Inhibitors of YAP / TAZ and TEAD interaction, their manufacture, pharmaceutical compositions and uses

Abstract

The present disclosure provides an inhibitor of the interaction between YAP / TAZ and TEAD represented by the following formula I, and its manufacture, pharmaceutical composition and use. The compounds provided in the present disclosure, as inhibitors of the interaction between YAP / TAZ and TEAD, can be used for the treatment or prevention of diseases mediated by the interaction between YAP / TAZ and TEAD. [Formula 1] TIFF2025508449000353.tif73114

Description

[Technical Field]

[0001] [mutual citation] This application claims the benefit of Chinese Patent Application No. 202210158641.4, filed February 21, 2022, Chinese Patent Application No. 202210344511.X, filed March 31, 2022, Chinese Patent Application No. 202210794926.7, filed July 5, 2022, Chinese Patent Application No. 202211544166.0, filed December 1, 2022, and Chinese Patent Application No. 202211559809.9, filed December 6, 2022, the entireties of which are incorporated herein by reference.

[0002] [Technical field] The present invention relates to inhibitors of the interaction between YAP / TAZ and TEAD, their preparation, pharmaceutical compositions and uses. [Background technology]

[0003] The Hippo pathway is involved in regulating cell growth, proliferation, and apoptosis, and plays an important role in regulating functions such as organ size, cancer development, tissue regeneration, and the regeneration and differentiation of stem and progenitor cells. Research has shown that this pathway has tumor-inhibitory effects in mammals, and abnormal activation of key effector molecules within the pathway is closely related to the development and progression of various tumors. Furthermore, the Hippo pathway interacts with other pathways, such as Wnt, Notch, Hedgehog, and MAPK / ERK, to cooperatively regulate cell fate. Dysregulation of this pathway also has important implications for other diseases besides tumors.

[0004] The Hippo signaling pathway is highly conserved throughout evolution. The core of the Hippo signaling pathway in mammalian cells contains a kinase chain consisting of the protein kinases MST1 / 2 (member of Ste20-like kinase, its Drosophila homolog is Hippo) and LATS1 / 2 (large tumor suppressor 1 / 2, its Drosophila homolog is Warts) and their adaptor proteins SAV1 and Mob1 (Mps one binder kinase activator-like 1A and 1B, its Drosophila homolog is Mats). This kinase chain can phosphorylate the transcriptional coactivators YAP (Yes-Associated Protein) and TAZ (Transcription coactivator with PDZ binding motif, also known as WWTR1, the Drosophila equivalent of Yorkie).

[0005] LATS1 / 2, a central component of the mammalian Hippo pathway, belong to the nuclear Dbf2-related (NDR) kinase family and are activated by binding to the scaffolding proteins Mob1A / B. LATS1 / 2 can also be directly activated after phosphorylation by MST1 / 2. LATS1 / 2 kinases can phosphorylate multiple sites on the downstream effector YAP, of which Ser127 phosphorylation plays a key role in YAP inhibition. Ser127-phosphorylated YAP binds to cytoplasmic 14-3-3 proteins and is trapped in the cytoplasm, preventing it from entering the nucleus and performing its transcriptional functions, thereby inhibiting the growth-promoting and anti-apoptotic activities of YAP. Similarly, LATS1 / 2 kinases can phosphorylate multiple sites on the transcription factor TAZ, of which Ser89 phosphorylation plays a key role in TAZ inhibition. Phosphorylated TAZ is retained or sequestered in the cytoplasm. Simultaneously, phosphorylated YAP or TAZ is further recognized and degraded by the ubiquitin ligase SCF β-TRCP. Thus, when the Hippo pathway is "on," YAP and / or TAZ are phosphorylated and inactivated, remaining in the cytoplasm. Conversely, when the Hippo pathway is "off," YAP and / or TAZ are dephosphorylated and activated, and are often found localized in the nucleus.

[0006] The transcription factor YAP itself does not contain a DNA-binding domain. After activated YAP enters the nucleus, it must bind to transcription factors to cooperatively execute its transcriptional functions. The transcription factors to which YAP most strongly binds after entering the nucleus are TEADs. The human TEAD family proteins include TEAD1, TEAD2, TEAD3, and TEAD4. Together with TEADs (or other transcription factors, e.g., Smad1, RUNX, ErbB4, and p73), YAP can initiate the transcription of downstream genes, including connective tissue growth factor (CTGF), Gli2, Birc5, Birc2, fibroblast growth factor 1 (FGF1), and amphiregulin (AREG). Similar to YAP, unphosphorylated TAZ enters the nucleus and binds to various DNA-binding transcription factors, such as peroxisome proliferation-activated receptor γ (PPARγ), thyroid transcription factor-1 (TTF-1), Pax3, TBX5, RUNX, TEAD1, and Smad2 / 3 / 4. Most of the genes whose expression is activated by the YAP or TAZ transcription factor complexes are associated with cell growth and proliferation.

[0007] Based on the previous findings, the Hippo-YAP pathway regulates organ size and normal physiological function by controlling cell proliferation and apoptosis, and is tightly regulated under normal physiological conditions. Inactivation of protein kinases in the Hippo pathway or activation of YAP can promote tumorigenesis. In fact, aberrant activation of the Hippo pathway is a key event in the development and progression of various malignant tumors. Increased expression levels and increased nuclear localization of YAP or TAZ were observed in tumors such as non-small cell lung cancer, breast cancer, head and neck cancer, esophageal cancer, ovarian cancer, liver cancer, prostate cancer, mesothelioma, and skin cancer.

[0008] Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy that often presents with nonspecific and insidious clinical symptoms, with many patients already presenting with advanced disease at the time of diagnosis. Treatment options for surgically unresectable MPM are very limited, and the current first-line pemetrexed / platinum therapy is ineffective, resulting in a median overall survival of only approximately one year, leaving a relatively large unmet clinical need. Abnormal activation of the Hippo-YAP pathway is present in approximately 70% of MPM patients and is considered an important cancer driver gene. Reducing the activity of the Hippo-YAP pathway via biological means and chemical small molecules has shown favorable tumor growth inhibitory activity, indicating that Hippo-YAP is a potential target for MPM treatment.

[0009] Lung cancer is currently one of the world's leading cancer death rates. While various clinical treatments, including targeted therapy and immunotherapy, are currently available, these treatments often suffer from low response rates or recurrence. Recent studies have demonstrated that the YAP signaling pathway mediates tumor cell dormancy and resists apoptosis, resulting in resistance to lung cancer therapeutics such as EGFR inhibitors. Inhibition of the Hippo-YAP signaling pathway can enhance tumor cell sensitivity to EGFR-targeted drugs, suggesting that clinical combination use of these drugs could improve therapeutic efficacy.

[0010] Liver cancer is a cancer with a high incidence in China, and current clinical progress in treatment has been very limited, resulting in significant unmet clinical needs. YAP is a key gene regulating the development and progression of liver cancer. Multiple in vivo experiments have shown that overexpression of YAP alone without the introduction of other oncogenes or knockdown of its upstream regulator MST1-2 in mouse liver induces the development of hepatocellular carcinoma. Furthermore, knockdown of YAP expression in an established liver cancer mouse model significantly inhibited tumor growth and promoted the differentiation of tumor cells into functional hepatic parenchymal-like cells, accompanied by recovery of liver function, suggesting that YAP may be a therapeutic target for liver cancer.

[0011] KRas mutations are common in pancreatic ductal adenocarcinoma (PDAC), and targeting KRas is thought to have broad clinical potential in PDAC. In PDAC mouse models, targeting KRas can inhibit tumor growth, potentially leading to tumor recurrence. Studies have shown that YAP plays an important role in inducing epithelial-mesenchymal transition (EMT) by regulating Fos. Knocking down YAP expression in recurrent tumors can reinhibit tumor growth, suggesting that targeting YAP may also have clinical potential in PDAC.

[0012] Inhibitors targeting BRAF and MEK are widely used clinically in various tumors, including melanoma, colon cancer, and thyroid cancer, but they also face problems of resistance and recurrence after treatment. Studies have shown that Hippo-YAP, a pathway that promotes tumor cell proliferation, is overactivated in multiple drug-resistant tumor models, and that inhibition of its activity significantly increases sensitivity to BRAF / MEK inhibitors, suggesting the possibility of clinical drug combination therapy.

[0013] In vitro, overexpression of YAP or TAZ in mammalian epithelial cells leads to cellular transformation. Enhanced YAP / TAZ transcriptional activity induces EMT (epithelial-mesenchymal transition), endowing stem cells with breast cancer cell characteristics. Summary of the Invention [Problem to be solved by the invention]

[0014] In summary, therapeutic strategies targeting the Hippo-Yap pathway are likely to provide new ideas for the treatment of various tumors. The development of specific small molecules that disrupt the interaction between YAP / TAZ and TEAD, attenuate the transcriptional activity of YAP, and thereby inhibit tumorigenesis caused by the aberrant Hippo pathway is expected to be a novel strategy for tumor treatment and has the potential for widespread clinical use. [Means for solving the problem]

[0015] The present disclosure provides inhibitors of the interaction between YAP / TAZ and TEAD. The present disclosure further provides methods for producing the inhibitors, pharmaceutical compositions containing the inhibitors, and uses thereof in the treatment or prevention of diseases mediated by the interaction between YAP / TAZ and TEAD.

[0016] In one aspect, the present disclosure provides a compound represented by Formula I below, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof:

[0017] [ka]

[0018] In the formula: X1 is O and NR a is selected from X2 is selected from C and N; X3 is selected from C and N; Y5 and Y6 are independently a bond, O, S, N, -S(O)-, -S(O)2-, C, CH(R 13 ), C(R 13 )2, C(R 13 ), -OCH2-, -N(R 12 )CH2-, -CH2CH2- and N(R 12 and Y5 and Y6 are not simultaneously a bond; Y1 and Y4 are independently a bond, O, N, C, S, -S(O)-, -C(O)-, -S(O)2-, CH, CH2, NH, C(R 13 ), CH(R 13 ), C(R 13 )2 and N(R 12 ) with the proviso that Y1 and Y4, Y1 and Y5, Y4 and Y6 are not simultaneously a bond, O, S, -S(O)- or -S(O)2-, and satisfy the valence bond rule; Alternatively, Y1, Y4 and Y6 are optionally C(R 13)2, two R on the same carbon atom 13 form a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered heterocyclyl together with the C atom linked thereto to form a spiro ring structure with ring B; Alternatively, the ring atoms of Y1 or Y6, the ring atoms of Y4 and the substituents linked to said ring atoms together form a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, a substituted or unsubstituted 4- to 9-membered heterocyclyl, a substituted or unsubstituted 6- to 10-membered aryl or a substituted or unsubstituted 5- to 10-membered heteroaryl, which together with ring B form a fused ring structure; Alternatively, X2 may be a ring atom of Y6 and R 11 together with the ring atoms linked to and the substituents linked to said ring atoms form a substituted or unsubstituted 5- or 6-membered cyclohydrocarbyl, a substituted or unsubstituted 5- or 6-membered heterocyclyl, a substituted or unsubstituted phenyl, or a substituted or unsubstituted 5- or 6-membered heteroaryl, which together with rings A and B form a tricyclic structure; Ring B is a 5-, 6-, or 7-membered heterocycle, a benzene ring, or a 5-, 6-, or 7-membered heteroaryl ring, and Ring B optionally contains one or more R 13 and / or R 12 and optionally further substituted by 1, 2 or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted alkyl, -NR'R'' and substituted or unsubstituted alkoxy; R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R3 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted alkyl, or R4 and R5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; Alternatively, R4 or R5, together with R6 and the atoms connected thereto, form a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each further optionally contain one or two heteroatoms selected from N and O; R7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R9 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and substituted or unsubstituted alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted alkyl, -NR'R'', and substituted or unsubstituted alkoxy; Each R not involved in ring formation 12 is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6- to 14-membered aryl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 alkyl; Each R not involved in ring formation 13 are independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted C6-14 aryl-S(O)2-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)- and NR'R''-C(O)-, or two R on the same carbon atom 13 forms an oxo (=O) or thio (=S) group, R 13 or R 12 after participating in ring formation, the ring atoms may optionally be replaced by 1 to 3 heteroatoms selected from O, N and S; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl; R a is selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0019] In another aspect, the present disclosure provides a pharmaceutical composition comprising a therapeutically or prophylactically effective amount of a compound represented by Formula I of the present disclosure or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc), or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.

[0020] In another aspect, the present disclosure provides use of a compound represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc), or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, in the manufacture of a medicament for treating or preventing a disease mediated by the interaction between YAP / TAZ and TEAD.

[0021] In another aspect, the present disclosure provides use of a compound represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc), or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, for treating or preventing a disease. In some embodiments, the present disclosure further provides use of a compound represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc, etc.) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, in the treatment or prevention of a disease mediated by the interaction between YAP / TAZ and TEAD.

[0022] In yet another aspect, the present disclosure provides a method for treating or preventing a disease mediated by the interaction between YAP / TAZ and TEAD, comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by Formula I of the present disclosure or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc, etc.) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure.

[0023] More detailed technical solutions and descriptions of the present disclosure are as follows: DETAILED DESCRIPTION OF THE INVENTION

[0024] The following specific embodiments are provided to enable those skilled in the art to more clearly understand the contents of the present disclosure. It should be noted that these embodiments are provided for illustrative purposes only, and are not intended to limit the scope of protection of the present application.

[0025] I. Terminology In the following description, some specific details are set forth to provide a thorough understanding of various embodiments. However, those skilled in the art should understand that the technical solutions of the present disclosure may be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments. Unless the context clearly indicates otherwise, throughout the specification and claims, the terms "comprises," "having," and variations thereof, such as "containing," are to be interpreted in an open and inclusive sense, i.e., "including but not limited to." Furthermore, the headings provided herein are merely for convenience and do not interpret the scope or meaning of the claimed disclosure.

[0026] As used herein, the term "in one embodiment" means that a particular feature, structure, or characteristic described with respect to that embodiment is included in at least one embodiment. Thus, the appearances of the phrase "in one embodiment" in various places throughout this specification do not necessarily all refer to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Also, as used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. Furthermore, it should be noted that the term "or" is generally used in its sense to include "and / or" unless the context clearly indicates otherwise.

[0027] For definitions of standard chemical terms, references may be made (e.g., Carey and Sundberg "ADVANCED ORGANIC CHEMISTRY 4TH ED." Vols. A (2000) and B (2001), Plenum Press, New York). Unless otherwise specified, conventional methods within the skill of the art, such as mass spectrometry, NMR, IR and UV / VIS spectroscopy, and pharmacological methods, are used. Unless a specific definition is provided, terms used herein in the relevant descriptions of analytical chemistry, synthetic organic chemistry, medicine, and medicinal chemistry are known in the art. Standard techniques can be used for chemical synthesis, chemical analysis, pharmaceutical manufacture, formulation, and delivery, and patient treatment. For example, reactions and purifications can be carried out using kit manufacturer's instructions or by methods known in the art or described herein. The techniques and methods described above can generally be carried out according to conventional methods known in the art, as described in various general and more specific references cited and discussed herein. As used herein, groups and substituents thereof may be selected by one skilled in the art to provide stable structural moieties and compounds.

[0028] When a substituent is depicted by a conventional chemical formula written from left to right, the substituent also includes the chemically equivalent substituent that would result if the structural formula were written from right to left, e.g., -CHO is equivalent to -OCH-.

[0029] Certain chemical groups defined herein are preceded by a shorthand symbol that indicates the total number of carbon atoms present in that group. For example, C1-C6 alkyl refers to an alkyl, as defined below, having a total of 1 to 6 carbon atoms. The total number of carbon atoms in the shorthand symbol does not include carbons that may be present in substituents of said group.

[0030] In this disclosure, when a particular variable is referred to as being "selected from," this indicates that the variable is selected from any one of the options listed after the colon, or, where possible, that the variable is selected from one or more of the options listed after the colon.

[0031] All numerical ranges referred to in this disclosure are intended to include both the two endpoints of the range, all integers within the range, and subranges formed by such integers.

[0032] In addition to the above, as used in the specification and claims of this disclosure, unless specifically stated otherwise, the following terms have the meanings indicated below.

[0033] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0034] "Hydroxy" refers to the group --OH.

[0035] "Hydroxyalkyl" refers to an alkyl, as defined below, substituted with hydroxy (-OH).

[0036] "Carbonyl" refers to the group -C(=O)-.

[0037] "Oxo" refers to the group =O.

[0038] "Thio" refers to the group ═S.

[0039] "Nitro" refers to -NO2.

[0040] "Cyano" refers to -CN.

[0041] "Amino" refers to -NH2.

[0042] "Substituted amino" refers to amino substituted by one or two alkyl, alkylcarbonyl, aralkyl, aryl, heteroaryl, heterocyclyl, or heteroaralkyl, as defined below, such as monoalkylamino, dialkylamino, alkylcarbonylamino, aralkylamino, heteroaralkylamino, heterocyclylamino, heteroarylamino, and arylamino. In some embodiments herein, a "substituted amino" is represented as -NR'R", wherein R' and R' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl, provided that at least one of R' and R'' is not H.

[0043] "Carboxy" refers to --COOH.

[0044] -C(O) refers to -C(=O).

[0045] In the present disclosure, the term "Ci-Cj" represents a range of carbon atoms, where i and j are integers, and the range includes the endpoints (i.e., i and j) and each integer between the endpoints, where j is greater than i. For example, C1-C6 represents a range of 1 to 6 carbon atoms, including 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, and 6 carbon atoms. Also, for example, the term "C1-C12" represents 1 to 12, particularly 1 to 10, particularly 1 to 8, particularly 1 to 6, particularly 1 to 5, particularly 1 to 4, particularly 1 to 3, or particularly 1 to 2 carbon atoms.

[0046] In this disclosure, the term "alkyl," as a group or part of another group (e.g., in groups such as alkyl substituted with a halogen (e.g., fluorine, chlorine, bromine, or iodine)), refers to a fully saturated straight or branched hydrocarbon chain group composed only of carbon and hydrogen atoms attached to the remainder of the molecule through single bonds, e.g., having 1 to 12 (preferably 1 to 8, more preferably 1 to 6) carbon atoms. In some embodiments, alkyl contains 1 to 11 carbon atoms. In some embodiments, alkyl contains 1 to 10 carbon atoms, 1 to 9 carbon atoms, 1 to 8 carbon atoms, 1 to 7 carbon atoms, 1 to 6 carbon atoms, 1 to 5 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, or 1 to 2 carbon atoms. Non-limiting examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, tert-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, and the like. Each alkyl in the various embodiments of the present disclosure is preferably a C1-C4 alkyl. In some embodiments, the carbon chain length of the alkyl may be 8 to 22 carbon atoms and is preferably an aliphatic chain. Unless otherwise specified herein, the alkyl may be optionally substituted.

[0047] In this disclosure, the term "alkenyl," as a group or part of another group, refers to a straight or branched hydrocarbon chain with one or more carbon-carbon double bonds (-C=C-) composed solely of carbon and hydrogen atoms connected to the remainder of the molecule through single bonds. In some embodiments, an alkenyl contains 2 to 12 carbon atoms. In some embodiments, an alkenyl contains 2 to 11 carbon atoms. In some embodiments, an alkenyl contains 2 to 10 carbon atoms, 2 to 9 carbon atoms, 2 to 8 carbon atoms, 2 to 7 carbon atoms, 2 to 6 carbon atoms, 2 to 5 carbon atoms, 2 to 4 carbon atoms, 2 to 3 carbon atoms, and even in some embodiments, an alkenyl contains 2 carbon atoms. Non-limiting examples of alkenyl include vinyl, 1-propenyl, 2-propenyl (allyl), isopropenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 1-octenyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, Includes 4-nonenyl, 5-nonenyl, 6-nonenyl, 7-nonenyl, 8-nonenyl, 1-decenyl, 2-decenyl, 3-decenyl, 4-decenyl, 5-decenyl, 6-decenyl, 7-decenyl, 8-decenyl, 9-decenyl, 1-undecenyl, 2-undecenyl, 3-undecenyl, 4-undecenyl, 5-undecenyl, 6-undecenyl, 7-undecenyl, 8-undecenyl, 9-undecenyl, 10-undecenyl, 1-dodecenyl, 2-dodecenyl, 3-dodecenyl, 4-dodecenyl, 5-dodecenyl, 6-dodecenyl, 7-dodecenyl, 8-dodecenyl, 9-dodecenyl, 10-dodecenyl and 11-dodecenyl. Unless stated otherwise in the specification, an alkenyl may be optionally substituted.

[0048] In this disclosure, the term "alkynyl," as a group or part of another group, refers to a straight or branched hydrocarbon chain with one or more carbon-carbon triple bonds (-C≡C-) composed solely of carbon and hydrogen atoms connected to the rest of the molecule through single bonds. In some embodiments, alkynyl contains 2 to 12 carbon atoms. In some embodiments, alkynyl contains 2 to 11 carbon atoms. In some embodiments, alkynyl contains 2 to 10 carbon atoms, 2 to 9 carbon atoms, 2 to 8 carbon atoms, 2 to 7 carbon atoms, 2 to 6 carbon atoms, 2 to 5 carbon atoms, 2 to 4 carbon atoms, 2 to 3 carbon atoms, and in some embodiments, alkynyl contains 2 carbon atoms. Non-limiting examples of alkynyl include ethynyl, propynyl, butynyl, pentynyl, and the like. Unless stated otherwise specifically in the specification, alkynyl may be optionally substituted.

[0049] In this disclosure, the term "alkoxy," as a group or part of another group, refers to an "-O-alkyl" group, where alkyl has the meaning described above.

[0050] In this disclosure, the term "haloalkyl" as a group or part of another group refers to an alkyl group substituted with one or more halogens, where alkyl has the meaning described above, and the number of halogens may be up to the number of replaceable hydrogens of the alkyl.

[0051] In the present disclosure, the term "acyl," as a group or part of another group, refers to the monovalent group remaining after removal of the hydroxyl group from an aliphatic carboxylic acid, and can be represented by the general formula "GC(=O)-," where G represents H or an alkyl, alkenyl, or alkynyl as defined above. For example, specific examples of C1-C4 acyl include, but are not limited to, formyl, acetyl, propionyl, butyryl, etc.

[0052] In this disclosure, the term "cyclohydrocarbyl," as a group or part of another group, refers to a saturated or partially unsaturated non-aromatic monocyclic or polycyclic hydrocarbon group or moiety (representing a structural unit of an organic molecule) consisting solely of carbon and hydrogen atoms, optionally having one or more carbon-carbon double bonds (-C=C-) or carbon-carbon triple bonds (-C≡C-), which can be attached to the remainder of the molecule through any suitable carbon atom, and includes "cycloalkyl," "cycloalkenyl," and "cycloalkynyl." In some embodiments, the cyclohydrocarbyl contains 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 ring carbon atoms. Non-limiting examples of cyclohydrocarbyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, 1-cyclohex-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and cyclooctynyl. Unless otherwise stated herein, carbon atoms of cyclohydrocarbyls may be optionally oxidized (forming an oxo (=O) group), and cyclohydrocarbyls may be optionally substituted.

[0053] In this disclosure, the term "cycloalkyl," as a group or part of another group, refers to a saturated non-aromatic monocyclic or polycyclic hydrocarbon group or moiety composed solely of carbon and hydrogen atoms, which may be attached to the remainder of the molecule through any suitable carbon atom. In some embodiments, a cycloalkyl contains 3 to 12 ring carbon atoms, 3 to 10 ring carbon atoms, 3 to 9 ring carbon atoms, 3 to 8 ring carbon atoms, 3 to 7 ring carbon atoms, 3 to 6 ring carbon atoms, 3 to 5 ring carbon atoms, 4 to 12 ring carbon atoms, 4 to 10 ring carbon atoms, 4 to 9 ring carbon atoms, 4 to 8 ring carbon atoms, 4 to 7 ring carbon atoms, 4 to 6 ring carbon atoms, or 4 to 5 ring carbon atoms. Non-limiting examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Unless otherwise stated herein, carbon atoms of a cycloalkyl may be optionally oxidized (forming an oxo (=O) group), and cycloalkyl may be optionally substituted.

[0054] In this disclosure, the term "cycloalkenyl," as a group or part of another group, refers to a partially unsaturated non-aromatic monocyclic or polycyclic hydrocarbon group or moiety composed solely of carbon and hydrogen atoms and having one or more carbon-carbon double bonds (-C=C-), which may be attached to the remainder of the molecule through any suitable carbon atom. In some embodiments, a cycloalkenyl contains 5 to 12 ring carbon atoms, 5 to 10 ring carbon atoms, 5 to 9 ring carbon atoms, 5 to 8 ring carbon atoms, 5 to 7 ring carbon atoms, or 5 to 6 ring carbon atoms. Non-limiting examples of cycloalkenyls include cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless otherwise stated herein, carbon atoms of a cycloalkenyl may be optionally oxidized (to form an oxo (=O) group), and a cycloalkenyl may be optionally substituted.

[0055] In this disclosure, the term "cycloalkynyl," as a group or part of another group, refers to a partially unsaturated non-aromatic monocyclic or polycyclic hydrocarbon group or moiety composed solely of carbon and hydrogen atoms and having one or more carbon-carbon triple bonds (-C=C-), which may be attached to the remainder of the molecule through any suitable carbon atom. In some embodiments, a cycloalkynyl contains 8 to 12 ring carbon atoms, 8 to 11 ring carbon atoms, 8 to 10 ring carbon atoms, or 8 to 9 ring carbon atoms. Non-limiting examples of cycloalkynyl include cyclooctynyl, and the like. Unless otherwise stated herein, the carbon atoms of a cycloalkynyl are optionally oxidized (to form an oxo (=O) group), and the cycloalkynyl can be optionally substituted.

[0056] In this disclosure, the term "spirocyclyl" or "spirocycle" as a group or part of another group refers to a ring system composed of multiple (e.g., two, three, or more) rings, in which at least two rings are cyclohydrocarbyls bonded to each other by shared carbon atoms. In some embodiments, a spirocyclyl contains 6 to 12 ring carbon atoms, 6 to 11 ring carbon atoms, 6 to 10 ring carbon atoms, 6 to 9 ring carbon atoms, 6 to 8 ring carbon atoms, or 6 to 7 ring carbon atoms. Non-limiting examples of spirocyclyls include, but are not limited to, spiro[5.5]undecyl, spiro-pentadienyl, spiro[3.6]decyl, and the like. Unless otherwise specified herein, a spirocyclyl may be optionally substituted.

[0057] In this disclosure, the term "fused cyclyl" or "fused ring" (also called "fused ring") as a group or part of another group refers to a ring system composed of multiple (e.g., two, three, or more) rings, in which at least two rings are cyclohydrocarbyls bonded to each other by sharing two adjacent carbon atoms (i.e., at least two rings share one covalent bond such that bridgehead atoms are directly bonded). In some embodiments, the fused cyclyl contains 5 to 12 ring carbon atoms, 5 to 11 ring carbon atoms, 5 to 10 ring carbon atoms, 5 to 9 ring carbon atoms, 5 to 8 ring carbon atoms, 5 to 7 ring carbon atoms, or 5 to 6 ring carbon atoms. Non-limiting examples of fused cyclyls include, but are not limited to, 2,3-indenyl, 1,2,3,4-tetrahydro-naphthyl, 5,6,7,8-tetrahydro-naphthyl, 8,9-dihydro-7H-benzocycloheptyl-6-yl, 6,7,8,9-tetrahydro-5H-benzocycloheptenyl, 5,6,7,8,9,10-hexahydro-benzocyclooctenyl, etc. Unless stated otherwise in the specification, a fused cyclyl may be optionally substituted.

[0058] In this disclosure, the term "bridged cyclyl" or "bridged ring" as a group or part of another group refers to a ring system composed of multiple (e.g., two, three, or more) rings, in which at least two rings are cyclohydrocarbyls linked to each other by three or more shared carbon atoms (the at least two rings are separated by two bridgehead atoms through a bridge containing at least one atom). In some embodiments, the bridged cyclyl contains 8 to 12 ring carbon atoms, 8 to 11 ring carbon atoms, 8 to 10 ring carbon atoms, or 8 to 9 ring carbon atoms. Non-limiting examples of bridged cyclyls include, but are not limited to, bicyclo[1.1.1]pentenyl, bicyclo[2.2.1]heptenyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.1]octenyl, bicyclo[3.3.1]nonyl, bicyclo[3.3.3]undecyl, adamantyl, etc. Unless otherwise stated in the specification, bridged cyclyls may be optionally substituted.

[0059] In this disclosure, the term "heterocyclyl" or "heterocycle," as a group or part of another group, refers to a stable saturated or partially unsaturated non-aromatic cyclic group or moiety consisting of carbon atoms (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 carbon atoms) and heteroatoms (e.g., 1 to 6 heteroatoms, more preferably 1, 2, or 3 heteroatoms) selected from nitrogen, phosphorus, oxygen, and sulfur (preferably nitrogen, oxygen, or sulfur). In some embodiments, the heterocyclyl contains 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 ring atoms, e.g., 3 to 20 ring atoms, 3 to 19 ring atoms, 3 to 18 ring atoms, 3 to 17 ring atoms, 3 to 16 ring atoms, 3 to 15 ring atoms, 4 to 12 ring atoms, 4 to 10 ring atoms, 4 to 9 ring atoms, 4 to 8 ring atoms, 4 to 7 ring atoms, 4 to 6 ring atoms, or 4 to 5 ring atoms. Unless otherwise described herein, a heterocyclyl may be a monocyclic, bicyclic, tricyclic, or polycyclic ring system, and may include a fused / condensed ring system (i.e., a fused-ring heterocyclyl, e.g., a 4- to 9-membered fused-ring heterocyclyl), a bridged ring system (i.e., a bridged heterocyclyl, e.g., a 6- to 12-membered bridged heterocyclyl), or a spiro ring system (i.e., a spiro heterocyclyl, e.g., a 6- to 12-membered spiro heterocyclyl). A fused-ring heterocyclyl refers to a ring system composed of multiple (e.g., two, three, or more) rings, in which at least two rings are heterocyclyls bonded to each other by sharing two adjacent atoms (i.e., said at least two rings share one covalent bond so that the bridgehead atoms are directly connected), and is preferably a bicyclic fused-ring heterocyclyl.A bridged heterocyclyl refers to a ring system consisting of multiple (e.g., two, three, or more) rings, wherein at least two rings are heterocyclyls bonded to each other by sharing three or more atoms (the at least two rings are separated by two bridgehead atoms through a bridge containing at least one atom). A spiroheterocyclyl refers to a ring system consisting of multiple (e.g., two, three, or more) rings, wherein at least two rings are heterocyclyls bonded to each other by sharing one carbon atom. The nitrogen, carbon, or sulfur atom of the heterocyclyl may be optionally oxidized, and the nitrogen atom may be optionally quaternized. A heterocyclyl may be linked to the remainder of the molecule by a single bond through a carbon atom or heteroatom. In some cases, a heterocyclyl may be carbon-linked, nitrogen-linked, or sulfur-linked. In some embodiments, a heterocyclyl is carbon-linked. In some embodiments, a heterocyclyl is nitrogen-linked. In some embodiments, a heterocyclyl is sulfur-linked. Unless stated otherwise in the specification, a heterocyclyl may be optionally substituted.

[0060] Heterocyclyl also includes groups in which the heterocyclyl group is fused to a saturated, partially unsaturated, or fully unsaturated (i.e., aromatic) cyclohydrocarbyl, aryl, heterocyclyl, or heteroaryl. In heterocyclyls containing fused rings, one or more of the rings may be aryl or heteroaryl as defined below. Examples of fused heterocyclyls include, but are not limited to, phenyl- or pyridyl-fused heterocyclyl, and quinolinyl, isoquinolinyl, quinoxalinyl, quinozinyl, quinazolinyl, azaindolizinyl, pteridinyl, chromenyl, isochromenyl, indolyl, isoindolyl, indolizinyl, indazolyl, purinyl, benzofuranyl, isobenzofuranyl, benzimidazolyl, benzothienyl, benzothiazolyl, carbazolyl, phenazinyl, phenothiazinyl, phenanthridinyl, imidazo[1,2-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridyl, [1,2,3]triazolo[4,3-a]pyridine-fused heterocyclyl, and the like.

[0061] In some embodiments, heterocyclyl is a stable 4- to 12-membered, 5- to 12-membered, 6- to 10-membered, 4- to 10-membered, or 4- to 9-membered non-aromatic monocyclic, bicyclic, tricyclic, or polycyclic group (including fused, bridged, or spirocyclic groups) containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, for example, a stable 5- to 10-membered (e.g., 4- to 9-membered) non-aromatic monocyclic, bicyclic, tricyclic, or polycyclic group (including fused, bridged, or spirocyclic groups) containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur. Examples of heterocyclyl are pyrrolidinyl, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, thiomorpholinyl, 2,7-diaza-spiro[3.5]nonan-7-yl, 2-oxa-6-aza-spiro[3.3]heptan-6-yl, 2-oxa-6-aza-spiro[3.4]octan-7-yl, 8-oxa-2-aza-spiro[4.5]decan-6-yl, 2,5-diaza-bicyclo[2.2.1]heptan-2-yl, azetidinyl, oxetanyl, thietanyl, thiolanyl, pyranyl, tetrahydropyranyl, thiopyranyl, thiopyranyl, tetrahydro ... Indyl, tetrahydrofuranyl, oxazinyl, dioxolanyl, tetrahydroisoquinolinyl, decahydroisoquinolinyl, imidazolinyl, imidazolidinyl, quinolinyl, thiazolidinyl, isothiazolidinyl, isoxazolidinyl, dihydroindolyl, octahydroindolyl, octahydroisoindolyl, pyrazolidinyl, phthalimido, dioxothiomorpholinyl, dioxothiolanyl, dioxothietanyl, thianil, dioxothianil, thiomorpholinyl, 1,4-oxathianyl, and the like.

[0062] In this disclosure, "aryl" or "aryl ring," as a group or part of another group, refers to a conjugated hydrocarbon ring system group or moiety having 6 to 18 carbon atoms (e.g., 6 to 14 carbon atoms or 6 to 10 carbon atoms, e.g., 6, 7, 8, 9, or 10 carbon atoms). Aryl may be a monocyclic, bicyclic, tricyclic, or polycyclic ring system, and may further be fused to a cyclohydrocarbyl or heterocyclyl as defined above. In the case of a polycyclic system, all rings may be aromatic, but only one ring need be aromatic. Examples of aryl include, but are not limited to, phenyl, naphthyl, anthracenyl, phenanthrenyl, fluorenyl, 2,3-dihydro-1H-isoindolyl, 2-benzoxazolinone, 2H-1,4-benzoxazin-3(4H)-on-7-yl, and the like. Unless otherwise specified herein, aryl may be optionally substituted.

[0063] In this disclosure, the term "heteroaryl" or "heteroaryl ring," as a group or part of another group, refers to a conjugated ring system group or moiety having carbon atoms (e.g., 1 to 15 carbon atoms, 1 to 14 carbon atoms, 1 to 13 carbon atoms, 1 to 12 carbon atoms, 1 to 11 carbon atoms, 1 to 10 carbon atoms, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms) and heteroatoms selected from nitrogen, oxygen, and sulfur (e.g., 1 to 6 heteroatoms, more preferably 1, 2, or 3 heteroatoms) within the ring. In some embodiments, the heteroaryl contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 ring atoms, e.g., 5 to 20 ring atoms, 5 to 19 ring atoms, 5 to 18 ring atoms, 5 to 17 ring atoms, 5 to 16 ring atoms, 5 to 15 ring atoms, 5 to 14 ring atoms, 5 to 13 ring atoms, 5 to 12 ring atoms, 5 to 10 ring carbon atoms, 5 to 9 ring atoms, 5 to 8 ring atoms, 5 to 7 ring atoms, or 5 to 6 ring atoms. Unless otherwise stated herein, the aryl may be a monocyclic, bicyclic, tricyclic, or polycyclic ring system, and may be further fused to a cyclohydrocarbyl, aryl, or heterocyclyl as defined above. The nitrogen, carbon, or sulfur atom of a heteroaryl may be optionally oxidized, and the nitrogen atom may be optionally quaternized. For purposes of this disclosure, heteroaryl is preferably a stable 5- to 12-membered aromatic group containing 1 to 5 heteroatoms selected from nitrogen, oxygen, and sulfur, more preferably a stable 5- to 10-membered aromatic group containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur, or a 5- to 6-membered aromatic group containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, and sulfur. Unless otherwise specified herein, heteroaryl may be optionally substituted.

[0064] Examples of heteroaryl include thienyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, oxadiazolyl, isoxazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzimidazolyl, benzomorpholinyl, benzisodiazolyl, benzotriazolyl, benzopyrazolyl, imidazopyridyl, pyridomorpholinyl, pyrazolopyridyl, indolyl, furyl, pyrrolyl, triazolyl, tetrazolyl, triazinyl, pyridinonyl, pyrimidinonyl, pyridazinonyl, indolizinyl, isoindolyl, indazolyl, isoindazolyl, purinyl, quinolinyl, isoquinolinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, pteridinyl, carbazolyl, and carbolinyl. , phenanthridinyl, phenanthrolinyl, acridinyl, phenazinyl, isothiazolyl, benzothiazolyl, benzothienyl, oxatriazolyl, cinnolinyl, quinazolinyl, indolizinyl, o-phenanthronyl, phenoxazinyl, phenothiazinyl, 4,5,6,7-tetrahydrobenzo[b]thienyl, naphthopyridyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-c]pyrimidinyl, [1,2,4]triazolo[4,3-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,2-b]pyridazinyl and imidazo[1,2-a]pyrazinyl.

[0065] In the present disclosure, all cyclic groups may be present as substituents on a core, or may themselves be present as part of a chain structure (including straight and branched chains), the core, or a part of the core.

[0066] In the present disclosure, the term "heteroarylalkyl" refers to an alkyl as defined above substituted by a heteroaryl as defined above.

[0067] In this disclosure, "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and the description includes both situations in which the event or circumstance occurs and situations in which it does not occur.

[0068] In this disclosure, the term "substituted," whether preceded by the term "optionally" (i.e., equivalent to substituted or unsubstituted), refers to the replacement of one or more hydrogen atoms of a specified group or moiety with a "suitable substituent." As used herein, the number of substituents may be one or more, i.e., 1, 2, 3, 4, 5, 6, or more, depending on the nature of the substituted group and substituent. For example, if the substituent of ethyl is a halogen, the group may be substituted with 1, 2, 3, 4, or 5 substituents, depending on the structure of the substituted group, such as trifluoromethyl, pentafluoroethyl, etc. In some embodiments, the number of substituents is 1, 2, or 3. In some embodiments, the number of substituents is 1 or 2. In some embodiments, the number of substituents is 1. It is understood that "substitution" or "substituted by" includes the implicit condition that such substitutions are performed according to the allowable valence of the substituted atom and that the substitution produces a stable or chemically feasible compound, e.g., a compound that does not spontaneously transform by rearrangement, cyclization, elimination, etc. Unless otherwise specified, an "optionally substituted" group may have a suitable substituent at each substitutable position of the group, and when more than one position of any given structure is substituted with one or more substituents selected from a specified group, the substituents may be the same or different at each position. Those of skill in the art should understand that, where appropriate, the substituents themselves may be substituted. Unless otherwise specified as "unsubstituted," chemical moieties referred to herein should be understood to include substituted variants. For example, reference to an "aryl" group or moiety implicitly includes unsubstituted aryl groups and substituted variants.

[0069] Throughout this application, the above "suitable substituents" include, but are not limited to, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, cyano, hydroxy, amino, monoalkylamino, dialkylamino, nitro, aryl, heteroaryl, cyclohydrocarbyl (e.g., cycloalkyl, cycloalkenyl, etc.), heterocyclyl, etc., as described herein, and these groups as substituents are also optionally substituted, such as alkyl, alkenyl, alkynyl, haloalkyl alkyl, haloalkenyl alkenyl, haloalkynyl alkynyl, alkoxy, monoalkylamino alkyl, dialkylamino alkyl, aryl, heteroaryl, cyclohydrocarbyl, and heterocyclyl, which may themselves be optionally substituted, e.g., they may be optionally substituted with one or more groups selected from alkyl, halogen, haloalkyl, alkoxy, hydroxy, amino, monoalkylamino, dialkylamino, nitro, aryl, heteroaryl, cyclohydrocarbyl, and heterocyclyl.

[0070] In some embodiments, the "suitable substituents" are hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, C1-C4 alkoxycarbonyl, cyano, -S(O)2-C1-C4 alkyl optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -NR'R", -S(O)2-NR'R", -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl, C3-C8 cyclohydrocarbyloxy, and optionally C1-C4 alkyl, haloC1 and 6-14 membered aryl, 5-10 membered heteroaryl, C-C cyclohydrocarbyl, and 4-9 membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -C alkyl, C-C alkoxy, haloC-C alkoxy, halogen, cyano, C-C alkyl-S(O)-, hydroxy, carboxyl, -NR'R", 6-14 membered aryl, 5-10 membered heteroaryl, C-C cyclohydrocarbyl, and 4-9 membered heterocyclyl, where R' and R" are each independently selected from H and C-C alkyl. In some embodiments, the "suitable substituents" are hydroxy, amino, halogen, substituted or unsubstituted alkyl, -NR'R", and substituted or unsubstituted alkoxy, where R' and R" are each independently selected from H, C-C alkyl, C-C cycloalkyl, C-C alkyl-S(O)-, and haloC-C alkyl. In some embodiments, the "suitable substituents" are selected from deuterium, hydroxy, cyano, C1-C4 alkyl, halogen, and C1-C4 alkoxy. In some embodiments, the "suitable substituents" are selected from deuterium, hydroxy, methyl, F, and methoxy. In some embodiments, the "suitable substituents" are selected from hydroxy, halogen, C1-C4 alkoxy, cyano, and -S(O)2-C1-C4 alkyl. In some embodiments, the "suitable substituents" are selected from hydroxyhalogen, hydroxy, cyano, -S(O)2-C1-C4 alkyl, C1-C4 alkyl, and C1-C4 alkoxy.In some embodiments, the "suitable substituents" are selected from hydroxy C1-C4 alkyl, C1-C4 alkoxy, and cyano. In some embodiments, the "suitable substituents" are F, hydroxy, and cyano.

[0071] As used herein, the terms "moiety," "structural moiety," "chemical moiety," "group," and "chemical group" refer to specific fragments or functional groups in a molecule. A chemical moiety is typically considered to be a chemical entity embedded in or attached to a molecule.

[0072] Those skilled in the art will also understand that in the methods described below, the functional groups of intermediate compounds may need to be protected by suitable protecting groups. Such functional groups include hydroxy, amino, amidino, guanidino, sulfhydryl, and carboxyl. Suitable hydroxy protecting groups include trialkylsilyl or diarylalkylsilyl (e.g., tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or trimethylsilyl), tetrahydropyranyl, benzyl, and the like. Suitable amino, amidino, and guanidino protecting groups include tert-butoxycarbonyl, benzyloxycarbonyl, and the like. Suitable sulfhydryl protecting groups include -C(O)-R X (where R X where R is alkyl, aryl or aralkyl), p-methoxybenzyl, triphenylmethyl, etc. Suitable carboxyl protecting groups include alkyl esters, aryl esters or aralkyl esters.

[0073] Protecting groups can be introduced and removed according to standard techniques known to those skilled in the art and described herein. The use of protecting groups is described in detail in Greene, TW and PGM Wuts, Protective Groups in Organi Synthesis, (1999), 4th Ed., Wiley. The protecting group may also be a polymer resin.

[0074] As used herein, a "subject" refers to a mammal, such as a primate, rat, mouse, cow, horse, pig, sheep, goat, dog, or cat, particularly a primate, and more particularly a human. In some embodiments, a "mammal" is selected from a human; a pet or livestock animal, such as a laboratory animal, cat, dog, pig, cow, sheep, goat, horse, or rabbit; or a non-domestic animal, such as a wild animal. The subject may be suspected of having or at risk for cancer, such as prostate cancer, breast cancer, ovarian cancer, bladder cancer, glioblastoma, melanoma, renal cell carcinoma, mantle cell lymphoma, pancreatic cancer, hepatocellular carcinoma, endometrial cancer, or salivary gland cancer, or may be suspected of having or at risk for alopecia, acne, hirsutism, ovarian cysts, polycystic ovarian disease, precocious puberty, spinal-bulbar muscular atrophy, or age-related macular degeneration. Those skilled in the art are familiar with diagnostic methods for various cancers, such as prostate cancer, breast cancer, ovarian cancer, bladder cancer, glioblastoma, melanoma, renal cell carcinoma, mantle cell lymphoma, pancreatic cancer, hepatocellular carcinoma, endometrial cancer, and salivary gland cancer, as well as diagnostic methods for alopecia, acne, hirsutism, ovarian cysts, polycystic ovarian disease, precocious puberty, spinal and bulbar muscular atrophy, and age-related macular degeneration, and clinical characteristics for cancers, such as prostate cancer, breast cancer, ovarian cancer, bladder cancer, glioblastoma, melanoma, renal cell carcinoma, mantle cell lymphoma, pancreatic cancer, hepatocellular carcinoma, endometrial cancer, and salivary gland cancer, as well as clinical characteristics for alopecia, acne, hirsutism, ovarian cysts, polycystic ovarian disease, precocious puberty, spinal and bulbar muscular atrophy, and age-related macular degeneration. In some embodiments, the subject has been identified or diagnosed as suffering from a disease.

[0075] As used herein, the term "pharmaceutically acceptable" refers to a substance (e.g., a carrier or diluent) that does not affect the biological activity or properties of the active ingredient of a drug (i.e., a compound of the present disclosure or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof), and is relatively non-toxic, i.e., the substance can be administered to an individual without causing an adverse biological response or interacting in an undesirable manner with any of the components included in the pharmaceutical composition. Pharmaceutically acceptable carriers or excipients include, but are not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonicity agent, solvent, or emulsifier approved for human or veterinary use by the U.S. Food and Drug Administration (FDA).

[0076] The term "pharmaceutical composition" refers to a formulation comprising a compound of the present disclosure or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof, and a vehicle commonly accepted in the art for delivering a biologically (pharmacologically) active compound to a mammal (e.g., a human). Such a vehicle includes a pharmaceutically acceptable carrier or excipient. The purpose of a pharmaceutical composition is to facilitate administration to an organism and promote absorption of the active ingredient, thereby exerting its biological (pharmacological) activity. Generally, a pharmaceutical composition of the present disclosure contains 0.1% to 99.5% by weight of the active drug ingredient (i.e., a compound of the present disclosure or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite). In some embodiments, the pharmaceutical compositions of the present disclosure comprise 0.5% to 90% by weight, e.g., 1%, 1.5%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, or 50% by weight of the active pharmaceutical ingredient.

[0077] The compounds of the present disclosure can exist in a variety of different forms or derivatives, and all such forms or derivatives are within the scope of the present disclosure. Such forms or derivatives include, for example, tautomers, stereoisomers (e.g., enantiomers, diastereomers), racemic mixtures, geometric isomers, salts, prodrugs, solvates, isotopic substitutions, various crystalline or polycrystalline forms, and metabolites (specifically referred to herein as active metabolites).

[0078] In the present disclosure, the term "pharmaceutically acceptable salts" includes pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0079] "Pharmaceutically acceptable acid addition salt" means a salt formed with an inorganic or organic acid that retains the biological effectiveness of the free base without other adverse effects. Inorganic acid salts include, but are not limited to, hydrochloride, hydrobromide, sulfate, nitrate, phosphate, and the like. Organic acid salts include, but are not limited to, formate, acetate, 2,2-dichloroacetate, trifluoroacetate, propionate, caproate, caprylate, decanoate, undecylenate, glycolate, gluconate, lactate, sebacate, adipate, glutarate, malonate, oxalate, maleate, succinate, fumarate, tartrate, citrate, palmitate, stearate, oleate, cinnamate, laurate, malate, glutamate, pyroglutamate, aspartate, benzoate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, alginate, ascorbate, salicylate, 4-aminosalicylate, naphthalenedisulfonate, and the like. These salts can be prepared by methods known in the art.

[0080] "Pharmaceutically acceptable base addition salt" means a salt formed with an inorganic or organic base that retains the biological effectiveness of the free acid without other adverse effects. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Preferred inorganic salts are ammonium, sodium, potassium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, primary amines, secondary amines, and tertiary amines, naturally occurring substituted amines, substituted amines including cyclic amines, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, triethanolamine, dimethylethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, choline, betaine, ethylenediamine, glucosamine, methylglucosamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, and basic ion exchange resins such as polyamine resins. Preferred organic bases include isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. These salts can be prepared by methods known in the art.

[0081] As used herein, the term "prodrug" refers to a compound that, after administration, is metabolized (i.e., converted in the body) to a pharmacologically active compound of the present disclosure. If a compound of the present disclosure itself is poorly absorbed in the gastrointestinal tract, it can be prepared as a prodrug to increase its bioavailability. Examples of prodrugs of compounds of the present disclosure include simple esters of carboxyl-containing compounds (e.g., C , which can be prepared according to methods known in the art). 1-4 esters obtained by condensation with alcohols; esters of hydroxy-containing compounds (e.g., C 1-4 Monocarboxylic acid, C 3-6esters obtained by condensation with dicarboxylic acids or their anhydrides, such as succinic anhydride or fumaric anhydride; imines of amino-containing compounds (e.g., C according to methods known in the art); 1-4 imines obtained by condensation with an aldehyde or ketone; carbamates of compounds containing an amino group, such as the esters described by Leu et al. (J. Med. Chem., 42:3623-3628 (1999)) and Greenwald et al. (J. Med. Chem., 42:3657-3667 (1999)); aldehyde acetals or ketone acetals of hydroxy-containing compounds (e.g., such acetals obtained by condensation with chloromethyl methyl ether or chloromethyl ethyl ether according to methods known in the art).

[0082] As used herein, the term "solvate" refers to an aggregate comprising one or more molecules of a compound of the present disclosure and one or more solvent molecules. The solvent may be water, in which case the solvate may be a hydrate. Alternatively, the solvent may be an organic solvent. Thus, the compounds of the present disclosure may exist as hydrates, including monohydrates, dihydrates, hemihydrates, sesquihydrates, trihydrates, tetrahydrates, etc., as well as corresponding solvated forms. While the compounds of the present disclosure may be true solvates, in other cases, the compounds of the present disclosure may remain merely amorphous water or a mixture of water and some external solvent.

[0083] As used herein, "stereoisomer" refers to a compound made up of the same atoms and bonded by the same bonds, but having a different three-dimensional structure. The present disclosure encompasses various stereoisomers and mixtures thereof.

[0084] When compounds of the present disclosure contain alkene double bonds, unless otherwise specified, the compounds of the present disclosure are intended to include both E- and Z-geometric isomers.

[0085] "Tautomer" refers to an isomer formed by the migration of a proton from one atom of a molecule to another atom of the same molecule. All tautomeric forms of the compounds of the present disclosure are also included within the scope of the present disclosure.

[0086] The compounds of the present disclosure, or pharmaceutically acceptable salts thereof, may contain one or more chiral carbon atoms and may therefore produce enantiomers, diastereomers, and other stereoisomeric forms. Each chiral carbon atom may be defined as (R)- or (S)- based on its stereochemistry. The present disclosure is intended to encompass all possible isomers, including their racemic and optically pure forms. The preparation of the compounds of the present disclosure may involve the selection of racemates, diastereomers, or enantiomers as starting materials or intermediates. Optically active isomers may be prepared using chiral synthons or chiral reagents, or separated using conventional techniques, such as crystallization and chiral chromatography.

[0087] Conventional techniques for producing / separating the individual isomers include chiral synthesis from suitable optically pure precursors or separation of the racemate (or racemate of a salt or derivative) using, for example, chiral high-performance liquid chromatography, see, for example, Gerd Gubitz and Martin G. Schmid (Eds.), Chiral Separations, Methods and Protocols, Methods in Molecular Biology, Vol. 243, 2004; A. M. Stalcup, Chiral Separations, Annu. Rev. Anal. Chem. 3:341-63, 2010; Fumiss et al. (eds.), VOGEL'S ENCYCLOPEDIA OF PRACTICAL ORGANIC CHEMISTRY.sup.TH ED., Longman Scientific and Technical Ltd., Essex, 1991, 809-816; Heller, Acc. Chem. Res. 1990, 23, 2000. 128, the disclosure of which is incorporated herein by reference in its entirety.

[0088] The present disclosure also includes all suitable isotopic substitutions (also called isotopic variants) of the compounds of the present disclosure or their pharmaceutically acceptable salts. An isotopic variant of a compound of the present disclosure or its pharmaceutically acceptable salt is defined as one in which at least one atom is replaced by an atom having the same atomic number but an atomic mass different from the atomic mass generally found in nature. Isotopes that can be incorporated into the compounds of the present disclosure and their pharmaceutically acceptable salts include, but are not limited to, isotopes of H, C, N, and O, for example: 2 H, 3 H, 11 C. 13 C. 14 C. 15 N, 17 O. 18 O. 35 S, 18 F, 36 Cl and 125I. Isotopic variations of the compounds described herein or pharmaceutically acceptable salts thereof can be prepared using appropriate isotopic variations of suitable reagents via conventional techniques.

[0089] Unless otherwise stated herein, the wavy line in each structure or group generally indicates the point at which that structure or group is attached to the rest of the compound.

[0090] As used herein, the terms "crystal," "crystalline form," and "polycrystalline" can be used interchangeably and refer to a crystalline structure in which a compound (or its salt, solvate, or other derivative, such as a prodrug or metabolite) can crystallize in different crystalline stacking arrangements (all having the same elemental composition). Crystal forms generally differ in X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability, and solubility. One crystalline form may dominate due to recrystallization solvent, crystallization rate, storage temperature, or other factors. Polycrystalline compounds can be produced by crystallization under different conditions.

[0091] As used herein, the terms "metabolite" and "active metabolite" can be used interchangeably and refer to derivatives having the same pharmacological activity that are produced during metabolic processing of a parent active drug ingredient in the body of a subject; for example, such metabolites can be produced by oxidation, reduction, hydrolysis, amidation, deamidation, esterification, deesterification, enzymatic cleavage, etc., of the administered compound or salt or prodrug.

[0092] As used herein, "prevention" refers to preventing the occurrence of a disease or condition in a mammal (preferably a human), particularly when the mammal is susceptible to the condition but has not yet been diagnosed with the condition, or to preventing the recurrence of a disease or condition that has been cured in a mammal (preferably a human).

[0093] As used herein, "treatment" includes the treatment of the disease or condition of concern in a mammal (preferably a human) suffering from the disease or condition of concern, and includes one or more of the following aspects: (i) inhibiting the disease or condition, i.e., inhibiting its progression; (ii) alleviating the disease or condition, i.e., relieving the disease or condition; and (iii) alleviating the symptoms of the disease or condition, i.e., reducing pain without resolving the underlying disease or condition.

[0094] An "effective amount" refers to a therapeutically effective amount or a prophylactically effective amount. A "therapeutically effective amount" refers to an amount effective to achieve the desired therapeutic result (relieving to some extent one or more symptoms of the disease or condition being treated, such as a reduction in tumor size, an increase in lifespan, or an increase in life expectancy) at a necessary dosage and for a necessary period of time. A therapeutically effective amount of a compound can vary depending on factors such as the disease state, age, sex, and weight of the subject, and the ability of the compound to induce a desired response in the subject. Dosage regimens can be adjusted to provide an optimal therapeutic response. A therapeutically effective amount is also an amount in which any toxic or detrimental effects of the compound exceed the therapeutically beneficial effects. A "prophylactically effective amount" refers to an amount effective to achieve the desired prophylactic result (preventing disease onset in subjects at risk of developing the disease and preventing disease recurrence in subjects who have been cured of the disease) at a necessary dosage and for a necessary period of time. Generally, a prophylactic dose is administered to a subject before or during an early stage of disease, such that the prophylactically effective amount is less than the therapeutically effective amount. An appropriate effective amount for a particular case can be determined using techniques such as a dose escalation study.

[0095] As used herein, the terms "dosing," "dosing," "administration," and the like refer to methods by which a compound or pharmaceutical composition can be delivered to the site of desired biological action. Any administration method known in the art can be used in the present disclosure. Such methods include, but are not limited to, oral administration, duodenal administration, parenteral administration (including intrapulmonary, intranasal administration; intrathecal, intravenous, subcutaneous, intraperitoneal, intramuscular, and intraarterial injection or infusion), topical administration, and rectal administration. Administration techniques used in the compounds and methods described herein are well known to those of skill in the art and are discussed, for example, in Goodman and Gilman, The Pharmacological Basis of Therapeutics, current ed.; Pergamon; and Remington's, Pharmaceutical Sciences (current edition), Mack Publishing Co., Easton, Pa. In a preferred embodiment, the compounds of the present disclosure or their pharmaceutically acceptable salts, enantiomers, diastereomers, tautomers, solvates, isotopic substitutions, polycrystals, prodrugs, or metabolites, or pharmaceutical compositions thereof, are administered orally.

[0096] As used herein, the terms "combination," "drug combination," "coadministration," or "combination therapy" refer to a drug treatment resulting from the mixing or combining of one or more active ingredients, including combinations of fixed and non-fixed active ingredients, and further including the combination of two or more different therapeutic approaches. The term "fixed combination" refers to the simultaneous administration to a patient of at least one compound described herein and at least one other active ingredient in the form of a single entity or single formulation. The term "non-fixed combination" refers to the simultaneous administration, combined administration, or sequential administration at variable intervals of at least one compound described herein and at least one other active ingredient as a single entity to a patient. These terms can also be used for cocktail therapy, such as the administration of three or more active ingredients.

[0097] For the avoidance of doubt, in this disclosure, compounds depicted with wedge bonds (eg, compound 67) are single-configuration compounds determined by absolute stereochemistry.

[0098] II. Compounds In one aspect, the present disclosure provides a compound represented by Formula I below, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof:

[0099] [ka]

[0100] In the formula: X1 is O and NR a is selected from X2 is selected from C and N; X3 is selected from C and N; Y5 and Y6 are independently a bond, O, S, N, -S(O)-, -S(O)2-, C, CH(R 13 ), C(R 13 )2, C(R 13 ), -OCH2-, -N(R 12 )CH2-, -CH2CH2- and N(R 12 and Y5 and Y6 are not simultaneously a bond; Y1 and Y4 are independently a bond, O, N, C, S, -S(O)-, -C(O)-, -S(O)2-, CH, CH2, NH, C(R 13 ), CH(R 13 ), C(R 13 )2 and N(R 12 ) with the proviso that Y1 and Y4, Y1 and Y5, Y4 and Y6 are not simultaneously a bond, O, S, -S(O)- or -S(O)2-, and satisfy the valence bond rule; Alternatively, Y1, Y4 and Y6 are optionally C(R 13 )2, two R on the same carbon atom 13together with the C atom linked thereto, form a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered heterocyclyl to form a spiro ring structure with ring B; Alternatively, the ring atoms of Y1 or Y6, the ring atoms of Y4 and the substituents linked to said ring atoms together form a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, a substituted or unsubstituted 4- to 9-membered heterocyclyl, a substituted or unsubstituted 6- to 10-membered aryl or a substituted or unsubstituted 5- to 10-membered heteroaryl, forming a fused ring structure with ring B; Alternatively, X2 may be a ring atom of Y6 and R 11 and the ring atoms connected to said ring atoms together form a substituted or unsubstituted 5- or 6-membered cyclohydrocarbyl, a substituted or unsubstituted 5- or 6-membered heterocyclyl, a substituted or unsubstituted phenyl, or a substituted or unsubstituted 5- or 6-membered heteroaryl, forming a triple fused ring structure with rings A and B; Ring B is a 5-, 6-, or 7-membered heterocycle, a benzene ring, or a 5-, 6-, or 7-membered heteroaryl ring, and Ring B is optionally substituted by one or more R13 and / or R12 that are not involved in the ring formation, and is further optionally substituted by 1, 2, or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted alkyl, -NR'R'' and substituted or unsubstituted alkoxy; R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R3 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted alkyl, or R4 and R5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; Alternatively, R4 or R5 and R6 and the atoms connected thereto together form a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each further optionally contain one or two heteroatoms selected from N and O; R7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R9 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and substituted or unsubstituted alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted alkyl, -NR'R'', and substituted or unsubstituted alkoxy; Each R not involved in ring formation 12 is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6- to 14-membered aryl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 alkyl; Each R not involved in ring formation 13 are independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted C6-14 aryl-S(O)2-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)- and NR'R''-C(O)-, or two R on the same carbon atom 13 forms an oxo (=O) or thio (=S) group, R 13 or R 12 after participating in ring formation, the ring atoms may optionally be replaced by 1 to 3 heteroatoms selected from O, N and S; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl; R a is selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0101] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl.

[0102] In some embodiments, the compound of Formula I has the structure of Formula Ia:

[0103] [ka]

[0104] In some embodiments, the compound of Formula I has the structure of Formula Ib:

[0105] [ka]

[0106] In the formula: Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

[0107] In some embodiments, ring A is a benzene ring or a 6-membered heteroaryl ring.

[0108] In some embodiments, ring A is a benzene ring or a pyridine ring.

[0109] In some embodiments, the compound of Formula I has the structure of Formula IIa:

[0110] [ka]

[0111] In the formula: Y4 is selected from C, CH and N; Y6 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, a 4- to 9-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, wherein the 4- to 9-membered heterocyclyl and the 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; R 15is H, halogen, oxo (=O), thio (=S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6-10 membered aryl-S(O)2-, substituted or unsubstituted 4-9 membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl-C(O)-, substituted or selected from unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 6- to 10-membered aryl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2, 3 or 4.

[0112] In some embodiments, X2 is selected from C and N; X3 is selected from C and N; Y1 is selected from a bond, O, NH, —N(CH3)—, CH2, and —CH(CH3)—; Y5 is selected from O, S, N, CH2, CH, NH, -N(CH3)-, -OCH2-, -NHCH2-, -N(CH3)CH2- and -CH2CH2-; Y4 is selected from C, CH or N; Y6 is selected from C, CH or N; R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; n is 0 or 1, R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R3 is selected from substituted or unsubstituted aryl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0113] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0114] In some embodiments, R1 is selected from cyano, —C(O)NH2, and —C(O)NHCH3, and R2 is selected from H, fluorine, and methoxy; R3 is phenyl; R4 and R5 are each independently selected from H and C1-C4 alkyl; R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, the substituents of which are 1, 2 or 3 and include hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O)2-C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and selected from 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered hydrocarbon group and 4-9 membered heterocyclyl optionally substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0115] [ka]

[0116] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0117] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0118] [ka]

[0119] is selected from.

[0120] In some embodiments, the compound of Formula I has the structure of Formula IIb:

[0121] [ka]

[0122] In the formula: Y1 is selected from C, CH and N; Y4 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, a 4- to 9-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, wherein the 4- to 9-membered heterocyclyl and the 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; R 15is H, halogen, oxo (=O), thio (=S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6-10 membered aryl-S(O)2-, substituted or unsubstituted 4-9 membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl-C(O)-, substituted or selected from unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 6- to 10-membered aryl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2, 3 or 4.

[0123] In some embodiments, X2 and X3 are C; Y1 is selected from C, CH and N; Y4 is selected from C, CH and N; Y5 is selected from a bond, O, S, -S(O)-, -S(O)2-, -C(O)-, N, NH, -N(CH3)-, CH2, -CH(CH3)-, -OCH2-, -NHCH2-, -N(CH3)CH2- and -CH2CH2-; Y6 is selected from a bond, O, S, -S(O)-, -S(O)2-, -C(O)-, N, CH2, CH, NH, -N(CH3)-, -OCH2-, -NHCH2-, -N(CH3)CH2- and -CH2CH2-, and Y5 and Y6 are not simultaneously bonds; R 15is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; n is 0 or 1, R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R3 is selected from substituted or unsubstituted aryl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0124] In some embodiments, R1 is selected from cyano, -C(O)NH2, and -C(O)NHCH3; R2 is selected from H, fluorine and methoxy; R3 is phenyl; R4 and R5 are each independently selected from H and C1-C4 alkyl; R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, the substituents of which are 1, 2 or 3 and are selected from hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O)2-C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and any optionally selected from 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0125] [ka]

[0126] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0127] In some embodiments, Ring D is a 3- to 6-membered cyclohydrocarbyl, a 4- to 6-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 8-membered heteroaryl, wherein the 4- to 6-membered heterocyclyl and the 5- to 8-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; and R 15is selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl. Preferably, said C1-C4 acyl, C1-C4 alkoxy, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; R′ and R″ are each independently selected from H and C1-C4 alkyl; and n is 0, 1 or 2.

[0128] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0129] [ka]

[0130] In some embodiments, R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, —NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl; R′ and R″ are each independently selected from H and C1-C4 alkyl; and n is 0 or 1.

[0131] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0132] In some embodiments, the compound of Formula I has a structure represented by Formula IIc:

[0133] [ka]

[0134] In the formula: Ring E is a 3- to 8-membered cyclohydrocarbyl or a 4- to 9-membered heterocyclyl, wherein the 4- to 9-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 alkyl, C1-C4 acyl and C1-C4 alkoxy optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2, 3 or 4.

[0135] In some embodiments, X2 and X3 are C; Y1 is selected from O or CH2; Y5 is selected from a bond, O, NH, —N(CH3)—, CH2, and —CH(CH3)—; Y6 is selected from a bond, O, S, N, CH2, CH, NH, and -N(CH3)-; R 16 is selected from halogen, C1-C4 alkyl, hydroxy, C1-C4 acyl and C1-C4 alkoxy; R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R3 is selected from substituted or unsubstituted aryl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0136] In some embodiments, R1 is selected from cyano, -C(O)NH2, and -C(O)NHCH3; R2 is selected from H, fluorine and methoxy; R3 is phenyl; R4 and R5 are each independently selected from H and C1-C4 alkyl; R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, the substituents of which are 1, 2 or 3 and are selected from hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O)2-C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and any optionally selected from 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0137] [ka]

[0138] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0139] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0140] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0141] [ka]

[0142] is selected from.

[0143] In some embodiments, the compound of Formula I has a structure represented by Formula IId:

[0144] [ka]

[0145] In the formula: Ring E is a 3- to 8-membered cyclohydrocarbyl or a 4- to 9-membered heterocyclyl, wherein the 4- to 9-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 alkyl, C1-C4 acyl and C1-C4 alkoxy optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2, 3 or 4.

[0146] In some embodiments, X2 and X3 are C; Y4 is selected from O or CH2; Y5 is selected from a bond, O, NH, —N(CH3)—, CH2, and —CH(CH3)—; Y6 is selected from a bond, O, S, N, CH2, CH, NH, and -N(CH3)-; R 16 is selected from halogen, C1-C4 alkyl, hydroxy, C1-C4 acyl and C1-C4 alkoxy; R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R3 is selected from substituted or unsubstituted aryl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0147] In some embodiments, R1 is selected from cyano, -C(O)NH2, and -C(O)NHCH3; R2 is selected from H, fluorine and methoxy; R3 is phenyl; R4 and R5 are each independently selected from H and C1-C4 alkyl; R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, the substituents of which are 1, 2 or 3 and are selected from hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O)2-C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and any optionally selected from 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0148] [ka]

[0149] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0150] In some embodiments, Ring E is a 3- to 6-membered cyclohydrocarbyl or a 4- to 6-membered heterocyclyl, wherein the 4- to 6-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; and R 16 is selected from H, halogen, C1-C4 alkyl, hydroxy and acetyl; and n is 0 or 1.

[0151] In some embodiments, Ring E is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, tetrahydropyranyl, azetidinyl, azacyclopentyl, or piperidinyl; and R 16 is selected from H, fluorine, methyl, ethyl, hydroxy and acetyl; and n is 0 or 1.

[0152] In some embodiments, the compound of Formula I has a structure represented by Formula IIe:

[0153] [ka]

[0154] In the formula: X2 is C, Y6 is selected from C, CH and N; Ring F is a 5- or 6-membered cyclohydrocarbyl, a 5- or 6-membered heterocyclyl, a phenyl, or a 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 15is H, halogen, oxo (=O), thio (=S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6-10 membered aryl-S(O)2-, substituted or unsubstituted 4-9 membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted substituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 6- to 10-membered aryl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2 or 3.

[0155] In some embodiments, ring F is phenyl or a 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S, and / or R 15is selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″-C(O)—, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl. In some embodiments, the C1-C4 acyl, C1-C4 alkoxy, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted with 1, 2, or 3 substituents selected from F, hydroxy, and cyano, where R′ and R″ are each independently selected from H and C1-C4 alkyl, and n is 0, 1, or 2.

[0156] In some embodiments, ring F is a 5-membered heteroaryl, wherein the 5-membered heteroaryl contains 1 or 2 heteroatoms selected from O and N, and / or R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, —NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, where R′ and R″ are each independently selected from H and C1-C4 alkyl. In some embodiments, n is 0 or 1.

[0157] In some embodiments, Ring F is pyrrolyl, furanyl, pyrazolyl, imidazolyl, oxazolyl, or isoxazolyl.

[0158] In some embodiments, Y, Y, and Y are independently selected from O, CH, CH, —CH(CH)—, N, NH, and —N(CH)—; Ring F is phenyl or a 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″-C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and n is 0 or 1; R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R3 is selected from substituted or unsubstituted aryl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0159] In some embodiments, R1 is selected from cyano, -C(O)NH2, and -C(O)NHCH3; R2 is selected from H, fluorine and methoxy; R3 is phenyl; R4 and R5 are each independently selected from H and C1-C4 alkyl; R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, the substituents of which are 1, 2 or 3 and are selected from hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O)2-C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and any optionally selected from 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0160] [ka]

[0161] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0162] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0163] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0164] [ka]

[0165] is selected from.

[0166] In some embodiments, the compound of Formula IIa has the structure of Formula IIIa:

[0167] [ka]

[0168] In the formula: D1 is O, S, S(O), S(O)2, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , C.R. f -NR e ,

[0169] [ka]

[0170] is selected from D3 is O, S, S(O), S(O)2, N, NR e , (CR f ) p and (CR f R g ) p is selected from The condition is that D1 and D2, D1 and D3 are not simultaneously O, S, -S(O)- or -S(O)2-, and satisfy the valence bond law; Each R eis independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R f is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R gis independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Or R on the same carbon atom f and R g forms an oxo (=O) or thio (=S), and Each p is independently 1, 2, 3 or 4, preferably 1 or 2.

[0171] In some embodiments, X2 is selected from C and N; X3 is selected from C and N; Y1 is selected from a bond, O, NH, —N(CH3)—, CH2, and —CH(CH3)—; Y5 is selected from O, S, N, CH2, CH, NH, -N(CH3)-, -OCH2-, -NHCH2-, -N(CH3)CH2- and -CH2CH2-; Y4 is selected from C, CH or N; Y6 is selected from C, CH or N; D1 is O, S, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, N, NR e , (CR f ) p and (CR f R g ) pis selected from D3 is O, S, N, NR e , (CR f ) p and (CR f R g ) p is selected from R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R3 is selected from substituted or unsubstituted aryl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0172] In some embodiments, R1 is selected from cyano, -C(O)NH2, and -C(O)NHCH3; R2 is selected from H, fluorine and methoxy; R3 is phenyl; R4 and R5 are each independently selected from H and C1-C4 alkyl; R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, the substituents of which are 1, 2 or 3 and include hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O)2-C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and and 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0173] [ka]

[0174] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0175] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0176] [ka]

[0177] is selected from.

[0178] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0179] In some embodiments, the compound of Formula IIb has the structure of Formula IIIb:

[0180] [ka]

[0181] In the formula: D1 is O, S, S(O), S(O)2, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , C.R. f -NR e ,

[0182] [ka]

[0183] is selected from D3 is O, S, S(O), S(O)2, N, NR e , (CR f ) p and (CR f R g ) p is selected from The condition is that D1 and D2, D1 and D3 are not simultaneously O, S, -S(O)- or -S(O)2-, and satisfy the valence bond law; Each R eis independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R f is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R gis independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Or R on the same carbon atom f and R g forms an oxo (=O) or thio (=S), and Each p is independently 1, 2, 3 or 4, preferably 1 or 2.

[0184] In some embodiments, X2 and X3 are C; Y1 is selected from C, CH and N; Y4 is selected from C, CH and N; Y5 is selected from a bond, O, S, -S(O)-, -S(O)2-, -C(O)-, N, NH, -N(CH3)-, CH, CH2, -CH(CH3)-, -OCH2-, -NHCH2-, -N(CH3)CH2- and -CH2CH2-; Y6 is selected from a bond, O, S, -S(O)-, -S(O)2-, -C(O)-, N, CH2, CH, -CH(CH3)-, NH, -N(CH3)-, -OCH2-, -NHCH2-, -N(CH3)CH2- and -CH2CH2-, and Y5 and Y6 are not simultaneously bonds; D1 is O, S, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, N, NRe , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , C.R. f -NR e ,

[0185] [ka]

[0186] is selected from D3 is O, S, N, NR e , (CR f ) p and (CR f R g ) p is selected from R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R3 is selected from substituted or unsubstituted aryl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0187] In some embodiments, R1 is selected from cyano, -C(O)NH2, and -C(O)NHCH3; R2 is selected from H, fluorine and methoxy; R3 is phenyl; R4 and R5 are each independently selected from H and C1-C4 alkyl; R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, the substituents of which are 1, 2 or 3 and are selected from hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O)2-C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and any optionally selected from 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0188] [ka]

[0189] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0190] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0191] [ka]

[0192] is selected from.

[0193] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0194] In some embodiments, the compound of Formula IIIa has the structure of Formula IVa:

[0195] [ka]

[0196] In the formula: Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

[0197] In some embodiments, the compound of Formula IIIb has the structure of Formula IVb:

[0198] [ka]

[0199] In the formula: Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

[0200] In some embodiments, the compound of formula IIe has the structure of formula IVc:

[0201] [ka]

[0202] In the formula: Y7, Y8 and Y9 are independently a bond, O, S, S(O), S(O)2, N, or NR e , C.R. f and CR f R g with the proviso that at most one of Y7, Y8 and Y9 is a bond, and Y7 and Y8, Y8 and Y9 are not simultaneously O, S, -S(O)- or -S(O)2-, and satisfy the valence bond rule; Each R eis independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R f is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R gis independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Or R on the same carbon atom f and R g forms an oxo (=O) or thio (=S) group, Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

[0203] In some embodiments, Ring C is a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl, wherein the 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, the 6- to 12-membered nitrogen-containing spiroheterocyclyl, and the 6- to 12-membered nitrogen-containing fused heterocyclyl each optionally further contain 1 or 2 heteroatoms selected from N and O.

[0204] In some embodiments, Ring C is a 4-9 membered monocyclic or fused ring heterocyclyl optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen, and C1-C4 alkoxy.

[0205] In some embodiments, Ring C is the following group optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, methyl, F, and methoxy:

[0206] [ka]

[0207] where the wavy lines represent the attachment points of the bonds.

[0208] In some embodiments, Ring C is optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, methyl, F, and methoxy.

[0209] [ka]

[0210] is.

[0211] In some embodiments, R1 is selected from cyano and -C(=O)NR'R'' wherein R' and R'' are each independently selected from H, C1-C4 alkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl.

[0212] In some embodiments, R1 is selected from cyano and -C(=O)NR'R'' wherein R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl.

[0213] In some embodiments, R 1 is selected from cyano, —C(═O)NH 2 , and —C(═O)NHCH 3 .

[0214] In some embodiments, R1 is cyano, -C(=O)NH2, -C(=O)NHCH3, and

[0215] [ka]

[0216] is selected from In some embodiments, R1 is -C(O)NR'R''.

[0217] In some embodiments, R1 is -C(O)NHR', wherein R' is selected from H and C1-C4 alkyl.

[0218] In some embodiments, R1 is -C(O)NHR', wherein R' is selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0219] In some embodiments, R1 is -C(O)NH2.

[0220] In some embodiments, R1 is -C(O)NHCH3.

[0221] In some embodiments, R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, and substituted or unsubstituted C1-C4 alkoxy.

[0222] In some embodiments, R2 is selected from H, halogen, C1-C4 alkyl, and C1-C4 alkoxy.

[0223] In some embodiments, R2 is selected from H, halogen, C1-C3 alkyl, and C1-C3 alkoxy.

[0224] In some embodiments, R2 is selected from H, halogen, and methoxy.

[0225] In some embodiments, R2 is halogen.

[0226] In some embodiments, R2 is selected from fluorine and chlorine.

[0227] In some embodiments, R2 is fluorine.

[0228] In some embodiments, R3 is selected from phenyl or heteroaryl unsubstituted or substituted with 1 to 3 substituents selected from hydroxy, halogen, C1-C4 alkyl, haloC1-C4 alkyl, and C1-C4 alkoxy.

[0229] In some embodiments, R3 is selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl.

[0230] In some embodiments, R3 is selected from substituted or unsubstituted phenyl and substituted or unsubstituted pyridyl.

[0231] In some embodiments, R3 is phenyl, fluorophenyl, or pyridyl.

[0232] In some embodiments, R3 is phenyl.

[0233] In some embodiments, R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3-6 membered substituted or unsubstituted ring, the ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S.

[0234] In some embodiments, R4 and R5 are each independently selected from H and substituted or unsubstituted alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3-6 membered substituted or unsubstituted ring, the ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S.

[0235] In some embodiments, R4 and R5 are each independently selected from H, substituted or unsubstituted C1-C3 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3-6 membered substituted or unsubstituted ring, optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S.

[0236] In some embodiments, R4 and R5 are each independently selected from H and substituted or unsubstituted C1-C4 alkyl.

[0237] In some embodiments, R4 and R5 are each independently selected from H and substituted or unsubstituted C1-C3 alkyl.

[0238] In some embodiments, R4 and R5 are each independently selected from H and C1-C3 alkyl.

[0239] In some embodiments, R4 and R5 are each independently selected from H and methyl.

[0240] In some embodiments, R4 and R5 are both H.

[0241] In some embodiments, R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 6-14 membered aryl, substituted or unsubstituted 5-10 membered heteroaryl, substituted or unsubstituted 4-9 membered monocyclic or fused ring heterocyclyl, substituted or unsubstituted 6-12 membered bridged cyclyl, substituted or unsubstituted 6-12 membered bridged heterocyclyl, substituted or unsubstituted 6-12 membered spirocyclyl, and substituted or unsubstituted 6-12 membered spiroheterocyclyl.

[0242] In some embodiments, R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, or substituted or unsubstituted C2-C6 alkynyl, having 1, 2, or 3 substituents, and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, —S(O)2—C1-C4 alkyl optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, —S(O)2—NR′R″, —S(O)2—NH2, —C(O)—C1-C4 alkyl, and —NR′—C(O)—C1-C4 alkyl. alkyl and optionally substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl.

[0243] In some embodiments, R6 is H, C1-C4 alkyl optionally substituted with 1, 2 or 3 substituents selected from hydroxy, halogen, C1-C4 alkoxy, cyano and C1-C4 alkyl-S(O)2-, 3- to 8-membered cyclohydrocarbyl optionally substituted with 1, 2 or 3 substituents selected from halogen, hydroxy, cyano, C1-C4 alkyl-S(O)2-, C1-C4 alkyl and C1-C4 alkoxy, optionally halogen, hydroxy, cyano, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl and C1-C4 alkoxy, and 6- to 12-membered bridged cyclyl, 6- to 12-membered spirocyclyl, 6- to 12-membered bridged heterocyclyl or 6- to 12-membered spiroheterocyclyl, each optionally substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, C1-C4 alkoxy and cyano.

[0244] In some embodiments, R6 is -LWZ, where L is a bond or substituted or unsubstituted C1-C4 alkyl, W is a bond, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 6-14 membered aryl, substituted or unsubstituted 5-10 membered heteroaryl, substituted or unsubstituted 4-9 membered monocyclic or fused ring heterocyclyl, substituted or unsubstituted 6-12 membered bridged cyclyl, substituted or unsubstituted 6-12 membered bridged hetero ... and Z is hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, —S(O)2—C1-C4 alkyl, —S(O)2—NR′R″, —S(O)2—NH2, cyano, —C(O)—C1-C4 alkyl, —O-3- to 8-membered cyclohydrocarbyl, or —NR′—C(O)—C1-C4 alkyl, where R′ and R″ are each independently H or C1-C4 alkyl.

[0245] In some embodiments, the -LWZ is

[0246] [ka]

[0247] where the wavy line represents the attachment point of the bond.

[0248] In some embodiments, R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl, or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen, and C1-C4 alkoxy.

[0249] In some embodiments, R or R and R and the atoms connected thereto together form the following group, optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, methyl, F, and methoxy:

[0250] [ka]

[0251] where the wavy lines represent the attachment points of the bonds.

[0252] In some embodiments, R4 or R5 and R6 together with the atoms connected thereto are optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, methyl, F, and methoxy.

[0253] [ka]

[0254] Form.

[0255] In some embodiments, R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C2-C4 alkenyl, and substituted or unsubstituted C2-C4 alkynyl.

[0256] In some embodiments, R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C1-C3 haloalkyl, substituted or unsubstituted C1-C3 alkoxy, substituted or unsubstituted C2-C4 alkenyl, and substituted or unsubstituted C2-C4 alkynyl.

[0257] In some embodiments, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy.

[0258] In some embodiments, R7 and R8 are each independently selected from fluorine and chlorine.

[0259] In some embodiments, R7 is chlorine and R8 is fluorine.

[0260] In some embodiments, R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen.

[0261] In some embodiments, R9 is selected from H, C1-C3 alkyl, C1-C3 alkoxy, hydroxy, and halogen.

[0262] In some embodiments, R9 is selected from H, methyl, methoxy, hydroxy, and F.

[0263] In some embodiments, R9 is H.

[0264] In some embodiments, R 10is selected from H, halogen and C1-C4 alkyl.

[0265] In some embodiments, R 10 is selected from H, halogen and C1-C3 alkyl.

[0266] In some embodiments, R 10 is selected from H, F and methyl.

[0267] In some embodiments, R 10 is H.

[0268] In some embodiments, R 11 is selected from H, hydroxy, amino, halogen, C1-C3 alkyl, —NR′R″ and C1-C3 alkoxy, where R′ and R″ are independently selected from C1-C4 alkyl.

[0269] In some embodiments, R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0270] In some embodiments, R 11 is H.

[0271] In some embodiments, R that is not involved in ring formation 12When present, it is each independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)- and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl-C(O)- and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano.

[0272] In some embodiments, R that is not involved in ring formation 12 When present, each independently is selected from H, acetyl, propionyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 6-membered heterocyclyl, 3- to 5-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkyl optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano.

[0273] In some embodiments, R that is not involved in ring formation 13 When present, each independently is selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)- and NR'R''-C(O)-, or two R on the same carbon atom 13forms oxo (=O) or thio (=S), wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C6 alkyl, C1-C4 alkyl-S(O)2- and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano.

[0274] In some embodiments, R that is not involved in ring formation 13 When present, each is independently selected from H, fluorine, chlorine, C1-C4 acyl, hydroxy, cyano, C1-C4 alkoxy, C1-C6 alkyl, C1-C4 alkyl-S(O)2-, and 3- to 4-membered cyclohydrocarbyl-C(O)-.

[0275] In some embodiments, R' and R'' are each independently selected from H and C1-C4 alkyl.

[0276] In some embodiments, R′ and R″ are each independently selected from H, methyl, and ethyl.

[0277] In some embodiments, R a is selected from H, methyl and ethyl.

[0278] In some embodiments, R 14 is H, halogen or C1-C4 alkyl.

[0279] In some embodiments, R 14 is H or methyl.

[0280] In some embodiments, R 14 is H.

[0281] In some embodiments, R 15is selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted 4-9 membered heterocyclyl, NR′R″-C(O)—, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, 4-9 membered heterocyclyl, 3-8 membered cyclohydrocarbyl, 3-8 membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy, and cyano, and R′ and R″ are each independently selected from H and C1-C4 alkyl.

[0282] In some embodiments, R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, and R′ and R″ are each independently selected from H and C1-C4 alkyl.

[0283] In some embodiments, R 16 is selected from halogen, C1-C4 alkyl, hydroxy, C1-C4 acyl and C1-C4 alkoxy.

[0284] In some embodiments, R 16 is selected from H, halogen, C1-C4 alkyl, hydroxy and acetyl.

[0285] In some embodiments, R 16 is selected from H, hydroxy, halogen and C1-C4 alkyl.

[0286] In some embodiments, R 16is selected from H, fluorine, methyl, ethyl, hydroxy and acetyl.

[0287] In some embodiments, R 16 is H, hydroxy or methyl.

[0288] In some embodiments, R 16 is H.

[0289] In some embodiments, n is 0, 1, 2, 3, or 4.

[0290] In some embodiments, n is 0, 1, or 2.

[0291] In some embodiments, n is 0 or 1.

[0292] In some embodiments, X 1 is O.

[0293] In some embodiments, X 1 is NH.

[0294] In some embodiments, X1 is N(CH3).

[0295] In some embodiments, X2 is C.

[0296] In some embodiments, X2 is N.

[0297] In some embodiments, X3 is C.

[0298] In some embodiments, X3 is N.

[0299] In some embodiments, Y5 is O, S, N, CH(R 13 ), C(R 13 ), -OCH2-, -N(R 12 )CH2-, -CH2CH2- or N(R 12 ) is selected.

[0300] In some embodiments, Y5 is selected from a bond, O, S, -S(O)-, N, CH2, CH, -C(O)-, -CH(OH)-, NH, -N(CH3)-, -OCH2-, -NHCH2-, -N(CH3)CH2-, and -CH2CH2-.

[0301] In some embodiments, Y5 is selected from O, S, N, CH2, CH, NH, and -N(CH3)-.

[0302] In some embodiments, Y5 is selected from a bond, O, S, N, CH2, CH, NH, and -N(CH3)-.

[0303] In some embodiments, Y5 is selected from a bond, O, CH2, NH, -N(CH3)-, and -CH(CH3)-.

[0304] In some embodiments, Y5 is O.

[0305] In some embodiments, Y5 is CH or CH2.

[0306] In some embodiments, Y5 is NH or N.

[0307] In some embodiments, Y6 is O, N, —S(O)—, —SO2—, S, CH(R 13 ), C(R 13 ), -OCH2-, -N(R 12 )CH2-, -CH2CH2- and N(R 12 ) is selected.

[0308] In some embodiments, Y6 is selected from a bond, O, S, -S(O)-, -S(O)2-, N, CH, -C(O)-, CH2, NH, -N(CH3)-, -N(C2H4OH)-, -N(C(O)CH3)-, -N(C(O)C2H5)-, -OCH2-, -NHCH2-, -N(CH3)CH2-, and -CH2CH2-.

[0309] In some embodiments, Y6 is selected from O, S, N, CH2, CH, NH, and -N(CH3)-.

[0310] In some embodiments, Y6 is selected from a bond, O, S, N, CH, CH2, NH, and -N(CH3)-.

[0311] In some embodiments, Y1 and Y4 are independently selected from a bond, O, N, NH, -N(CH3)-, CH, CH2, and -CH(CH3)-, and Y1 and Y4 are not simultaneously a bond or O.

[0312] In some embodiments, Y 1 is selected from a bond, O, NH, —N(CH 3 )—, CH 2 , and —CH(CH 3 )—.

[0313] In some embodiments, Y 1 is selected from O or CH 2 .

[0314] In some embodiments, Y1 is a bond, O, N, CH, CH2, NH, CH(R 13 ), C(R 13 )2 and N(R 12 ) and Y4 is a bond, O, N, CH, CH2, NH, CH(R 13 ), C(R 13 )2 and N(R 12 ) and And, Y1 and Y4 are not a bond or O at the same time.

[0315] In some embodiments, Y1 is selected from a bond, O, NH, —N(CH3)—, CH2, and —CH(CH3)—; Y4 is selected from a bond, O, NH, -N(CH3)-, CH2, and -CH(CH3)-; And, Y1 and Y4 are not a bond or O at the same time.

[0316] In some embodiments, Y5 is selected from O, S, N, CH2, CH, NH and -N(CH3)-; Y6 is selected from O, S, N, CH2, CH, NH and -N(CH3)-; Y1 is selected from a bond, O, NH, —N(CH3)—, CH2, and —CH(CH3)—; Y4 is selected from a bond, O, NH, -N(CH3)-, CH2, and -CH(CH3)-; And, Y1 and Y4 are not a bond or O at the same time.

[0317] In some embodiments, Y1 is selected from a bond, O, NH, —N(CH3)—, CH2, and —CH(CH3)—; Y5 is selected from O, S, N, CH2, CH, NH and -N(CH3)-; And Y1 and Y5 are not O at the same time.

[0318] In some embodiments, ring B may optionally contain one or more R 13 and / or R 12 In addition to being substituted by, it may be further optionally substituted by 1, 2 or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, -NR'R'' and substituted or unsubstituted C1-C4 alkoxy.

[0319] In some embodiments, ring B may optionally contain one or more R 13 and / or R 12 and optionally further substituted by 1, 2 or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted C1-C3 alkyl, -NR'R'', and substituted or unsubstituted C1-C3 alkoxy.

[0320] In some embodiments, the rings A and B and their substituents together form one of the following groups:

[0321] [ka]

[0322] [ka]

[0323] where R1 is cyano or —C(O)NR′R″, R2 is H or halogen, and R 11 is H, hydroxy, -NR'R'', halogen or C1-C4 alkyl, and R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 acyl; R f is selected from H, halogen, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, preferably said C1-C4 alkyl, C1-C4 alkoxy, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)— and C1-C4 acyl are optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and the wavy line indicates the attachment point of the bond.

[0324] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0325] [ka]

[0326] and R2 is H or F, and R 11 is H and R eis selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CHCHOH, acetyl, propionyl, and cyclopropionyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy, —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 , methyl, ethyl, cyclopropyl, and cyclobutyl.

[0327] In some embodiments, R1 is cyano, -C(O)NH2, or -C(O)NHCH3, R2 is H or F, and R 11 is H and R e is selected from H, methyl, ethyl, cyclopropyl, cyclobutyl, —CHCHOH, acetyl, propionyl, and cyclopropionyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy, methyl, ethyl, cyclopropyl and cyclobutyl.

[0328] In some embodiments, R1 is —C(O)NH2 or —C(O)NHCH3, R2 is F, and R 11 is H and R e is selected from H, methyl, cyclopropyl and acetyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , —CH 2 OH, methoxy and methyl.

[0329] In some embodiments, R1 is —C(O)NH2 or —C(O)NHCH3, R2 is F, and R 11 is H and R e is selected from H, methyl, cyclopropyl and acetyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy and methyl.

[0330] In some embodiments, the ring A and ring B and their substituents together form one of the following groups:

[0331] [ka]

[0332] [ka]

[0333] [ka]

[0334] where R1 is cyano or —C(O)NR′R″, R2 is H or halogen, and R 11 is H, hydroxy, -NR'R'', halogen or C1-C4 alkyl, and R 14 is H, halogen, or C1-C4 alkyl, n is 0, 1, or 2, and R 16 is selected from H, hydroxy, halogen and C1-C4 alkyl, and R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 acyl; R f is selected from H, halogen, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, preferably said C1-C4 alkyl, C1-C4 alkoxy, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)— and C1-C4 acyl are optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and the wavy line indicates the attachment point of the bond.

[0335] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0336] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0337] [ka]

[0338] and R2 is H or F, and R 11 is H and R 14 is H or methyl, n is 0, 1 or 2, and R 16 is H, hydroxy or methyl, and R e is selected from H, methyl, deuterated methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CHCHOH, acetyl, propionyl, and cyclopropionyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy, methyl, ethyl, cyclopropyl and cyclobutyl.

[0339] In some embodiments, R1 is cyano, -C(O)NH2, or -C(O)NHCH3, R2 is H or F, and R 11 is H and R 14 is H or methyl, n is 0, 1 or 2, and R 16 is H, hydroxy or methyl, and R e is selected from H, methyl, ethyl, cyclopropyl, cyclobutyl, —CHCHOH, acetyl, propionyl and cyclopropionyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy, methyl, ethyl, cyclopropyl and cyclobutyl.

[0340] In some embodiments, R1 is -C(O)NH2, -C(O)NHCH3, and

[0341] [ka]

[0342] and R2 is F and R 11 is H and R 14 is H and R 16 is H and R e is selected from H, methyl, deuterated methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, cyclopropyl, and acetyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , —CH 2 OH, methoxy and methyl.

[0343] In some embodiments, R1 is —C(O)NH2 or —C(O)NHCH3, R2 is F, and R 11 is H and R 14 is H and R 16 is H and R e is selected from H, methyl, ethyl, cyclopropyl, and acetyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy and methyl.

[0344] In some embodiments, the ring A and ring B and their substituents together form one of the following groups:

[0345] [ka]

[0346] where R1 is cyano or —C(O)NR′R″, R2 is H or halogen, and R 14 is H, halogen, or C1-C4 alkyl, n is 0, 1, or 2, and R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 acyl; R f is selected from H, halogen, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, preferably said C1-C4 alkyl, C1-C4 alkoxy, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)— and C1-C4 acyl are optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and the wavy line indicates the attachment point of the bond.

[0347] In some embodiments, R1 is cyano, -C(O)NH2, -C(O)NHCH3, and

[0348] [ka]

[0349] and R2 is H or F, and R 14 is H or methyl, n is 0, 1 or 2, and R e is selected from H, methyl, deuterated methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CHCHOH, acetyl, propionyl, and cyclopropionyl; R fis selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy, methyl, ethyl, —CH 2 OH, cyclopropyl, and cyclobutyl.

[0350] In some embodiments, R1 is cyano, -C(O)NH2, or -C(O)NHCH3, R2 is H or F, and R 14 is H or methyl, n is 0, 1 or 2, and R e is selected from H, methyl, cyclopropyl, cyclobutyl, —CHCHOH, acetyl, propionyl and cyclopropionyl; R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy, methyl, ethyl, cyclopropyl and cyclobutyl.

[0351] In some embodiments, X2 is selected from C and N; X3 is selected from C and N; Y5 and Y6 are independently O, S, N, -S(O)-, -S(O)2-, CH(R 13 ), C(R 13 )2, C(R 13 ), -OCH2-, -N(R 12 )CH2-, -CH2CH2- and N(R 12 and Y5 and Y6 are not simultaneously a bond; Y1 is a bond, O, N, CH, CH2, NH, CH(R 13 ), C(R 13 )2 and N(R 12 ) and Y4 is a bond, O, N, CH, CH2, NH, CH(R 13 ), C(R 13 )2 and N(R 12 ) and Ring B may optionally contain one or more R 13 and / or R 12and optionally further substituted by 1, 2 or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, -NR'R'' and substituted or unsubstituted C1-C4 alkoxy; R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R3 is selected from substituted or unsubstituted aryl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R4 or R5 and R6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; Each R not involved in ring formation 12 are independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, 3- to 8-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 alkyl, wherein said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R not involved in ring formation 13 are independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)- and NR'R''-C(O)-, wherein said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, C1-C4 alkyl-S(O)2- and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, or two R on the same carbon atom are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, or two R on the same carbon atom are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, 13 forms an oxo (=O) or thio (=S) group, R' and R'' are each independently selected from H and C1-C4 alkyl; Here, the dotted line indicates the presence or absence of a double bond.

[0352] In some embodiments, R' and R'' are further each independently selected from C3-C6 cycloalkyl.

[0353] In some embodiments, R1 is

[0354] [ka]

[0355] is.

[0356] In some embodiments, X2 is selected from C and N; X3 is selected from C and N; Y5 is selected from O, S, -S(O)-, -S(O)2-, N, CH2, CH, -C(O)-, NH and -N(CH3)-; Y6 is selected from O, S, -S(O)-, -S(O)2-, N, CH2, CH, -C(O)-, NH and -N(CH3)-; Y1 is selected from a bond, O, NH, —N(CH3)—, CH2, and —CH(CH3)—; Y4 is selected from a bond, O, NH, -N(CH3)-, CH2, and -CH(CH3)-; H on ring B may be further optionally substituted with 1, 2 or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, -NR'R'' and substituted or unsubstituted C1-C4 alkoxy; R1 is selected from cyano, —C(O)NH2 and —C(O)NHCH3; R2 is selected from H, fluorine and methoxy; R3 is phenyl; R4 and R5 are each independently selected from H and C1-C4 alkyl; R6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, the substituents of which are 1, 2 or 3 and are selected from hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O)2-C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', -S(O)2-NH2, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and any optionally selected from 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, -NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, 3-8 membered cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having one, two, or three substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, —NR′—C(O)—C1-C4 alkyl, —S(O)2—C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted by one, two, or three groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O)2—C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O)2—NR′R″, —S(O)2—NH2, and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0357] [ka]

[0358] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ).

[0359] In some embodiments, ring A and ring B and their ring substituents together form one of the following groups:

[0360] [ka]

[0361] [ka]

[0362] [ka]

[0363] [ka]

[0364] where R1 is cyano or —C(O)NR′R″, R2 is H or halogen, and R 11 is H, hydroxy, -NR'R'', halogen or C1-C4 alkyl, and R 14 is H, halogen, or C1-C4 alkyl, n is 0, 1, or 2, and R 16 is selected from H, hydroxy, halogen and C1-C4 alkyl, and R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 acyl; R f is selected from H, halogen, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, preferably said C1-C4 alkyl, C1-C4 alkoxy, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)— and C1-C4 acyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and the wavy line indicates the attachment point of the bond; X1 is O, R3 is selected from phenyl unsubstituted or substituted with 1, 2 or 3 substituents selected from hydroxy, halogen, C1-C4 alkyl, haloC1-C4 alkyl and C1-C4 alkoxy; R4 is selected from H and C1-C4 alkyl; R5 is selected from H and C1-C4 alkyl; R6 is H, C1-C4 alkyl optionally substituted with 1, 2 or 3 substituents selected from hydroxy, halogen, C1-C4 alkoxy, cyano and -S(O)2-C1-C4 alkyl, 3- to 8-membered cyclohydrocarbyl optionally substituted with 1, 2 or 3 substituents selected from halogen, hydroxy, cyano, -S(O)2-C1-C4 alkyl, C1-C4 alkyl and C1-C4 alkoxy, optionally halogen, hydroxy, cyano, - S(O)2--C1-C4 alkyl, 4- to 9-membered monocyclic or fused-ring heterocyclyl substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl and C1-C4 alkoxy, and 6- to 12-membered bridged cyclyl, 6- to 12-membered spirocyclyl, 6- to 12-membered bridged heterocyclyl or 6- to 12-membered spiroheterocyclyl, each optionally substituted by 1, 2 or 3 substituents selected from C1-C4 alkyl, C1-C4 alkoxy and cyano; or R4 or R5 and R6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0365] [ka]

[0366] where the wavy line represents the attachment point of the bond, R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl.

[0367] In some embodiments, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl.

[0368] In some embodiments, ring A and ring B and their ring substituents together form one of the following groups:

[0369] [ka]

[0370] where R1 is —C(O)NR′R″, R2 is F, and R 11 is H, F or methyl, and R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CHCHOH, —CHCH(CH)OH, —CHCHOCH, and acetyl; R f is selected from H, F, Cl, hydroxy, cyano, —NR′R″, methoxy, ethoxy, —CHOH, —CHCHOH, —CHCHOCH, C1-C6 alkyl, and 3-6 membered cyclohydrocarbyl, where R′ and R″ are each independently selected from H and methyl, and the wavy line indicates the attachment point of the bond. In some embodiments, R′ and R″ are each independently cyclopropyl.

[0371] In some embodiments, R1 is -C(O)NR'R'', R2 is F, and R 11 is H, F or methyl, and R e is selected from H, methyl, ethyl, cyclopropyl, cyclobutyl, —CHCHOH, —CHCHOCH and acetyl; R fis selected from H, F, Cl, hydroxy, cyano, —NR′R″, methoxy, ethoxy, C1-C6 alkyl, and 3-6 membered cyclohydrocarbyl, where R′ and R″ are each independently selected from H and methyl.

[0372] In some embodiments, ring A and ring B and their ring substituents together form one of the following groups:

[0373] [ka]

[0374] [ka]

[0375] where R1 is —C(O)NR′R″, R2 is F, and R 11 is H, F or methyl, and R 14 is H, F or methyl, n is 0, 1 or 2, and R 16 is selected from H, hydroxy and methyl; R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CHCHOH, —CHCHOCH and acetyl; R f is selected from H, F, Cl, hydroxy, cyano, —NR′R″, methoxy, ethoxy, —CHOH, C1-C6 alkyl, and 3-6 membered cyclohydrocarbyl, where R′ and R″ are each independently selected from H and methyl, and the wavy line indicates the attachment point of the bond. In some embodiments, R′ and R″ are each independently cyclopropyl.

[0376] In some embodiments, R1 is -C(O)NR'R'', R2 is F, and R 11is H, F or methyl, and R 14 is H, F or methyl, n is 0, 1 or 2, and R 16 is selected from H, hydroxy and methyl; R e is selected from H, methyl, ethyl, cyclopropyl, cyclobutyl, —CHCHOH, —CHCHOCH and acetyl; R f is selected from H, F, Cl, hydroxy, cyano, —NR′R″, methoxy, ethoxy, C1-C6 alkyl, and 3-6 membered cyclohydrocarbyl, where R′ and R″ are each independently selected from H and methyl.

[0377] In some embodiments, the compound is selected from the following compounds:

[0378] [ka]

[0379] In some embodiments, the compound is selected from the following compounds:

[0380] [ka]

[0381] In the formula, ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, and the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O. Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

[0382] In some embodiments, the compound is selected from the following compounds:

[0383] [ka]

[0384] In the formula: Y4 is selected from C, CH and N; Y6 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, a 4- to 9-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, wherein the 4- to 9-membered heterocyclyl and the 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is H, halogen, oxo (=O), thio (=S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6-10 membered aryl-S(O)2-, substituted or unsubstituted 4-9 membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl-C(O)-, substituted or selected from unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 6- to 10-membered aryl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2, 3 or 4.

[0385] In some embodiments, the compound is selected from the following compounds:

[0386] [ka]

[0387] In the formula: Y1 is selected from C, CH and N; Y4 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, a 4- to 9-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, wherein the 4- to 9-membered heterocyclyl and the 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is H, halogen, oxo (=O), thio (=S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6-10 membered aryl-S(O)2-, substituted or unsubstituted 4-9 membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl-C(O)-, substituted or selected from unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 6- to 10-membered aryl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2, 3 or 4.

[0388] In some embodiments, the compound is selected from the following compounds:

[0389] [ka]

[0390] In the formula: Ring E is a 3- to 8-membered cyclohydrocarbyl or a 4- to 9-membered heterocyclyl, wherein the 4- to 9-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 alkyl, C1-C4 acyl and C1-C4 alkoxy optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2, 3 or 4.

[0391] In some embodiments, the compound is selected from the following compounds:

[0392] [ka]

[0393] In the formula: Ring E is a 3- to 8-membered cyclohydrocarbyl or a 4- to 9-membered heterocyclyl, wherein the 4- to 9-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 alkyl, C1-C4 acyl and C1-C4 alkoxy optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2, 3 or 4.

[0394] In some embodiments, the compound is selected from the following compounds:

[0395] [ka]

[0396] In the formula: Y4 is selected from C, CH and N; Y6 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, a 4- to 9-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, wherein the 4- to 9-membered heterocyclyl and the 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; D1 is O, S, S(O), S(O)2, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , C.R. f -NR e ,

[0397] [ka]

[0398] is selected from D3 is O, S, S(O), S(O)2, N, NR e , (CR f ) p and (CR f R g ) p is selected from The condition is that D1 and D2, D1 and D3 are not simultaneously O, S, -S(O)- or -S(O)2-, and satisfy the valence bond law; Each R eis independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R f is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R gis independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Or R on the same carbon atom f and R g forms an oxo (=O) or thio (=S) group, Each p is independently 1, 2, 3 or 4, preferably 1 or 2.

[0399] In some embodiments, D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p ,

[0400] [ka]

[0401] is selected from.

[0402] In some embodiments, the compound is selected from the following compounds:

[0403] [ka]

[0404] In the formula: Y1 is selected from C, CH and N; Y4 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, a 4- to 9-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, wherein the 4- to 9-membered heterocyclyl and the 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; D1 is O, S, S(O), S(O)2, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , C.R. f -NR e ,

[0405] [ka]

[0406] is selected from D3 is O, S, S(O), S(O)2, N, NR e , (CR f ) p and (CR f R g ) p is selected from The condition is that D1 and D2, D1 and D3 are not simultaneously O, S, -S(O)- or -S(O)2-, and satisfy the valence bond law; Each R eis independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R f is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R gis independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Or R on the same carbon atom f and R g forms an oxo (=O) or thio (=S) group, Each p is independently 1, 2, 3 or 4, preferably 1 or 2.

[0407] In some embodiments, D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p ,

[0408] [ka]

[0409] is selected from.

[0410] In some embodiments, the compound is selected from the following compounds:

[0411] [ka]

[0412] In the formula: Y4 is selected from C, CH and N; Y6 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, a 4- to 9-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, wherein the 4- to 9-membered heterocyclyl and the 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; D1 is O, S, S(O), S(O)2, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , C.R. f -NR e ,

[0413] [ka]

[0414] is selected from D3 is O, S, S(O), S(O)2, N, NR e , (CR f ) p and (CR f R g ) p is selected from The condition is that D1 and D2, D1 and D3 are not simultaneously O, S, -S(O)- or -S(O)2-, and satisfy the valence bond law; Each R eis independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R f is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R gis independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Or R on the same carbon atom f and R g forms an oxo (=O) or thio (=S) group, each p is independently 1, 2, 3 or 4, preferably 1 or 2; Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

[0415] In some embodiments, in Formula XIVa, D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p ,

[0416] [ka]

[0417] is selected from.

[0418] In some embodiments, the compound is selected from the following compounds:

[0419] [ka]

[0420] In the formula: Y1 is selected from C, CH and N; Y4 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, a 4- to 9-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, wherein the 4- to 9-membered heterocyclyl and the 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; D1 is O, S, S(O), S(O)2, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , C.R. f -NR e ,

[0421] [ka]

[0422] is selected from D3 is O, S, S(O), S(O)2, N, NR e , (CRf ) p and (CR f R g ) p is selected from The condition is that D1 and D2, D1 and D3 are not simultaneously O, S, -S(O)- or -S(O)2-, and satisfy the valence bond law; Each R e is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R f is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Or R on the same carbon atom f and R g forms an oxo (=O) or thio (=S) group, each p is independently 1, 2, 3 or 4, preferably 1 or 2; Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

[0423] In some embodiments, in Formula XIVb, D2 is O, S, S(O), S(O)2, N, NR e , (CR f ) p , (CR f R g ) p ,

[0424] [ka]

[0425] is selected from.

[0426] In some embodiments, the compound is selected from the following compounds:

[0427] [ka]

[0428] In the formula: X2 is C, Y6 is selected from C, CH and N; Ring F is a 5- or 6-membered cyclohydrocarbyl, a 5- or 6-membered heterocyclyl, a phenyl, or a 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is H, halogen, oxo (=O), thio (=S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6-10 membered aryl-S(O)2-, substituted or unsubstituted 4-9 membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl-C(O)-, substituted or selected from unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 6- to 10-membered aryl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; n is 0, 1, 2 or 3.

[0429] In some embodiments, the compound is selected from the following compounds:

[0430] [ka]

[0431] In the formula: X2 is C, Y6 is selected from C, CH and N; Ring F is a 5- or 6-membered cyclohydrocarbyl, a 5- or 6-membered heterocyclyl, a phenyl, or a 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S; Y7, Y8 and Y9 are independently a bond, O, S, S(O), S(O)2, N, or NR e , C.R. f and CR f R g with the proviso that at most one of Y7, Y8 and Y9 is a bond, and Y7 and Y8, Y8 and Y9 are not simultaneously O, S, -S(O)- or -S(O)2-, and satisfy the valence bond rule; Each R eis independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R f is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R gis independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O)— and 3- to 6-membered cyclohydrocarbyl-C(O)— are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Or R on the same carbon atom f and R g forms an oxo (=O) or thio (=S) group, Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

[0432] In some embodiments, the compound is selected from the following compounds:

[0433] [ka]

[0434] In the formula: D1 is O, S, S(O), S(O)2, N, NR e , C.R.f R g , C.R. f and C(=O), D2 is O, S, S(O), S(O)2, N, NR e , C.R. f R g , C.R. f and C(=O), D3 is O, S, S(O), S(O)2, N, NR e , C.R. f R g , C.R. f and C(=O), D4 is O, S, S(O), S(O)2, N, NR e , C.R. f R g , C.R. f and C(=O), and wherein the ring in which D1, D2, D3 and D4 are located satisfies the valence bond rule and contains at most two C(=O) and three N atoms; Each R e is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl; and each R f is independently selected at each occurrence from H, halogen, hydroxy, cyano, oxo, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkoxy and C1-C4 alkyl being optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Y5 and Y6 are independently a bond, O, S, N, -S(O)-, -S(O)2-, C, CH(R 13 ), C(R 13 )2 and N(R 12 and Y5 and Y6 are not simultaneously a bond; R1 is selected from cyano and —C(O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R3 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl; R6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; Alternatively, R4 or R5 and R6 and the atoms connected thereto together form a substituted or unsubstituted 4- to 6-membered heterocyclyl, the 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from N and O; R7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and substituted or unsubstituted C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, -NR'R'' and substituted or unsubstituted C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl; Each p is independently 1, 2, 3, or 4.

[0435] In some embodiments, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, deuterated methyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CH2CH2OH, —CH2CH2OCH3, and acetyl.

[0436] In some embodiments, in XVa, the C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted with 1, 2, or 3 substituents selected from F, hydroxy, and cyano.

[0437] In some embodiments, the compound is selected from the following compounds:

[0438] [ka]

[0439] In the formula: D1 is O, S, S(O), S(O)2, N, NR e , C.R. f R g , C.R. f and C(=O), D2 is O, S, S(O), S(O)2, N, NR e , C.R. f R g , C.R. f and C(=O), D3 is O, S, S(O), S(O)2, N, NR e , C.R. f R g , C.R. f and C(=O), D4 is O, S, S(O), S(O)2, N, NR e , C.R. f R g , C.R. f and C(=O), and wherein the ring in which D1, D2, D3 and D4 are located satisfies the valence bond rule and contains up to two C(=O) and three N atoms; Each R e is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl; and each R f is independently selected at each occurrence from H, halogen, hydroxy, cyano, oxo, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkoxy and C1-C4 alkyl being optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Y5 and Y6 are independently a bond, O, S, N, -S(O)-, -S(O)2-, C, CH(R 13 ), C(R 13 )2 and N(R 12 and Y5 and Y6 are not simultaneously a bond; R2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxy, and halogen; R10 is selected from H, halogen and substituted or unsubstituted C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, -NR'R'' and substituted or unsubstituted C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl; Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O; Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl; Each p is 0, 1, 2, 3, or 4.

[0440] In some embodiments, in XVb, the C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted with 1, 2, or 3 substituents selected from F, hydroxy, and cyano.

[0441] In some embodiments, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, deuterated methyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CH2CH2OH, —CH2CH2OCH3, and acetyl.

[0442] In some embodiments, the compound is selected from the following compounds:

[0443] [ka]

[0444] In the formula: D1 is N and CR f is selected from D4 is N and CR f and D1 and D4 are not simultaneously N; R e is selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl; and each R f is independently selected at each occurrence from H, halogen, hydroxy, cyano, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkoxy and C1-C4 alkyl being optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Y5 and Y6 are independently a bond, O, S, N, -S(O)-, -S(O)2-, C, CH(R 13 ), C(R 13 )2 and N(R 12 and Y5 and Y6 are not simultaneously a bond; R2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl; R6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; Alternatively, R4 or R5 and R6 and the atoms connected thereto together form a substituted or unsubstituted 4- to 6-membered heterocyclyl, the 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from N and O; R7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and substituted or unsubstituted C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, -NR'R'' and substituted or unsubstituted C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl; R h is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy.

[0445] In some embodiments, R eis selected from H, methyl, difluoromethyl, trifluoromethyl, deuterated methyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CH2CH2OH, —CH2CH2OCH3, and acetyl.

[0446] In some embodiments, the compound is selected from the following compounds:

[0447] [ka]

[0448] In the formula: D1 is N and CR f is selected from D4 is N and CR f and D1 and D4 are not simultaneously N; R e is selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl; and each R f is independently selected at each occurrence from H, halogen, hydroxy, cyano, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkoxy and C1-C4 alkyl being optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Y5 and Y6 are independently a bond, O, S, N, -S(O)-, -S(O)2-, C, CH(R 13 ), C(R 13 )2 and N(R 12 and Y5 and Y6 are not simultaneously a bond; R2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R9 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and substituted or unsubstituted C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, -NR'R'' and substituted or unsubstituted C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl; R h is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R i is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; p is 1, 2 or 3.

[0449] q is 0, 1, 2, 3 or 4.

[0450] In some embodiments, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, deuterated methyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CH2CH2OH, —CH2CH2OCH3, and acetyl.

[0451] In some embodiments, the compound is selected from the following compounds:

[0452] [ka]

[0453] [ka]

[0454] [ka]

[0455] [ka]

[0456] [ka]

[0457] [ka]

[0458] [ka]

[0459] [ka]

[0460] [ka]

[0461] [ka]

[0462] [ka]

[0463] [ka]

[0464] In another aspect, the present disclosure provides a compound represented by formula Ya:

[0465] [ka]

[0466] In the formula: X1 is O and NR a is selected from R3 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted alkyl, or R4 and R5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; Alternatively, R4 or R5 and R6 and the atoms connected thereto together form a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each further optionally contain one or two heteroatoms selected from N and O; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R9 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and substituted or unsubstituted alkyl.

[0467] In yet another aspect, the present disclosure provides a method for manufacturing a semiconductor device comprising:

[0468] [ka]

[0469] (i) converting the halogen Hal1 in formula Ya-1 to QBQ by palladium-catalyzed coupling of a borate ester under alkaline conditions to give Ya-2; (ii) converting Ya-2 to the potassium trifluoroborate salt of Ya-3 in an organic solvent at room temperature; (iii) acid-catalyzed conversion of Ya-3 to Ya using a chlorinating reagent in an organic solvent; The present invention provides a method for producing a compound of formula Ya, comprising:

[0470] In the formula: X1 is O and NR a where R a is selected from H and C1-C4 alkyl; R3 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted alkyl, or R4 and R5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; Alternatively, R4 or R5 and R6 and the atoms connected thereto together form a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each further optionally contain one or two heteroatoms selected from N and O; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R9 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and substituted or unsubstituted alkyl; Hal1 is a halogen, QBQ is boric acid or a boric acid ester, Pg is a nitrogen protecting group.

[0471] In some embodiments, the organic solvent in step (ii) is selected from polar organic solvents. In some embodiments, the organic solvent in step (ii) is selected from methanol, ethanol, acetone, and acetonitrile. In some embodiments, the organic solvent in step (ii) is acetonitrile.

[0472] In some embodiments, the organic solvent in step (iii) is selected from polar organic solvents, hi some embodiments, the organic solvent in step (iii) is selected from acetonitrile, acetone, 1,2-dichloroethane, dioxane, and cyclopentyl methyl ether.

[0473] In yet another aspect, the present disclosure provides a compound represented by formula Za:

[0474] [ka]

[0475] In the formula, Pg is a nitrogen protecting group.

[0476] In some embodiments, Pg is Boc.

[0477] In yet another aspect, the present disclosure provides a method for manufacturing a semiconductor device comprising:

[0478] [ka] 78

[0479] (i) conversion of halogen Hal1 of formula Za-1 to QBQ by palladium-catalyzed coupling of a borate ester under alkaline conditions to give Za-2; (ii) adding aqueous potassium bifluoride solution to convert QBQ to potassium trifluoroborate in an organic solvent at room temperature to obtain Za-3; (iii) acid-catalyzed conversion of Za-3 to Za using a chlorinating reagent in an organic solvent; The present invention provides a method for producing a compound of formula Za, comprising:

[0480] In the formula, Hal1 is a halogen, QBQ is a boronic acid or boronic acid ester, and Pg is a nitrogen protecting group.

[0481] In some embodiments, the organic solvent in step (ii) is selected from polar organic solvents. In some embodiments, the organic solvent in step (ii) is selected from methanol, ethanol, acetone, and acetonitrile. In some embodiments, the organic solvent in step (ii) is acetonitrile.

[0482] In some embodiments, the organic solvent in step (iii) is selected from polar organic solvents, hi some embodiments, the organic solvent in step (iii) is selected from acetonitrile, acetone, 1,2-dichloroethane, dioxane, and cyclopentyl methyl ether.

[0483] The present disclosure further includes pharmaceutically acceptable salts, enantiomers, diastereomers, tautomers, solvates, isotopic derivatives, polycrystalline forms, prodrugs, or metabolites of each of the compounds represented by Formula I above.

[0484] As used herein, "stereoisomer" refers to a compound made up of the same atoms and bonded by the same bonds, but having a different three-dimensional structure. The present disclosure encompasses various stereoisomers and mixtures thereof.

[0485] When compounds of the present disclosure contain alkene double bonds, unless otherwise specified, the compounds of the present disclosure are intended to include both E- and Z-geometric isomers.

[0486] "Tautomer" refers to an isomer formed by the migration of a proton from one atom of a molecule to another atom of the same molecule. All tautomeric forms of the compounds of the present disclosure are also included within the scope of the present disclosure.

[0487] The compounds of the present disclosure, or pharmaceutically acceptable salts thereof, may contain one or more chiral carbon atoms and may therefore produce enantiomers, diastereomers, and other stereoisomeric forms. Each chiral carbon atom may be defined as (R)- or (S)- based on its stereochemistry. The present disclosure is intended to encompass all possible isomers, as well as their racemic and optically pure forms. Preparation of the compounds of the present disclosure may involve the selection of racemates, diastereomers, or enantiomers as starting materials or intermediates. Optically active isomers may be prepared using chiral synthons or chiral reagents, or separated using conventional techniques, such as crystallization and chiral chromatography.

[0488] Conventional techniques for producing / separating the individual isomers include chiral synthesis from suitable optically pure precursors or separation of the racemate (or racemate of a salt or derivative) using, for example, chiral high performance liquid chromatography, e.g., GGeR a ld Gubitz and Martin G. Schmid(Eds.), ChiR a l SepaR a tions, Methods and Protocols, Methods in Molecular Biology, Vol. 243, 2004;AM Stalcup, ChiR a l SepaR a tions, Annu. Rev. Anal. Chem. 3:341-63, 2010;Fumiss et al.(eds.), VOGEL'S ENCYCLOPEDIA OF PR aReference may be made to CTICAL ORGANIC CHEMISTRY.sup.TH ED., Longman Scientific and Technical Ltd., Essex, 1991, 809-816; Heller, Acc. Chem. Res. 1990, 23, 128, the disclosures of which are incorporated herein by reference in their entirety.

[0489] The present disclosure also includes all suitable isotopic substitutions (also called isotopic variants) of the compounds of the present disclosure or their pharmaceutically acceptable salts. An isotopic variant of a compound of the present disclosure or its pharmaceutically acceptable salt is defined as one in which at least one atom is replaced with an atom having the same atomic number but an atomic mass different from the atomic mass generally found in nature. Isotopes that can be incorporated into the compounds of the present disclosure and their pharmaceutically acceptable salts include, but are not limited to, isotopes of H, C, N, and O, for example: 2 H, 3 H, 11 C. 13 C. 14 C. 15 N, 17 O. 18 O. 35 S, 18 F, 36 Cl and 125 I. Isotopic variations of the compounds described herein or pharmaceutically acceptable salts thereof can be prepared using appropriate isotopic variations of suitable reagents via conventional techniques.

[0490] In the present disclosure, the term "pharmaceutically acceptable salts" includes pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0491] "Pharmaceutically acceptable acid addition salt" means a salt formed with an inorganic or organic acid that retains the biological effectiveness of the free base without other adverse effects. Inorganic acid salts include, but are not limited to, hydrochloride, hydrobromide, sulfate, nitrate, phosphate, and the like. Organic acid salts include, but are not limited to, formate, acetate, 2,2-dichloroacetate, trifluoroacetate, propionate, caproate, caprylate, decanoate, undecylenate, glycolate, gluconate, lactate, sebacate, adipate, glutarate, malonate, oxalate, maleate, succinate, fumarate, tartrate, citrate, palmitate, stearate, oleate, cinnamate, laurate, malate, glutamate, pyroglutamate, aspartate, benzoate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, alginate, ascorbate, salicylate, 4-aminosalicylate, naphthalenedisulfonate, and the like. These salts can be prepared by methods known in the art.

[0492] "Pharmaceutically acceptable base addition salt" means a salt formed with an inorganic or organic base that retains the biological effectiveness of the free acid without other adverse effects. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Preferred inorganic salts are ammonium, sodium, potassium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, primary amines, secondary amines, and tertiary amines, naturally occurring substituted amines, substituted amines including cyclic amines, and basic ion exchange resins such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, triethanolamine, dimethylethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, choline, betaine, ethylenediamine, glucosamine, methylglucosamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, and polyamine resins. Preferred organic bases include isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. These salts can be prepared by methods known in the art.

[0493] As used herein, the term "prodrug" refers to a compound that, after administration, is metabolized (i.e., converted in the body) into a pharmacologically active compound of the present disclosure. If a compound of the present disclosure itself is poorly absorbed in the gastrointestinal tract, it can be formulated as a prodrug to improve its bioavailability. Examples of prodrugs of compounds of the present disclosure include simple esters of carboxyl-containing compounds (e.g., esters obtained by condensation with a C1-C4 alcohol according to methods known in the art); esters of hydroxy-containing compounds (e.g., esters obtained by condensation with a C1-C4 monocarboxylic acid, a C3-C6 dicarboxylic acid, or an anhydride thereof, such as succinic anhydride or fumaric anhydride, according to methods known in the art); imines of amino-containing compounds (e.g., imines obtained by condensation with a C1-C4 aldehyde or ketone according to methods known in the art); carbamates of amino-containing compounds, such as those described by Leu et al. (J. Med. Chem., 42:3623-3628 (1999)) and Greenwald et al. (J. Med. Chem., 42:3623-3628 (1999)). Chem., 42:3657-3667 (1999)); aldehyde acetals or ketone acetals of hydroxy-containing compounds (e.g., such acetals obtained by condensation with chloromethyl methyl ether or chloromethyl ethyl ether according to methods known in the art).

[0494] III. Preparation of Compounds As used herein, compounds of formula I can be prepared by the following general synthetic route.

[0495] [ka]

[0496] R1 to R in each structural formula 10 , R 11, X1 to X3, Y1 to Y6 are as defined in any one of the above embodiments, G is boric acid, potassium trifluoroborate, boric acid ester, or the like, X is a halogen, preferably Br or I, R1' is a convertible functional group of R1, preferably cyano or an ester, which can be converted to R1 under appropriate conditions, and Pg is a nitrogen protecting group, preferably tert-butoxycarbonyl (tBuOC(O)-).

[0497] The method includes the following:

[0498] When R1 and R1' are both cyano, a compound of formula I can be obtained by steps 1 and 3. In step 1, compounds of formula Xa and Xb are coupled via a palladium catalyst, a ligand, and a base to obtain a compound of formula Xc. When R1' and / or R2 are not H, the compound of formula Xc usually includes a pair of axial chiral isomers. In step 3, Pg is removed from the compound of formula Xc under appropriate conditions to obtain a compound of formula I.

[0499] When R1 is CONH2 and R1' is cyano, a compound represented by formula I can be obtained by steps 1, 2, and 3. In step 1, compounds represented by formulas Xa and Xb are coupled via a palladium catalyst, a ligand, and a base to obtain a compound represented by formula Xc. When R1' and / or R2 are not H, the compound represented by formula Xc usually includes a pair of axial chiral isomers. In step 2, compounds represented by formula Xc are hydrolyzed to an amide represented by formula Xd via a copper catalyst, preferably copper acetate. In step 3, compounds represented by formula Xd are subjected to removal of Pg under appropriate conditions to obtain a compound represented by formula I.

[0500] When R1 is CONR'R'', and R' and R'' are not both H, and R1' is cyano or methyl formate (-COOCH3), the reaction sequence of steps 1, 4, 5, and 3 can be used to obtain a compound of formula I. In step 1, compounds of formula Xa and Xb are coupled via a palladium catalyst, a ligand, and a base to obtain a compound of formula Xc. When R1' and / or R2 are not H, the compound of formula Xc usually contains a pair of axial chiral isomers. In step 4, compounds of formula Xc are hydrolyzed with an inorganic base to obtain a compound of formula Xc', and the inorganic base is preferably sodium hydroxide, lithium hydroxide, potassium hydroxide, etc. In step 5, compounds of formula Xc' and R'R''NH are condensed via a condensing agent to obtain a compound of formula Xd. In step 3, compounds of formula Xd are subjected to removal of Pg under appropriate conditions to obtain a compound of formula I.

[0501] Other compounds of the present disclosure can be prepared by reference to the reaction flow charts above.

[0502] When G in formula Xa is BF3K and R7 is chlorine, formula Ya can be synthesized according to Scheme 2 below.

[0503] [ka]

[0504] R3 to R6, R8 to R 10 and X1 are as defined in any one of the preceding embodiments, preferably R8 is F, R9 and R 10 is H, R3 is phenyl, and R4 or R5 and R6 together with the C and N to which they are connected

[0505] [ka]

[0506] and formula Za can be synthesized according to Scheme 3 below.

[0507] [ka]

[0508] In the synthetic pathways Scheme 2 and Scheme 3, Hal1 is a halogen, preferably Br or I, and QBQ is a boric acid or a boric acid ester, preferably boric acid (B(OH)2) or a pinacol boronate ester.

[0509] [ka]

[0510] , diisopropyl borate or

[0511] [ka]

[0512] where Pg is a nitrogen-protecting group, preferably tert-butoxycarbonyl (tBuOC(O)-). In the synthetic pathways shown in Figures 2 and 3, step 1 is to convert the halogen (Hal1) of formula Ya-1 or formula Za-1 to boric acid or boric acid ester (QBQ), which can then be subjected to palladium-catalyzed coupling of the boric acid ester under alkaline conditions. In the case of palladium-catalyzed coupling, the palladium catalyst is preferably [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex, the boric acid ester is preferably pinacol borate ester, the base used is preferably potassium acetate, the reaction solvent is preferably toluene, and the reaction temperature is preferably 75-105°C. In step 2, boric acid or boric acid ester (QBQ) is added to an organic solvent (preferably an alcoholic solvent) with an aqueous potassium bifluoride solution at room temperature to convert it to potassium trifluoroborate salt Ya-3. Step 3: Ya-3 is chlorinated in an organic solvent under an acid catalyst using a chlorinating agent to obtain Ya, the organic solvent is preferably acetonitrile, the chlorinating agent is preferably N-chlorosuccinimide, the acid is preferably p-toluenesulfonic acid, and the reaction temperature is preferably -10°C to 40°C.

[0513] IV. Pharmaceutical Compositions, Methods, Uses and Other Embodiments In another aspect, the present disclosure provides a pharmaceutical composition, comprising a compound represented by Formula I of the present disclosure or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, and a pharmaceutically acceptable carrier or excipient.

[0514] In another aspect, the present disclosure provides use of a compound represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc, etc.), or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, in the manufacture of a medicament for treating or preventing a disease mediated by the interaction between YAP / TAZ and TEAD.

[0515] In another aspect, the present disclosure provides use of a compound represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc), or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, for treating or preventing a disease. In some embodiments, the present disclosure further provides use of a compound represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc, etc.) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, for treating or preventing a disease mediated by the interaction between YAP / TAZ and TEAD.

[0516] In yet another aspect, the present disclosure provides a method for treating or preventing a disease mediated by the interaction between YAP / TAZ and TEAD, comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by Formula I of the present disclosure or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc, etc.) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure.

[0517] The compounds of the present disclosure represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) or pharmaceutically acceptable salts, enantiomers, diastereomers, tautomers, solvates, isotopic derivatives, polycrystals, prodrugs, or metabolites thereof are inhibitors of the interaction between YAP / TAZ and TEAD, more specifically, they are inhibitors of the interaction between YAP and TEAD. Therefore, the compounds of the present disclosure represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) or pharmaceutically acceptable salts, enantiomers, diastereomers, tautomers, solvates, isotopic derivatives, polycrystals, prodrugs, or metabolites thereof are used to treat or prevent diseases mediated by the interaction between YAP / TAZ and TEAD.

[0518] As used herein, the term "diseases mediated by the interaction between YAP / TAZ and TEAD" refers to diseases in which the interaction between YAP / TAZ and TEAD is involved in the onset and / or progression of the disease, and the goals of alleviation, treatment and / or prevention can be achieved by inhibiting the expression and / or activity of YAP and TEAD, or by inhibiting or cleaving the YAP-TEAD protein interaction.

[0519] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is tumor, liver fibrosis, and kidney fibrosis.

[0520] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is a benign tumor.

[0521] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is a malignant tumor, for example, a carcinoma or a sarcoma.

[0522] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is a solid tumor or a hematological tumor.

[0523] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is mesothelioma (e.g., pleural mesothelioma (such as malignant pleural mesothelioma), peritoneal mesothelioma, pericardial mesothelioma, or vaginal mesothelioma), cervical squamous cell carcinoma, endometrial cancer, bladder urothelial carcinoma, cutaneous squamous cell carcinoma, poroma (e.g., benign poroma), sweat duct carcinoma, epithelioid hemangioendothelioma, breast cancer (e.g., triple-negative breast cancer), lung cancer (e.g., non-small cell lung cancer), ovarian cancer, colorectal cancer, melanoma, pancreatic cancer, cancer, prostate cancer, stomach cancer, esophageal cancer (e.g., esophageal squamous cell carcinoma or esophageal adenocarcinoma), liver cancer (e.g., hepatocellular carcinoma or hepatoblastoma), bile duct cancer, schwannoma, kidney cancer, sarcoma (e.g., rhabdomyosarcoma, embryonal rhabdomyosarcoma, osteosarcoma, undifferentiated pleomorphic sarcoma, Kaposi's sarcoma, and soft tissue sarcomas (such as rare soft tissue sarcomas)), bone cancer, brain cancer (e.g., ependymoma (e.g., supratentorial ependymoma such as pediatric supratentorial ependymoma), neuroblastoma, medulloblastoma, glioma, or meningioma), or head and neck cancer (e.g., head and neck squamous cell carcinoma).

[0524] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is mesothelioma (e.g., pleural mesothelioma (such as malignant pleural mesothelioma), peritoneal mesothelioma, pericardial mesothelioma, or vaginal mesothelioma). In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is malignant pleural mesothelioma (MPM), a rare thoracic malignancy. Abnormal activation of the Hippo-YAP pathway is present in approximately 70% of MPM patients and is considered an important cancer driver gene, and reducing the activity of the Hippo-YAP pathway via biological means and chemical small molecules shows good tumor growth inhibitory activity.

[0525] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is breast cancer (e.g., triple-negative breast cancer).

[0526] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is lung cancer (eg, non-small cell lung cancer).

[0527] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is colorectal cancer.

[0528] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is pancreatic cancer (eg, pancreatic ductal adenocarcinoma (PDAC)).

[0529] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is gastric cancer.

[0530] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is liver cancer (eg, hepatocellular carcinoma or hepatoblastoma).

[0531] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is brain cancer (e.g., supratentorial ependymoma, such as pediatric supratentorial ependymoma), neuroblastoma, medulloblastoma, glioma, or meningioma).

[0532] In some embodiments, the disease mediated by the interaction between YAP / TAZ and TEAD is head and neck cancer (e.g., head and neck squamous cell carcinoma).

[0533] Because the YAP signaling pathway mediates tumor cell dormancy and resists apoptosis, inhibiting the Hippo-YAP signaling pathway can enhance tumor cell sensitivity to targeted drugs. Furthermore, Hippo-YAP, a pathway that promotes tumor cell proliferation, is overactivated in multiple drug-resistant tumor models, and inhibiting its activity can significantly improve the sensitivity of treated tumor cells to related inhibitors. Thus, in some embodiments, a compound of the present disclosure represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc, etc.), or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystal, prodrug, or metabolite thereof, can be used to increase the sensitivity of treated tumor cells to targeted drugs (e.g., EGFR inhibitors, BRAF targeted inhibitors, MEK targeted inhibitors, etc.), thereby enhancing the therapeutic efficacy of these targeted drugs.

[0534] As used herein, the terms "dosing," "dosing," "administration," and the like refer to methods by which a compound or pharmaceutical composition can be delivered to the site of desired biological action. Any administration method known in the art can be used in the present disclosure. Such methods include, but are not limited to, oral administration, duodenal administration, parenteral administration (including intrapulmonary, intranasal administration; intrathecal, intravenous, subcutaneous, intraperitoneal, intramuscular, and intraarterial injection or infusion), topical administration, and rectal administration. Administration techniques used in the compounds and methods described herein are well known to those of skill in the art and are discussed, for example, in Goodman and Gilman, The Pharmacological Basis of Therapeutics, current ed.; Pergamon; and Remington's, Pharmaceutical Sciences (current edition), Mack Publishing Co., Easton, Pa. In a preferred embodiment, the compounds of the present disclosure or pharmaceutically acceptable salts, enantiomers, diastereomers, tautomers, solvates, isotopic substitutions, polycrystals, prodrugs, or metabolites thereof, or pharmaceutical compositions thereof, are administered orally.

[0535] In some embodiments, a compound of the present disclosure represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition thereof, is used in combination with another pharmacologically active compound, for example, to treat cancer. For example, in some embodiments, a compound of Formula I of the present disclosure or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, is selected from the group consisting of compounds having the following pharmacological activity: The compound may be administered simultaneously, sequentially, or in combination with one or more of the following: a chemotherapeutic agent, for example, a mitotic inhibitor (e.g., a taxane compound (e.g., paclitaxel or docetaxel), a vinca alkaloid (e.g., vincristine, vinblastine, vinorelbine, or vinflunine)), another anticancer agent such as a metal platinum complex (e.g., cisplatin, carboplatin, or oxaliplatin), an antimetabolite (e.g., a pyrimidine antagonist, such as 5-fluorouracil, 5-fluoro-2-4(1H,3H)-pyrimidinedione (5FU), or gemcitabine), or a hormonal antitumor agent (e.g., flutamide).In some embodiments, a compound of the present disclosure represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotope, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, is used in combination with a tumor immunotherapeutic agent known in the art (e.g., an anti-PD1 antibody), for the treatment of cancer. In some embodiments, a compound of the present disclosure represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotope, polycrystal, prodrug, or metabolite thereof, or a pharmaceutical composition of the present disclosure, is used in combination with conventional radiation therapy.

[0536] As used herein, the terms "combination," "drug combination," "coadministration," or "combination therapy" refer to a drug treatment resulting from the mixing or combining of one or more active ingredients, including combinations of fixed and non-fixed active ingredients, and further including the combination of two or more different therapeutic approaches. The term "fixed combination" refers to the simultaneous administration to a patient of at least one compound described herein and at least one other active ingredient in the form of a single entity or single formulation. The term "non-fixed combination" refers to the simultaneous administration, combined administration, or sequential administration at variable intervals of at least one compound described herein and at least one other active ingredient as a single entity to a patient. These terms can also be used for cocktail therapy, such as the administration of three or more active ingredients.

[0537] In the present disclosure, a pharmaceutical composition comprises a compound represented by Formula I of the present disclosure or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystal, prodrug, or metabolite thereof, and a pharmaceutically acceptable carrier or excipient (which is a medium commonly accepted in the art for delivering biologically active compounds to mammals (e.g., humans)). The purpose of preparing an active compound into a pharmaceutical composition is to facilitate administration to an organism and promote absorption of the active ingredient, thereby allowing it to exert its biological activity. Generally, pharmaceutical compositions of the present disclosure contain 0.1% to 99.5% by weight of the pharmaceutically active ingredient. In some embodiments, pharmaceutical compositions of the present disclosure contain 0.5% to 90% by weight, e.g., 1%, 1.5%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, or 50% by weight of the active pharmaceutical ingredient.

[0538] In some embodiments, the pharmaceutical composition of the present disclosure comprises a compound represented by Formula I or any subformula thereof (including, but not limited to, Ia, Ib, IIa, IIb, IIc, IId, IIe, IIIa, IIIb, IVa, IVb, IVc, XI, XIa, XIb, XIIa, XIIb, XIIc, XIId, XIIe, XIIIa, XIIIb, XIVa, XIVb, and XIVc) of the present disclosure, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotope substitute, polycrystal, prodrug, or metabolite thereof, and further comprises other known anticancer agents, e.g., chemotherapeutic agents, e.g., Examples of such anticancer agents include, but are not limited to, other anticancer agents such as mitotic inhibitors (e.g., taxane compounds (e.g., paclitaxel or docetaxel), vinca alkaloids (e.g., vincristine, vinblastine, vinorelbine, or vinflunine)), metal platinum complexes (e.g., cisplatin, carboplatin, or oxaliplatin), antimetabolites (e.g., pyrimidine antagonists, 5-fluorouracil, 5-fluoro-2-4(1H,3H)-pyrimidinedione (5FU), gemcitabine, etc.), hormonal antitumor agents (e.g., flutamide), and tumor immunotherapeutic agents (e.g., anti-PD1 antibodies).

[0539] In other aspects, the present disclosure also provides the following embodiments.

[0540] 1. A compound represented by the following formula I or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotope-substituted compound, polycrystal, prodrug or metabolite thereof:

[0541] [ka]

[0542] In the formula: X1 is O and NR a is selected from X2 is selected from C or N; X3 is selected from C or N; Y5 is a bond, O, S, N, S(=O), SO2, or CHR 13 , C(R 13 )2, CR 13 , -OCH2-, -NCH2-, -CH2CH2- or NR 12 is selected from Y1, Y4 and Y6 are independently a bond, O, N, C, S, -S(O)-, -SO2-, CH, CH2, NH, CHR 13 , CHR 13 , C(R 13 )2 or NR 12 or Y1, Y4 and Y6 are optionally selected from C(R 13 )2, two R 13 form a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered heterocyclyl together with the C atom linked thereto to form a spiro ring structure with ring B, or form a ring atom of Y1 or Y6 and a ring atom of Y4 and a substituent R linked to said ring atom 13 and / or R 12 constitutes a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, a substituted or unsubstituted 4- to 9-membered heterocyclyl, a substituted or unsubstituted 6- to 10-membered aryl, or a substituted or unsubstituted 5- to 10-membered heteroaryl, and forms a fused structure with ring B; Ring B is a 5- or 6-membered heterocyclic, carbocyclic or heteroaryl ring, and Ring B optionally contains R 13 and / or R 12 and optionally further substituted by 1 to 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted alkyl, -NR'R'' and substituted or unsubstituted alkoxy; R1 is selected from cyano and —C(═O)NR′R″; R2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R3 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R4 and R5 are each independently selected from H, halogen, and substituted or unsubstituted alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3-6 membered substituted or unsubstituted ring, said ring optionally containing 1-3 heteroatoms selected from O, N, and S; R6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocyclyl; Alternatively, R4 or R5 and R6 and the C and N linked thereto together form a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a 6- to 12-membered bridged heterocyclyl, or a 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each further optionally contain 1 or 2 heteroatoms selected from O or N; R7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R9 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and substituted or unsubstituted alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted alkyl, -NR'R'', and substituted or unsubstituted alkoxy; Each R 12is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 6- to 14-membered aryl-S(O)2-, 4- to 9-membered heterocyclyl, NR'R''-C(O)-, C3-C8 cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 alkyl; Each R 13 are independently selected from H, halogen, oxo (=O), substituted or unsubstituted C1-C4 acyl, -OH, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted C6-14 aryl-S(O)2-, C3-C6 cyclohydrocarbyl-C(O)-, and -C(O)-NR'R''; And R 13 or R 12 after participating in ring formation, the ring atoms may optionally be replaced by 1 to 3 heteroatoms selected from O, N and S; R' and R'' are each independently selected from H, C1-C4 alkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl; Ra is selected from H or C1-C4 alkyl.

[0543] Here, the dotted line indicates the presence or absence of a double bond.

[0544] 2. The compound of embodiment 1, wherein the compound of Formula I has the structure of Formula Ia:

[0545] [ka]

[0546] In the formula, Y1 and Y4 are independently a bond, O, N, CH, CH2, CHR 13, C.R. 13 , C(R 13 )2 or NR 12 and Y and Y are not simultaneously a bond or O; Y5 and Y6 are independently O, N, S, -S(O)-, -SO2-, CH, CH2, NH, CHR 13 , C.R. 13 , C(R 13 )2 or NR 12 is selected from Ring B, R1~R 13 , X2 and X3 are as defined in embodiment 1; Here, the dotted line indicates the presence or absence of a double bond.

[0547] 3. The compound of embodiment 1 or 2, wherein the compound of Formula I has the structure of Formula Ib: or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof:

[0548] [ka]

[0549] In the formula, Y1, Y4, Y5, and Y6 are as defined in embodiment 2, and R1 to R3, R7 to R 13 , X2 and X3 are as defined in embodiment 1.

[0550] Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or the substituted or unsubstituted 6- to 12-membered spiroheterocyclyl may further optionally contain 1, 2, or 3 heteroatoms selected from N and O; Here, the dotted line indicates the presence or absence of a double bond.

[0551] 4. Y1 or Y4 or Y5 or Y6 is NR 12 If R 12 is selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted 4-9 membered heterocyclyl, NR'R''-C(O)-, C3-C8 cyclohydrocarbyl-C(O)- and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, and preferably, The compound according to any one of embodiments 1 to 3, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein 4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)2-, 4- to 9-membered heterocyclyl, and C1-C4 alkyl are optionally substituted by 1 to 3 substituents selected from F, hydroxy, and cyano.

[0552] 5. Y1 or Y4 or Y5 or Y6 is NR 12 If R 12is selected from H, acetyl, propionyl, C1-C3 alkoxy, C1-C3 alkyl-S(O)2-, 4- to 6-membered heterocyclyl, C3-C5 cyclohydrocarbyl-C(O)- and substituted or unsubstituted C1-C4 alkyl, preferably wherein said C1-C4 alkyl is optionally substituted with 1 to 3 substituents selected from F, hydroxy, and cyano; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopically substituted product, polycrystal, prodrug, or metabolite thereof, according to any one of embodiments 1 to 4.

[0553] 6. Y1 or Y4 or Y5 or Y6 is optionally CHR 13 , C.R. 13 or C(R 13 )2, then R 13 is selected from H, halogen, oxo (=O), substituted or unsubstituted C1-C4 acyl, -OH, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O)2-, C3-C6 cyclohydrocarbyl-C(O)-, and -C(O)-NR'R'', wherein R' and R'' are each independently selected from H and C1-C4 alkyl, and preferably, the C1-C4 acyl, C1-C4 alkoxy, and C1-C6 alkyl are optionally substituted with 1 to 3 substituents selected from F, hydroxy, and cyano; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof.

[0554] 7. Y1 or Y4 or Y5 or Y6 is optionally CHR 13 , C.R. 13 or C(R 13 )2, then R 13is selected from H, fluorine, chlorine, oxo (=O), C1-C4 acyl, -OH, cyano, C1-C4 alkoxy, C1-C6 alkyl, C1-C4 alkyl-S(O)2-, and C3-C4 cyclohydrocarbyl-C(O)-; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopically substituted derivative, polycrystalline product, prodrug, or metabolite thereof.

[0555] 8. The compound of embodiment 1, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof, wherein the compound of Formula I has the structure of Formula IIa:

[0556] [ka]

[0557] In the formula, R1 to R 13 , X2, X3, Y1 and Y5 are as defined in embodiment 1; Y4 is selected from C, CH or N; Y6 is selected from C, CH or N; Ring D is a C3-C8 cyclohydrocarbyl, a C4-C9 heterocyclyl, a C5-C10 heteroaryl, or a C6-C10 aryl, wherein the C4-C9 heterocyclyl and the C5-C10 heteroaryl optionally contain 1 to 3 heteroatoms selected from O, N, and S; R 15is selected from H, halogen, oxo (=O), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', -C(O)-NR'R'', substituted or unsubstituted C1-C4 alkyl-S(O)2-, substituted or unsubstituted C6-C14 aryl-S(O)2-, 4-9 membered heterocyclyl, NR'R''-C(O)-, C3-C8 cyclohydrocarbyl, C3-C8 cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1 to 3 substituents selected from F, hydroxy and cyano; each n is independently 0, 1, 2, 3, or 4; Here, the dotted line indicates the presence or absence of a double bond.

[0558] 9. The compound of embodiment 1, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof, wherein the compound of Formula I has the structure of Formula IIb:

[0559] [ka]

[0560] In the formula, R1 to R 13 , X2, X3, Y5 and Y6 are as defined in embodiment 1; Y1 is selected from C, CH or N; Y4 is selected from C, CH or N; Ring D, R 15 and N is as defined in embodiment 8; Here, the dotted line indicates the presence or absence of a double bond.

[0561] 10. Ring D is a C3-C6 cyclohydrocarbyl, a C4-C6 heterocyclyl, a C5-C8 heteroaryl, or a C6-C10 aryl, wherein the C4-C6 heterocyclyl and C5-C8 heteroaryl optionally contain 1 to 3 heteroatoms selected from O, N, and S; R 15 is selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', -C(O)-NR'R'', 4- to 9-membered heterocyclyl, NR'R''-C(O)-, C3-C8 cyclohydrocarbyl, C3-C8 cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, and preferably the C1-C4 acyl, C1-C4 alkoxy, cyano, -NR'R'', -C(O)-NR'R'', 4- to 9-membered heterocyclyl, NR'R''-C(O)-, C3-C8 cyclohydrocarbyl, C3-C8 cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl. 10. The compound of embodiment 8 or 9, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof, wherein alkoxy, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted with 1 to 3 substituents selected from F, hydroxy, and cyano; R' and R'' are each independently selected from H, C1-C4 alkyl; and n is 0, 1, or 2.

[0562] 11.R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, —C(O)—NR′R″, NR′R″-C(O)—, C3-C8 cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl; R′ and R″ are each independently selected from H, C1-C4 alkyl; and n is 0 or 1.

[0563] 12. The compound of embodiment 1, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof, wherein the compound of Formula I has the structure of Formula IIc:

[0564] [ka]

[0565] In the formula, R1 to R 13 , X2, X3, Y1, Y5 and Y6 are as defined in embodiment 1; Ring E is a C3-C8 cyclohydrocarbyl or a C4-C9 heterocyclyl, said C4-C9 heterocyclyl optionally containing 1 to 3 heteroatoms selected from O, N and S; R 16 is selected from halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 acyl, C1-C4 alkoxy and C1-C4 alkyl are optionally substituted by 1 to 3 substituents selected from F, hydroxy and cyano.

[0566] n is 0, 1, 2, 3 or 4; Here, the dotted line indicates the presence or absence of a double bond.

[0567] 13. The compound of embodiment 1, wherein the compound of Formula I has the structural formula IIc:

[0568] [ka]

[0569] In the formula, R1 to R13 , X2, X3, Y4, Y5 and Y6 are as defined in embodiment 1; Ring E, R 16 and N is as defined in embodiment 12; Here, the dotted line indicates the presence or absence of a double bond.

[0570] 14. Ring E is a C3-C6 cyclohydrocarbyl or a C4-C6 heterocyclyl, wherein the C4-C6 heterocyclyl optionally contains 1 to 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, C1-C4 alkyl, and hydroxy; and n is 0 or 1; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof;

[0571] 15. Ring E is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, azetidinyl, or azacyclopentyl, and R 16 is selected from H, fluorine, methyl, ethyl, and hydroxy; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystal, prodrug, or metabolite thereof.

[0572] 16. The compound of embodiment 8, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof, wherein the compound of Formula IIa has the structure represented by Formula IIIa:

[0573] [ka]

[0574] In the formula, R1 to R 13, X2, X3, Y1 and Y5 are as defined in embodiment 1; Y4 and Y6 are as described in embodiment 8; D1 is O, S, S(O)2, N, NR e , C.R. f and CR f R g is selected from D2 is O, S, S(O)2, N, NR e , (CR f ) p and (CR f R g ) p is selected from D3 is O, S, S(O)2, N, NR e , (CR f ) p and (CR f R g ) p is selected from Each R e are independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O)2-, 4- to 9-membered heteroaryl, 4- to 9-membered heterocyclyl, NR'R''-C(O)-, C3-C6 cyclohydrocarbyl, C3-C6 cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, and preferably, said C1-C4 acyl, C1-C4 alkoxy, and C1-C4 alkyl are optionally substituted with 1 to 3 substituents selected from F, hydroxy, and cyano.

[0575] Each R fare independently selected from H, halogen, oxo (=O), substituted or unsubstituted C1-C4 acyl, -OH, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, C3-C6 cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)2-, C3-C6 cyclohydrocarbyl-C(O)- and -C(O)-NR'R'', wherein R' and R'' are each independently selected from H and C1-C4 alkyl, and preferably said C1-C4 acyl, C1-C4 alkoxy and C1-C4 alkyl are optionally substituted with 1 to 3 substituents selected from F, hydroxy and cyano.

[0576] Each R g are independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, -OH, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, C3-C6 cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O)2-, C3-C6 cyclohydrocarbyl-C(O)- and -C(O)-NR'R'', where R' and R'' are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy and C1-C4 alkyl are optionally substituted with 1 to 3 substituents selected from F, hydroxy and cyano. Each p is independently an integer from 1 to 4, preferably 1 or 2.

[0577] Here, the dotted line indicates the presence or absence of a double bond.

[0578] 17. The compound of embodiment 9, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof, wherein the compound of Formula IIb has the structure of Formula IIIb:

[0579] [ka]

[0580] In the formula, R1 to R 13 , X2, X3, Y5 and Y6 are as defined in embodiment 1; Y1 and Y4 are as described in embodiment 9; D1, D2 and D3 are as described in embodiment 16; Here, the dotted line indicates the presence or absence of a double bond.

[0581] 18. The compound of embodiment 16, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof, wherein the compound of formula IIIa has the structure of formula IVa:

[0582] [ka]

[0583] In the formula, R1 to R 13 , X2, X3, Y1 and Y5 are as defined in embodiment 1; Y4 and Y6 are as described in embodiment 8; D1, D2 and D3 are as described in embodiment 16; Ring C is as described in embodiment 3; Here, the dotted line indicates the presence or absence of a double bond.

[0584] 19. The compound of embodiment 17, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof, wherein the compound of formula IIIb has the structure of formula IVb:

[0585] [ka]

[0586] In the formula, R1 to R13 , X2, X3, Y5 and Y6 are as defined in embodiment 1; Y1 and Y4 are as described in embodiment 9; D1, D2 and D3 are as described in embodiment 16; Ring C is as described in embodiment 3; Here, the dotted line indicates the presence or absence of a double bond.

[0587] 20. The compound according to any one of embodiments 1 to 19, wherein R1 is -C(=O)NR'R'' and R' and R'' are each independently selected from H, C1-C4 alkyl, C1-C4 alkyl-S(O)2-, and haloC1-C4 alkyl, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof.

[0588] 21. The compound according to any one of embodiments 1 to 20, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein R1 is -C(=O)NHR', and R' is selected from H and C1-C4 alkyl.

[0589] 22. A compound according to any one of embodiments 1 to 21, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R1 is -C(=O)NH2.

[0590] 23. A compound according to any one of embodiments 1 to 21, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R1 is -C(=O)NHCH3.

[0591] 24. The compound according to any one of embodiments 1 to 23, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R2 is selected from H, halogen, C1-C4 alkyl and C1-C4 alkoxy.

[0592] 25. The compound according to any one of embodiments 1 to 24, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R2 is selected from H, halogen and methoxy.

[0593] 26. The compound according to any one of embodiments 1 to 25, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R2 is selected from halogen.

[0594] 27. The compound according to any one of embodiments 1 to 26, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R2 is selected from fluorine and chlorine.

[0595] 28. A compound according to any one of embodiments 1 to 27, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R2 is fluorine.

[0596] 29. The compound according to any one of embodiments 1 to 28, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R3 is selected from substituted or unsubstituted aryl.

[0597] 30. The compound according to any one of embodiments 1 to 29, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R3 is selected from substituted or unsubstituted phenyl.

[0598] 31. The compound according to any one of embodiments 1 to 30, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R3 is phenyl.

[0599] 32. The compound according to any one of embodiments 1 to 31, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that R4 and R5 are each independently selected from H, substituted or unsubstituted alkyl, or R4 and R5 together with the carbon atoms connected thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1 to 3 heteroatoms selected from O, N, and S.

[0600] 33. The compound according to any one of embodiments 1 to 32, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopically substituted, polycrystalline, prodrug, or metabolite thereof, characterized in that R4 and R5 are each independently selected from H, substituted or unsubstituted C1-C4 alkyl.

[0601] 34. The compound according to any one of embodiments 1 to 33, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein R4 and R5 are each independently selected from H, C1-C3 alkyl.

[0602] 35. The compound according to any one of embodiments 1 to 34, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein R4 and R5 are each independently selected from H and methyl.

[0603] 36. The compound according to any one of embodiments 1 to 35, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein R4 and R5 are both H.

[0604] 37. The compound according to any one of embodiments 1 to 36, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that R7 and R8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl.

[0605] 38. The compound according to any one of embodiments 1 to 37, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein R7 and R8 are each independently selected from H, halogen, cyano, methyl, and methoxy.

[0606] 39. The compound according to any one of embodiments 1 to 38, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that R7 and R8 are each independently selected from fluorine and chlorine.

[0607] 40. The compound according to any one of embodiments 1 to 39, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R7 is chlorine and R8 is fluorine.

[0608] 41. The compound according to any one of embodiments 1 to 40, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that R9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen.

[0609] 42. The compound according to any one of embodiments 1 to 41, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R9 is selected from H, methyl, methoxy, hydroxy and F.

[0610] 43. The compound according to any one of embodiments 1 to 42, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R9 is H.

[0611] 44.R 10 is selected from H, halogen, and C1-C4 alkyl; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof.

[0612] 45.R 10 is selected from H, F, and methyl; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof;

[0613] 46.R 10 is H; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopically substituted derivative, polycrystalline product, prodrug, or metabolite thereof.

[0614] 47.R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy, wherein R′ and R″ are independently selected from C1-C4 alkyl; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof.

[0615] 48.R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy, and —NCH3; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof.

[0616] 49.R 11 is H; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic derivative, polycrystalline form, prodrug, or metabolite thereof.

[0617] 50. A compound according to any one of embodiments 1 to 49, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that X2 is C.

[0618] 51. A compound according to any one of embodiments 1 to 49, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that X2 is N.

[0619] 52. The compound according to any one of embodiments 1 to 51, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that X3 is C.

[0620] 53. The compound according to any one of embodiments 1 to 50, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that X3 is N.

[0621] 54. The compound according to any one of embodiments 1 to 53, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein Y5 is selected from a bond, O, S, N, CH2, CH, NH, and NCH3.

[0622] 55. The compound according to any one of embodiments 1 to 54, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that Y5 is O.

[0623] 56. The compound according to any one of embodiments 1 to 54, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that Y5 is CH or CH2.

[0624] 57. The compound according to any one of embodiments 1 to 54, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that Y5 is NH or N.

[0625] 58. The compound according to any one of embodiments 2 to 7, 9, 12 to 13, 17 and 19 to 56, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that Y6 is selected from a bond, O, S, N, CH, CH2, NH or NCH3.

[0626] 59. The compound according to any one of embodiments 2 to 7, 8, 12, 16 and 18 to 53, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that Y1 is selected from a bond, O, NH, -NCH3, CH, CH2 and -CH(CH3)-.

[0627] 60. The compound according to any one of embodiments 1 to 59, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopically substituted form, polycrystalline form, prodrug, or metabolite thereof, characterized in that R6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C8 cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl.

[0628] 61. R6 is H, substituted C1-C6 alkyl, substituted C1-C6 alkoxy, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl, the substituents of which are 1 to 3 and are selected from hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, C1-C4 alkyl optionally substituted with halogen -S(O)2-, sulfonyl, C1-C4 alkyl optionally substituted with halogen, -S(O)2-NR'R'', sulfonamide, -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1 -C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, C3-C8 cyclohydrocarbyl and 4-9 membered heterocyclyl substituted by a substituent selected from C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, halogen, cyano, C1-C4 alkyl-S(O)2-, hydroxy, carboxy, NR'R'', 6-14 membered aryl, 5-10 membered heteroaryl, C3-C8 cyclohydrocarbyl and 4-9 membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R6 is a substituted C3-C8 cyclohydrocarbyl or a substituted 4-9 membered monocyclic or fused ring heterocyclyl having 1 to 3 substituents selected from halogen, hydroxy, cyano, -NR'R'', C1-C4 alkoxy, haloC1-C4 alkoxy, -C(O)-C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein the C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1 to 3 groups selected from halogen, hydroxy, and -NR'R'', wherein R' and R'' are each independently selected from H and C1-C4 alkyl; or 61. The compound of any one of embodiments 1-60, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof, wherein R6 is a substituted 6- to 12-membered bridged cyclyl, a substituted 6- to 12-membered bridged heterocyclyl, a substituted 6- to 12-membered spirocyclyl, or a substituted 6- to 12-membered spiroheterocyclyl, wherein the substituents are 1 to 3 and are selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, C1-C4 alkyl-S(O)2-, hydroxy, halogen, and NR'R''; wherein R' and R'' are each independently selected from H and C1-C4 alkyl.

[0629] 62. R6 is -LWZ, where L is a bond or substituted or unsubstituted C1-C4 alkyl, W is a bond, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C3-C8 cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted 4- to 9-membered heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, and Z is hydrogen, halogen, C1-C4 aryl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl. or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopically substituted form, polycrystalline form, prodrug, or metabolite thereof;

[0630] 63. The compound according to embodiment 62, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein -LWZ is selected from the following (the wavy line indicates the attachment position of the bond):

[0631] [ka]

[0632] 64. The compound according to any one of embodiments 1 to 2, 4 to 17 and 20 to 62, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, wherein R4 or R5 and R6 and the C and N linked thereto together form a 4-9 membered heterocyclyl optionally substituted by 1 to 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy.

[0633] 65. The compound according to any one of embodiments 1 to 2, 4 to 17, 20 to 62 and 64, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R4 or R5 and R6 and the C and N connected thereto together form the following group, which may be substituted with 1 to 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0634] [ka]

[0635] where the wavy lines indicate the bond connection positions.

[0636] 66. R4 or R5 and R6 and the C and N connected thereto may be substituted together with 1 to 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy.

[0637] [ka]

[0638] or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopically substituted derivative, polycrystal, prodrug, or metabolite thereof, wherein the compound according to any one of embodiments 1 to 2, 4 to 17, 20 to 62, and 64 to 65 forms

[0639] 67. The compound according to any one of embodiments 3 and 18-19, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, wherein ring C is a 4-9-membered heterocyclyl optionally substituted by 1-3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen, and C1-C4 alkoxy.

[0640] 68. The compound according to any one of embodiments 3, 18-19 and 67, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, wherein ring C is the following group, optionally substituted with 1 to 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy:

[0641] [ka]

[0642] where the wavy lines indicate the bond connection positions.

[0643] 69. Ring C may be substituted with 1 to 3 substituents selected from H, deuterium, hydroxy, methyl, F, and methoxy.

[0644] [ka]

[0645] or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopically substituted derivative, polycrystal, prodrug, or metabolite thereof, according to any one of embodiments 3, 18-19, and 67-68, wherein

[0646] 70. The compound according to any one of embodiments 1 to 7, 29 to 46, and 50 to 69, wherein ring A and ring B and the substituents thereof of formula I, Ia, and Ib together form one of the following groups: or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof.

[0647] [ka]

[0648] In each of the above groups, R1 is cyano or —C(═O)NR′R″, R2 is H or halogen, and R 11 is H, OH, —NR′R″, halogen or C1-C4 alkyl, and R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, C3-C6 cyclohydrocarbyl, substituted or unsubstituted C1-C4 acyl, and R f is selected from H, halogen, —OH, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, and C3-C6 cyclohydrocarbyl, wherein the substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, and substituted or unsubstituted C1-C4 alkyl are optionally substituted with 1 to 3 substituents selected from F, hydroxy, and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and the wavy line indicates the attachment point of the bond.

[0649] 71. R1 is cyano, -C(=O)NH2 or -C(=O)NHCH3, R2 is H or F, and R 11 is H and R e is selected from H, methyl, ethyl, cyclopropyl, cyclobutyl, ethylhydroxy, acetyl, propionyl, and cyclopropionyl; R f is selected from H, F, Cl, —OH, cyano, —NH2, methoxy, methyl, ethyl, cyclopropyl, and cyclobutyl; or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof.

[0650] 72. R1 is -C(=O)NH2 or -C(=O)NHCH3, R2 is F, and R 11 is H and R e is selected from H, methyl, cyclopropyl and acetyl; R f or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystalline form, prodrug, or metabolite thereof, wherein is selected from H, F, Cl, —OH, cyano, —NH2, methoxy, and methyl.

[0651] 73. The compound according to any one of embodiments 1, 8 to 19, 29 to 46, and 50 to 69, wherein ring A and ring B and the substituents thereof of formula I, or ring A, ring B and ring D and the substituents thereof of formulas IIa, IIb, IIIa, IIIb, IVa, and IVb, or ring A, ring B and ring E and the substituents thereof of formulas IIc and IId, together form any one of the following groups:

[0652] [ka]

[0653] [ka]

[0654] [ka]

[0655] In each of the above groups, R1 is cyano or —C(═O)NR′R″, R2 is H or halogen, and R 11 is H, OH, —NR′R″, halogen or C1-C4 alkyl, and R 14 is H, halogen, or C1-C4 alkyl, n is 0, 1, or 2, and R 16 is selected from H, hydroxy, halogen and C1-C4 alkyl, and R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, C3-C6 cyclohydrocarbyl, substituted or unsubstituted C1-C4 acyl, and R f is selected from H, halogen, —OH, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, C3-C6 cyclohydrocarbyl, preferably said C1-C4 acyl, C1-C4 alkoxy and C1-C4 alkyl are optionally substituted with 1 to 3 substituents selected from F, hydroxy and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and the wavy line indicates the attachment point of the bond.

[0656] 74. R1 is cyano, -C(=O)NH2 or -C(=O)NHCH3, R2 is ...

Claims

1. A compound represented by the following formula I or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof. 【Chemistry 1】 (In the formula, X １ is O and NR ａ is selected from X ２ is selected from C and N; X ３ is selected from C and N, preferably, ring A is a benzene ring or a 6-membered heteroaryl ring, more preferably, ring A is a benzene ring or a pyridine ring; Y ５ and Y ６ are independently a bond, O, S, N, -S(O)-, -S(O) ２ -, C, CH(R １３ ), C(R １３ ) ２ , C(R １３ ), -OCH ２ -, -N(R １２ ) CH ２ -, -CH ２ CH ２ - and N(R １２ ) and Y ５ and Y ６ is not a bond at the same time, Y １ and Y ４ are independently a bond, O, N, C, S, -S(O)-, -C(O)-, or -S(O) ２ -, CH, CH ２ , NH, C(R １３ ), CH(R １３ ), C(R １３ ) ２ and N(R １２ ) and the condition is Y １ and Y ４ , Y １ and Y ５ , Y ４ and Y ６ are simultaneously a bond, O, S, -S(O)- or -S(O) ２ - and satisfying the valence bond law, Or, Y １ , Y ４ and Y ６ is arbitrarily C(R １３ ) ２ When two R １３ together with the C atom linked thereto, form a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered heterocyclyl to form a spiro ring structure with ring B; Or, Y １ or Y ６ Ring atoms and Y ４ wherein the ring atoms and the substituents attached to said ring atoms together form a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, a substituted or unsubstituted 4- to 9-membered heterocyclyl, a substituted or unsubstituted 6- to 10-membered aryl, or a substituted or unsubstituted 5- to 10-membered heteroaryl, forming a fused ring structure with Ring B; Or, X ２ Is Y ６ Ring atoms and R １１ and the substituents attached to said ring atoms together form a substituted or unsubstituted 5- or 6-membered cyclohydrocarbyl, a substituted or unsubstituted 5- or 6-membered heterocyclyl, a substituted or unsubstituted phenyl, or a substituted or unsubstituted 5- or 6-membered heteroaryl, forming a triple fused ring structure with rings A and B; Ring B is a 5-, 6-, or 7-membered heterocycle, a benzene ring, or a 5-, 6-, or 7-membered heteroaryl ring, and Ring B may optionally contain one or more R rings that are not involved in ring formation. １３ and / or R １２ and optionally further substituted by 1, 2 or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted alkyl, —NR′R″ and substituted or unsubstituted alkoxy; R １ is selected from cyano and —C(O)NR′R″; R ２ is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R ３ is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R ４ and R ５ are each independently selected from H, halogen and substituted or unsubstituted alkyl, or R ４ and R ５ together with the carbon atoms attached thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2 or 3 heteroatoms selected from O, N and S; R ６ is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; Or, R ４ or R ５ and R ６ and the atoms connected thereto together form a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each further optionally contain one or two heteroatoms selected from N and O; R ７ is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R ８ is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R ９ is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, hydroxy, and halogen; R １０ is selected from H, halogen and substituted or unsubstituted alkyl; R １１ is selected from H, hydroxy, amino, halogen, substituted or unsubstituted alkyl, —NR′R″ and substituted or unsubstituted alkoxy; Each R not involved in ring formation １２ are independently H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) ２ -, substituted or unsubstituted 6- to 14-membered aryl-S(O) ２ -, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 alkyl; Each R not involved in ring formation １３ are independently H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O) ２ -, substituted or unsubstituted C6-14 aryl-S(O) ２ -, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)- and NR'R''-C(O)-, or two R's on the same carbon atom １３ forms an oxo (=O) or thio (=S) group, R １３ or R １２ is involved in ring formation, the ring atoms may optionally be replaced by 1 to 3 heteroatoms selected from O, N and S; R' and R'' are each independently H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O) ２ - and haloC1-C4 alkyl; R ａ is selected from H and C1-C4 alkyl; where the dotted line indicates the presence or absence of a double bond.)

2. The compound of claim 1, wherein the compound of formula I has a structure represented by formula Ia or 1b: 【Chemistry 2】 【Transformation 3】 (In formula 1b, Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

3. R not involved in ring formation １２ When present, each independently is H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl-S(O) ２ -, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 alkyl, wherein R' and R'' are each independently selected from H and C1-C4 alkyl, and preferably the C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)-. ２ -, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl-C(O)- and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; When R 12 is present and not participating in ring formation, it is each independently selected from H, acetyl, propionyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 6-membered heterocyclyl, 3- to 5-membered cyclohydrocarbyl-C(O)- and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkyl optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; When R 13 is present that does not participate in ring formation, it is each independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″-C(O)—, or two R 13 on the same carbon atom form oxo (═O) or thio (═S), where R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C6 alkyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that, when R 13 not participating in ring formation is present, it is each independently selected from H, fluorine, chlorine, C1-C4 acyl, hydroxy, cyano, C1-C4 alkoxy, C1-C6 alkyl, C1-C4 alkyl-S(O) 2 - and 3-4 membered cyclohydrocarbyl-C(O)-.

4. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that: (1) The compound represented by formula I has a structure represented by formula IIa: 【Chemistry 4】 (In the formula, Y ４ is selected from C, CH and N; Y ６ is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, 4- to 9-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein said 4- to 9-membered heterocyclyl and 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; R １５ is H, halogen, oxo (=O), thio (=S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkyl-S(O) ２ -, substituted or unsubstituted 6- to 10-membered aryl-S(O) ２ -, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)-, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably the C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)-. ２ -, 6- to 10-membered aryl-S(O) ２ -, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2, 3 or 4; (2) The compound represented by formula I has a structure represented by formula IIb: 【Transformation 5】 (In the formula, Y 1 is selected from C, CH and N; Y 4 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, 4- to 9-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein said 4- to 9-membered heterocyclyl and 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is selected from H, halogen, oxo (═O), thio (═S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 6- to 10-membered aryl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 —, 6- to 10-membered aryl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2, 3 or 4; Preferably, in formula IIa and IIb, Ring D is a 3- to 6-membered cyclohydrocarbyl, a 4- to 6-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 8-membered heteroaryl, wherein said 4- to 6-membered heterocyclyl and 5- to 8-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; and R 15 is selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl. preferably, said C1-C4 acyl, C1-C4 alkoxy, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; R′ and R″ are each independently selected from H and C1-C4 alkyl; and n is 0, 1 or 2; Preferably, in formula IIa and IIb, R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl and C1-C4 alkyl, where R′ and R″ are each independently selected from H and C1-C4 alkyl, and n is 0 or 1; (3) The compound represented by formula I has a structure represented by formula IIc: 【Transformation 6】 (In the formula, Ring E is a 3- to 8-membered cyclohydrocarbyl or a 4- to 9-membered heterocyclyl, wherein said 4- to 9-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 alkyl, C1-C4 acyl and C1-C4 alkoxy optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2, 3 or 4; (4) The compound represented by formula I has a structure represented by formula IId: 【Transformation 7】 (In the formula, Ring E is a 3- to 8-membered cyclohydrocarbyl or a 4- to 9-membered heterocyclyl, wherein said 4- to 9-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 alkyl, C1-C4 acyl and C1-C4 alkoxy optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2, 3 or 4; Preferably, in formula IIc and IId, ring E is a 3- to 6-membered cyclohydrocarbyl or a 4- to 6-membered heterocyclyl, wherein said 4- to 6-membered heterocyclyl contains 1, 2 or 3 heteroatoms selected from O, N and S; R 16 is selected from H, halogen, C1-C4 alkyl, hydroxy and acetyl; n is 0 or 1; More preferably, in formula IIc and IId, ring E is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, tetrahydropyranyl, azetidinyl, azacyclopentyl or piperidinyl, R 16 is selected from H, fluorine, methyl, ethyl, hydroxy and acetyl, and n is 0 or 1; (5) The compound represented by formula I has a structure represented by formula IIe: 【Transformation 8】 (In the formula, X 2 is C; Y 6 is selected from C, CH and N; Ring F is a 5- or 6-membered cyclohydrocarbyl, 5- or 6-membered heterocyclyl, phenyl, or 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is selected from H, halogen, oxo (═O), thio (═S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 6- to 10-membered aryl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 —, 6- to 10-membered aryl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2 or 3; Preferably, ring F is phenyl or a 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heteroaryl contains 1, 2 or 3 heteroatoms selected from O, N and S; and / or R 15 is selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, and is preferably or said C1-C4 acyl, C1-C4 alkoxy, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and n is 0, 1 or 2; More preferably, ring F is a 5-membered heteroaryl, wherein said 5-membered heteroaryl contains 1 or 2 heteroatoms selected from O and N; and / or R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and n is 0 or 1; Ring F is pyrrolyl, furyl, pyrazolyl, imidazolyl, oxazolyl, or isoxazolyl; (6) The compound of formula I has a structure represented by formula IIIa: 【Chemistry 9】 (In the formula, D 1 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f and CR f R g ; D 2 is O, S, S(O), S(O) 2 , N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NRe, N-NR e , CR f -NR e , 【Chemistry 10】 is selected from D 3 is selected from O, S, S(O), S(O) 2 , N, NR e , (CR f ) p and (CR f R g ) p ; The condition is that D 1 and D 2 , D 1 and D 3 are not simultaneously O, S, —S(O)— or —S(O) 2 —, and satisfy the valence bond rule; Each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R f in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; or R f and R g on the same carbon atom form an oxo (═O) or thio (═S); each p is independently 1, 2, 3, or 4, preferably 1 or 2; (7) The compound of formula IIb has a structure represented by formula IIIb: 【Chemistry 11】 (In the formula, D 1 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f and CR f R g ; D 2 is O, S, S(O), S(O) 2 , N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , CR f -NR e , 【Chemistry 12】 is selected from D 3 is selected from O, S, S(O), S(O) 2 , N, NR e , (CR f ) p and (CR f R g ) p ; The condition is that D 1 and D 2 , D 1 and D 3 are not simultaneously O, S, —S(O)— or —S(O) 2 —, and satisfy the valence bond rule; Each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R f in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; or R f and R g on the same carbon atom form an oxo (═O) or thio (═S); each p is independently 1, 2, 3, or 4, preferably 1 or 2; (8) The compound of formula I has a structure represented by formula IVa: 【Chemistry 13】 (In the formula, Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl; (9) The compound of formula I has a structure represented by IVb having the following formula: 【Chemistry 14】 (In the formula, Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl; (10) The compound of formula I has a structure represented by formula IVc: 【Chemistry 15】 (In the formula, Y 7 , Y 8 and Y 9 are independently selected from a bond, O, S, S(O), S(O) 2 , N, NR e , CR f and CR f R g , with the proviso that at most one of Y 7 , Y 8 and Y 9 is a bond, and Y 7 and Y 8 , Y 8 and Y 9 are not simultaneously O, S, —S(O)— or —S(O) 2 —, and satisfy the valence bond rule; Each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R f in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; or R f and R g on the same carbon atom form an oxo (═O) or thio (═S); Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl.

5. R １ is —C(O)NR′R″, Preferably, R 1 is —C(O)NHR′, wherein R′ is selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; More preferably, R 1 is —C(O)NH 2 , —C(O)NHCH 3 and 【Chemistry 16】 and / or R 2 is selected from H, halogen, C1-C4 alkyl and C1-C4 alkoxy; Preferably, R 2 is selected from H, halogen and methoxy; More preferably, R 2 is halogen; More preferably, R 2 is selected from fluorine and chlorine; More preferably, R 2 is fluorine; and / or R 3 is selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; Preferably, R 3 is selected from substituted or unsubstituted phenyl and substituted or unsubstituted pyridyl; More preferably, R 3 is phenyl, fluorophenyl or pyridyl; and / or R 4 and R 5 are each independently selected from H and substituted or unsubstituted alkyl, or R 4 and R 5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2 or 3 heteroatoms selected from O, N and S; Preferably, R 4 and R 5 are each independently selected from H and substituted or unsubstituted C1-C4 alkyl; Preferably, R 4 and R 5 are each independently selected from H and C1-C3 alkyl; More preferably, R 4 and R 5 are each independently selected from H and methyl; More preferably, R 4 and R 5 are both H; and / or R 7 and R 8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C2-C4 alkenyl, and substituted or unsubstituted C2-C4 alkynyl; Preferably, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl and methoxy; More preferably, R 7 and R 8 are each independently selected from fluorine and chlorine; More preferably, R 7 is chlorine and R 8 is fluorine; and / or R 9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; Preferably, R 9 is selected from H, methyl, methoxy, hydroxy and F; More preferably, R 9 is H; and / or R 10 is selected from H, halogen and C1-C4 alkyl; Preferably, R 10 is selected from H, F and methyl; More preferably, R 10 is H; and / or R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy, where R′ and R″ are independently selected from C1-C4 alkyl; Preferably, R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ); More preferably, R 11 is H; and / or X 2 is C or N; and / or X 3 is C or N; and / or Y 5 is selected from a bond, O, S, —S(O)—, N, CH 2 , CH, —C(O)—, —CH(OH)—, NH, —N(CH 3 )—, —OCH 2 —, —NHCH 2 —, —N(CH 3 )CH 2 —, and —CH 2 CH 2 —; Preferably, Y 5 is O, or Y 5 is CH or CH 2 , or Y 5 is NH or N; and / or Y 6 is selected from a bond, O, S, —S(O)—, —S(O) 2 —, N, CH, —C(O)—, CH 2 , NH, —N(CH 3 )—, —N(C 2 H 4 OH)—, —N(C(O)CH 3 )—, —N(C(O)C 2 H 5 )—, —OCH 2 —, —NHCH 2 —, —N(CH 3 )CH 2 — and —CH 2 CH 2 —; The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that Y 1 and Y 4 are independently selected from a bond, O, N, NH, -N(CH 3 )-, CH, CH 2 and -CH(CH 3 )-, and Y 1 and Y 4 are not simultaneously a bond or O.

6. (1) R ６ is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; Preferably, R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, having 1, 2 or 3 substituents, and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, —S(O) 2 —C1-C4 alkyl optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —C(O)—C1-C4 alkyl, —NR′—C(O)—C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl and 4- to 9-membered heterocyclyl substituted by 1, 2 or 3 substituents selected from —, hydroxy, carboxy, —NR′R″, 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl and 4- to 9-membered heterocyclyl, where R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; More preferably, R 6 is -L-W-Z, where L is a bond or substituted or unsubstituted C1-C4 alkyl, W is a bond, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 6-14 membered aryl, substituted or unsubstituted 5-10 membered heteroaryl, substituted or unsubstituted 4-9 membered monocyclic or fused ring heterocyclyl, substituted or unsubstituted 6-12 membered bridged cyclyl, substituted or unsubstituted 6-12 membered bridged heterocyclyl, substituted or unsubstituted 6-12 membered spirocyclyl or substituted or unsubstituted 6-12 membered spiroheterocyclyl, and Z is hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, —S(O) 2 —C1-C4 alkyl, —S(O) 2 —NR′R″, —S(O) 2 —NH 2, cyano, —C(O)—C1-C4 alkyl, —O-3 to 8-membered cyclohydrocarbyl, or —NR′—C(O)—C1-C4 alkyl, where R′ and R″ are each independently H or C1-C4 alkyl; More preferably, said -LWZ is selected from: 【Chemistry 17】 (wherein the wavy line represents the point of attachment of the bond); and / or (2) R 4 or R 5 and R 6 and the atoms connected thereto together form a 4- to 9-membered monocyclic or fused-ring heterocyclyl, a 6- to 12-membered bridged heterocyclyl, or a 6- to 12-membered spiroheterocyclyl, optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen, and C1-C4 alkoxy; More preferably, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: [Chemistry 18] (wherein the wavy line represents the point of attachment of the bond); or R 4 or R 5 and R 6 together and the atom connected thereto are optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy. 【Chemistry 19】 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, which forms:

7. The compound of claim 1 or 2, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that: (1) Ring C is a 4-9 membered monocyclic or fused ring heterocyclyl optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen, and C1-C4 alkoxy; Preferably, Ring C is the following group optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Chemistry 20】 (Here, the wavy lines represent the bond attachment positions.) More preferably, Ring C is optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy. 【Chemistry 21】 or (2) The ring A and the ring B and the substituents thereof together form one of the following groups: 【Chemistry 22-1】 【Chemistry 22-2】 wherein R 1 is cyano or —C(O)NR′R″; R 2 is H or halogen; R 11 is H, hydroxy, —NR′R″, halogen or C1-C4 alkyl; R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, and substituted or unsubstituted C1-C4 acyl; and R f is selected from H, halogen, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, and substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, preferably said C1-C4 alkyl, C1-C4 alkoxy, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)—, and C1-C4 acyl are optionally substituted with 1, 2, or 3 substituents selected from F, hydroxy, and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and the wavy line indicates the point of attachment of the bond; or (3) The ring A and the ring B and the substituents thereof together form one of the following groups: 【Chemistry 23-1】 【Chemistry 23-2】 【Chemistry 23-3】 wherein R 1 is cyano or —C(O)NR′R″; R 2 is H or halogen; R 11 is H, hydroxy, —NR′R″, halogen or C1-C4 alkyl; R 14 is H, halogen or C1-C4 alkyl; n is 0, 1 or 2; R 16 is selected from H, hydroxy, halogen and C1-C4 alkyl; R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and substituted or unsubstituted C1-C4 acyl; and R f is selected from H, halogen, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, and substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, preferably said C1-C4 alkyl, C1-C4 alkoxy, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)—, and C1-C4 acyl are optionally substituted with 1, 2, or 3 substituents selected from F, hydroxy, and cyano, wherein R′ and R″ are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl, and the wavy line indicates the point of attachment of the bond; or (4) The ring A, the ring B and the substituents thereof together form one of the following groups: 【Chemistry 24】 wherein R 1 is cyano or —C(O)NR′R″; R 2 is H or halogen; R 14 is H, halogen or C1-C4 alkyl; n is 0, 1 or 2; R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, and substituted or unsubstituted C1-C4 acyl; and R f is selected from H, halogen, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, and substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, preferably said C1-C4 alkyl, C1-C4 alkoxy, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)—, and C1-C4 acyl are optionally substituted with 1, 2, or 3 substituents selected from F, hydroxy, and cyano, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, and the wavy line indicates the point of attachment of the bond; or (5) Ring A and ring B and their ring substituents together form one of the following groups: 【Chemistry 25-1】 【Chemistry 25-2】 【Chemistry 25-3】 wherein R 1 is cyano or —C(O)NR′R″; R 2 is H or halogen; R 11 is H, hydroxy, —NR′R″, halogen or C1-C4 alkyl; R 14 is H, halogen or C1-C4 alkyl; n is 0, 1 or 2; R 16 is selected from H, hydroxy, halogen and C1-C4 alkyl; R e is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and substituted or unsubstituted C1-C4 acyl; and R f is selected from H, halogen, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, preferably said C1-C4 alkyl, C1-C4 alkoxy, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)— and C1-C4 acyl are optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, wherein R′ and R″ are each independently selected from H, C1-C4 alkyl and C3-C6 cycloalkyl, and the wavy line indicates the point of attachment of the bond; X 1 is O; R 3 is selected from unsubstituted phenyl or phenyl substituted with 1, 2 or 3 substituents selected from hydroxy, halogen, C1-C4 alkyl, haloC1-C4 alkyl and C1-C4 alkoxy; R 4 is selected from H and C1-C4 alkyl; R 5 is selected from H and C1-C4 alkyl; R 6 is H, C1-C4 alkyl optionally substituted with 1, 2 or 3 substituents selected from hydroxy, halogen, C1-C4 alkoxy, cyano and —S(O) 2 —C1-C4 alkyl, 3- to 8-membered cyclohydrocarbyl optionally substituted with 1, 2 or 3 substituents selected from halogen, hydroxy, cyano, —S(O) 2 —C1-C4 alkyl, C1-C4 alkyl and C1-C4 alkoxy, 4- to 9-membered monocyclic or fused-ring heterocyclyl optionally substituted with 1, 2 or 3 substituents selected from halogen, hydroxy, cyano, —S(O) 2 —C1-C4 alkyl, C1-C4 alkyl and C1-C4 alkoxy, and selected from a 6- to 12-membered bridged cyclyl, a 6- to 12-membered spirocyclyl, a 6- to 12-membered bridged heterocyclyl, or a 6- to 12-membered spiroheterocyclyl, each substituted by 1, 2, or 3 substituents selected from C4 alkoxy and cyano; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Chemistry 26】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R 9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; or (6) Ring A and ring B and their ring substituents together form one of the following groups: 【Chemistry 27】 wherein R 1 is —C(O)NR′R″, R 2 is F, R 11 is H, F or methyl, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CH 2 CH 2 OH, —CH 2 CH 2 (CH 3 ) OH, —CH 2 CH 2 OCH 3 and acetyl, and R f is H, F, Cl, hydroxy, cyano, —NR′R″, methoxy, ethoxy, —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 , C1-C6 alkyl, and 3- to 6-membered cyclohydrocarbyl, where R′ and R″ are each independently selected from H and methyl, and the wavy line indicates the point of attachment of the bond; or (7) Ring A, ring B and their ring substituents together form one of the following groups: 【Chemistry 28】 wherein R 1 is —C(O)NR′R″, R 2 is F, R 11 is H, F or methyl, R 14 is H, F or methyl, n is 0, 1 or 2, R 16 is selected from H, hydroxy and methyl, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CH 2 CH 2 OH, —CH 2 CH 2 (CH 3 ) OH, —CH 2 CH 2 OCH 3 and acetyl, and R f is H, F, Cl, hydroxy, cyano, —NR′R″, methoxy, ethoxy, —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 , C1-C6 alkyl, and 3- to 6-membered cyclohydrocarbyl, where R′ and R″ are each independently selected from H, methyl, and cyclopropyl, and the wavy line indicates the point of attachment of the bond; Preferably, in (2), R 1 is cyano, —C(O)NH 2 or —C(O)NHCH 3 , R 2 is H or F, R 11 is H, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CH 2 CH 2 OH, —CH 2 CH 2 (CH 3 ) OH, acetyl, propionyl and cyclopropionyl, and R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 , methoxy, methyl, ethyl, cyclopropyl and cyclobutyl; Preferably, in (2), R 1 is —C(O)NH 2 or —C(O)NHCH 3 , R 2 is F, R 11 is H, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, —CH 2 CH 2 OH, —CH 2 CH 2 (CH 3 ) OH, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, cyclopropyl, and acetyl, and R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 , methoxy, and methyl; In (3), R 1 is cyano, —C(O)NH 2 or —C(O)NHCH 3 , R 2 is H or F, R 11 is H, R 14 is H or methyl, n is 0, 1 or 2, R 16 is H, hydroxy or methyl, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, cyclopropyl, cyclobutyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, —CH 2 CH 2 OH, —CH 2 CH 2 (CH 3 ) OH, acetyl, propionyl and cyclopropionyl, and R f is H, F, Cl, hydroxy, cyano, —NH 2 , —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2) selected from 2OCH3, methoxy, methyl, ethyl, cyclopropyl and cyclobutyl; Preferably, R 1 is —C(O)NH 2 or —C(O)NHCH 3 , R 2 is F, R 11 is H, R 14 is H, R 16 is H, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, trifluoropropyl, oxocyclobutyl, 1,1-difluorocyclobutyl, cyclopropyl, —CH 2 CH 2 OH, —CH 2 CH 2 (CH 3 ) OH and acetyl, and R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy, —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 and methyl; In (4), R 1 is cyano, —C(O)NH 2 or —C(O)NHCH 3 , R 2 is H or F, R 14 is H or methyl, n is 0, 1 or 2, R e is selected from H, methyl, difluoromethyl, trifluoromethyl, ethyl, fluoroethyl, difluoroethyl, trifluoroethyl, isopropyl, ethyl, cyclopropyl, cyclobutyl, —CH 2 CH 2 OH, —CH 2 CH 2 (CH 3 ) OH, acetyl, propionyl and cyclopropionyl, and R f is selected from H, F, Cl, hydroxy, cyano, —NH 2 , methoxy, —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 , methyl, ethyl, cyclopropyl and cyclobutyl.

8. (1) X ２ is selected from C and N; X ３ is selected from C and N; Y ５ and Y ６ are independently O, S, N, -S(O)-, -S(O) ２ -, CH(R １３ ), C(R １３ ) ２ , C(R １３ ), -OCH ２ -, -N(R １２ ) CH ２ -, -CH ２ CH ２ - and N(R １２ ) and Y ５ and Y ６ is not a bond at the same time, Y １ is a bond, O, N, CH, CH ２ , NH, CH(R １３ ), C(R １３ ) ２ and N(R １２ ) are selected from Y ４ is a bond, O, N, CH, CH ２ , NH, CH(R １３ ), C(R １３ ) ２ and N(R １２ ) are selected from Ring B may optionally include one or more R １３ and / or R １２ and optionally further substituted by 1, 2 or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, —NR′R″ and substituted or unsubstituted C1-C4 alkoxy; R １ is selected from cyano and —C(O)NR′R″; R ２ is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R ３ is selected from substituted or unsubstituted aryl; R ４ and R ５ are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R ４ and R ５ together with the carbon atoms attached thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2 or 3 heteroatoms selected from O, N and S; R ６ is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 6-14 membered aryl, substituted or unsubstituted 5-10 membered heteroaryl and substituted or unsubstituted 4-9 membered monocyclic or fused ring heterocyclyl, substituted or unsubstituted 6-12 membered bridged cyclyl, substituted or unsubstituted 6-12 membered bridged heterocyclyl, substituted or unsubstituted 6-12 membered spirocyclyl and substituted or unsubstituted 6-12 membered spiroheterocyclyl; Or, R ４ or R ５ and R ６ and the atoms connected thereto together form a 4- to 9-membered monocyclic or fused-ring heterocyclyl, a 6- to 12-membered bridged heterocyclyl, or a 6- to 12-membered spiroheterocyclyl optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen, and C1-C4 alkoxy; R ７ and R ８ are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R ９ is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R １０ is selected from H, halogen and C1-C4 alkyl; R １１ is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; Each R not involved in ring formation １２ are independently H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl-S(O) ２ -, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR'R''-C(O)-, 3- to 8-membered cyclohydrocarbyl-C(O)-, and substituted or unsubstituted C1-C4 alkyl, wherein said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) ２ -, 4- to 9-membered heterocyclyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R not involved in ring formation １３ are independently H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, -NR'R'', substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkyl-S(O) ２ -, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)- and NR'R''-C(O)-, wherein said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, C1-C4 alkyl-S(O) ２ - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, or two R on the same carbon atom. １３ forms an oxo (=O) or thio (=S) group, R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl; where the dotted line indicates the presence or absence of a double bond; (2) X 2 is selected from C and N; X 3 is selected from C and N; Y 5 is selected from O, S, —S(O)—, —S(O) 2 —, N, CH 2 , CH, —C(O)—, NH and —N(CH 3 )—; Y 6 is selected from O, S, —S(O)—, —S(O) 2 —, N, CH 2 , CH, —C(O)—, NH and —N(CH 3 )—; Y 1 is selected from a bond, O, NH, —N(CH 3 )—, CH 2 and —CH(CH 3 )—; Y 4 is selected from a bond, O, NH, —N(CH 3 )—, CH 2 and —CH(CH 3 )—; The H on ring B may be further optionally substituted with 1, 2 or 3 substituents selected from hydroxy, amino, halogen, substituted or unsubstituted C1-C4 alkyl, —NR′R″ and substituted or unsubstituted C1-C4 alkoxy; R 1 is cyano, —C(O)NH 2 , —C(O)NHCH 3 and 【Chemistry 29】 is selected from R 2 is selected from H, fluorine and methoxy; R 3 is phenyl; R 4 and R 5 are each independently selected from H and C1-C4 alkyl; R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, which has 1, 2 or 3 substituents and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O) 2 -C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O) 2 -NR'R'', -S(O) 2 -NH 2 , -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, a substituted or unsubstituted 6- to 12-membered spirocyclyl, or a substituted or unsubstituted 6- to 12-membered heterocyclyl. a 12-membered spiroheterocyclyl having one, two or three substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 and —NR′—C(O)—C1-C4 alkyl, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Transformation 30】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R ９ is selected from H, methyl, methoxy, hydroxy and F; The compound according to claim 1 or 2, characterized in that R 10 is selected from H, F and methyl, and R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and -NH(CH 3 ), or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof.

9. (1) In formula IIa, X ２ is selected from C and N; X ３ is selected from C and N; Y １ is a bond, O, NH, -N(CH ３ ) -, CH ２ and -CH(CH ３ ) - is selected from Y ５ are O, S, N, and CH ２ , CH, NH, -N(CH ３ ) -, -OCH ２ --NHCH ２ -, -N(CH ３ ) CH ２ - and -CH ２ CH ２ - is selected from, Y ４ is selected from C, CH or N; Y ６ is selected from C, CH or N; R １５ is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″-C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; n is 0 or 1; R １ is selected from cyano and —C(O)NR′R″; R ２ is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R ３ is selected from substituted or unsubstituted aryl; R ４ and R ５ are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R ４ and R ５ together with the carbon atoms attached thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2 or 3 heteroatoms selected from O, N and S; R ６ is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3-8 membered cyclohydrocarbyl, substituted or unsubstituted 6-14 membered aryl, substituted or unsubstituted 5-10 membered heteroaryl and substituted or unsubstituted 4-9 membered monocyclic or fused ring heterocyclyl, substituted or unsubstituted 6-12 membered bridged cyclyl, substituted or unsubstituted 6-12 membered bridged heterocyclyl, substituted or unsubstituted 6-12 membered spirocyclyl and substituted or unsubstituted 6-12 membered spiroheterocyclyl; Or, R ４ or R ５ and R ６ and the atoms connected thereto together form a 4- to 9-membered monocyclic or fused-ring heterocyclyl, a 6- to 12-membered bridged heterocyclyl, or a 6- to 12-membered spiroheterocyclyl optionally substituted with 1, 2, or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen, and C1-C4 alkoxy; R ７ and R ８ are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R ９ is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R １０ is selected from H, halogen and C1-C4 alkyl; R １１ is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl; and where the dotted line indicates the presence or absence of a double bond, Preferably, R 1 is cyano, —C(O)NH 2 , —C(O)NHCH 3 and 【Chemistry 31】 is selected from R 2 is selected from H, fluorine and methoxy; R ３ is phenyl, R 4 and R 5 are each independently selected from H and C1-C4 alkyl; R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, which has 1, 2 or 3 substituents and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O) 2 -C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O) 2 -NR'R'', -S(O) 2 -NH 2 , -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Chemistry 32】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R 9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ); (2) In formula IIb, X 2 and X 3 are C; Y 1 is selected from C, CH and N; Y 4 is selected from C, CH and N; Y 5 is selected from a bond, O, S, —S(O)—, —S(O) 2 —, —C(O)—, N, NH, —N(CH 3 )—, CH 2 , —CH(CH 3 )—, —OCH 2 —, —NHCH 2 —, —N(CH 3 )CH 2 —, and —CH 2 CH 2 —; Y 6 is selected from a bond, O, S, —S(O)—, —S(O) 2 —, —C(O)—, N, CH 2 , CH, NH, —N(CH 3 )—, —OCH 2 —, —NHCH 2 —, —N(CH 3 )CH 2 — and —CH 2 CH 2 —, and Y 5 and Y 6 are not simultaneously a bond; R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; n is 0 or 1; R 1 is selected from cyano and —C(O)NR′R″; R 2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 3 is selected from substituted or unsubstituted aryl; R 4 and R 5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R 4 and R 5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R 6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R 4 or R 5 and R 6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R 7 and R 8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl; and where the dotted line indicates the presence or absence of a double bond, Preferably, R 1 is cyano, —C(O)NH 2 , —C(O)NHCH 3 and 【Transformation 33】 is selected from R 2 is selected from H, fluorine and methoxy; R 3 is phenyl; R 4 and R 5 are each independently selected from H and C1-C4 alkyl; R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, which has 1, 2 or 3 substituents and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O) 2 -C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O) 2 -NR'R'', -S(O) 2 -NH 2 , -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Transformation 34】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R 9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; and R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ); (3) In formula IIc, X 2 and X 3 are C; Y 1 is selected from O or CH 2 ; Y 5 is selected from a bond, O, NH, —N(CH 3 )—, CH 2 and —CH(CH 3 )—; Y 6 is selected from a bond, O, S, N, CH 2 , CH, NH and —N(CH 3 )—; R 16 is selected from halogen, C1-C4 alkyl, hydroxy, C1-C4 acyl and C1-C4 alkoxy; R 1 is selected from cyano and —C(O)NR′R″; R 2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 3 is selected from substituted or unsubstituted aryl; R 4 and R 5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R 4 and R 5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R 6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R 4 or R 5 and R 6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R 7 and R 8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl; or where the dotted line indicates the presence or absence of a double bond, Preferably, R 1 is cyano, —C(O)NH 2 , —C(O)NHCH 3 and 【Chemistry 35】 is selected from R 2 is selected from H, fluorine and methoxy; R 3 is phenyl; R 4 and R 5 are each independently selected from H and C1-C4 alkyl; R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, which has 1, 2 or 3 substituents and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O) 2 -C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O) 2 -NR'R'', -S(O) 2 -NH 2 , -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Transformation 36】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R 9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ); (4) In formula IId, X 2 and X 3 are C; Y 4 is selected from O or CH 2 ; Y 5 is selected from a bond, O, NH, —N(CH 3 )—, CH 2 and —CH(CH 3 )—; Y 6 is selected from a bond, O, S, N, CH 2 , CH, NH and —N(CH 3 )—; R 16 is selected from halogen, C1-C4 alkyl, hydroxy, C1-C4 acyl and C1-C4 alkoxy; R 1 is selected from cyano and —C(O)NR′R″; R 2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 3 is selected from substituted or unsubstituted aryl; R 4 and R 5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R 4 and R 5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R 6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R 4 or R 5 and R 6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R 7 and R 8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl; and where the dotted line indicates the presence or absence of a double bond, Preferably, R １ is cyano, —C(O)NH ２ , -C(O)NHCH ３ and 【Chemistry 37】 is selected from R 2 is selected from H, fluorine and methoxy; R 3 is phenyl; R 4 and R 5 are each independently selected from H and C1-C4 alkyl; R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, which has 1, 2 or 3 substituents and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O) 2 -C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O) 2 -NR'R'', -S(O) 2 -NH 2 , -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Transformation 38】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R 9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ); (5) In formula IIe, Y 1 , Y 4 and Y 5 are independently selected from O, CH, CH 2 , —CH(CH 3 )—, N, NH and —N(CH 3 )—; Ring F is phenyl or a 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is selected from H, fluorine, chlorine, acetyl, hydroxy, C1-C4 alkoxy, cyano, —NR′R″, NR′R″—C(O)—, 3- to 8-membered cyclohydrocarbyl-C(O)—, C1-C4 haloalkyl, and C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; and n is 0 or 1; R 1 is selected from cyano and —C(O)NR′R″; R 2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 3 is selected from substituted or unsubstituted aryl; R 4 and R 5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R 4 and R 5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R 6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R 4 or R 5 and R 6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R 7 and R 8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl; and where the dotted line indicates the presence or absence of a double bond, Preferably, R 1 is cyano, —C(O)NH 2 , —C(O)NHCH 3 and 【Chemistry 39】 is selected from R 2 is selected from H, fluorine and methoxy; R 3 is phenyl; R 4 and R 5 are each independently selected from H and C1-C4 alkyl; R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, which has 1, 2 or 3 substituents and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O) 2 -C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O) 2 -NR'R'', -S(O) 2 -NH 2 , -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Chemistry 40】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R 9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ); In Formula IIIa, X 2 is selected from C and N; X 3 is selected from C and N; Y 1 is selected from a bond, O, NH, —N(CH 3 )—, CH 2 and —CH(CH 3 )—; Y 5 is selected from O, S, N, CH 2 , CH, NH, —N(CH 3 )—, —OCH 2 —, —NHCH 2 —, —N(CH 3 )CH 2 —, and —CH 2 CH 2 —; Y 4 is selected from C, CH or N; Y 6 is selected from C, CH or N; D 1 is selected from O, S, N, NR e , CR f and CR f R g ; D2 is selected from O, S, N, NR e , N—NR e , C(O)—NR e , CR f —NR e , (CR f ) p and (CR f R g ) p ; D 3 is selected from O, S, N, NR e , (CR f ) p and (CR f R g ) p ; R 1 is selected from cyano and —C(O)NR′R″; R 2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 3 is selected from substituted or unsubstituted aryl; R 4 and R 5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R 4 and R 5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R 6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R 4 or R 5 and R 6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R 7 and R 8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, and C3-C6 cycloalkyl; and where the dotted line indicates the presence or absence of a double bond, Preferably, R 1 is cyano, —C(O)NH 2 , —C(O)NHCH 3 and 【Chemistry 41】 is selected from R 2 is selected from H, fluorine and methoxy; R 3 is phenyl; R 4 and R 5 are each independently selected from H and C1-C4 alkyl; R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, which has 1, 2 or 3 substituents and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O) 2 -C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O) 2 -NR'R'', -S(O) 2 -NH 2 , -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Chemistry 42】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R 9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; and R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and —NH(CH 3 ); (7) In formula IIIb, X 2 and X 3 are C; Y 1 is selected from C, CH and N; Y 4 is selected from C, CH and N; Y 5 is selected from a bond, O, S, —S(O)—, —S(O) 2 —, —C(O)—, N, NH, —N(CH 3 )—, CH, CH 2 , —CH(CH 3 )—, —OCH 2 —, —NHCH 2 —, —N(CH 3 )CH 2 —, and —CH 2 CH 2 —; Y 6 is selected from a bond, O, S, —S(O)—, —S(O) 2 —, —C(O)—, N, CH 2 , CH, —CH(CH 3 )—, NH, —N(CH 3 )—, —OCH 2 —, —NHCH 2 —, —N(CH 3 )CH 2 — and —CH 2 CH 2 —, and Y 5 and Y 6 are not simultaneously a bond; D 1 is selected from O, S, N, NR e , CR f and CR f R g ; D 2 is selected from O, S, N, NR e , C(O)—NR e , N—NR e , CR f —NR e , (CR f ) p and (CR f R g ) p ; D 3 is selected from O, S, N, NR e , (CR f ) p and (CR f R g ) p ; R 1 is selected from cyano and —C(O)NR′R″; R 2 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 3 is selected from substituted or unsubstituted aryl; R 4 and R 5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl, or R 4 and R 5 together with the carbon atoms to which they are attached form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2, or 3 heteroatoms selected from O, N, and S; R 6 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl, substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, and substituted or unsubstituted 6- to 12-membered spiroheterocyclyl; or R 4 or R 5 and R 6 and the atoms connected thereto together form a 4-9 membered monocyclic or fused ring heterocyclyl, a 6-12 membered bridged heterocyclyl or a 6-12 membered spiroheterocyclyl optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, cyano, C1-C4 alkyl, halogen and C1-C4 alkoxy; R 7 and R 8 are each independently selected from H, halogen, cyano, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen and C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, C1-C4 alkyl, —NR′R″ and C1-C4 alkoxy; R' and R'' are each independently selected from H and C1-C4 alkyl; where the dotted line indicates the presence or absence of a double bond; Preferably, R 1 is cyano, —C(O)NH 2 , —C(O)NHCH 3 and 【Chemistry 43】 is selected from R 2 is selected from H, fluorine and methoxy; R 3 is phenyl; R 4 and R 5 are each independently selected from H and C1-C4 alkyl; R 6 is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl or substituted or unsubstituted C2-C6 alkynyl, which has 1, 2 or 3 substituents and is selected from the group consisting of hydroxy, halogen, C1-C4 alkoxy optionally substituted with halogen, cyano, S(O) 2 -C1-C4 alkyl- optionally substituted with halogen, C1-C4 alkyl optionally substituted with halogen, -S(O) 2 -NR'R'', -S(O) 2 -NH 2 , -C(O)-C1-C4 alkyl, -NR'-C(O)-C1-C4 alkyl and optionally C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkynyl, halogen, cyano, C1-C4 alkyl-S(O) 2 selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl substituted by 1, 2, or 3 substituents selected from -, hydroxy, carboxy, -NR'R'', 6- to 14-membered aryl, 5- to 10-membered heteroaryl, 3- to 8-membered cyclohydrocarbyl, and 4- to 9-membered heterocyclyl, where R' and R'' are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl or a substituted or unsubstituted 4- to 9-membered monocyclic or fused-ring heterocyclyl having 1, 2, or 3 substituents selected from halogen, hydroxy, cyano, —NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , —NR′—C(O)—C1 to C4 alkyl, —S(O) 2 selected from —C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, —C(O)—C1-C4 alkyl, and C1-C4 alkoxycarbonyl, wherein said C1-C4 alkyl and C1-C4 alkoxy are optionally substituted with 1, 2, or 3 groups selected from halogen, hydroxy, and —NR′R″, wherein said R′ and R″ are each independently selected from H and C1-C4 alkyl; or R 6 is a substituted or unsubstituted 6- to 12-membered bridged cyclyl, substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, substituted or unsubstituted 6- to 12-membered spirocyclyl, or substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, having 1, 2, or 3 substituents selected from C1-C4 alkyl, haloC1-C4 alkyl, C1-C4 alkoxy, haloC1-C4 alkoxy, cyano, —S(O) 2 —C1-C4 alkyl, hydroxy, halogen, NR′R″, —S(O) 2 —NR′R″, —S(O) 2 —NH 2 , and —NR′—C(O)—C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl; Alternatively, R 4 or R 5 and R 6 and the atoms connected thereto together form the following group, optionally substituted with 1, 2 or 3 substituents selected from H, deuterium, hydroxy, methyl, F and methoxy: 【Chemistry 44】 where the wavy line represents the attachment point of the bond, R 7 and R 8 are each independently selected from H, halogen, cyano, methyl, and methoxy; R 9 is selected from H, methyl, methoxy, hydroxy and F; R 10 is selected from H, F and methyl; The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite thereof, characterized in that R 11 is selected from H, hydroxy, amino, fluorine, chlorine, methyl, methoxy and -NH(CH 3 ).

10. The compound of claim 1 or 2, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that: (1) The compound is selected from the following compounds: 【Chemistry 45】 In the formula, the definitions of R 1 to R 11 , X 1 to X 3 and Y 1 to Y 6 are as set forth in claims 1 to 9; (2) The compound is selected from the following compounds: 【Chemistry 46】 wherein ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl; (3) The compound is selected from the following compounds: 【Chemistry 47】 (In the formula, Y 4 is selected from C, CH and N; Y 6 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, 4- to 9-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein said 4- to 9-membered heterocyclyl and 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is selected from H, halogen, oxo (═O), thio (═S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 6- to 10-membered aryl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 —, 6- to 10-membered aryl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2, 3 or 4; (4) The compound is selected from the following compounds: 【Chemistry 48】 (In the formula, Y 1 is selected from C, CH and N; Y 4 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, 4- to 9-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein said 4- to 9-membered heterocyclyl and 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is selected from H, halogen, oxo (═O), thio (═S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 6- to 10-membered aryl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 —, 6- to 10-membered aryl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2, 3 or 4; (5) The compound is selected from the following compounds: 【Chemistry 49】 (In the formula, Ring E is a 3- to 8-membered cyclohydrocarbyl or a 4- to 9-membered heterocyclyl, wherein said 4- to 9-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 alkyl, C1-C4 acyl and C1-C4 alkoxy optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2, 3 or 4; (6) The compound is selected from the following compounds: [Transformation 50] (In the formula, Ring E is a 3- to 8-membered cyclohydrocarbyl or a 4- to 9-membered heterocyclyl, wherein said 4- to 9-membered heterocyclyl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 16 is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl, hydroxy, substituted or unsubstituted C1-C4 acyl and substituted or unsubstituted C1-C4 alkoxy, preferably said C1-C4 alkyl, C1-C4 acyl and C1-C4 alkoxy optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2, 3 or 4; (7) The compound is selected from the following compounds: 【Chemistry 51】 (In the formula, Y 4 is selected from C, CH and N; Y 6 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, 4- to 9-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein said 4- to 9-membered heterocyclyl and 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; D 1 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f and CR f R g ; D 2 is O, S, S(O), S(O) 2 , N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , CR f -NR e , 【Chemistry 52】 is selected from D 3 is selected from O, S, S(O), S(O) 2 , N, NR e , (CR f ) p and (CR f R g ) p ; The condition is that D 1 and D 2 , D 1 and D 3 are not simultaneously O, S, —S(O)— or —S(O) 2 —, and satisfy the valence bond rule; Each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R f in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Alternatively, R f and R g on the same carbon atom form an oxo (═O) or thio (═S), and each p is independently 1, 2, 3, or 4, preferably 1 or 2; (8) The compound is selected from the following compounds: 【Chemistry 53】 (In the formula, Y 1 is selected from C, CH and N; Y 4 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, 4- to 9-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein said 4- to 9-membered heterocyclyl and 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; D 1 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f and CR f R g ; D 2 is O, S, S(O), S(O) 2 , N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NRe, N-NR e , CR f -NR e , 【Chemistry 54】 is selected from D 3 is selected from O, S, S(O), S(O) 2 , N, NR e , (CR f ) p and (CR f R g ) p ; The condition is that D 1 and D 2 , D 1 and D 3 are not simultaneously O, S, —S(O)— or —S(O) 2 —, and satisfy the valence bond rule; Each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R f in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Alternatively, R f and R g on the same carbon atom form an oxo (═O) or thio (═S), and each p is independently 1, 2, 3, or 4, preferably 1 or 2; (9) The compound is selected from the following compounds: 【Transformation 55】 (In the formula, Y 4 is selected from C, CH and N; Y 6 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, 4- to 9-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein said 4- to 9-membered heterocyclyl and 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; D 1 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f and CR f R g ; D 2 is O, S, S(O), S(O) 2 , N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NRe, N-NR e , CR f -NR e , 【Transformation 56】 is selected from D 3 is selected from O, S, S(O), S(O) 2 , N, NR e , (CR f ) p and (CR f R g ) p ; The condition is that D 1 and D 2 , D 1 and D 3 are not simultaneously O, S, —S(O)— or —S(O) 2 —, and satisfy the valence bond rule; Each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R f in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Alternatively, R f and R g on the same carbon atom form an oxo (═O) or thio (═S); each p is independently 1, 2, 3, or 4, preferably 1 or 2; and Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl; (10) The compound is selected from the following compounds: 【Chemistry 57】 (In the formula, Y 1 is selected from C, CH and N; Y 4 is selected from C, CH and N; Ring D is a 3- to 8-membered cyclohydrocarbyl, 4- to 9-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein said 4- to 9-membered heterocyclyl and 5- to 10-membered heteroaryl contain 1, 2, or 3 heteroatoms selected from O, N, and S; D 1 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f and CR f R g ; D 2 is O, S, S(O), S(O) 2 , N, NR e , (CR f ) p , (CR f R g ) p , C(O)-NR e , N-NR e , CR f -NR e , 【Chemistry 58】 is selected from D 3 is selected from O, S, S(O), S(O) 2 , N, NR e , (CR f ) p and (CR f R g ) p ; The condition is that D 1 and D 2 , D 1 and D 3 are not simultaneously O, S, —S(O)— or —S(O) 2 —, and satisfy the valence bond rule; Each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R f in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; or R f and R g on the same carbon atom form an oxo (═O) or thio (═S); each p is independently 1, 2, 3, or 4, preferably 1 or 2; and Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl; (11) The compound is selected from the following compounds: 【Chemistry 59】 (In the formula, X 2 is C; Y 6 is selected from C, CH and N; Ring F is a 5- or 6-membered cyclohydrocarbyl, 5- or 6-membered heterocyclyl, phenyl, or 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S; R 15 is selected from H, halogen, oxo (═O), thio (═S), substituted or unsubstituted C1-C4 acyl, hydroxy, substituted or unsubstituted C1-C4 alkoxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 6- to 10-membered aryl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 8-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl and substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 —, 6- to 10-membered aryl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 8-membered cyclohydrocarbyl, 3- to 8-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano, and n is 0, 1, 2 or 3; (12) The compound is selected from the following compounds: 【Transformation 60】 (In the formula, X 2 is C; Y 6 is selected from C, CH and N; Ring F is a 5- or 6-membered cyclohydrocarbyl, 5- or 6-membered heterocyclyl, phenyl, or 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms selected from O, N, and S; Y 7 , Y 8 and Y 9 are independently selected from a bond, O, S, S(O), S(O) 2 , N, NR e , CR f and CR f R g , with the proviso that at most one of Y 7 , Y 8 and Y 9 is a bond, and Y 7 and Y 8 , Y 8 and Y 9 are not simultaneously O, S, —S(O)— or —S(O) 2 —, and satisfy the valence bond rule; Each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl-S(O) 2 -, 4- to 9-membered heterocyclyl, 3- to 6-membered cyclohydrocarbyl, 3- to 6-membered cyclohydrocarbyl-C(O)-, C1-C4 haloalkyl, and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Each R f in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Each R g in each occurrence is independently selected from H, halogen, substituted or unsubstituted C1-C4 acyl, hydroxy, cyano, —NR′R″, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)— and NR′R″—C(O)—, wherein R′ and R″ are each independently selected from H and C1-C4 alkyl, preferably said C1-C4 acyl, C1-C4 alkoxy, C1-C4 alkyl, 3- to 6-membered cyclohydrocarbyl, C1-C4 alkyl-S(O) 2 - and 3- to 6-membered cyclohydrocarbyl-C(O)- are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy and cyano; Alternatively, R f and R g on the same carbon atom form an oxo (═O) or thio (═S), and Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl; (13) The compound has a structure represented by the following formula XVa: 【Chemistry 61】 (In the formula, D 1 is O, S, S(O), S(O) 2 , N, NR e , CR f R g , CR f and C(= O) D 2 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f R g , CR f and C(═O); D 3 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f R g , CR f and C(═O); D 4 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f R g , CR f and C(═O), and wherein the ring in which D1, D2, D3 and D4 are located satisfies the valence bond rule and contains up to two C(═O) and three N atoms; each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl; each R f in each occurrence is independently selected from H, halogen, hydroxy, cyano, oxo, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkoxy and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Y 5 and Y 6 are independently selected from a bond, O, S, N, —S(O)—, —S(O) 2 —, C, CH(R 13 ), C(R 13 ) 2 and N(R 12 ), and Y 5 and Y 6 are not simultaneously a bond; R 1 is selected from cyano and —C(O)NR′R″; R 2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R 3 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R 4 and R 5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl; R 6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; or R 4 or R 5 and R 6 and the atom connected thereto together form a substituted or unsubstituted 4- to 6-membered heterocyclyl, said 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from N and O; R 7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted C1 to C4 alkyl, —NR′R″ and substituted or unsubstituted C1 to C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O) 2 -, and haloC1-C4 alkyl; each p is independently 1, 2, 3, or 4; (14) The compound has a structure represented by the following formula XVb: 【Transformation 62】 (In the formula, D 1 is selected from O, S, S(O), S(O) 2 , N, NR c , CR f R g , CR f and C(═O); D 2 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f R g , CR f and C(═O); D 3 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f R g , CR f and C(═O); D 4 is selected from O, S, S(O), S(O) 2 , N, NR e , CR f R g , CR f and C(═O), and wherein the ring in which D1, D2, D3 and D4 are located satisfies the valence bond rule and contains up to two C(═O) and three N atoms; each R e in each occurrence is independently selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl; each R f in each occurrence is independently selected from H, halogen, hydroxy, cyano, oxo, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkoxy and C1-C4 alkyl are optionally substituted by 1, 2, or 3 substituents selected from F, hydroxy, and cyano; Y 5 and Y 6 are independently selected from a bond, O, S, N, —S(O)—, —S(O) 2 —, C, CH(R 13 ), C(R 13 ) 2 and N(R 12 ), and Y 5 and Y 6 are not simultaneously a bond; R 2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R 7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted C1 to C4 alkyl, —NR′R″ and substituted or unsubstituted C1 to C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O) 2 -, and haloC1-C4 alkyl; Ring C is a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein the 4- to 12-membered monocyclic or fused-ring heterocyclyl, the 6- to 12-membered bridged heterocyclyl, and the 6- to 12-membered spiroheterocyclyl each optionally further contain one or two heteroatoms selected from N and O, and Ring C is preferably a substituted or unsubstituted 4- to 8-membered nitrogen-containing monocyclic heterocyclyl, a substituted or unsubstituted 6- to 12-membered nitrogen-containing spiroheterocyclyl, or a substituted or unsubstituted 6- to 12-membered nitrogen-containing fused heterocyclyl, and each p is 0, 1, 2, 3, or 4; (15) The compound is selected from the following compounds: 【Transformation 63】 (In the formula, D 1 is selected from N and CR f ; D 4 is selected from N and CR f , and D1 and D4 are not simultaneously N; R e is selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4- to 9-membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl, substituted or unsubstituted 3- to 6-membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl; each occurrence of R f is independently selected from H, halogen, hydroxy, cyano, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkoxy and C1-C4 alkyl optionally substituted with 1, 2 or 3 substituents selected from F, hydroxy and cyano; Y 5 and Y 6 are independently selected from a bond, O, S, N, —S(O)—, —S(O) 2 —, C, CH(R 13 ), C(R 13 ) 2 and N(R 12 ), and Y 5 and Y 6 are not simultaneously a bond; R 2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R 4 and R 5 are each independently selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl; R 6 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; or R 4 or R 5 and R 6 and the atom connected thereto together form a substituted or unsubstituted 4- to 6-membered heterocyclyl, said 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from N and O; R 7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted C1 to C4 alkyl, —NR′R″ and substituted or unsubstituted C1 to C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O) 2 -, and haloC1-C4 alkyl; R h is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; or (16) The compound has a structure represented by the following formula XVIb: 【Chemistry 64】 (In the formula, D 1 is selected from N and CR f ; D 4 is selected from N and CR f , and D1 and D4 are not simultaneously N; R e is selected from H, substituted or unsubstituted C1-C4 acyl, substituted or unsubstituted C1-C4 alkoxy, cyano, substituted or unsubstituted C1-C4 alkyl-S(O) 2 —, substituted or unsubstituted 4-9 membered heterocyclyl, NR′R″—C(O)—, substituted or unsubstituted 3-6 membered cyclohydrocarbyl, substituted or unsubstituted 3-6 membered cyclohydrocarbyl-C(O)—, substituted or unsubstituted C1-C4 haloalkyl, and substituted or unsubstituted C1-C4 alkyl; each R f in each occurrence is independently selected from H, halogen, hydroxy, cyano, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkyl, preferably said C1-C4 alkoxy and C1-C4 alkyl are optionally substituted by 1, 2 or 3 substituents selected from F, hydroxy, and cyano; Y 5 and Y 6 are independently selected from a bond, O, S, N, —S(O)—, —S(O) 2 —, C, CH(R 13 ), C(R 13 ) 2 and N(R 12 ), and Y 5 and Y 6 are not simultaneously a bond; R 2 is selected from H, halogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkoxy; R 7 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 8 is selected from H, halogen, cyano, nitro, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R 9 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxy, and halogen; R 10 is selected from H, halogen, and substituted or unsubstituted C1-C4 alkyl; R 11 is selected from H, hydroxy, amino, halogen, substituted or unsubstituted C1 to C4 alkyl, —NR′R″ and substituted or unsubstituted C1 to C4 alkoxy; R' and R'' are each independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-S(O) 2 -, and haloC1-C4 alkyl; R h is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; R i is selected from H, halogen, substituted or unsubstituted C1-C4 alkyl and substituted or unsubstituted C1-C4 alkoxy; p is 1, 2 or 3, and q is 0, 1, 2, 3 or 4.

11. The compound of claim 1, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, characterized in that the compound is selected from the following compounds: 【Chemistry 65-1】 【Chemistry 65-2】 【Chemistry 65-3】 【Chemistry 65-4】 【Transformation 65-5】 【Transformation 65-6】 【Transformation 65-7】 【Transformation 65-8】 【Transformation 65-9】 【Chemistry 65-10】 【Chemistry 65-11】 【Chemistry 65-12】 【Chemistry 65-13】 【Chemistry 65-14】 【Chemistry 65-15】

12. 12. A compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug, or metabolite thereof, comprising a compound according to any one of claims 1 to 11, and a pharmaceutically acceptable carrier or excipient; The pharmaceutical composition further comprises other known anti-cancer agents, including, but not limited to, chemotherapeutic agents such as mitotic inhibitors, for example, taxane compounds (e.g., paclitaxel or docetaxel), vinca alkaloids (e.g., vincristine, vinblastine, vinorelbine, or vinflunine), metal platinum complexes (e.g., cisplatin, carboplatin, or oxaliplatin), antimetabolites (e.g., pyrimidine antagonists such as 5-fluorouracil, 5-fluoro-2-4(1H,3H)-pyrimidinedione (5FU), and gemcitabine), hormonal anti-tumor agents (e.g., flutamide), and tumor immunotherapeutics (e.g., anti-PD1 antibodies).

13. 13. Use of a compound according to any one of claims 1 to 11 or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, isotopic substitution, polycrystal, prodrug or metabolite, or a pharmaceutical composition according to claim 12, in the manufacture of a medicament for treating or preventing a disease mediated by the interaction between YAP / TAZ and TEAD, Preferably, the disease mediated by the interaction between YAP / TAZ and TEAD is tumor, liver fibrosis, and kidney fibrosis. Preferably, the tumor includes benign tumor and malignant tumor, particularly cancer or sarcoma such as solid tumor or blood tumor. More preferably, the disease mediated by the interaction between YAP / TAZ and TEAD is mesothelioma (e.g., pleural mesothelioma (e.g., malignant pleural mesothelioma), peritoneal mesothelioma, pericardial mesothelioma, or vaginal mesothelioma), cervical squamous cell carcinoma, endometrial cancer, bladder urothelial carcinoma, cutaneous squamous cell carcinoma, poroma (e.g., benign poroma), sweat duct carcinoma, epithelioid hemangioendothelioma, breast cancer (e.g., thrombus, bladder cancer, bladder cancer, bladder cancer, thrombus ... and / or glioma, or meningioma, or head and neck cancer (e.g., head and neck squamous cell carcinoma).

14. A compound represented by formula Ya or Za. 【Chemical Formula 66】 【Transformation 67】 (In formula Ya, X １ is O and NR ａ is selected from R ３ is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R ４ and R ５ are each independently selected from H, halogen and substituted or unsubstituted alkyl, or R ４ and R ５ together with the carbon atoms attached thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2 or 3 heteroatoms selected from O, N and S; R ６ is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; Or, R ４ or R ５ and R ６ and the atoms connected thereto together form a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each further optionally contain one or two heteroatoms selected from N and O; R ８ is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R ９ is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, hydroxy, and halogen; R １０ is selected from H, halogen and substituted or unsubstituted alkyl; (In formula Za, Pg is a nitrogen protecting group, preferably Boc.)

15. A method for producing a compound represented by formula Ya or Za, comprising: (1) A method for producing a compound represented by formula Ya or Za, comprising the following steps: (i) Palladium-catalyzed coupling of a borate ester under alkaline conditions to obtain the halogen Hal in formula Ya-1 １ converting the compound into Q-B-Q to obtain Ya-2; (ii) converting Ya-2 to the potassium trifluoroborate salt of Ya-3 in an organic solvent at room temperature; (iii) acid-catalyzed conversion of Ya-3 to Ya using a chlorinating reagent in an organic solvent; 【Transformation 68】 (In the formula, X １ is O and NR ａ and R ａ is selected from H and C1-C4 alkyl; R ３ is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; R ４ and R ５ are each independently selected from H, halogen and substituted or unsubstituted alkyl, or R ４ and R ５ together with the carbon atoms attached thereto form a 3- to 6-membered substituted or unsubstituted ring, said ring optionally containing 1, 2 or 3 heteroatoms selected from O, N and S; R ６ is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclohydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; Or, R ４ or R ５ and R ６ and the atoms connected thereto together form a substituted or unsubstituted 4- to 12-membered monocyclic or fused-ring heterocyclyl, a substituted or unsubstituted 6- to 12-membered bridged heterocyclyl, or a substituted or unsubstituted 6- to 12-membered spiroheterocyclyl, wherein said 4- to 12-membered monocyclic or fused-ring heterocyclyl, 6- to 12-membered bridged heterocyclyl, and 6- to 12-membered spiroheterocyclyl each further optionally contain one or two heteroatoms selected from N and O; R ８ is selected from H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; R ９ is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, hydroxy, and halogen; R １０ is selected from H, halogen and substituted or unsubstituted alkyl; Hal １ is a halogen, Q-B-Q is boric acid or a borate ester, Pg is a nitrogen protecting group. A method for preparing a compound of formula Za, comprising the steps of: (i) conversion of halogen Hal 1 of formula Za-1 to Q-B-Q by palladium-catalyzed coupling of a borate ester under alkaline conditions to give Za-2; (ii) adding aqueous potassium hydrogen fluoride solution and converting Q-B-Q with potassium trifluoroborate in an organic solvent at room temperature to obtain Za-3; (iii) acid-catalyzed conversion of Za-3 to Za using a chlorinating reagent in an organic solvent; 【Transformation 69】 (In the formula, Hal １ is a halogen, Q-B-Q is a boronic acid or boronic acid ester, and Pg is a nitrogen protecting group.

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