.0 Hz, 2H), 3.90 (s, 3H). [, Alternatively, the following synthetic route can be used. , ] [, ② , ] Step 1: Synthesis of compound N-(4-(4-(benzyloxy)-3-cyanopyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzylamine To a 500 mL three-necked flask equipped with a magnetic stirrer and a condenser, intermediates A-5 (9.76 g, 40 mmol), A-4 (14.5 g, 48 mmol), potassium carbonate (15.56 g, 120 mmol), tetrakis(triphenylphosphine)palladium (2.3 g, 4 mmol), 1,4-dioxane (200 mL), and water (40 mL) were added sequentially. Under nitrogen protection, the mixture was heated to 105 °C and reacted for 4 hours with stirring. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (200 mL), filtered, and the filter cake was washed with ethyl acetate (30 mL). The filtrate was washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 21 g of a pale yellow oil. Ethyl acetate (50 mL) was added to the reaction solution with stirring, and the solution was heated in an oil bath to dissolve it. The solution was then slowly cooled to room temperature, and a large amount of white solid precipitated. The solution was filtered, the filter cake was washed with ethyl acetate, and dried under vacuum to give 12.4 g of white solid, with a yield of 66.4%. LC-MS (APCI): m / z = 468.2 (M+1)+. Step 2 Synthesis of intermediate B-2 N-(4-(4-(4-(benzyloxy)-3-cyanopyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzylamine (40 g, 85.65 mmol), methanol (300 mL), dichloromethane (200 mL), and palladium on carbon (10%, 4 g) were added to a 1 L three-necked flask equipped with a magnetic stirrer. Hydrogen gas was purged, and the mixture was stirred at room temperature for 16 hours. The mixture was filtered, and the filtrate was collected. The filter cake was added to a reaction flask, and N,N-dimethylformamide (100 mL) was added. The mixture was heated to 60 °C and stirred for 4 hours. After filtration, the filter cake was washed with N,N-dimethylformamide and added back to the reaction flask. N,N-dimethylformamide (100 mL) was added, and the mixture was heated to 60 °C and stirred for 4 hours. After filtration, the filter cake was washed with N,N-dimethylformamide. The filtrates were combined, and methanol, dichloromethane, and a small amount of toluene were removed by rotary evaporation. Water (300 mL) was slowly added dropwise under stirring in an oil bath at 60 °C. Heating was stopped, and the mixture was allowed to cool naturally to room temperature. A large amount of grayish-white solid precipitated in the system. The mixture was filtered, the filter cake was washed with water, and dried under vacuum to obtain 27 g of grayish-white solid, with a yield of 83.6%. LC-MS (APCI): m / z = 378.2 (M+1)+. 1H NMR (400 MHz, DMSO- D 6) δ (ppm): 12.36 (s, 1H), 8.93 (t, J = 6.0 Hz, 1H), 7.77-7.76 (m, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.53-7.49 (m, 3H), 7.36-7.31 (m, 1H), 7.20-7.16 (m, 1H), 6.31 (d, J = 8.0 Hz, 1H), 4.58 (d, J = 6.4 Hz, 2H), 3.89 (s, 3H).

[0183] [, intermediate , ] [, B-3 N-(4-(3- , ] [, amino , ] [, -7- , ] [, bromine , ] [, -1H- , ] [, Pyrazol , ] [, [4,3-c] , ] [, Pyridine , ] [, -4- , ] [, base , ] [, ) , ] [, benzyl , ] [, )-5- , ] [, fluorine , ] [, -2- , ] [, Preparation of methoxybenzamide , ] [, The following synthetic route was adopted. , ] Step 1: Synthesis of compound N-(4-(5-bromo-3-cyano-4-hydroxypyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzamide Intermediate B-2 (4.0 g, 10.6 mmol, synthesized via route ①) and N,N-dimethylformamide (20 mL) were added to a 250 mL single-necked flask equipped with a magnetic stirrer. The mixture was stirred until dissolved, and then N-bromosuccinimide (2.5 g, 14 mmol) was added. The reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere. The reaction solution was poured into 200 mL of stirred ice water, resulting in the precipitation of a large amount of white solid. The solid was filtered, washed with ice water, and the filter cake was dissolved in 100 mL of dichloromethane. The solution was dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 3.0 g of white solid, with a yield of 70%. LC-MS (APCI): m / z = 457.03 (M+2)+. 1H NMR (400 MHz, DMSO- D 6) δ (ppm): 12.90 (s, 1H), 8.94 (t, J = 6.0 Hz, 1H), 8.37 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.54-7.49 (m, 3H), 7.37-7.32 (m, 1H), 7.21-7.18 (m, 1H), 4.59 (d, J = 6.0 Hz, 2H), 3.91 (s, 3H). Step 2: Synthesis of compound N-(4-(5-bromo-4-chloro-3-cyanopyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzylamine N-(4-(5-bromo-3-cyano-4-hydroxypyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzamide (3.0 g, 6.6 mmol) and phosphorus oxychloride (20 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer. The mixture was evacuated and purged with nitrogen three times, then heated to 90 °C and stirred overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate (100 mL), and with stirring, saturated sodium bicarbonate aqueous solution (80 mL) was carefully added. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (50 mL × 2). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 2.0 g of white solid, yield 65%. LC-MS (APCI): m / z = 474.99 (M+1)+. Step 3: Synthesis of intermediate B-3 N-(4-(5-bromo-4-chloro-3-cyanopyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzamide (2.0 g, 4.2 mmol) and N,N-dimethylmethoxybenzamide (20 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer and stirred until dissolved. Hydrazine hydrate (2.1 g, 42 mmol, 80%) was added, and the mixture was heated to 110 °C and stirred for 2 hours. After cooling to room temperature, saturated brine (80 mL) was added, and the organic phase was separated. The aqueous phase was extracted with ethyl acetate (50 mL × 2). The combined organic phases were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 1.5 g of a white solid, 55% yield. LC-MS (APCI): m / z = 471.05 (M+2)+. 1H NMR (400 MHz, DMSO- D 6) δ (ppm): 12.68 (s, 1H), 8.87 (t, J = 6.0 Hz, 1H), 8.37 (s, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.53-7.48 (m, 3H), 7.36-7.31 (m, 1H), 7.20-7.17 (m, 1H), 4.84 (br s, 2H), 4.59 (d, J = 6.0 Hz, 2H), 3.90 (s, 3H).

[0184] [, intermediate , ] [, B-4 N-(4-(3- , ] [, amino , ] [, -7- , ] [, iodine , ] [, -1H- , ] [, Pyrazol , ] [, [4,3-c] , ] [, Pyridine , ] [, -4- , ] [, base , ] [, ) , ] [, benzyl , ] [, )-5- , ] [, fluorine , ] [, -2- , ] [, Preparation of methoxybenzamide , ] [, The following synthetic route was adopted. , ] Step 1: Synthesis of compound N-(4-(3-cyano-4-hydroxy-5-iodopyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzamide Intermediate B-2 (20 g, 53 mmol, synthesized via route ②) and acetonitrile (300 mL) were added to a 500 mL three-necked flask equipped with a magnetic stirrer. N-iodobutyric acid (14.4 g, 48 mmol) was added with stirring. Under nitrogen protection, the mixture was heated to 70 °C and reacted for 4 hours with stirring. After cooling to room temperature, the mixture was filtered, the filter cake was washed with ethyl acetate, and dried under vacuum at 80 °C to give 20.5 g of a grayish-white solid, yield 76.9%. LC-MS (APCI): m / z = 504.0 (M+1)+. 1H NMR (400 MHz, DMSO- D 6) δ (ppm): 12.74 (s, 1H), 8.93 (t, J = 6.0 Hz, 1H), 8.38 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.54-7.49 (m, 3H), 7.37-7.32 (m, 1H), 7.21-7.18 (m, 1H), 4.59 (d, J = 6.0 Hz, 2H), 3.90 (s, 3H). Step 2: Synthesis of compound N-(4-(4-chloro-3-cyano-5-iodopyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzylamine N-(4-(3-cyano-4-hydroxy-5-iodopyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzamide (7 g, 13.9 mmol) and phosphorus oxychloride (21 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer and a condenser. The mixture was heated to 80 °C with stirring and reacted for 4 hours, during which time the system gradually dissolved. Most of the phosphorus oxychloride was removed by rotary evaporation. Ethyl acetate (70 mL) was added and stirred until completely dissolved. The mixture was cooled to 5 °C in an ice-water bath, and ice water (50 mL) was slowly added. The mixture was stirred for 10 minutes, and the phases were separated. The aqueous phase was adjusted to pH 11 with 4% sodium hydroxide solution and extracted with ethyl acetate (50 mL). The organic phases were combined and adjusted to pH 9 with saturated sodium bicarbonate solution. The organic phases were separated, washed with saturated sodium bicarbonate solution (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 6.0 g of white solid, with a yield of 82.7%. LC-MS (APCI): m / z = 522.0 (M+1) +. Step 3: Synthesis of intermediate B-4 N-(4-(4-chloro-3-cyano-5-iodopyridin-2-yl)benzyl)-5-fluoro-2-methoxybenzamide (6 g, 11.5 mmol) and N,N-dimethylmethoxybenzamide (30 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer and a condenser. The mixture was stirred until dissolved, and then hydrazine hydrate (5 g, 50 mmol, 50%) was added. The mixture was heated to 80 °C with stirring and reacted for 2 hours. The reaction mixture was poured into water (60 mL), extracted with dichloromethane (30 mL × 3), and the organic phases were combined. The mixture was washed successively with water (30 mL × 3), saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 2.88 g of a yellow solid, yield 48.4%. LC-MS (APCI): m / z = 518.1 (M+1) +. 1H NMR (400 MHz, DMSO- D 6) δ (ppm): 12.64 (s, 1H), 8.88 (t, J = 6.0 Hz, 1H), 8.37 (s, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.53-7.48 (m, 3H), 7.36-7.31 (m, 1H), 7.20-7.17 (m, 1H), 4.84 (br s, 2H), 4.59 (d, J = 6.0 Hz, 2H), 3.91 (s, 3H).

[0185] [, intermediate , ] [, B-5 N-(4-(3- , ] [, amino , ] [, -7- , ] [, iodine , ] [, -1H- , ] [, Pyrazol , ] [, [4,3-c] , ] [, Pyridine , ] [, -4- , ] [, base , ] [, )-3- , ] [, Fluorobenzyl, ] [, )-5- , ] [, fluorine , ] [, -2- , ] [, Preparation of methoxybenzamide , ] [, The following synthetic route was adopted. , ] [, , ] Step 1: Synthesis of compound N-(4-bromo-3-fluorobenzyl)-5-fluoro-2-methoxybenzylamine Add 3-fluoro-4-bromobenzylamine hydrochloride (5.0 g, 20.8 mmol), 3-fluoro-6-methoxybenzoic acid (4.2 g, 24.9 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (5.2 g, 20.97 mmol), 1-hydroxybenzotriazole (3.65 g, 20.97 mmol), and dichloromethane (50 mL) to a 50 mL single-necked flask equipped with a magnetic stirrer. Evacuate the mixture three times with nitrogen, stir thoroughly in an ice bath, and add N,N-diisopropylethylamine (9.0 mL, 62.25 mmol). Stir the mixture overnight at room temperature. Cool to room temperature, quench the reaction with saturated brine (50 mL), separate the organic phase, and extract the aqueous phase with dichloromethane (50 mL × 2). Combine the organic phases and extract with saturated brine (50 mL × 2). Washed with anhydrous sodium sulfate (mL), dried, filtered, concentrated, and passed through a silica gel column to give 6.6 g of white solid, yield 89.9%. LC-MS (APCI): m / z = 356.0 (M+1)+. Step 2: Synthesis of compound 5-fluoro-N-(3-fluoro-4-boronate benzyl)-2-methoxybenzylamine N-(4-bromo-3-fluorobenzyl)-5-fluoro-2-methoxybenzamide (5.0 g, 14.08 mmol), pinacol diborate (5.0 g, 19.69 mmol), dichloromethane-[1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (1.14 g, 1.4 mmol), potassium acetate (4.1 g, 42.2 mmol), 1,4-dioxane (40 mL), and N,N-dimethylmethamide (10 mL) were added to a 250 mL three-necked flask equipped with a magnetic stirrer and a condenser. The flask was evacuated and purged with nitrogen three times, and the mixture was stirred overnight at 100 °C. The reaction was quenched by adding saturated brine (30 mL) after cooling to room temperature. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (40 mL × 2). The organic phases were combined, washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 5.6 g of white solid, yield 98.7%. LC-MS (APCI): m / z = 404.0 (M+1) +. Step 3: Synthesis of compound N-(4-(4-(benzyloxy)-3-cyanopyridin-2-yl)-3-fluorobenzyl)-5-fluoro-2-methoxybenzylamine To a 100 mL three-necked flask equipped with a magnetic stirrer and a condenser, 5-fluoro-N-(3-fluoro-4-borate pinacol ester benzyl)-2-methoxybenzylamine (3.0 g, 7.44 mmol), intermediate A-5 (2.18 g, 8.93 mmol), tetra(triphenylphosphine)palladium (859.9 mg, 0.744 mmol), sodium carbonate (2.37 g, 22.32 mmol), 1,4-dioxane (30 mL), and water (7 mL) were added. The mixture was evacuated and purged with nitrogen three times, and stirred overnight at 90 °C. After cooling to room temperature, the reaction was quenched with saturated brine (30 mL), the organic phase was separated, and the aqueous phase was extracted with ethyl acetate (30 mL × 2). The combined organic phases were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 2.17 g of a white solid, yield 60.1%. LC-MS (APCI): m / z = 486.0 (M+1) +. Step 4: Synthesis of compound N-(4-(3-cyano-4-hydroxypyridin-2-yl)-3-fluorobenzyl)-5-fluoro-2-methoxybenzamide N-(4-(4-(4-(benzyloxy)-3-cyanopyridin-2-yl)-3-fluorobenzyl)-5-fluoro-2-methoxybenzamide (2.1 g, 4.33 mmol), palladium on carbon (5%, 210 mg), and methanol (30 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer. The mixture was evacuated and purged with hydrogen three times, and stirred overnight at room temperature. The mixture was filtered, the filter cake was washed with methanol, the organic phases were combined, and concentrated to give 1.7 g of white solid, yield 99.4%. LC-MS (APCI): m / z = 396.0 (M+1)+. Step 5: Synthesis of compound N-(4-(3-cyano-4-hydroxy-5-iodopyridin-2-yl)-3-fluorobenzyl)-5-fluoro-2-methoxybenzamide N-(4-(4-(4-(benzyloxy)-3-cyanopyridin-2-yl)-3-fluorobenzyl)-5-fluoro-2-methoxybenzylamine (1.7 g, 4.3 mmol), N-iodobutyridimine (1.1 g, 4.84 mmol), and acetonitrile (40 mL) were added sequentially to a 100 mL single-necked flask equipped with a magnetic stirrer. The mixture was evacuated and purged with hydrogen three times, and stirred overnight at 60 °C. The mixture was filtered, washed with ethyl acetate, and the residue was collected and dried to give 1.55 g of a white solid, yield 69.2%. LC-MS (APCI): m / z = 522.0 (M+1)+. Step 6: Synthesis of compound N-(4-(4-chloro-3-cyano-5-iodopyridin-2-yl)-3-fluorobenzyl)-5-fluoro-2-methoxybenzamide N-(4-(3-cyano-4-hydroxy-5-iodopyridin-2-yl)-3-fluorobenzyl)-5-fluoro-2-methoxybenzamide (1.7 g, 4.3 mmol) and phosphorus oxychloride (15 mL) were added to a 50 mL single-necked flask equipped with a magnetic stirrer. The mixture was evacuated and purged with hydrogen three times, and stirred at 90 °C for 1 hour. After cooling to room temperature, the mixture was concentrated under reduced pressure, and the reaction was quenched with saturated sodium bicarbonate aqueous solution (30 mL). The mixture was extracted with ethyl acetate (30 mL × 2), and the organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 1.07 g of white solid, yield 66.73%. LC-MS (APCI): m / z = 540.0 (M+1) +. Step 7 Synthesis of intermediate B-5 N-(4-(4-chloro-3-cyano-5-iodopyridin-2-yl)-3-fluorobenzyl)-5-fluoro-2-methoxybenzamide (500 mg, 0.93 mmol), hydrazine hydrate (0.15 mL, 0.79 mmol), and N,N-dimethylmethoxymethylamine (5 mL) were added to a 20 mL sealed tube equipped with a magnetic stirrer. The tube was sealed and stirred at 110 °C for 2 hours. After cooling to room temperature, the reaction was quenched with saturated brine (10 mL). The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (10 mL × 2). The organic phases were combined, washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 400 mg of white solid, yield 80.4%. LC-MS (APCI): m / z = 536.0 (M+1)+.

[0186] [, intermediate , ] [, B-6 N-(4-(3- , ] [, amino , ] [, -7- , ] [, iodine , ] [, -1H- , ] [, Pyrazol , ] [, [4,3-c] , ] [, Pyridine , ] [, -4- , ] [, base , ] [, )-3- , ] [, Methylbenzyl , ] [, )-5- , ] [, fluorine , ] [, -2- , ] [, Preparation of methoxybenzamide , ] [, The following synthetic route was adopted. , ] [, , ] Step 1: Synthesis of compound 2-(4-bromo-3-methylbenzyl)isodihydroindole-1,3-dione 3-Methyl-4-bromobenzyl bromide (5.0 g, 18.9 mmol), potassium phthalimide (3.85 g, 20.8 mmol), and N,N-dimethylformamide (50 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer and condenser. The mixture was evacuated and purged with nitrogen three times. The mixture was stirred overnight at 60 °C. After cooling to room temperature, the reaction was quenched with saturated brine (50 mL). The organic phase was separated, and the aqueous phase was extracted with dichloromethane (50 mL × 2). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 6.2 g of white solid, yield 99.7%. LC-MS (APCI): m / z = 330.0 (M+1)+. Step 2: Synthesis of compound (4-bromo-3-methylphenyl)methylamine 2-(4-bromo-3-methylbenzyl)isodihydroindole-1,3-dione (5.92 g, 18 mmol) and methanol (50 mL) were added to a 250 mL three-necked flask equipped with a magnetic stirrer and a condenser. The mixture was evacuated and purged with nitrogen three times. The mixture was stirred thoroughly at 50 °C. Hydrazine hydrate (2.5 mL, 39.6 mmol) was added, and the mixture was heated under reflux for 1 hour. After cooling to room temperature, the reaction was quenched with saturated brine (30 mL). The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (50 mL × 2). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 3.58 g of a colorless oily liquid, yield 99.7%. LC-MS (APCI): m / z = 200.0 (M+1) +. Step 3: Synthesis of compound N-(4-bromo-3-methylbenzyl)-5-fluoro-2-methoxybenzamide Add (4-bromo-3-methylphenyl)methylamine (3.58 g, 17.9 mmol), 3-fluoro-6-methoxybenzoic acid (5.1 g, 29.9 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (6.23 g, 32.5 mmol), 1-hydroxybenzotriazole (4.39 g, 24.07 mmol), and dichloromethane (50 mL) to a 250 mL three-necked flask equipped with a magnetic stirrer. Evacuate the mixture and purge with nitrogen three times. Stir thoroughly in an ice bath. Add N,N-diisopropylethylamine (10.8 mL, 75.2 mmol) dropwise. Stir the reaction overnight at room temperature. Cool to room temperature and quench the reaction with saturated brine (50 mL). Separate the organic phase. Extract the aqueous phase with dichloromethane (50 mL × 2). Combine the organic phases and extract with saturated brine (50 mL × 2). Wash with mL of the solution, dry to anhydrous sodium sulfate, filter, concentrate, and pass through a silica gel column to give 4.71 g of white solid, yield 74.9%. LC-MS (APCI): m / z = 352.0 (M+1)+. Step 4: Synthesis of compound 5-fluoro-2-methoxy-N-(3-methyl-4-boronate benzyl)benzylamine N-(4-bromo-3-methylbenzyl)-5-fluoro-2-methoxybenzamide (4.71 g, 13.4 mmol), pinacol diborate (4.08 g, 16.08 mmol), dichloromethane-[1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (1.09 g, 1.34 mmol), potassium acetate (3.95 g, 40.2 mmol), 1,4-dioxane (40 mL), and N,N-dimethylmethamide (10 mL) were added to a 250 mL three-necked flask equipped with a magnetic stirrer and a condenser. The flask was evacuated and purged with nitrogen three times, and the mixture was stirred overnight at 100 °C. The reaction was quenched by adding saturated brine (30 mL) after cooling to room temperature. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (40 mL × 2). The organic phases were combined, washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 4.5 g of white solid, yield 84.1%. LC-MS (APCI): m / z = 400.0 (M+1) +. Step 5: Synthesis of compound N-(4-(4-(benzyloxy)-3-cyanopyridin-2-yl)-3-methylbenzyl)-5-fluoro-2-methoxybenzamide To a 100 mL three-necked flask equipped with a magnetic stirrer and a condenser, add 5-fluoro-2-methoxy-N-(3-methyl-4-borate pinacol ester benzyl)benzylamine (3.0 g, 7.5 mmol), intermediate A-5 (2.2 g, 9.0 mmol), tetra(triphenylphosphine)palladium (866.7 mg, 0.75 mmol), sodium carbonate (2.4 g, 22.5 mmol), 1,4-dioxane (30 mL), and water (7 mL). Evacuate the mixture and purge with nitrogen three times. Stir the mixture overnight at 90 °C. Cool to room temperature, quench the reaction with saturated brine (30 mL), separate the organic phase, extract the aqueous phase with ethyl acetate (30 mL × 2), combine the organic phases, wash with saturated brine (30 mL), dry to anhydrous sodium sulfate, filter, concentrate, and pass through a silica gel column to give 1.56 g of white solid, yield 43.2%. LC-MS (APCI): m / z = 482.0 (M+1) +. Step 6: Synthesis of compound N-(4-(3-cyano-4-hydroxypyridin-2-yl)-3-methylbenzyl)-5-fluoro-2-methoxybenzamide N-(4-(4-(4-(benzyloxy)-3-cyanopyridin-2-yl)-3-methylbenzyl)-5-fluoro-2-methoxybenzamide (1.56 g, 3.24 mmol), palladium on carbon (5%, 156 mg), and methanol (30 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer. The mixture was evacuated and purged with hydrogen three times, and stirred overnight at room temperature. The mixture was filtered, the filter cake was washed with methanol, the organic phases were combined, and concentrated to give 1.26 g of white solid, yield 99.4%. LC-MS (APCI): m / z = 392.0 (M+1)+. Step 7: Synthesis of compound N-(4-(3-cyano-4-hydroxy-5-iodopyridin-2-yl)-3-methylbenzyl)-5-fluoro-2-methoxybenzamide N-(4-(3-cyano-4-hydroxypyridin-2-yl)-3-methylbenzyl)-5-fluoro-2-methoxybenzamide (1.26 g, 3.23 mmol), N-iodobutyldiimidimide (801.8 g, 3.56 mmol), and acetonitrile (30 mL) were added to a 100 mL single-necked flask equipped with a magnetic stirrer. The mixture was evacuated and purged with nitrogen three times, and stirred overnight at 60 °C. The mixture was filtered, washed with ethyl acetate, and the residue was collected and dried to give 992 mg of a white solid, yield 59.4%. LC-MS (APCI): m / z = 518.0 (M+1)+. Step 8: Synthesis of compound N-(4-(4-chloro-3-cyano-5-iodopyridin-2-yl)-3-methylbenzyl)-5-fluoro-2-methoxybenzamide N-(4-(3-cyano-4-hydroxy-5-iodopyridin-2-yl)-3-methylbenzyl)-5-fluoro-2-methoxybenzamide (992 mg, 1.92 mmol) and phosphorus oxychloride (10 mL) were added to a 50 mL single-necked flask equipped with a magnetic stirrer. The mixture was evacuated and purged with nitrogen three times, and stirred at 90 °C for 2 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure, and the reaction was quenched with saturated sodium bicarbonate aqueous solution (30 mL). The mixture was extracted with ethyl acetate (30 mL × 2), and the organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 337 mg of white solid, yield 32.8%. LC-MS (APCI): m / z = 536.0 (M+1) +. Step 9: Synthesis of intermediate B-6 N-(4-(4-chloro-3-cyano-5-iodopyridin-2-yl)-3-methylbenzyl)-5-fluoro-2-methoxybenzamide (337 mg, 0.63 mmol), hydrazine hydrate (0.12 mL, 1.89 mmol), and N,N-dimethylmethoxymethylamine (5 mL) were added to a 15 mL sealed tube equipped with a magnetic stirrer. The tube was sealed and stirred at 110 °C for 2 hours. After cooling to room temperature, the reaction was quenched with saturated brine (10 mL). The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (10 mL × 2). The organic phases were combined, washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and passed through a silica gel column to give 300 mg of white solid, yield 89.7%. LC-MS (APCI): m / z = 532.0 (M+1)+.

[0187] [, intermediate , ] [, B-7 N-(4-(3- , ] [, amino , ] [, -7- , ] [, bromine , ] [, -6- , ] [, methyl , ] [, -1H- , ] [, Pyrazol , ] [, [4,3-c] , ] [, Pyridine , ] [, -4- , ] [, base , ] [, ) , ] [, benzyl , ] [, )-5- , ] [, fluorine , ] [, -2- , ] [, Preparation of methoxybenzamide , ] [, The following synthetic route was adopted. , ] [, , ] [, , ] Step 1: Synthesis of compound 2-(4-bromophenyl)-4-hydroxy-6-methylnicotinonitrile Intermediate A-2 (3 g, 12.71 mmol), ethyl acetoacetate (25.42 mmol, 3.3 g), and N-methylpyrrolidone (10 mL) were added to a container. The mixture was heated to 250 °C under microwave and reacted for 15 minutes. After cooling to room temperature, the solvent was removed by vacuum distillation. The residue was passed through a column ch...

Claims

1. A compound, which is a compound represented by formula (A), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate, or solvate thereof: wherein, Ring A is a benzene ring or a 5-6 membered heteroaryl ring; X1 is N, CD, or CH; X2 is N or CR2; R1 is H, D, halogen, -C(O)R a, -C(O)OR a, -C(O)NR bR c, -NR bR c, -NR aC(O)R b, -NR aC(O)OR b, -NR aC(O)NR bR c, -OR a, -OC(O)R a, -OC(O)NR bR c, -NR aS(O) 2R b, -S(O) 2NR bR c, -S(O)R a, -S(O) 2R a, -P(=O)R bR c, -OP(=O)R bR c, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 membered heterocyclic group, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R; wherein each Ra, Rb and Rc is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Rb and Rc together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl are substituted by one or more R. The 2-6-alkenyl, C2-6-ynyl, C6-10 aryl, and 5-10-membered heteroaryl groups are optionally substituted by one or more Rs; R2 is H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6-ynyl, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-12-membered heterocyclic, C2-6 alkenyl, C2-6-ynyl, C6-10 aryl, and 5-10-membered heteroaryl groups are optionally substituted by one or more R's; R3 and R4 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C2-6 alkenyl, C2-6-ynyl, C6-10 aryl, and 5-10-membered heteroaryl groups are optionally substituted by one or more R's; The 1-6 haloalkyl group is optionally substituted with one or more D molecules until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl group or a C1-6 haloalkyl group, wherein the C1-6 alkyl group and the C1-6 haloalkyl group are optionally substituted with one or more D molecules until fully deuterated;Rs and Rt are independently H, D, halogen, -ORa, -NRbRc, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; m is 0, 1, 2 or 3; n is 0, 1, 2, 3 or 4; each R is independently: 1) H, D, halogen, oxo, -C(O)Rd, -C(O)ORd, -C(O)NReRf, -NReRf, -NRdC(O)Re, -NRdC(O)ORe, -NRdC(O)NReRf, -ORd, -OC(O)Rd, -OC(O)NReRf, -NRdS(O)2Re, -S(O)2NReRf, -S(O)Rd, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, -C1-6 alkyl-C3-6 cycloalkyl, -C1-6 alkyl-3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, wherein the group is optionally substituted by one or more R''; or 3) two R's on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-12-membered heterocyclic, C6-10 aryl or 5-10 heteroaryl, wherein the group is optionally substituted by one or more R''; each R' is independently H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl or 5-10 membered heteroaryl, or two R' on the same atom or two adjacent atoms together with the atoms they are attached to form C 3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl are optionally substituted by one or more R'';Each Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic or 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more R''; each R'' is independently H, D, halogen, oxo, -C(O)Rg, -C(O)ORg, -C(O)NRhRj, -NRhRj, -NRgC(O)Rg h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C The 1-6-haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl groups are optionally substituted by one or more R''; each R'' is independently substituted by H, D, halogen, C1-6 alkyl, C1-6-haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C6-10 aryl, or 5-10-membered heteroaryl groups; wherein the C1-6 alkyl, C1-6-haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C6-10 aryl, or 5-10-membered heteroaryl groups are optionally substituted by one or more D, halogen, C1-6 alkyl, C1-6-haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C6-10 aryl, or 5-10-membered heteroaryl groups; wherein each R'' is substituted by one or more D, halogen, C1-6 alkyl, C1-6-haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C6-10 aryl, or 5-10-membered heteroaryl groups; wherein each R'' is substituted by one or more D, halogen, C3-6 alkyl, C4-6-haloalkyl, C5-6 cycloalkyl, 3-7-membered heterocyclic, C6-10 aryl, or 5-10-membered heteroaryl groups; wherein each R'' is substituted by one or more R''; g, R h and R j are independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or R h and R j together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl;The C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted with one or more D groups until fully deuterated.

2. The compound as claimed in claim 1, which is a compound represented by formula (II): wherein, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Y1 is N or CR12; R10, R11, and R12 are independently: 1) H, D, halogen, oxo, -C(O)Rd, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 membered heteroaryl, wherein said groups are optionally substituted by one or more R”; or 3) R 11 and R 12 together with the atoms to which they are attached form C 3-6 cycloalkyl, optionally substituted with one or more R”; or 4) R 10 and R 11 or R 11 and R 12 together with the atoms to which they are attached form a 3-12-membered heterocyclic group or a 5-10-membered heteroaryl group, wherein said group is optionally substituted with one or more R”; or 5) R 11 and R 12 together with the atoms to which they are attached form a C 6-10 aryl group, optionally substituted with one or more R”; wherein each R d, Re and R f is independently H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclic group, C 2-6 alkenyl, C 2-6 ynyl, C 6-10 aryl or 5-10-membered heteroaryl group, or Re and R f together with the atoms to which they are attached form a 3-7-membered heterocyclic group or a 5-10-membered heteroaryl group; wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted by one or more R's;Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Rh and R j, together with the atoms they are attached to, forms a 3-7 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic group, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 membered heteroaryl groups are optionally substituted with one or more D atoms until fully deuterated; preferably, wherein X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R t is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; Y1 is N or C12;R10 is H, a C1-6 alkyl, a C1-6 haloalkyl, a C3-6 cycloalkyl, or a 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R''; R11 and R12 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D's until fully deuterated; or R11 and R12 together with the atoms to which they are attached form a C3-6 cycloalkyl group, which is optionally substituted by one or more R''s; or R10 and R11 or R11 and R' ... R12, together with the atoms to which they are attached, forms a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, or a 5-10 membered heteroaryl group, wherein said groups are optionally substituted by one or more R”; or R11 and R12, together with the atoms to which they are attached, form a C6-10 aryl group, which is optionally substituted by one or more R”; each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or a 3-7 membered heterocyclic group, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more D until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein said C1-6 alkyl and C The 1-6 haloalkyl group is optionally substituted with one or more D atoms until fully deuterated; preferably, X2 is N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H; R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y1 is N or CR12; R10 is H, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more R''; preferably, R 10 is H, C1-3 alkyl, or C1-3 haloalkyl, wherein the C1-3 alkyl and C1-3 haloalkyl are optionally substituted with one or more D until fully deuterated; R11 and R12 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated;Preferably, R11 and R12 are independently H or D; or, R11 and R12 together with the atoms they are attached to form a C3-6 cycloalkyl group, optionally substituted with one or more R''s; preferably, R11 and R12 together with the atoms they are attached to form a cyclohexyl group, optionally substituted with one or more R''s; or R10 and R11 or R11 and R12 together with the atoms they are attached to form a 3-7 membered monocyclic heterocyclic group, optionally substituted with one or more R''s; preferably, R10 and R11 or R11 and R12 together with the atoms they are attached to form a 6 membered heterocyclic group having one or two cyclic heteroatoms selected from N, optionally substituted with one or more R''s; or R10 and R11 or R11 and R''s R10 and R11, together with the atoms they are attached to, form a 6-12 fused bicyclic heterocycle, optionally substituted with one or more R''s; preferably, R10 and R11, or R11 and R12, together with the atoms they are attached to, form an 8-10 fused bicyclic heterocycle having one or two ring heteroatoms selected from N, optionally substituted with one or more R''s; or R11 and R12, together with the atoms they are attached to, form a C6-10 aryl group, optionally substituted with one or more R''s; preferably, R11 and R12, together with the atoms they are attached to, form a phenyl group, optionally substituted with one or more R''s; or R10 and R11, or R11 and R12, together with the atoms they are attached to, form a 5-10 heteroaryl group, optionally substituted with one or more R''s; preferably, R10 and R11, or R11 and R''s... 12, together with the atoms they are attached to, form a 5- or 6-membered heteroaryl group having one or two cyclic heteroatoms selected from N, wherein said group is optionally substituted by one or more R”; each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7-membered heterocyclic group, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7-membered heterocyclic group is optionally substituted by one or more D until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein said C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C 1-6 haloalkyl groups, wherein the C1-6 alkyl groups and C1-6 haloalkyl groups are optionally substituted with one or more D atoms, up to complete deuteration.

3. The compound as claimed in claim 1, which is a compound represented by formula (II-1): wherein, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D or a halogen; preferably, Rt is H, D or F; Y1 is N, CH or CD; R10 and R11 together with the atoms to which they are attached form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted with one or more R”; preferably, R10 and R11 together with the atoms to which they are attached form a 6 membered heterocyclic group having 1 or 2 ring heteroatoms selected from N, which is optionally substituted with one or more R”; or R10 and R11 together with the atoms to which they are attached form a 6-12 membered fused bicyclic heterocycle, which is optionally substituted with one or more R”; preferably, R R10 and R11, together with the atoms to which they are attached, form an 8-10 fused bicyclic heterocycle having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R”; or R10 and R11, together with the atoms to which they are attached, form a 5-10 cyclic heteroaryl group, optionally substituted by one or more R”; preferably, R10 and R11, together with the atoms to which they are attached, form a 6-cyclic heteroaryl group having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R”; each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 cyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C The 3-6 cycloalkyl and 3-7 membered heterocyclic groups are optionally substituted with one or more D groups until fully deuterated; preferably, each R' is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D groups until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D groups until fully deuterated; preferably, wherein R5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y1 is N, CH, or CD; R10 and R11, together with the atoms they are attached to, form the following groups: , , , , , , , , , , , , , Alternatively, the group may be optionally substituted with one or more D atoms until fully deuterated; preferably, R10 and R11 together with the atoms to which they are attached form the following groups: , , , , or, the group may be optionally substituted with one or more D atoms until fully deuterated.

4. The compound as claimed in claim 1, which is a compound represented by formula (III): wherein, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R13, R14, and R15 are independently: 1) H, D, halogen, oxo, -C(O)Rd, -C(O)ORd, -C(O)NReRf, -NReR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 membered heteroaryl, wherein said groups are optionally substituted by one or more R”; or 3) R 13 and R 14 or R 13 and R 15, together with the atoms to which they are attached, form a 3-12 membered heterocyclic group or a 5-10 membered heteroaryl group, wherein said group is optionally substituted by one or more R”; wherein each Rd, Re and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic group, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 membered heteroaryl, or Re and Rf, together with the atoms to which they are attached, form a 3-7 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic group, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 membered heteroaryl groups are optionally substituted by one or more R”;Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Rh and R j, together with the atoms they are attached to, forms a 3-7 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic group, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 membered heteroaryl groups are optionally substituted with one or more D atoms until fully deuterated; preferably, wherein X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R t is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; R13 is H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl or 3-7 heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl and 3-7 heterocyclic group are optionally substituted by one or more R”;R14 and R15 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; or, R13 with R14 or R13 with R15 together with the atoms to which they are attached form a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, or a 5-10 membered heteroaryl group, wherein the group is optionally substituted by one or more R”; each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C4-6 cycloalkyl, C5 ... The 3-6 cycloalkyl and 3-7 membered heterocyclic groups are optionally substituted with one or more D groups until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D groups until fully deuterated; preferably, X2 is N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H; R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D groups until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, R t is H, D, or F; R13 is H, C1-6 alkyl, C1-6 haloalkyl, or a 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R13 is H, C1-3 alkyl, C1-3 haloalkyl, or a 6 membered heterocyclic group having one or two ring heteroatoms selected from N, wherein the C1-3 alkyl, C1-3 haloalkyl, and 6 membered heterocyclic group are optionally substituted by one or more R”; R14 and R15 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; preferably, R14 and R15 are independently H or D; or, R13 and R14 or R R13 and R15 together with the atoms to which they are attached form a 3-7 member monocyclic heterocyclic group, which is optionally substituted by one or more R”; preferably, R13 and R14 or R13 and R15 together with the atoms to which they are attached form a 6 member heterocyclic group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R”.R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 6-12 fused bicyclic heterocycle, optionally substituted by one or more R”; preferably, R13 and R14 or R13 and R15, together with the atoms they are attached to, form an 8-10 fused bicyclic heterocycle having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R”; or R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 5-10 fused heteroaryl group, optionally substituted by one or more R”; preferably, R13 and R14 or R13 and R15, together with the atoms they are attached to, form a 6-fused heteroaryl group having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R”; each R” is independently D, -C(O)OR g, -C(O)NR hR j, -NR gC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 heterocyclic group are optionally substituted with one or more D groups until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, C1-6 haloalkyl, or 3-7 heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 heterocyclic group are optionally substituted with one or more D groups until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D groups until fully deuterated.

5. The compound as claimed in claim 1, which is a compound represented by formula (III-1): wherein, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D atoms until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D or a halogen; preferably, Rt is H, D or F; R13 and R14 or R13 and R15 together with the atoms to which they are attached form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted with one or more R''; preferably, R13 and R14 or R13 and R15 together with the atoms to which they are attached form a 6 membered heterocyclic group having one or two ring heteroatoms selected from N, which is optionally substituted with one or more R''; or R13 and R14 or R13 and R'' R15, together with the atoms to which they are attached, forms a 6-12 fused bicyclic heterocycle, optionally substituted by one or more R”; preferably, R13 and R14 or R13 and R15, together with the atoms to which they are attached, form an 8-10 fused bicyclic heterocycle having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R”; or R13 and R14 or R13 and R15, together with the atoms to which they are attached, form a 5-10 fused heteroaryl group, optionally substituted by one or more R”; preferably, R13 and R14 or R13 and R15, together with the atoms to which they are attached, form a 6-fused heteroaryl group having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R”; each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C 1-6-haloalkyl, C3-6 cycloalkyl, or 3-7-membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7-membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated; preferably, each R' is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D groups until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D groups until fully deuterated; preferably, wherein R5 is F; R6 is methyl or -CD3; Rt is H, D, or F; R13 and R14 or R13 and R 15 are formed together with the atoms to which they are attached, wherein the groups are optionally substituted with one or more D atoms, up to complete deuteration.

6. The compound as claimed in claim 1, which is a compound represented by formula (IV): wherein, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Y2 is O or S; R16 and R17 are independently 1) H, D, halogen, oxo, -C(O)Rd, -C(O)ORd, -C(O)NReRf, -NReR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 membered heteroaryl, wherein said groups are optionally substituted by one or more R”; or 3) R 16 and R 17 together with the atoms to which they are attached form C3-6 cycloalkyl, 3-12 membered heterocyclic, C 6-10 aryl or 5-10 heteroaryl, wherein the group is optionally substituted by one or more R”; or wherein each Rd, Re and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Re and Rf together with the atoms to which they are attached form a 3-7 heterocyclic or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more R”;Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R's on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more Ds until fully deuterated; wherein each Rg, Rh and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Rh and R j, together with the atoms they are attached to, forms a 3-7 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic group, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 membered heteroaryl groups are optionally substituted with one or more D atoms until fully deuterated; preferably, wherein X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R t is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; Y2 is O or S;R16 and R17 are independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic groups, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic groups are optionally substituted by one or more R”; or R16 and R17 together with the atoms to which they are attached form a C3-6 cycloalkyl group, which is optionally substituted by one or more R”; or R16 and R17 together with the atoms to which they are attached form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted by one or more R”; or R16 and R17 together with the atoms to which they are attached form a 6-12 membered fused bicyclic heterocycle, which is optionally substituted by one or more R”; or R16 and R17 together with the atoms to which they are attached form a C6-10 aryl group, which is optionally substituted by one or more R”; or R16 and R 17, together with the atoms they are attached to, form 5-10-membered heteroaryl groups, which are optionally substituted by one or more R”; each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7-membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7-membered heterocyclic group are optionally substituted by one or more D until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; preferably, wherein X2 is N or CR2; R2 is H, D, or a halogen; preferably, R R2 is H, D, or F; preferably, R2 is H; R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted by one or more D until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y2 is O or S; R16 and R17 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R"; preferably, R10 is H, D, C1-3 alkyl, or C1-3 haloalkyl, wherein the C1-3 alkyl and C 1-3 haloalkyl groups are optionally substituted with one or more D atoms until fully deuterated; or, R16 and R17, together with the atoms to which they are attached, form C3-6 cycloalkyl groups, which are optionally substituted with one or more R''.Preferably, R16 and R17, together with the atoms they are attached to, form a cyclohexyl group, which is optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a 3-7 member monocyclic heterocyclic group, which is optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form a 6 member heterocyclic group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a 6-12 member fused bicyclic heterocycle, which is optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form an 8-10 member fused bicyclic heterocycle having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a C 6-10 aryl groups, optionally substituted with one or more R''; preferably, R16 and R17 together with the atoms they are attached to form a phenyl group, optionally substituted with one or more R''; or R16 and R17 together with the atoms they are attached to form a 5-10 heteroaryl group, optionally substituted with one or more R''; preferably, R16 and R17 together with the atoms they are attached to form a 6-membered heteroaryl group having one or two cyclic heteroatoms selected from N, optionally substituted with one or more R''; each R'' is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C4-7 heterocyclic group is a 5-10 heteroaryl group. The 3-6 cycloalkyl and 3-7 heterocyclic groups are optionally substituted with one or more D groups until fully deuterated; preferably, each R' is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D groups until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D groups until fully deuterated.

7. The compound as claimed in claim 1, which is a compound represented by formula (IV-1): wherein, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D or a halogen; preferably, Rt is H, D or F; Y2 is O or S; R16 and R17 together with the atoms to which they are attached form a C3-6 cycloalkyl group, which is optionally substituted with one or more R”; preferably, R16 and R17 together with the atoms to which they are attached form a cyclohexyl group, which is optionally substituted with one or more R”; or R16 and R17 together with the atoms to which they are attached form a 3-7 membered monocyclic heterocyclic group, which is optionally substituted with one or more R”; preferably, R16 and R R17, together with the atoms they are attached to, forms a 6-membered heterocyclic group having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a 6-12 membered fused bicyclic heterocycle, optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form an 8-10 membered fused bicyclic heterocycle having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a C6-10 aryl group, optionally substituted by one or more R''; preferably, R16 and R17, together with the atoms they are attached to, form a phenyl group, optionally substituted by one or more R''; or R16 and R17, together with the atoms they are attached to, form a 5-10 membered heteroaryl group, optionally substituted by one or more R''; preferably, R16 and R''... 17, together with the atoms they are attached to, form a 6-membered heteroaryl group having one or two cyclic heteroatoms selected from N, which is optionally substituted by one or more R”; each R” is independently D, -C(O)ORg, -C(O)NRhRj, -NRgC(O)Rh, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 heterocyclic group are optionally substituted by one or more D until fully deuterated; preferably, each R” is independently D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C The 1-6 alkyl and C1-6 haloalkyl groups are optionally substituted with one or more D groups until fully deuterated; preferably, R5 is F; R6 is methyl or -CD3;Rt is H, D, or F; Y2 is O or S; R16 and R17, together with the atoms they are attached to, form groups such as , , or , wherein said groups are optionally substituted with one or more D atoms until complete deuteration.

8. The compound as claimed in claim 1, which is a compound represented by formula (V): wherein, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; n is 0, 1, 2, 3, or 4; Y1 is N or CR12; preferably, Y1 is N; Y2 is N or CR13; R10 is H, C1-6 alkyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 ... 1-6-haloalkyl, C4-6 cycloalkyl, or 5-6-membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, and 5-6-membered heterocyclic group are optionally substituted by one or more R”; R11, R12, and R13 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; or, R10 and R11 together with the atoms to which they are attached form a 5-10-membered heterocyclic group or a 5-6-membered heteroaryl group, wherein the 5-10-membered heterocyclic group and the 5-6-membered heteroaryl group are optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R 12, together with the atoms to which they are attached, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; wherein R” is H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -OR g, -OC(O)R g, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, C 1-6 alkyl, C 1-6 haloalkyl, C 4-6 cycloalkyl or 4-6 membered heterocyclic group, wherein the C 1-6 alkyl, C 1-6 haloalkyl, C 4-6 cycloalkyl and 4-6 membered heterocyclic group are optionally substituted by one or more D until fully deuterated;Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted by one or more D, up to complete deuteration; preferably, X2 is CR2; R2 is H, D, or -CH(CH3)(CF3); R5 is F; R6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Y1 is N or CR12; preferably, Y Y1 is N; Y2 is N or CR13; R10 is H, Me, CHF2, CH2CF3 or piperidinyl, optionally substituted by one or more R”; R11 is H, D or Me; R12 and R13 are independently H or D; or, R10 and R11 together with the atoms they are attached to form a 5-10 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-10 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R12 together with the atoms they are attached to form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; wherein R” is Me, Et, -C(O)ORg, -C(O)NRhRj, -NRgC(O)R h or oxocyclic butyl; each Rg, Rh and Rj is independently H, D, C1-6 alkyl or C1-6 haloalkyl; preferably, wherein X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is halogen; R6 is C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; n is 0, 1, 2, 3 or 4; Y 1 is N or CR 12; preferably, Y 1 is N; Y 2 is N or CR 13;R10 is H, a C1-6 alkyl, a C1-6 haloalkyl, a C4-6 cycloalkyl, or a 5-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C4-6 cycloalkyl, and 5-6 membered heterocyclic group are optionally substituted by one or more R”; R11, R12, and R13 are independently H, D, a halogen, a C1-6 alkyl, or a C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; or, R10 and R11 together with the atoms to which they are attached form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; or, when Y1 is CR12, R10 and R 12, together with the atoms to which they are attached, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; wherein R” is H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -OR g, -OC(O)R g, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, C 1-6 alkyl, C 1-6 haloalkyl, C 4-6 cycloalkyl, or 4-6 membered heterocyclic group, wherein the C 1-6 alkyl, C 1-6 haloalkyl, C 4-6 cycloalkyl, and 4-6 membered heterocyclic group are optionally substituted by one or more D until fully deuterated; wherein each R g, R h and Rj are independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted by one or more D until fully deuterated; preferably, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; R5 is a halogen; R6 is a C 1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated;n is 0, 1, 2, 3, or 4; Y1 is N or CR12; preferably, Y1 is N; Y2 is N or CR13; R10 is H, C1-6 alkyl, C1-6 haloalkyl, or 5-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 5-6 membered heterocyclic group are optionally substituted by one or more R''; R11 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D'' until fully deuterated; R12 and R13 are independently H, D, or halogen; or, R10 and R' ... 11, together with the atoms to which they are attached, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; or, when Y1 is CR 12, R 10 and R 12, together with the atoms to which they are attached, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; wherein R” is H, D, halogen, -C(O)ORg, -C(O)NRhRj, C1-6 alkyl, C1-6 haloalkyl, or 4-6 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 4-6 membered heterocyclic group are optionally substituted by one or more D until fully deuterated; wherein each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C 1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; preferably, wherein X2 is CR2; R2 is H, D or -CH(CH3)(CF3); R5 is F; R6 is Me; Rt is H or D; n is 0, 1, 2, 3 or 4; Y1 is N or CR12; preferably, Y1 is N; Y2 is N or CR13; R10 is H, Me, CHF2, CH2CF3 or pirimidinyl, which is optionally substituted with one or more R"; R11 is H, D or Me; R12 and R13 are independently H or D; or, R10 and R 11, together with the atoms to which they are attached, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; or, when Y1 is CR 12, R 10 and R 12, together with the atoms to which they are attached, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; wherein R” is Me, Et, -C(O)OR g, -C(O)NR hR j or oxobutyl;Each of Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl; preferably, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; n is 0, 1, 2, 3, or 4; Y1 is N or CR2. 12; Preferably, Y1 is N; Y2 is N or CR 13; R10, R11, R12 and R13 are independently H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; or, R10 and R11 together with the atoms to which they are attached form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; or, when Y1 is CR 12, R10 and R12 together with the atoms to which they are attached form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; wherein R” is H, D, halogen, C 1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, wherein X2 is CR2; R2 is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Rt is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3 or 4; Y 1 is N or CR 12; preferably, Y 1 is N; Y 2 is N or CR 13; R 10 is H, C 1-6 alkyl or C 1-6 haloalkyl, wherein the C 1-6 alkyl and C 1-6 haloalkyl are optionally substituted with one or more D until fully deuterated;R11 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R12 and R13 are independently H, D, or halogen; or, R10 and R11 together with the atoms to which they are attached form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted with one or more R”; or, when Y1 is CR12, R10 and R12 together with the atoms to which they are attached form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted with one or more R”; wherein R” is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms; The 1-6 haloalkyl group is optionally substituted with one or more D atoms until fully deuterated; preferably, wherein X2 is CR2; R2 is H, D, or -CH(CH3)(CF3); R5 is F; R6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Y1 is N or CR12; preferably, Y1 is N; Y2 is N or CR13; R10 is H, Me, CHF2, or CH2CF3; R11 is H, D, or Me; R12 and R13 are independently H or D; or, R10 and R11 together with the atoms to which they are attached form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted with one or more R''; or, when Y1 is CR12, R10 and R'' are substituted with one or more D atoms ... 12, together with the atoms to which they are attached, form a 5-6 membered heterocyclic group or a 5-6 membered heteroaryl group, wherein the 5-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one or more R”; wherein R” is Me or Et.

9. The compound as claimed in claim 1, which is a compound represented by formula (VI): wherein, X2 is N or CR2; preferably, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; n is 0, 1, 2, 3, or 4; R10 is H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; The 1-6 haloalkyl group is optionally substituted with one or more D molecules until fully deuterated; R12 and R13 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl group are optionally substituted with one or more D molecules until fully deuterated; preferably, X2 is CR2; R2 is H, D, or -CH(CH3)(CF3); R5 is F; R6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; R10 is H, Me, CHF2, or CH2CF3; R12 and R13 are independently H or D.

10. The compound as claimed in claim 1, which is a compound represented by formula (VII): wherein, X2 is N or CR2; preferably, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; n is 0, 1, 2, 3, or 4; Y3 is O or S; R10 and R11 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl. 1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; or, R10 and R11 together with the atoms to which they are attached form a C5-8 cycloalkyl, a 5-6 heterocyclic group, a C6-10 aryl group, or a 5-6 heteroaryl group, wherein the C5-8 cycloalkyl, 5-6 heterocyclic group, C6-10 aryl group, and 5-6 heteroaryl group are optionally substituted with one or more R”; wherein R” is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; preferably, wherein X2 is CR2; R2 is H, D, halogen, or -CH(CH3)(CF3); R5 is F; R6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Y3 is O or S; R10 is H, Me, CHF2, or CH2CF3; R11 is H or D; or, R10 and R11 together with the atoms they are attached to form a C5-8 cycloalkyl, a 5-6 heterocyclic group, a C6-10 aryl, or a 5-6 heteroaryl, wherein the C5-8 cycloalkyl, 5-6 heterocyclic group, C6-10 aryl, and 5-6 heteroaryl are optionally substituted by one or more R”; wherein R” is Me or Et.

11. The compound as claimed in claim 1, wherein it is a compound represented by formula (VIII), formula (VIII-1), or formula (VIII-2): wherein, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; preferably, R2 is H or D; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; n is 0, 1, 2, 3, or 4; Z1 is N or CR20; Z2 is N or CR21; Z3 is N or CR22; Z4 is N or CR20. 23; R20, R22, and R23 are independently H, D, halogen, -OC(O)Rd, -NRdC(O)Re, -C(O)NReRf, -C(O)ORd, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated, and R20, R22, and R23 are independently optionally substituted with one or more R''; R21 is H, D, halogen, -ORd, -NReRf, -C(O)Rd, -OC(O)Rd, -NRdC(O)Re, -C(O)NReRf, -C(O)ORd, -S(O)2NReRf, -S(O)Rd, -S(O)2R d, -P(=O)ReRf, -OP(=O)ReRf, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, and 4-7 heterocyclic group are optionally substituted by one or more D until fully deuterated, and R21 is optionally substituted by one or more R”; wherein each Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-8 cycloalkyl, 3-7 heterocyclic group, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-8 cycloalkyl, C3-8 cycloalkyl, C3-7 heterocyclic group, C6-10 aryl, or 5-10 heteroaryl group is substituted by one or more D. 3-8 cycloalkyl, 3-7 heterocyclic, C6-10 aryl and 5-10 heteroaryl groups are optionally substituted with one or more D groups until fully deuterated, and are optionally substituted with one or more R groups.Wherein R” is H, D, halogen, -OR g, -NR hR j, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7-membered heterocyclic group, wherein R” is optionally substituted by one or more D, halogen, C1-6 alkyl, or C1-6 haloalkyl; each R g, R h, and R j is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynylyl, C3-6 cycloalkyl, 3-7-membered heterocyclic group, C6-10 aryl, or 5-10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynylyl, C3-6 cycloalkyl, 3-7-membered heterocyclic group, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more D until fully deuterated; Preferably, X2 is CR2; R2 is H, D, F, Me, CHF2, CF3, or -CH(CH3)(CF3); preferably, R2 is H or D; R5 is F; R6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Z1 is N or CR20; Z2 is N or CR21; Z3 is N or CR22; Z4 is N or CR23; R20 is H or D; R21 is H, D, F, Cl, Me, CHF2, CF3, CH2CF3, -C(OH)(CH3)2, -ORd, -NRdC(O)Re, -S(O)Rd, -S(O)2Rd, -P(=O)ReR R22 is a 4-7 membered heterocyclic group, optionally substituted with one or more R”; R23 is H, D, -NR dC(O)Re or -C(O)NReRf, optionally substituted with one or more R”; R24 is H or D; wherein each R d, Re and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl and 4-7 membered heterocyclic group is optionally substituted with one or more R”; wherein R” is Me, Et, -OR g, -NR hRj or 4-7 membered heterocyclic group, wherein R” is optionally substituted with one or more D, halogen, C1-6 alkyl or C1-6 haloalkyl; each R g, R h and Rj is independently H, D, C1-6 alkyl or C1-6 haloalkyl; Preferably, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; preferably, R2 is H or D; R5 is a halogen.R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Rt is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3 or 4; Z1 is N or CR20; Z2 is N or CR21; Z3 is N or CR22; Z4 is N or CR23; R20, R22 and R23 are independently H, D, halogen, -OC(O)Rd, -NRdC(O)Re, -C(O)NReRf, -C(O)ORd, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is substituted with one or more D atoms until fully deuterated; The 1-6 alkyl and C1-6 haloalkyl groups are optionally substituted with one or more D groups until fully deuterated, and R20, R22, and R23 are independently and optionally substituted with one or more R” groups; R21 is H, D, halogen, -ORd, -NReRf, -OC(O)Rd, -NRdC(O)Re, -C(O)NReRf, -C(O)ORd, -S(O)Rd, -S(O)2Rd, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, and 4-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated, and R21 is optionally substituted with one or more R” groups; wherein each Rd, Re, and Rf is independently H, D, C 1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-8 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-8 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more Ds up to complete deuteration, and are optionally substituted with one or more R"; wherein R" is H, D, halogen, -OR g, -NR hR j, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 heterocyclic, wherein R" is optionally substituted with one or more Ds, halogens, C1-6 alkyl, or C1-6 haloalkyl;Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl are optionally substituted with one or more D until fully deuterated; preferably, X2 is CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; preferably, R2 is H or D; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; Rt is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; n is 0, 1, 2, 3 or 4; Z1 is N or CR20; Z2 is N or CR21; Z3 is N or CR22; Z4 is N or CR23; R20 and R23 are independently H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D atoms until fully deuterated; R R21 is H, D, halogen, -OR d, -NR dC(O)Re, -S(O)Rd, -S(O)2Rd, C1-6 alkyl, C1-6 haloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 4-7 membered heterocyclic group are optionally substituted with one or more D until fully deuterated, and R21 is optionally substituted with one or more R”; R22 is H, D, -NR dC(O)Re, or -C(O)NReRf, which is optionally substituted with one or more R”; wherein each Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or 4-7 membered heterocyclic group is... The 3-8 cycloalkyl and 4-7 heterocyclic groups are optionally substituted with one or more R”; wherein R” is H, D, halogen, -OR g, -NR hR j, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl or 4-7 heterocyclic group, wherein R” is optionally substituted with one or more D, halogen, C 1-6 alkyl or C 1-6 haloalkyl;Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D molecules until fully deuterated; preferably, X2 is CR2; R2 is H, D, Me, CHF2, or -CH(CH3)(CF3); preferably, R2 is H or D; R5 is F; R6 is Me; Rt is H or D; n is 0, 1, 2, 3, or 4; Z1 is N or CR20; Z2 is N or CR21; Z3 is N or CR22; Z4 is N or CR23; R20 is H or D; R21 is H, D, F, Cl, Me, CHF2, CF3, CH2CF3, -C(OH)(CH3)2, -OR R22 is H, D, -NR dC(O)Re, or -C(O)NReRf, or a 4-7 membered heterocyclic group, optionally substituted with one or more R”; R23 is H or D; wherein each Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or a 4-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, and 4-7 membered heterocyclic group is optionally substituted with one or more R”; wherein R” is Me, Et, -ORg, -NRhRj, or a 4-7 membered heterocyclic group, wherein R” is optionally substituted with one or more D, halogen, C1-6 alkyl, or C1-6 haloalkyl; Each Rg, Rh, and Rj is independently H, D, C1-6 alkyl, or C1-6 haloalkyl.

12. The compound as claimed in claim 1, which is a compound represented by formula (IX): wherein, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is halogen; R6 is C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Y3 is N or CR111; R18, R19, R110, and R111 are independently: 1) H, D, halogen, oxo, -C(O)Rd, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)R eR f, -OP(=O)R eR f; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 membered heteroaryl, wherein said groups are optionally substituted by one or more R”; or 3) R 18 and R 19 or R 18 and R R110 or R110 and R111, together with the atoms to which they are attached, form a C3-6 cycloalkyl, a 3-12-membered heterocyclic group, a C6-10 aryl, or a 5-10-membered heteroaryl group, wherein said group is optionally substituted by one or more R's; or wherein each Rd, Re, and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, a 3-7-membered heterocyclic group, a C2-6 alkenyl, a C2-6 ynyl, a C6-10 aryl, or a 5-10-membered heteroaryl group, or Re and Rf, together with the atoms to which they are attached, form a 3-7-membered heterocyclic group or a 5-10-membered heteroaryl group; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, a 3-7-membered heterocyclic group, a C2-6 alkenyl, a C2-6 ynyl, C The 6-10 aryl and 5-10 heteroaryl groups are optionally replaced by one or more R's;Each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10 heteroaryl, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Rh and R j, together with the N atom to which they are attached, forms a 3-7 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic group, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 membered heteroaryl groups are optionally substituted by one or more D atoms until fully deuterated; preferably, wherein X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D atoms until fully deuterated; R t is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; Y3 is N or CR111;R 18 is H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R''; R 110 is H, D, halogen, -NR dC(O)Re, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D'', up to complete deuteration; R 19 and R 111 are independently H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C'' are substituted by one or more D'', up to complete deuteration. 1-6 haloalkyl groups are optionally substituted with one or more D atoms until fully deuterated; or, R 18 and R 19, or R 18 and R 110, or R 110 and R 111 together with the atoms to which they are attached form a C 3-6 cycloalkyl, a 3-7 membered monocyclic heterocyclic group, a 6-12 membered fused bicyclic heterocyclic group, a C 6-10 aryl, or a 5-10 membered heteroaryl, wherein said groups are optionally substituted with one or more R''; or wherein each R d, Re, and R f is independently H, a C 1-6 alkyl, a C 1-6 haloalkyl, or a C 3-6 cycloalkyl, or Re and R f together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more R''; each R'' is independently D, a halogen, -C(O)ORg, or -NR. hR j, -NR gC(O)R h, -OR g, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl and 3-7 membered heterocyclic group are optionally substituted by one or more D until fully deuterated; wherein each R g, R h and R j is independently H or C 1-6 alkyl, or R h and R j together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C 1-6 alkyl and 3-7 membered heterocyclic group are optionally substituted by one or more D until fully deuterated; preferably, wherein X 2 is N or CR 2; R 2 is H, D or halogen; preferably, R 2 is H, D or F; preferably, R 2 is H; R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted by one or more D until fully deuterated; preferably, R6 is methyl or -CD3;Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y3 is N or CR111; R18 is H, D, a halogen, -C(O)NR eRf, -NR dC(O)Re, -OR d, -S(O)2Rd, -P(=O)ReRf, C1-6 alkyl, C1-6 haloalkyl, or a 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R''; preferably, R18 is a halogen, -C(O)NR eRf, -OR d, -S(O)2Rd, C1-6 alkyl, C1-6 haloalkyl, or a 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R'''; The 1-6-membered haloalkyl and the 3-7-membered heterocyclic group are optionally substituted with one or more R's; R110 is H, D, halogen, -NR dC(O)R e, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D's until fully deuterated; preferably, R19 is H or D; R19 and R111 are independently H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D's until fully deuterated; preferably, R110 is H or D; or, R18 and R19 or R18 and R110 or R110 and R R111, together with the atoms they are attached to, forms a 3-7 membered monocyclic heterocyclic group, which is optionally substituted by one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5- or 6-membered heterocyclic group having one or two cyclic heteroatoms selected from N, O, and S, wherein said group is optionally substituted by one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5-membered heterocyclic group having one or two cyclic heteroatoms selected from N, wherein said group is optionally substituted by one or more R''; or R18 and R19, or R18 and R110, or R110 and R'' R111, together with the atoms to which they are attached, forms a 6-12 fused bicyclic heterocycle, which is optionally substituted by one or more R”; preferably, R18 and R19 or R18 and R110 or R110 and R111, together with the atoms to which they are attached, form an 8-10 fused bicyclic heterocycle having 1-3 cyclic heteroatoms selected from N, O and S, which is optionally substituted by one or more R”;Preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form an 8-10 fused bicyclic heterocycle having one or two cyclic heteroatoms selected from N, optionally substituted by one or more R''; or R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5-10 cyclic heteroaryl group, optionally substituted by one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms they are attached to, form a 5 or 6 cyclic heteroaryl group having one to three cyclic heteroatoms selected from N, O, and S, optionally substituted by one or more R''; preferably, R18 and R19, or R18 and R110, or R110 and R''... R111, together with the atoms to which they are attached, forms a 5-membered heteroaryl group having 1-3 cyclic heteroatoms selected from N, O, and S, wherein said group is optionally substituted by one or more R”; preferably, R18 and R19, or R18 and R110, or R110 and R111, together with the atoms to which they are attached, form a 5-membered heteroaryl group having 1 or 2 cyclic heteroatoms selected from N, wherein said group is optionally substituted by one or more R”; wherein each Rd, Re, and Rf is independently H, C1-6 alkyl, C1-6 haloalkyl, or C3-6 cycloalkyl, or Re and Rf, together with the atoms to which they are attached, forms a 3-7-membered heterocyclic group; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7-membered heterocyclic group is optionally substituted by one or more R”; each R” is independently D, halogen, -C(O)ORg, -NRhRj, -NR gC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh, and Rj is independently H or C1-6 alkyl, or Rh and Rj together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; preferably, wherein X2 is CH; R5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y3 is N or CR111;R 18 and R 19, or R 18 and R 110, or R 110 and R 111, together with the atoms they are attached to, form a 5-membered heteroaryl group having one or two N-ring heteroatoms, wherein said group is optionally substituted by one or more R''s; each R'' is independently D, halogen, C1-6 alkyl, or C1-6 haloalkyl, or two R''s on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7-membered heterocyclic group; wherein said C1-6 alkyl, C1-6 haloalkyl, and 3-7-membered heterocyclic group are optionally substituted by one or more D's, up to complete deuteration.

13. The compound as claimed in claim 1, which is a compound represented by formula (IX-1): wherein, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted by one or more D until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D or a halogen; preferably, Rt is H, D or F; Y3 is N, CH or CD; preferably, Y3 is N or CH; R18 is H, D, a halogen, -C(O)NR eRf, -NR dC(O)Re, -OR d, -S(O) 2Rd, -P(=O)ReRf, C1-6 alkyl, C1-6 haloalkyl or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C The 1-6 haloalkyl and 3-7 membered heterocyclic groups are optionally substituted with one or more R”; preferably, R 18 is a halogen, -C(O)NR eR f, -OR d, -S(O) 2R d, C 1-6 alkyl, C 1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C 1-6 alkyl, C 1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more R”; wherein each R d, Re, and R f is independently H, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl, or Re and R f together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted with one or more R”; each R” is independently D, halogen, -C(O)OR g, -NR hR j, -NR gC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh, and Rj is independently H or C1-6 alkyl, or Rh and Rj together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; preferably, wherein R5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y3 is N or CH; R18 is H, F, Cl, or -CH 3、-CHF 2、-CF 3、-OCF 3、 ...Preferably, R 18 is F, Cl, -CH 3, -CHF 2, -CF 3, -OCF 3, ..., wherein the group is optionally substituted with one or more D atoms until complete deuteration; preferably, R 18 is -CH 3, ..., wherein the group is optionally substituted with one or more D atoms until complete deuteration.

14. The compound as claimed in claim 1, which is a compound represented by formula (X): wherein, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Y3 is N, CH, or CD; Y4 is N, CH, or CD; Y5 and Y6 are independently N or C and at least one of Y5 and Y6 is N; W1 is N or CR112; W 2 represents N or CR 113; W 3 represents N or CR 114; indicating a single or double bond; provided that the bicyclic ring containing Y 3, Y 4, Y 5, Y 6, W 1, W 2, and W 3 is an aromatic ring; R 112, R 113, and R 114 independently represent: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)ReRf, -OP(=O)ReRf; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, wherein said groups are optionally substituted by one or more R”; or 3) R112 and R113 or R113 and R114 together with the atoms to which they are attached to form C3-6 cycloalkyl, 3-12 heterocyclic, C6-10 aryl or 5-10 heteroaryl, wherein said groups are optionally substituted by one or more R”; or wherein each Rd, Re and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C 2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Re and Rf together with the atoms they are attached to form 3-7 heterocyclic groups or 5-10 heteroaryl groups;The C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 membered heteroaryl groups are optionally substituted by one or more R”; each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C 1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Rh and Rj together with the atoms they are attached to form a 3-7-membered heterocyclic or 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more D atoms until fully deuterated; preferably, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C 1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Y3 is N, CH or CD;Y4 is N, CH, or CD; Y5 and Y6 are independently N or C, and at least one of Y5 and Y6 is N; W1 is N or CR 112; W2 is N or CR 113; W3 is N or CR 114; indicates a single or double bond; provided that the bicyclic ring containing Y3, Y4, Y5, Y6, W1, W2, and W3 is an aromatic ring; R 112, R 113, and R 114 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C 1-6-haloalkyl and 3-7-membered heterocyclic groups are optionally substituted by one or more R”; or, R 112 and R 113 or R 113 and R 114 together with the atoms they are attached to form C 3-6 cycloalkyl, 3-7-membered monocyclic heterocyclic, 6-12-membered fused bicyclic heterocyclic, C 6-10 aryl, or 5-10-membered heteroaryl groups, wherein said groups are optionally substituted by one or more R”; wherein each R d, Re, and R f is independently H, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl, or Re and R f together with the atoms they are attached to form a 3-7-membered heterocyclic group; wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, and 3-7-membered heterocyclic groups are optionally substituted by one or more R”; each R” is independently D, halogen, -C(O)OR g, -NR hR j, -NR gC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh, and Rj is independently H or C1-6 alkyl, or Rh and Rj together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; preferably, X2 is N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H; R R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D or a halogen; preferably, Rt is H, D or F;Y3 is N, CH, or CD; preferably, Y3 is N or CH; Y4 is N, CH, or CD; preferably, Y4 is N or CH; Y5 and Y6 are independently N or C, and at least one of Y5 and Y6 is N; W1 is N or CR 112; W2 is N or CR 113; W3 is N or CR 114; indicating a single or double bond; provided that the bicyclic ring containing Y3, Y4, Y5, Y6, W1, W2, and W3 is an aromatic ring; R 112, R 113, and R 114 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)R e, -OR d, -S(O) 2R d, -P(=O)R eR f, C1-6 alkyl, C A 1-6-haloalkyl or 3-7-membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7-membered heterocyclic group are optionally substituted by one or more R”; preferably, R112, R113, and R114 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R”; or, R112 and R113 or R113 and R114 together with the atoms to which they are attached form a 3-7-membered heterocyclic group, which is optionally substituted by one or more R”; preferably, R112 and R113 or R113 and R114 together with the atoms to which they are attached form a 5- or 6-membered heterocyclic group having one or two independently selected cyclic heteroatoms chosen from N, O, and S, which is optionally substituted by one or more R”; wherein each Rd, R e and R f are independently H, C1-6 alkyl, C1-6 haloalkyl, or C3-6 cycloalkyl, or Re and R f together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; each R” is independently D, halogen, -C(O)OR g, -NR hR j, -NR gC(O)R h, -OR g, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more D until fully deuterated; wherein each R g, R h and Rj are independently H or C1-6 alkyl groups, or Rh and Rj together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D atoms, up to complete deuteration.

15. The compound as claimed in claim 1, wherein it is a compound represented by formula (X-1) or formula (X-2): wherein, R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more D until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y3 is N, CH, or CD; preferably, Y3 is N or CH; Y4 is N, CH, or CD; preferably, Y4 is N or CH; W1 is N or CR112; W2 is N or CR113; W3 is N or CR114; R112, R113, and R114 are independently H, D, a halogen, -C(O)NR eRf, -NR dC(O)R e, -OR d, -S(O) 2R d, -P(=O)R eR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R 112, R 113, and R 114 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R”; or, R 112 and R 113 or R 113 and R 114 together with the atoms to which they are attached form a 3-7 membered heterocyclic group, which is optionally substituted by one or more R”; preferably, R 112 and R 113 or R 113 and R 114, together with the atoms to which they are attached, forms a 5- or 6-membered heterocyclic group having one or two independent cyclic heteroatoms selected from N, O, and S, wherein said group is optionally substituted by one or more R”; wherein each Rd, Re, and Rf is independently H, C1-6 alkyl, C1-6 haloalkyl, or C3-6 cycloalkyl, or Re and Rf together with the atoms to which they are attached form a 3-7-membered heterocyclic group; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7-membered heterocyclic group is optionally substituted by one or more R”; each R” is independently D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C A 3-6 cycloalkyl or 3-7 membered heterocyclic group, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh and Rj is independently H or a C1-6 alkyl, or Rh and Rj together with the atoms they are attached to form a 3-7 membered heterocyclic group;The C1-6 alkyl and 3-7 heterocyclic groups are optionally substituted with one or more D groups until fully deuterated; preferably, R5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y3 is N or CH; Y4 is N or CH; W1 is N or CR112; W2 is N or CR113; W3 is N or CR114; R112, R113, and R114 are H; or, R112 and R113 or R113 and R114 together with the atoms they are attached to form a group: or, the group is optionally substituted with one or more D groups until fully deuterated.

16. The compound as claimed in claim 1, which is a compound represented by formula (XI): wherein, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; R5 is a halogen; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Y3 is N, CH, or CD; Y7 and Y8 are independently N or C and at least one of Y7 and Y8 is N; Y9 is N, CH, or CD; W4 is N or CR115; W 5 represents N or CR 116; W 6 represents N or CR 117; indicating a single or double bond; provided that the bicyclic ring containing Y 3, Y 7, Y 8, Y 9, W 4, W 5, and W 6 is an aromatic ring; R 115, R 116, and R 117 independently represent: 1) H, D, halogen, oxo, -C(O)R d, -C(O)OR d, -C(O)NR eR f, -NR eR f, -NR dC(O)R e, -NR dC(O)OR e, -NR dC(O)NR eR f, -OR d, -OC(O)R d, -OC(O)NR eR f, -NR dS(O) 2R e, -S(O) 2NR eR f, -S(O)R d, -S(O) 2R d, -P(=O)ReRf, -OP(=O)ReRf; or 2) C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, wherein said groups are optionally substituted by one or more R”; or 3) R115 and R116 or R116 and R117 together with the atoms to which they are attached to form C3-6 cycloalkyl, 3-12 heterocyclic, C6-10 aryl or 5-10 heteroaryl, wherein said groups are optionally substituted by one or more R”; or wherein each Rd, Re and Rf is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C 2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or Re and Rf together with the atoms they are attached to form 3-7 heterocyclic groups or 5-10 heteroaryl groups;The C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10 membered heteroaryl groups are optionally substituted by one or more R”; each R” is independently H, D, halogen, oxo, -C(O)R g, -C(O)OR g, -C(O)NR hR j, -NR hR j, -NR gC(O)R h, -NR gC(O)OR h, -NR gC(O)NR hR j, -OR g, -OC(O)R g, -OC(O)NR hR j, -NR gS(O) 2R h, -S(O) 2NR hR j, -S(O)R g, -S(O) 2R g, -P(=O)R hR j, -OP(=O)R hR j, C 1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl or 5-10 heteroaryl, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a C3-6 cycloalkyl, 3-7 heterocyclic, C6-10 aryl or 5-10 heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7 heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl and 5-10 heteroaryl are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh and Rj is independently H, D, C1-6 alkyl, C1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, or 5-10-membered heteroaryl, or Rh and Rj together with the atoms they are attached to form a 3-7-membered heterocyclic or 5-10-membered heteroaryl; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclic, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, and 5-10-membered heteroaryl are optionally substituted by one or more D atoms until fully deuterated; preferably, X2 is N or CR2; R2 is H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D atoms until fully deuterated; R5 is a halogen; R6 is a C 1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Rt is H, D, halogen, C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted with one or more D until fully deuterated; Y3 is N, CH or CD;Y7 and Y8 are independently N or C, and at least one of Y7 and Y8 is N; Y9 is N, CH, or CD; W4 is N or CR 115; W5 is N or CR 116; W6 is N or CR 117; indicating a single or double bond; provided that the bicyclic ring containing Y3, Y7, Y8, Y9, W4, W5, and W6 is an aromatic ring; R 115, R 116, and R 117 are independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C 1-6-haloalkyl and 3-7-membered heterocyclic groups are optionally substituted by one or more R”; or, R 115 and R 116 or R 116 and R 117 together with the atoms they are attached to form C 3-6 cycloalkyl, 3-7-membered monocyclic heterocyclic, 6-12-membered fused bicyclic heterocyclic, C 6-10 aryl, or 5-10-membered heteroaryl groups, wherein said groups are optionally substituted by one or more R”; wherein each R d, Re, and R f is independently H, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-6 cycloalkyl, or Re and R f together with the atoms they are attached to form a 3-7-membered heterocyclic group; wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, and 3-7-membered heterocyclic groups are optionally substituted by one or more R”; each R” is independently D, halogen, -C(O)OR g, -NR hR j, -NR gC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R'' on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; wherein each Rg, Rh, and Rj is independently H or C1-6 alkyl, or Rh and Rj together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl and 3-7 membered heterocyclic group are optionally substituted by one or more D's until fully deuterated; preferably, X2 is N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H; R 5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted by one or more D until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D or halogen;Preferably, Rt is H, D, or F; Y3 is N, CH, or CD; preferably, Y3 is N or CH; Y7 and Y8 are independently N or C, and at least one of Y7 and Y8 is N; Y9 is N, CH, or CD; preferably, Y4 is N or CH; W4 is N or CR115; W5 is N or CR116; W6 is N or CR117; indicating a single or double bond; provided that the bicyclic ring containing Y3, Y7, Y8, Y9, W4, W5, and W6 is an aromatic ring; R115, R116, and R117 are independently H, D, halogen, -C(O)NR eRf, -NR dC(O)Re, -OR d, -S(O) 2Rd, -P(=O)ReRf, C 1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R115, R116, and R117 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R”; or, R115 and R116 or R116 and R117 together with the atoms to which they are attached form a 3-7 membered heterocyclic group, which is optionally substituted by one or more R”; preferably, R115 and R116 or R116 and R117 together with the atoms to which they are attached form a 5- or 6-membered heterocyclic group, wherein the group is optionally substituted by one or more R”; wherein each Rd, Re, and Rf is independently H, C 1-6 alkyl, C1-6 haloalkyl, or C3-6 cycloalkyl, or Re and Rf together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; each R” is independently D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, or 3-7 membered heterocyclic group, or two R” on the same atom or two adjacent atoms together with the atoms they are attached to form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more D until fully deuterated; wherein each Rg, Rh, and Rj is independently H or C. 1-6 alkyl groups, or Rh and Rj together with the atoms to which they are attached, form 3-7 membered heterocyclic groups; wherein the C1-6 alkyl and 3-7 membered heterocyclic groups are optionally substituted with one or more D atoms, up to complete deuteration.

17. The compound as claimed in claim 1, wherein it is a compound represented by formula (XI-1) or formula (XI-2): wherein, X2 is N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H; R5 is a halogen; preferably, R5 is F; R6 is a C1-6 alkyl or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more D until fully deuterated; preferably, R6 is methyl or -CD3; Rt is H, D, or a halogen; preferably, Rt is H, D, or F; Y3 is N, CH, or CD; preferably, Y3 is N or CH; Y9 is N, CH, or CD; preferably, Y9 is N or CH; W4 is N or CR115; W5 is N or CR116; W6 is N or CR117; R115, R116, and R R117 is independently H, D, halogen, -C(O)NR eR f, -NR dC(O)Re, -OR d, -S(O) 2R d, -P(=O)ReR f, C1-6 alkyl, C1-6 haloalkyl, or 3-7 membered heterocyclic group, wherein the C1-6 alkyl, C1-6 haloalkyl, and 3-7 membered heterocyclic group are optionally substituted by one or more R”; preferably, R115, R116, and R117 are independently H, D, C1-6 alkyl, or C1-6 haloalkyl, wherein the C1-6 alkyl and C1-6 haloalkyl are optionally substituted by one or more R”; or, R115 and R116 or R116 and R117 together with the atoms to which they are attached form a 3-7 membered heterocyclic group, which is optionally substituted by one or more R”; preferably, R R115 and R116 or R116 and R117, together with the atoms they are attached to, form a 5- or 6-membered heterocyclic group having one or two independent cyclic heteroatoms selected from N, O, and S, wherein said group is optionally substituted by one or more R”; wherein each Rd, Re, and Rf is independently H, C1-6 alkyl, C1-6 haloalkyl, or C3-6 cycloalkyl, or Re and Rf, together with the atoms they are attached to, form a 3-7-membered heterocyclic group; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 3-7-membered heterocyclic group is optionally substituted by one or more R”; each R” is independently D, halogen, -C(O)ORg, -NRhRj, -NRgC(O)Rh, -ORg, C1-6 alkyl, C1-6 haloalkyl, C 3-6 cycloalkyl or 3-7 membered heterocyclic group, or two R's on the same atom or two adjacent atoms together with the atoms to which they are attached, form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl and 3-7 membered heterocyclic group are optionally substituted with one or more Ds until fully deuterated;Each of Rg, Rh, and Rj is independently H or a C1-6 alkyl group, or Rh and Rj together with the atoms to which they are attached form a 3-7 membered heterocyclic group; wherein the C1-6 alkyl group and the 3-7 membered heterocyclic group are optionally substituted with one or more D groups until fully deuterated; preferably, X2 is N or CR2; R2 is H, D, or a halogen; preferably, R2 is H, D, or F; preferably, R2 is H; R5 is F; R6 is methyl or -CD3; Rt is H, D, or F; Y3 is N or CH; Y9 is N or CH; W4 is N or CR115; W5 is N or CR116; W6 is N or CR117; R115, R116, and R117 are H; or, R115 and R116 or R116 and R 117, together with the atoms they are attached to, form groups such as: or, wherein said groups are optionally substituted with one or more D atoms until fully deuterated.

18. A compound selected from the group consisting of tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates, or solvates thereof:

19. A pharmaceutical composition comprising a compound as claimed in any one of claims 1 to 18 and a pharmaceutically acceptable excipient, and optionally, other therapeutic agents.

20. Use of a compound as claimed in any one of claims 1 to 18 or a pharmaceutical composition as claimed in claim 19 in the preparation of a medicament for treating and / or preventing diseases mediated by wild-type and / or mutant BTK kinases; preferably, the mutant BTK kinase is selected from BTK C481S, BTK C481F, BTK C481Y, BTK C481R, BTK C481T, BTK C481G, or BTK C481W; preferably, the mutant BTK kinase is BTK C481S; preferably, the mutant BTK kinase is BTK V416L, BTK A428D, BTK M437R, BTK T474I, or BTK L528W; preferably, the mutant BTK kinase is BTK T474I or BTK L528W.

21. The use as claimed in claim 20, wherein the BTK-mediated disease is selected from: allergic diseases, autoimmune diseases, inflammatory diseases, or cancer; preferably, wherein the BTK-mediated disease is a B-cell proliferative disease selected from chronic lymphocytic lymphoma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, acute lymphocytic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic myeloid monoglobulin leukemia, chronic neutrophilic leukemia, acute undifferentiated leukemia, anaplastic large cell lymphoma, prolymphocytic leukemia, juvenile myelomonocytic leukemia, adult T-cell leukemia, acute myeloid leukemia with trilineage myelodysplastic syndrome, mixed phenotype leukemia, myelodysplastic syndrome, myeloproliferative disorders, marginal zone lymphoma, or Waldenström macroglobulinemia; Preferably, the BTK-mediated disease is multiple myeloma.