Fused ring compound, pharmaceutical composition containing same and use thereof

Abstract

The present invention relates to a compound of formula (I), a pharmaceutical composition containing same, and the use thereof for preventing or treating a disease.

Description

TECHNICAL FIELD The present disclosure relates to a fused ring compound, a pharmaceutical composition comprising same, and use thereof in preventing or treating a disease. BACKGROUND Microsatellite instability (MSI) is a type of genomic damage caused by mismatch repair deficiency (dMMR). Although progress has been made in the treatment of microsatellite instability-high (MSI-H) cancers, tumor evolution and drug resistance remain major causes of treatment failure and death in cancer patients. For example, among dMMR colorectal cancer patients receiving PD-1 and PD-L1 checkpoint inhibitor therapies, about half of the patients experience primary resistance. See, e.g., Overman MJ et al., J Clin Oncol. 2018 Mar 10;36(8):773-779. There remains an unmet clinical need for new treatment options for patients who are refractory to currently available therapies. Werner helicase (WRN) is considered to be a synthetic lethal target for MSI-H cancers (see, e.g., Chan EM et al., Nature. 2019 Apr;568(7753):551-556). WRN is a member of the RecQ family of DNA helicases and plays an important role in maintaining genomic stability, DNA repair, replication, transcription, and telomere maintenance. Studies on WRN-dependent mechanisms have found that dinucleotide TA repeat sequences undergo large-scale expansion in MSI cells, and these expanded TA repeat sequences form secondary DNA structures that require unwinding by WRN helicase (see, e.g., van Wietmarschen N et al., Nature. 2020 Oct;586(7828):292-298). In the absence of WRN (or under conditions in which WRN helicase is inhibited), the expanded TA repeat sequences in MSI cells are cleaved by nucleases, ultimately leading to chromosomal breakage. Therefore, inhibition of WRN helicase is an effective strategy for treating cancers characterized by microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), including colorectal cancer, gastric cancer, or endometrial cancer. BRIEF SUMMARY The present application provides a compound as a WRN inhibitor, which can be used for preventing or treating a cancer characterized by microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). In addition, the compound of the present disclosure also has good physicochemical properties (e.g., solubility and physical and / or chemical stability), good pharmacokinetic properties (e.g., improved bioavailability, good metabolic stability, and suitable half life and duration of action), good safety (less toxicity (e.g., reduced cardiotoxicity), and / or fewer side effects), lower propensity to induce drug resistance, and other excellent properties. One aspect of the present disclosure provides a compound, or a pharmaceutically acceptable salt, an ester, a stereoisomer, an atropisomer, a tautomer, a polymorph, a solvate, a metabolite, an isotopically labeled compound, or a prodrug thereof, wherein the compound has a structure of formula (I): (I) wherein: --- represents a single bond or a double bond, with the proviso that two double bonds are not directly connected; W1, W2, W3, and W4 are each independently C or N, with the proviso that C is attached to one double bond; preferably, at least one of W1 and W2 is N, and / or at least one of W3 and W4 is N; is selected from R1, R3, R21, and R22, at each occurrence, are each independently selected from H, a deuterium atom, halogen, -OH, -NH2, -CN, -NO2, -SF5, =CH2, C1-6 alkyl, deuterated C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14- membered heteroaryl, C6-12 aralkyl, -C(=O)Ra, -OC(=O)Ra, -C(=O)ORa, -ORa, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRaRb, -S(=O)(=NRa)Rb, -NRaRb, -C(=O)NRaRb, -NRa-C(=O)Rb, -NRa-C(=O)ORb, -NRa- S(=O)2-Rb, -NRa-C(=O)-NRaRb, -P(=O)RaRb, -C1-6 alkylene-Ra, -C1-6 alkylene-ORa, -C1-6 alkylene-NRaRb, -O-C1-6 alkylene-NRaRb, (-C3-6 cyclohydrocarbylene)-CN, and (-C3-6 cyclohydrocarbylene)-C1- 6 alkyl; when m is greater than 1, two R3 located at the same ring atom or adjacent ring atoms, together with the group to which they are attached, optionally form a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, or a 5- to 14-membered heteroaromatic ring; R4 is b^-L2 \r4I. ; L2 is selected from -O-, -C(=O)-, -NRC(=O)-, -S-, -S(=O)-, -S(=O)2-, C1-6 alkylene, and -O-(C1-6 alkylene)-; R41 is selected from a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring; R, Ra, and Rb, at each occurrence, are each independently selected from H, C1-6 alkyl, C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and C6-12 aralkyl; ring B, ring X, and ring Z are each independently selected from a C3-6 hydrocarbon ring, a 3- to 10membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring; ring Y is absent or selected from a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring; when ring Y is absent, R22 is also absent; the alkylene, the alkyl, the alkenyl, the alkynyl, the cyclohydrocarbylene, the cyclohydrocarbyl, the hydrocarbon ring, the heterocyclyl, the heterocyclic ring, the aryl, the aromatic ring, the heteroaryl, the heteroaromatic ring, and the aralkyl described above, at each occurrence, are each optionally substituted with one or more substituents independently selected from the following: a deuterium atom, halogen, -OH, =O, -NH2, -CN, -NO2, =CH2, C1-6 alkyl, deuterated C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, -C(=O)Rc, -OC(=O)Rc, -C(=O)ORc, -ORc, -SRc, -S(=O)Rc, -S(=O)2Rc, -S(=O)2NRcRd, -NRcRd, -C(=O)NRcRd,  -NRc-C(=O)Rd,  -NRc-C(=O)ORd,  -NRc-S(=O)2-Rd,  -NRc-C(=O)-NRcRd, -C1-6 alkylene-ORc, -C1-6 alkylene-NRcRd, and -O-C1-6 alkylene-NRcRd; the alkylene, the alkyl, the alkenyl, =CH2, the alkynyl, the cyclohydrocarbyl, the heterocyclyl, the aryl, the heteroaryl, and the aralkyl are each further optionally substituted with one or more substituents independently selected from the following: halogen, -OH, =O, -C(=O)O-tert-butyl, -NH2, -CN, -NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, -C1-6 alkylene-C3-6 cyclohydrocarbyl, -O-C1-6 alkyl, and -C1-6 alkylene-O-C1-6 alkyl; Rc and Rd, at each occurrence, are each independently selected from: H, C1-6 alkyl, C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and C6-12 aralkyl, wherein the alkyl, the cyclohydrocarbyl, the heterocyclyl, the aryl, the heteroaryl, and the aralkyl are further optionally substituted with one or more substituents independently selected from the following: halogen, -OH, =O, -C(=O)O-tert-butyl, -NH2, -CN, -NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, and -C1-6 alkylene-O-C1-6 alkyl; and p, q, and m are each independently an integer selected from 1, 2, or 3. Another aspect of the present disclosure provides a pharmaceutical composition comprising a prophylactically or therapeutically effective amount of the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof of the present disclosure, and one or more pharmaceutically acceptable carriers. Another aspect of the present disclosure provides use of the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof of the present disclosure, or of the pharmaceutical composition of the present disclosure in preparing a medicament as a WRN inhibitor. Another aspect of the present disclosure provides the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof of the present disclosure, or the pharmaceutical composition of the present disclosure, for use as a WRN inhibitor. Another aspect of the present disclosure provides a method for preventing or treating a cancer (preferably a cancer characterized by microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR)), comprising administering to a subject in need thereof an effective amount of the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof of the present disclosure, or the pharmaceutical composition of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION Definitions Unless otherwise defined below, all technical and scientific terms used herein are intended to have the same meaning as commonly understood by those skilled in the art. Reference to the techniques used herein is intended to refer to techniques commonly understood in the art, including those variations of or equivalent alternatives to the techniques that are apparent to those skilled in the art. Although the following terms are believed to be well understood by those skilled in the art, the following definitions are set forth to better explain the present disclosure. The terms “include”, “comprise”, “have”, “contain”, or “involve”, and other variant forms thereof herein, are inclusive or open-ended and do not exclude other unrecited elements or method steps. As used herein, the term “alkylene” refers to saturated divalent hydrocarbyl, preferably saturated divalent hydrocarbyl having 1, 2, 3, 4, 5, or 6 carbon atoms, e.g., methylene, ethylene, propylene, or butylene. As used herein, the term “alkyl” is defined as a linear or branched saturated aliphatic hydrocarbon. In some embodiments, the alkyl has 1 to 12, e.g., 1 to 6, carbon atoms. For example, as used herein, the term “C1-6 alkyl” refers to a linear or branched group of 1 to 6 carbon atoms (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, or n-hexyl) that is optionally substituted with 1 or more (such as 1 to 3) suitable substituents such as halogen (in this case the group is referred to as “haloalkyl”) (e.g., CF3, C2F5, CHF2, CH2F, CH2CF3, CH2Cl, or -CH2CH2CF3). The term “C1-4 alkyl” refers to a linear or branched aliphatic hydrocarbon chain of 1 to 4 carbon atoms (i.e., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl). As used herein, the term “alkenyl” refers to linear or branched monovalent hydrocarbyl containing one or more double bonds and having 2 to 6 carbon atoms (“C2-6 alkenyl”). The alkenyl is, for example, -CH=CH2, -CH2CH=CH2, -C(CH3)=CH2, -CH2-CH=CH-CH3, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, or 4-methyl-3-pentenyl. When the compound of the present disclosure contains the alkenyl, the compound may be present in a pure E (entgegen) form, a pure Z (zusammen) form, or any mixture thereof. The term “alkenylene” is a corresponding divalent group, including, for example, “C2-6 alkenylene”, “C2-4 alkenylene”, and the like, specific examples of which include, but are not limited to: -CH=CH-, -CH2CH=CH-, -C(CH3)=CH-, butenylene, pentenylene, hexenylene, and the like. As used herein, the term “alkynyl” refers to monovalent hydrocarbyl containing one or more triple bonds and preferably having 2, 3, 4, 5, or 6 carbon atoms, e.g., ethynyl, 2-propynyl, 2-butynyl, or 1,3-butadiynyl. The alkynyl is optionally substituted with one or more (such as 1 to 3) identical or different substituents. The term “alkynylene” is a corresponding divalent group, including, for example, “C2-8 alkynylene”, “C2-6 alkynylene”, “C2-4 alkynylene”, and the like, examples of which include, but are not limited to, 5        ’,              ’,   '           ,              ^, and the like. The alkynylene is optionally substituted with one or more (such as 1 to 3) identical or different substituents. As used herein, the term “fused ring” refers to a ring system formed by two or more cyclic structures that share two adjacent atoms. As used herein, the term “spiro ring” refers to a ring system formed by two or more cyclic structures that share one ring atom. As used herein, the term “bridged ring” refers to a ring system formed by two or more cyclic structures that share two atoms not directly connected. As used herein, the terms “cyclohydrocarbylene”, “cyclohydrocarbyl”, and “hydrocarbon ring” refer to a saturated (i.e., “cycloalkylene” and “cycloalkyl”) or partially unsaturated (i.e., having one or more double and / or triple bonds within the ring) monocyclic or polycyclic hydrocarbon ring (including a spiro ring, fused ring, or bridged ring system) having, for example, 3 to 10 (suitably 3 to 8, and more suitably 3 to 6) ring carbon atoms, including, but not limited to, cyclopropyl(ene) (cyclopropane ring), cyclobutyl(ene) (cyclobutane ring), cyclopentyl(ene) (cyclopentane ring), cyclohexyl(ene) (cyclohexane ring), cycloheptyl(ene) (cycloheptane ring), cyclooctyl(ene) (cyclooctane ring), cyclononyl(ene) (cyclononane ring), cyclohexenyl(ene) (cyclohexene ring), and the like. As used herein, the term “cycloalkyl” refers to a saturated monocyclic or polycyclic (such as bicyclic) hydrocarbon ring (e.g., a monocyclic ring, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, or cyclononyl, or a bicyclic ring, including a spiro ring, fused ring, or bridged ring system (such as bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, bicyclo[3.2.1]octyl, bicyclo[5.2.0]nonyl, or decahydronaphthyl)) optionally substituted with 1 or more (such as 1 to 3) suitable substituents. The cycloalkyl has 3 to 15 carbon atoms. For example, the term “C3-6 cycloalkyl” refers to a saturated monocyclic or polycyclic (such as bicyclic) hydrocarbon ring of 3 to 6 ring-forming carbon atoms (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) optionally substituted with 1 or more (such as 1 to 3) suitable substituents, for example, cyclopropyl substituted with methyl. As used herein, the term “heterocyclyl” (or “heterocyclic ring”) refers to a saturated or partially unsaturated monocyclic or bicyclic group having 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms and one or more (e.g., one, two, three, or four) heteroatoms selected from O, S, N, and P in the ring, and the “heterocyclyl” (or “heterocyclic ring”) may contain -C(=O)- as a ring member. The heterocyclyl may be connected to the rest of the molecule by the carbon atom and / or the heteroatom (if present). In particular, 3- to 10-membered heterocyclyl is a group having 3 to 10 carbon atoms and heteroatoms in the ring, for example, but not limited to, oxiranyl, aziridinyl, azetidinyl, oxetanyl, tetrahydrofuranyl, dioxolinyl, pyrrolidinyl, pyrrolidinonyl, imidazolidinyl, pyrazolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, or trithianyl. As used herein, the term “heterocyclyl” (or “heterocyclic ring”) encompasses fused ring structures, the point of attachment of which to other groups may be on any ring of the fused ring structures. Thus, the heterocyclyl of the present disclosure further includes, but is not limited to, heterocyclyl fused with heterocyclyl, heterocyclyl fused with cycloalkyl, monoheterocyclyl fused with monoheterocyclyl, monoheterocyclyl fused with monocycloalkyl, aryl fused with heterocyclyl, and heteroaryl fused with heterocyclyl, e.g.,  3- to 7-membered (mono)heterocyclyl fused with 3- to 7-membered (mono)heterocyclyl, 3- to 7-membered (mono)heterocyclyl fused with (mono)cycloalkyl, 3- to 7membered (mono)heterocyclyl fused with C4-6 (mono)cycloalkyl, C6-10 aryl fused with 3- to 7membered heterocyclyl, and 5- to 6-membered heteroaryl fused with 3- to 7-membered heterocyclyl, examples of which include, but are not limited to, pyrrolidinyl fused with cyclopropyl, cyclopentyl fused with aziridinyl, pyrrolidinyl fused with cyclobutyl, pyrrolidinyl fused with pyrrolidinyl, pyrrolidinyl fused with piperidinyl, pyrrolidinyl fused with piperazinyl, piperidinyl fused with morpholinyl As used herein, the term “heterocyclyl” (or “heterocyclic ring”) encompasses bridged heterocyclyl (bridged heterocyclic ring) and spiro heterocyclyl (spiro heterocyclic ring). As used herein, the term “bridged heterocyclic ring” refers to a cyclic structure containing one or more (e.g., 1, 2, 3, or 4) heteroatoms (e.g., oxygen atoms, nitrogen atoms, and / or sulfur atoms) formed by two rings that share two ring atoms not directly connected, including, but not limited to, a 7- to 10membered bridged heterocyclic ring, a 8- to 10-membered bridged heterocyclic ring, a 7- to 10- membered nitrogen-containing bridged heterocyclic ring, a 7- to 10-membered oxygen-containing bridged heterocyclic ring, a 7- to 10-membered sulfur-containing bridged heterocyclic ring, and the like, e.g., HN , and The “nitrogen-containing bridged heterocyclic ring”, “oxygen-containing bridged heterocyclic ring”, or “sulfur-containing bridged heterocyclic ring” optionally further contains one or more other heteroatoms selected from oxygen, nitrogen, and sulfur. As used herein, the term “spiro heterocyclic ring” refers to a cyclic structure containing one or more (e.g., 1, 2, 3, or 4) heteroatoms (e.g., oxygen atoms, nitrogen atoms, sulfur atoms) formed by two or more rings that share one ring atom, including, but not limited to, a 5- to 10-membered spiro heterocyclic ring, a 6- to 10-membered spiro heterocyclic ring, a 6- to 10-membered nitrogen- containing spiro heterocyclic ring, a 6- to 10-membered oxygen-containing spiro heterocyclic ring, a HN 6- to 10-membered sulfur-containing spiro heterocyclic ring, and the like, e.g., The “nitrogen-containing spiro heterocyclic ring”, “oxygen-containing spiro heterocyclic ring”, or “sulfur-containing spiro heterocyclic ring” optionally further contains one or more other heteroatoms selected from oxygen, nitrogen, and sulfur. The term “6- to 10-membered nitrogen-containing spiro heterocyclyl” refers to spiro heterocyclyl containing a total of 6 to 10 ring atoms, and at least one of which is a nitrogen atom. As used herein, the terms “aryl(ene)” and “aromatic ring” refer to an all-carbon monocyclic or fused polycyclic aromatic group having a conjugated n-electron system. For example, as used herein, the terms “C6-10 aryl(ene)” and “C6-10 aromatic ring” refer to an aromatic group containing 6 to 10 carbon atoms, such as phenyl(ene) (benzene ring) or naphthyl(ene) (naphthalene ring). The aryl(ene) and aromatic ring are optionally substituted with 1 or more (such as 1 to 3) suitable substituents (e.g., halogen, -OH, -CN, -NO2, and C1-6 alkyl). The term “aralkyl” refers to alkyl substituted with aryl, wherein the aryl and the alkyl are as defined herein. Generally, the aryl may have 6 to 14 carbon atoms, and the alkyl may have 1 to 6 carbon atoms. Exemplary aralkyl includes, but is not limited to, benzyl, phenylethyl, phenylpropyl, and phenylbutyl. As used herein, the terms “heteroaryl(ene)” and “heteroaromatic ring” refer to a monocyclic, bicyclic, or tricyclic aromatic ring system, which has 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 ring atoms, in particular 1 or 2 or 3 or 4 or 5 or 6 or 9 or 10 carbon atoms, and contains at least one heteroatom which may be identical or different (the heteroatom is, for example, oxygen, nitrogen, or sulfur), and may be benzofused in each case. In particular, “heteroaryl(ene)” or “heteroaromatic ring” is selected from thienyl(ene) (thiophene ring), furyl(ene) (furan ring), pyrrolyl(ene) (pyrrole ring), oxazolyl(ene) (oxazole ring), thiazolyl(ene) (thiazole ring), imidazolyl(ene) (imidazole ring), pyrazolyl(ene) (pyrazole ring), isoxazolyl(ene) (isoxazole ring), isothiazolyl(ene) (isothiazole ring), oxadiazolyl(ene) (oxadiazole ring), triazolyl(ene) (triazole ring), thiadiazolyl(ene) (thiadiazole ring), and the like, as well as benzo derivatives thereof; or pyridinyl(ene) (pyridine ring), pyridazinyl(ene) (pyridazine ring), pyrimidinyl(ene) (pyrimidine ring), pyrazinyl(ene) (pyrazine ring), triazinyl(ene) (triazine ring), and the like, as well as benzo derivatives thereof. As used herein, the term “halogenated” or “halogen” group is defined to include F, Cl, Br, or I. As used herein, the term “alkylthio” refers to alkyl as defined above that is attached to a parent molecular moiety via a sulfur atom. Representative examples of C1-6 alkylthio include, but are not limited to, methylthio, ethylthio, tert-butylthio, and hexylthio. As used herein, the term “nitrogen-containing heterocyclic ring” refers to a saturated or partially unsaturated monocyclic or bicyclic group, which has 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 carbon atoms and at least one nitrogen atom in the ring, and may also optionally contain one or more (e.g., one, two, three, or four) ring members selected from N, O, S, S=O, and S(=O)2. The nitrogen-containing heterocyclic ring is attached to the rest of the molecule via any one of the ring members. The nitrogencontaining heterocyclic ring is preferably a saturated nitrogen-containing monocyclic ring. In particular, a 3- to 14-membered nitrogen-containing heterocyclic ring is a group having 3 to 14 carbon atoms and heteroatoms (at least one of which is a nitrogen atom) in the ring, including, but not limited to, a threemembered nitrogen-containing heterocyclic ring (e.g., aziridinyl), a four-membered nitrogencontaining heterocyclic ring (e.g., azetidinyl), a five-membered nitrogen-containing heterocyclic ring (e.g., pyrrolyl, pyrrolidinyl (pyrrolidine ring), pyrrolinyl, pyrrolidinonyl, imidazolyl, imidazolidinyl, imidazolinyl, pyrazolyl, or pyrazolinyl), a six-membered nitrogen-containing heterocyclic ring (e.g., piperidinyl (piperidine ring), morpholinyl, thiomorpholinyl, or piperazinyl), a seven-membered nitrogen-containing heterocyclic ring, and the like. The term “substitution” means that one or more (e.g., one, two, three, or four) hydrogen atoms on a specified atom are replaced with a selection from the designated group, provided that the normal valency of the atom specified under the present circumstances is not exceeded and that the replacement results in a stable compound. A combination of substituents and / or variables is permissible only if the combination results in a stable compound. If a substituent is described as “optionally substituted with...”, the substituent may be (1) unsubstituted or (2) substituted. If a carbon of a substituent is described as being optionally substituted with one or more of a list of substituents, then one or more hydrogen atoms on the carbon (to the extent of any hydrogen atoms present) may be replaced individually and / or together with an independently selected optional substituent. If a nitrogen of a substituent is described as being optionally substituted with one or more of a list of substituents, then one or more hydrogen atoms on the nitrogen (to the extent of any hydrogen atoms present) may each be replaced with an independently selected optional substituent. If a substituent is described as being “independently selected from” one group, each substituent is selected independently of the other. Thus, each substituent may be identical to or different from another (other) substituent(s). As used herein, the term “one or more” refers to 1 or more than 1, such as 2, 3, 4, 5, or 10, under reasonable conditions. Unless otherwise indicated, as used herein, the point of attachment of a substituent may be from any suitable position of the substituent. When a bond of a substituent is shown to pass through a bond connecting two atoms in the ring, the substituent may be bonded to any one of the ring-forming atoms in the substitutable ring. The present disclosure also includes all pharmaceutically acceptable isotopically labeled compounds, which are identical to the compounds of the present disclosure, except that one or more atoms are replaced by an atom having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number predominant in nature. Examples of isotopes suitable for incorporation into the compounds of the present disclosure include, but are not limited to, isotopes of hydrogen (e.g., deuterium (D, 2H) and tritium (T, 3H)); isotopes of carbon (e.g., 11C, 13C, and 14C); isotopes of chlorine (e.g., 36Cl); isotopes of fluorine (e.g., 18F); isotopes of iodine (e.g., 123I and 125I); isotopes of nitrogen (e.g., 13N and 15N); isotopes of oxygen (e.g., 15O, 17O, and 18O); isotopes of phosphorus (e.g., 32P); and isotopes of sulfur (e.g., 35S). Certain isotopically-labeled compounds of the present disclosure (e.g., those into which a radioactive isotope is incorporated) can be used in drug and / or substrate tissue distribution studies (e.g., assays). The radioactive isotopes tritium (i.e., 3H) and carbon-14 (i.e., 14C) are particularly useful for this purpose because of their ease of incorporation and detection. Substitution with positron emitting isotopes (e.g., 11C, 18F, 15O, and 13N) can be used to examine substrate receptor occupancy in positron emission tomography (PET) studies. The isotopically labeled compounds of the present disclosure can be prepared by processes analogous to those described in the accompanying routes and / or in the examples and preparations by using an appropriate isotopically labeled reagent in place of the non-labeled reagent previously employed. The pharmaceutically acceptable solvates of the present disclosure include those in which the crystallization solvent may be isotopically substituted, e.g., D2O, acetone-d6, or DMSO-d6. The term “stereoisomer” refers to an isomer formed due to at least one asymmetric center. In compounds having one or more (e.g., one, two, three, or four) asymmetric centers, racemic mixtures, single enantiomers, mixtures of diastereomers, and individual diastereomers may be generated. Certain individual molecules may also present as geometric isomers (cis / trans). Similarly, the compound of the present disclosure may present as a mixture of two or more structurally different forms in rapid equilibrium (commonly referred to as tautomers). Representative examples of tautomers include ketoenol tautomers, phenol-keto tautomers, nitroso-oxime tautomers, imine-enamine tautomers, and the like. It should be understood that the scope of the present application encompasses all such isomers or mixtures thereof in any proportion (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%). A solid line (-----), a solid wedge (——), or a dashed wedge (...........) may be used herein to depict carbon-carbon bonds of the compounds of the present disclosure. Depiction of a bond bonded to an asymmetric carbon atom using a solid line is intended to indicate that all possible stereoisomers (e.g., specific enantiomers and racemic mixtures) at the carbon atom are included. Depiction of a bond bonded to an asymmetric carbon atom using a solid or dashed wedge is intended to indicate that the shown stereoisomer is present. When a bond is present in a racemic mixture, solid and dashed wedges are used to define relative stereochemistry, rather than absolute stereochemistry. Unless otherwise indicated, the compounds of the present disclosure are intended to be present in the forms of stereoisomers (including cis and trans isomers, optical isomers (e.g., R and S enantiomers), diastereomers, geometric isomers, rotamers, conformers, atropisomers, and mixtures thereof). The compounds of the present disclosure may exhibit one or more types of isomerism, and consist of mixtures thereof (e.g., racemic mixtures and diastereomeric pairs). Atropisomers refer to compounds that can be separated into rotationally restricted isomers. It should be understood that certain compounds of the present disclosure may be present in free form for use in therapy or, where appropriate, in the form of a pharmaceutically acceptable derivative thereof. In the present disclosure, the pharmaceutically acceptable derivatives include, but are not limited to, pharmaceutically acceptable salts, esters, solvates, metabolites, or prodrugs, which upon administration to a patient in need thereof are capable of providing, directly or indirectly, the compound of the present disclosure or a metabolite or residue thereof. Thus, when reference is made herein to “the compound of the present disclosure”, it is also intended to encompass the various derivative forms of the compound described above. The pharmaceutically acceptable salts of the compounds of the present disclosure include acid addition salts and base addition salts thereof. A review of suitable salts is found in Stahl and Wermuth, “Handbook of Pharmaceutical Salts: Properties, Selection, and Use” (Wiley-VCH, 2002). Methods for preparing the pharmaceutically acceptable salts of the compounds of the present disclosure are known to those skilled in the art. As used herein, the term “ester” refers to an ester derived from each formula compound in the present application, including physiologically hydrolyzable esters (which can be hydrolyzed under physiological conditions to release the compounds of the present disclosure in the form of free acids or alcohols). The compounds of the present disclosure per se may also be esters. The compounds of the present disclosure may be present in the form of solvates (preferably hydrates), and the compounds of the present disclosure contain a polar solvent as a structural element of the crystal lattice of the compound, particularly, for example, water, methanol, or ethanol. The amount of the polar solvent, particularly water, may be present in a stoichiometric or non-stoichiometric ratio. Also included within the scope of the present disclosure are metabolites of the compounds of the present disclosure, i.e., substances formed in vivo upon administration of the compounds of the present disclosure. Such products may result, for example, from oxidation, reduction, hydrolysis, amidation, deamidation, esterification, deesterification, enzymatic digestion, and the like of the administered compound. Thus, the present disclosure includes metabolites of the compounds of the present disclosure, including compounds prepared by the process of contacting the compounds of the present disclosure with a mammal for a time sufficient to produce metabolites thereof. Further included within the scope of the present disclosure are prodrugs of the compounds of the present disclosure, which are certain derivatives of the compounds of the present disclosure that may themselves have relatively weak or no pharmacological activity and, upon administration into or onto the body, are converted to the compounds of the present disclosure having the desired activity by, for example, hydrolysis. Generally, such prodrugs will be functional group derivatives of the compounds, which are readily converted into desired therapeutically active compounds in vivo. Additional information on the use of prodrugs can be found in “Pro-drugs as Novel Delivery Systems”, volume 14, ACS Symposium Series (T. Higuchi and V. Stella) and “Bioreversible Carriers in Drug Design”, Pergamon Press, 1987 (E. B. Roche Ed., American Pharmaceutical Association). The prodrugs of the present disclosure may be prepared by, for example, replacing appropriate functional groups present in the compounds of the present disclosure with certain moieties known to those skilled in the art as “pro-moieties”, for example, as described in “Design of Prodrugs”, H. Bundgaard (Elsevier, 1985). The present disclosure further encompasses the compounds of the present disclosure containing a protective group. In any process of preparing the compounds of the present disclosure, it may be necessary and / or desirable to protect sensitive or reactive groups on any of the molecules concerned, thereby forming a chemically protected form of the compounds of the present disclosure. This can be achieved by conventional protective groups, as described, for example, in Protective Groups in Organic Chemistry, ed. J.F.W. McOmie, Plenum Press, 1973; and T.W. Greene & P.G.M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 1991, which are incorporated herein by reference. The protective groups may be removed at an appropriate subsequent stage by methods known in the art. As used herein, the term “about” means within ± 10%, preferably within ± 5%, and more preferably within ± 2% of the stated numerical value. Compound In some embodiments, the present disclosure provides a compound, or a pharmaceutically acceptable salt, an ester, a stereoisomer, an atropisomer, a tautomer, a polymorph, a solvate, a metabolite, an isotopically labeled compound, or a prodrug thereof, wherein the compound has a structure of formula (I): (I) wherein: --- represents a single bond or a double bond, with the proviso that two double bonds are not directly connected; W1, W2, W3, and W4 are each independently C or N, with the proviso that C is attached to one double bond; preferably, at least one of W1 and W2 is N, and / or at least one of W3 and W4 is N; is selected from and R1, R3, R21, and R22, at each occurrence, are each independently selected from H, a deuterium atom, halogen, -OH, -NH2, -CN, -NO2, -SF5, =CH2, C1-6 alkyl, deuterated C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14membered heteroaryl, C6-12 aralkyl, -C(=O)Ra, -OC(=O)Ra, -C(=O)ORa, -ORa, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRaRb, -S(=O)(=NRa)Rb, -NRaRb, -C(=O)NRaRb, -NRa-C(=O)Rb, -NRa-C(=O)ORb, -NRa-S(=O)2-Rb, -NRa-C(=O)-NRaRb, -P(=O)RaRb, -C1-6 alkylene-Ra, -C1-6 alkylene-ORa, -C1-6 alkylene-NRaRb,   -O-C1-6   alkylene-NRaRb,   (-C3-6   cyclohydrocarbylene)-CN, and   (-C3-6 cyclohydrocarbylene)-C1-6 alkyl; when m is greater than 1, two R3 located at the same ring atom or adjacent ring atoms, together with the group to which they are attached, optionally form a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, or a 5- to 14-membered heteroaromatic ring; R4 is L2 is selected from -O-, -C(=O)-, -NRC(=O)-, -S-, -S(=O)-, -S(=O)2-, C1-6 alkylene, and -O-(C1-6 alkylene)-; R41 is selected from a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring; R, Ra, and Rb, at each occurrence, are each independently selected from H, C1-6 alkyl, C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and C6-12 aralkyl; ring B, ring X, and ring Z are each independently selected from a C3-6 hydrocarbon ring, a 3- to 10membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring; ring Y is absent or selected from a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring; when ring Y is absent, R22 is also absent; the alkylene, the alkyl, the alkenyl, the alkynyl, the cyclohydrocarbylene, the cyclohydrocarbyl, the hydrocarbon ring, the heterocyclyl, the heterocyclic ring, the aryl, the aromatic ring, the heteroaryl, the heteroaromatic ring, and the aralkyl described above, at each occurrence, are each optionally substituted with one or more substituents independently selected from the following: a deuterium atom, halogen, -OH, =O, -NH2, -CN, -NO2, =CH2, C1-6 alkyl, deuterated C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, -C(=O)Rc, -OC(=O)Rc, -C(=O)ORc, -ORc, -SRc, -S(=O)Rc, -S(=O)2Rc, -S(=O)2NRcRd, -NRcRd, -C(=O)NRcRd, -NRc-C(=O)Rd, -NRc-C(=O)ORd, -NRc-S(=O)2-Rd, -NRc-C(=O)-NRcRd, -C1-6 alkylene-ORc, -C1-6 alkylene-NRcRd, and -O-C1-6 alkylene-NRcRd; the alkylene, the alkyl, the alkenyl, =CH2, the alkynyl, the cyclohydrocarbyl, the heterocyclyl, the aryl, the heteroaryl, and the aralkyl are each further optionally substituted with one or more substituents independently selected from the following: halogen, -OH, =O, -C(=O)O-tert-butyl, -NH2, -CN, -NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, -C1-6 alkylene-C3-6 cyclohydrocarbyl, -O-C1-6 alkyl, and -C1-6 alkylene-O-C1-6 alkyl; Rc and Rd, at each occurrence, are each independently selected from: H, C1-6 alkyl, C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and C6-12 aralkyl, wherein the alkyl, the cyclohydrocarbyl, the heterocyclyl, the aryl, the heteroaryl, and the aralkyl are further optionally substituted with one or more substituents independently selected from the following: halogen, -OH, =O, -C(=O)O-tert-butyl, -NH2, -CN, -NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, and -C1-6 alkylene-O-C1-6 alkyl; and p, q, and m are each independently an integer selected from 1, 2, or 3. In a preferred embodiment, the present disclosure provides a compound, or a pharmaceutically acceptable salt, an ester, a stereoisomer, an atropisomer, a tautomer, a polymorph, a solvate, a 5 metabolite, an isotopically labeled compound, or a prodrug thereof, wherein the compound has structures of the following formulas: 0 0=^X--^(R3)m NH X ) (R22)q (II) O "nX / RX 1 ¥ <R3^ N^N^ o;^ NH ' \ X ) f y\XXr2I)p (R22)q (IV) 0 nXvr4 r1X 11 °\ A i y NH f y\JX(R2’)p (R22)q (VI) o N^Ny 3 oyy^~(R)m NH ' \ x ) f y\1Xr21)p (R22)q (III) 0 r1xni\r N^NAo 0X^r3)1„ NH 'X x ) f y\XXr2i)p (R22)q (V) 0 N^^yR4 NH pY XlfK2’), (R22)q (VII) 0 (R22)q (VIII)                                               (IX) (X)                                                (XI). In some embodiments, ring B is a C3-6 hydrocarbon ring or a 3- to 10-membered heterocyclic ring. In a preferred embodiment, ring B is a cyclopentene ring, a cyclohexene ring, a pyrrolidine ring, an oxazolidine ring, a piperidine ring, a morpholine ring, or an azepane ring. In some embodiments, R1, at each occurrence, is each independently selected from H, halogen, C1-6 5 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, -S(=O)2Ra, -ORa, and -NRaRb, and Ra and Rb, at each occurrence, are each independently selected from H, C1-6 alkyl, C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and C6-12 aralkyl; preferably, R1, at each occurrence, is each independently selected from 3-to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and -NRaRb, wherein the alkyl, 10 the cyclohydrocarbyl, the heterocyclyl, the aryl, and the heteroaryl are each optionally substituted with one or more substituents independently selected from the following: halogen, -S(=O)2Rc, C1-6 alkyl, C2-6 alkenyl, =CH2, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, and 5- to 14membered heteroaryl; the alkyl, the alkenyl, =CH2, the cyclohydrocarbyl, the heterocyclyl, the aryl, and the heteroaryl are each further optionally substituted with one or more substituents independently 15 selected from the following: halogen, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, and -C1-6 alkylene-C3-6 cyclohydrocarbyl. In some embodiments, R1, at each occurrence, is each independently selected from H, halogen, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, -ORa, and -NRaRb, and preferably, R1, at each occurrence, is each independently selected from 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and -NRaRb, wherein the alkyl, the cyclohydrocarbyl, the heterocyclyl, the aryl, and the heteroaryl are each optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, C2-6 alkenyl, =CH2, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, and 5- to 14-membered heteroaryl; the alkyl, the alkenyl, =CH2, the cyclohydrocarbyl, the heterocyclyl, the aryl, and the heteroaryl are each further optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, and -C1-6 alkylene-C3-6 cyclohydrocarbyl. In some embodiments, R1, at each occurrence, is each independently C6-10 aryl or -NRaRb. In some embodiments, R1, at each occurrence, is each independently -NRaRb. \ I —\ .     .                   nH ( nH \ nH In a preferred embodiment, R1 is H, methyl, halogen, methoxy, /    , \    ,--- /     ,         , 10 or In a preferred embodiment, R1 is H, methyl, halogen, methoxy, N preferably / , or more In a preferred embodiment, R1 is H, methyl, halogen, methoxy, preferably /     ,       , . In some embodiments, R1 is / 10 In some embodiments, ring X is a benzene ring, a 5- to 6-membered heterocyclic ring, or a 5- to 6membered heteroaromatic ring, and ring Y is absent. In some embodiments, ring X is a benzene ring, and ring Y is a C3-6 hydrocarbon ring, a benzene ring, a 5- to 6-membered heterocyclic ring, or a 5- to 6-membered heteroaromatic ring. In some embodiments,           is In some embodiments, R21 and R22, at each occurrence, are each independently selected from H, 5 halogen, -SF5, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, -O-(C1-6 alkyl), - S(=O)2-(C1-6 alkyl), -S(=O)2-(C3-6 cyclohydrocarbyl), -S(=O)(=NRa)Rb, -P(=O)(C1-6 alkyl)2, (-C3-6 cyclohydrocarbylene)-CN, and  (-C3-6  cyclohydrocarbylene)-C1-6  alkyl, and the alkyl, the cyclohydrocarbylene, the cyclohydrocarbyl, and the heterocyclyl are each optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, and C1-6 10 haloalkyl. In a preferred embodiment, R21 and R22, at each occurrence, are each independently selected from H, halogen, -SF5, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, and -O-(C1-6 alkyl), and the alkyl, the cyclohydrocarbyl, and the heterocyclyl are each optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, and C1-6 haloalkyl. / ^Y ' / r22\ 15   In some embodiments,     q F O~CI f'XT    F^r F F              F F , Q „           V Aci o (R )P                           ^F •     1 + j f        F p                F p is selected from:      r             ,    r             , --- C / f CZzBr F F              F F              F F ,,  ,, . ; • . / ' ,  ,  ,,,, 21 In some embodiments, R3 is H, C1-6 alkyl, -ORa, or -SRa; preferably, R3 is H or C1-6 alkyl. In a preferred embodiment, R3 is H, methyl, ethyl, -O-CH3, or -S-CH3; most preferably, R3 is H or methyl. In a preferred embodiment, when m is greater than 1, two R3 located at the same ring atom or adjacent 10 ring atoms, together with the group to which they are attached, optionally form a C3-6 hydrocarbon ring (preferably a cyclopropyl ring), and the hydrocarbon ring is optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, ring Z is a 3- to 10-membered heterocyclic ring or a benzene ring, preferably a 5- to 10-membered heterocyclic ring, and more preferably a 5- to 6-membered heterocyclic ring; and 15 the heterocyclic ring and the benzene ring, at each occurrence, are each optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, and C1-6 haloalkyl. 10 In some embodiments, ring Z is , , , In some embodiments, L2 is -C(=O)-, C1-6 alkylene, or -NRC(=O)-, wherein R is H or C1-6 alkyl. In some embodiments, L2 is -C(=O)- or -NRC(=O)-, wherein R is H or C1-6 alkyl. In a preferred embodiment, L2 is -C(=O)-, -CH2-, or -CD2-. in a preferred embodiment, L2 is -C(=O)-. In some embodiments, R41 is selected from a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring, and the heterocyclic ring, the aromatic ring, and the heteroaromatic ring are each optionally substituted with one or more substituents independently selected from the following: halogen, -OH, C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, preferably, the heterocyclic ring, the aromatic ring, and the heteroaromatic ring at least being substituted with -OH or -O-C1-6 alkyl. 15 O OH O OH OH O O OH O OH In some embodiments,  -L2-R41  is , OH , OH O OH O OH O OH OH In some embodiments,  -L2-R41 OH n n AH      0 OH OH D D OH         II I ,,   , 10 5 O OH In some embodiments, -L2-R41 O OH In some embodiments, R41 is a 5- to 6-membered heteroaromatic ring, preferably a 6-membered 10 heteroaromatic ring, and more preferably a pyridine ring or a pyrimidine ring, which is at least substituted with one -OH. O OH 0 OH In some embodiments, -L2-R41 is , or OH The present disclosure encompasses technical solutions / compounds resulting from any combination of the various embodiments. In a preferred embodiment, the present disclosure provides a compound, or a pharmaceutically acceptable salt, an ester, a stereoisomer, an atropisomer, a tautomer, a polymorph, a solvate, a metabolite, an isotopically labeled compound, or a prodrug thereof, wherein the compound is selected from: Compound No. Structure Compound No. Structure C1 0 OH n^n a / nAnA..... O^a’ NH ci k C2 ,,    0 OH 0 l^'N fA / 'N\Nj N^N \= /  N^n^X^. °k NH t / kd °Co F F C3 .    0 OH 0 .__. M A / hk J N.^N N^A^kl k      - X----' 0^’ NH J0Ai °v F F C4 .    o OH o N^N n^nA_ °A NH A / ~ci °Y° F F C5 ,,    0 OH O ,-N k,N ) N ,N <0^ 1 iT \=N  N^NA_- °A'~ NH C^-ci °A° F F C6 ,,    O OH o lkwN'N^N^ N^N °k NH k / / Cl °Co F F C7 .,    O OH tw / A N   N'>^ 0¾^ NH VA-ci °y,o F F C8 .,    0 OH ? A?W 1W.A 0=^ NH O-O °>ro F F C9 .,    0 OH o V^i'YYA A n^n ..... NH C^ci F>\ F F C10 .,    0 OH 9 YW N A.N^J N = N A n a^. °A NH Az Cl F'7\~y^ F F C11 .,    0 OH n^-n \= / 0= / NH O-ci F-A F F C12 ..    0 OH 9 YY^V ,--, N A ,N, J N.=N i iT \= / nAA.-' op NH Ka~ci VA F F C17 .,    0 OH A-1 «-> °Y NH YAci F F C18 .,    0 OH 0 1 N hY = v / °A'' NH CJ--CI VA F F C19 0 OH ? TyW N-N ^^6..... Oy'' NH AY01 F F C20 O OH 0 / A / An\N^ N^N \= / n-'Y^Y— °A NH YY~ci f-A F F C21 0 OH O ,--- M J' ,N ) N ,N 1 if A / N^nA^, ° A NH O-ci F'7\'^ F F C22 ,   0 OH 9 Y^Vv W'N |fNj N^ / n^nA^ °Y NH O-Cl fA\ F F C23 ,    0 OH Y-n w Fy^ N^n ANJ N^N F^ / nAnA_ 0¾^ NH V^a~ci Fy / ^ F F C24 ,   0 OH 9 Vy^v F^ AnYNY N^N °A NH Y / ci F F C25 ,, o OH 9 YY^V / xAn      N^N A nAnA, °A NH YY~ci F-Y"^ F F C26 O OH 0 yn^Y^y n^n n' o..... °Y NH Y / Ac| °Co F F C27 0 OH O AN YYa N^N Oy''' NH ^Xci °^° F F C28 O OH O p^N ,--, N A / N. ) N ^N fy y w N o °=^'' NH vy~ci °Co F F C29 ,,    0 OH oy NH 0-ci x° C30 ,,    0 OH o VfVr n"n 0=-'' NH C31 ,,    0 OH <y^y~N^ANA N^N \=N N^~n 0¾^ NH CYi °^,o F F C32 ,,    0 OH ? rAV o^^AA n-n °A NH AAd Y C33 .    0 OH ? Yy W / yA-yA N"N oy NH O-CI :v C34 ,,    0 OH 9 Yy W ,--, M A ^N, J N-^N / \    / / N Y °\ / nA J A °y NH Az ci x° C35 .,    O OH N ^N / N rXX- 0¾^ NH ci °v° F F C36 ,    0 OH o \K\V u>X N^N f \— / N'XX^- 0^'' NH ^Xci °Co F F C37 / ,    0 OH 9 X W V'nX N^ 0^" NH X~ci X F F C38 .,    O OH o .--, N A .N. ) N ..N A k N= / °a' NH Cl Oyo F F C39 .,    0 OH 9 x^v v / NX N^N XN n^n^X NH C40 .,    O OH ? AAV fVAN"N °A NH C^ci °Co F F Vr-ci °v F F C41 .,    0 OH 9 X^V \^n'nXn^ n^n / nXA< 0¾^ NH C42 .,    O OH 9 \^n'nXn^ n^n / N^NA^ °v NH XzZ Cl ¥ A / Cl °A° F F C43 ,,    0 OH N^N \=^N^NA_ 0=0 NH 0 °yO F F C44 ,,    0 OH 9 N^N 0=A NH O-F °Co F F C45 ,,    0 OH 9 O / nVJ N^N \= / hANA_- 0=0 NH O-yl F F C46 ,,    0 OH 9 / --. N A,^N, J N.^N A jf \=N  N^n^V_- °y NH 0 v° F F C47 ,,    0 OH 9 .--, N A ,N. J N ^N \=N   N^''' / '-.,, 0=0 NH C^F °v F F C48 ,,    0 OH 9 (^N'n\nJ N^N \=N N^NA\__ 0=a' NH °yO F F C49 ,,    0 OH \ n.n^n^ n^n / n^nA_ 0=0 NH C50 .    0 OH o v w 0^''' NH C51 ,,    O OH 0^N n^n Oy' NH O" °Co F F C52 ,,    0 OH o Vn-W ony-V N"N N^'N^y, 0=a' NH °\^° F F C53 ,,    0 OH 9 O / nVJ N^N Vn nA07 Oy NH O-xl F F C54 ,,    0 OH 9 n^n \=N N^NA^ °=y NH °3) F F C55 ,,    O OH 9 W'n^n^ N^N oy-' NH o- C56 .    0 OH 9 v^-W Fy^N N-N^y^ N-^N nAnCK °0 NH °yO F F C57 ,,    O OH 9 o^nX>V^ N^N 0^' NH v F F C58 ,,    0 OH o y-AV N-"N ^tx oy NH °v F F C59 ,,    0 OH \ N^N / N^nA^ °A NH o- C60 ,,    O OH ya^v FyAAA'NV^ N^N F^' N^nA^ O^A NH C61 ,    0 OH ? Ya"Vv AnY^A n^n Ov^N AaX^ Oyy NH v F F C62 ,,    0 OH o Vn-W N"N N^yy\ °A NH °>A F F C63 ,,    0 OH 9 yy yN^ANA N^-N O=A NH A °yO F F C64 ,,    0 OH 9 fA7'N\N^ N^N nA AAA^ 0=a' NH °Ao F F C65 ,    o OH 9 YaVv f^nA'n;Vn^ n^n f^N n^nA_ O^A NH ^Xci °Ao F F C66 ,,    O OH 9 N X,N. > N.^N F^ / X / / ~N V fK^a a 1 H v N-^N^y^ °A NH AA-o A° F F C67 .,    O OH 0 r"'N 'n / »a N^N / NWyl O^''' NH iXci F F C68 .,    0 OH 9 v?Vy wn'W n^n /  N^N^y / °x NH CY^c| F^X'^ F F C69 .    O OH 0 N ]fV : --:- / "' NH VY"CI F F C70 .    0 OH YPn-Z t n^n / vZ nXY< °z NH ViZ Cl F-~Z F F C71 .    0 OH 9 AW WfYJ N"N F   NAN\^ O^''’ NH K^"ci F'7\'^ F F C72 .,    0 OH o Y-N W ZC-lX N^N F    N^nA^ °z NH Az Cl F-Z F F C73 .,    0 OH A4N'n\nJ n^n O^W' NH JX / Cl FyZ F F C74 ,,    0 OH □ AW wXX N"N °z NH K^z Cl F'7\~y^ F F C75 .,    0 OH N^N NH K^z ci VA F F C76 .,    0 OH o VyW z"iN"N °z NH k / Cl f^Y^^ F F C77 O OH o TVjZ N"N w Z-Ny oy NH O-ci F F C78 ,,    0 OH o y-W N"N vV °z NH Z / C| Fy^ F F C79 ,,    O OH o zy^Sr^r yy zn^z n-z ” n^n^ °y NH u-a f / \ F F C80 .,    0 OH o [Z^ykY 0^N y'N^N^ N^N °v^N N^Jy °z NH Kz~~ci F~Z~~^ F F C81 .,    O OH o ry^kyy Zy y N^yN^ N^N 'N^N / \ °y NH yyCi F~Z F F C82 .,    0 OH 9 >A^v ,—N Z, ,N,J N,^N 1 k \=N   N'J~^ °z NH Zjk~ci Fz / F F C83 .,    0 OH O y^N^YZ^ N^N 0= / NH X / PCI F F C84 ..    O OH ? Vy \ hYY N^N z YA °Y NH ^yci °Co F F C85 .,    0 OH O / nVJ N^N 0^' NH HHci Y 4 C86 .,    0 OH ? r / W ryziY^ N^N °Y NH Y / c| °\=° 4 C87 0 OH 0 nuA^ n^n \= / N^N^y-0= / NH HHcI F F C88 .,    0 OH 0 i^N^iiV N^N / / N / r 0= / NH F^y^^ F F C89 .,    O OH 9 Yp^V Y4\            N^N n^n^Y, 0=y NH Y / ci H-O 4 C90 0 OH ? r / W ,--.   N A ^N. J N,=N Ph । n n^nA^ 0= / NH Hz Cl °Co f5 C91 0 OH 9 rAV N^N \= / nA'A oP NH Y P F F C93 ,,    0 OH 9 Py^V PpN'N lfN^ N^N \=N    N"""^n Op NH ^Xci Po F F C95 ,,    O OH 9 pt^V 'npn       n^n / nPnP- °A NH o- A C97 ,,    0 OH 9 p^^V N / / , N, / N ,N pNp 7l P N^''r / '.^ °P NH CT P F F C92 0 OH o PyW m-P n^~ \=P^n^nA^ °P NH °v° p C94 ,,    O OH 9 PW fy / pp N^N \=N  N^n^P-. °A NH P / Cl °Co F F C96 ,,    0 OH 9 YA^V \P'N^N^ N^N ' nPnA..... °p NH °P° F F C98 ,,    O OH 9 ■My ...... °p NH O- °r C99 ,,    0 OH ,--V   N A ,N J N..N (AH \= / nAA- O^ NH 3 °yO F F C100 ,,    0 OH Y-„Vv ^yy-NAy-J N-^N ..... 0=A~' NH °v F F C101 .    0 OH ? nW ,__, N A N^ J N^N fATI \=N  N^nW^- o=a NH % C102 ,,    0 OH 9 / --. N A..N. J N .N \=N         ..... Oy''' NH °A F F C103 ,,    0 OH 0 z^zN-Nn^ n->n —n nA (—\ 1 0 v_ / \= / N^n-K^ NH :9^ C104 .,    0 OH 9 WWr n-nA,n^J n^n Q Tl           J I n^n / \^ °n NH Cn °yO F F C105 .,    0 OH 0 fA'iiA^ rwAH n^n < )    ^=7 n^n-A, NH F C106 ,,    O OH 9 / --K   N          J N^.N Aw 7 iT \=wan / < °a NH A fa \=j f F C107 ,,    0 OH ? Yf N^N \= / AyA, 0= / NH O= F'z F F C108 ,,    O OH O ,--, N A ,N, J N .N cfyff y< —( \i 0= / NH 0OO F a \A F F C109 .    0 OH o X--- / O^Z NH F-y F F C110 ,,    0 OH ? Yf ,--\ N / / ,N^ J N , N AA / / n'n T \= / N" 0= / NH ^ / ¾ F F S C111 .    0 OH 9 V^W / =.3            / n ;>n / f NH C^CI F-f^^ F F C112 .,    0 OH 0 r^N>ifi / / —\   / -N ,A^N^ J N^N _NvN / yy vv \= / n^nA. o / ^ NH of C113 ,     0 OH 0 N^N / —N    N—C   2—(( I |l '        N=%A. NH C114 .,    0 OH 0 \ N^N N N—C ')—(z 1    1 z     \= / / / v, NH of C115 ,,    0 OH AA              N.i>N \= / SYN Y, 0= / NH °Y F F C116 =,, ? / t y-zv>° 0° C0° C117 ,,    0 OH 9 Y^^V CY A 1 N'^N^y- 0= / NH °Y F F C118 ,,    0 OH 9 YY^V / / _ / zN~N    Y n> °\ A A N^N^y- °Y NH 0 F F C119 ,,    0 OH ? AW oaA iH 0.:= NH / C120 V= ? °V / ° Ho / rz\Y Ya 0° C0° C121 ,,          OH 9 aa aYnA n > \= / YN -Y^. 0= / NH o-°Yo F F C122 ? H y ---. N A ,N. J N, A Ha । Y H / \AnA_ 0= / NH 0" 0 F F C123 ,, o S\    II H 0 | N lfN>— \= / oA NH °Co F F C124 ,,      0 0 A j[ .r ^N'n\N^ N=V X= / N^n^x, dA NH O x° C125 ,,         OH 0 i^N AiA ^n-nO^ \= / n AN / k oA NH AAci F-A F F C126 ,,          OH 0 1 nAj 0 ,--. n A ,N / J N. / N 4 / An \= / N^Ny_, °A NH Ca °A° F F C127 ,,    0 OH y-N w 0 ,__. N A „N^ J N^N _AVn - O O / N^NA_ OcA NH :? C128 / ,    O OH o An W \ AaaVJ n"n /           N A^- OcA NH :v C129 ,    0 OH 0 0 , ,   N A ^N^ ) N^N A OX A 6 x= / n^nO_ oA NH F C130 / ,    0 OH o An'VX / 0  ,--.    N / ,-N J N, / N _Ay / n \= /   n'^ n- °A NH AAci FA^ F F C131 .,    0 OH 0 l^N TiA >- / -s N AaJ / \              / / N t — N N—C \J |l \= / / / A" A NH K^"01 F'7\ F F C132 ,,    0 OH s ' / A CHIT 0= / NH °yO F F C133 .    0 OH o ^n^A.nA nAM \= / n^"-nA- 0= / NH F C134 ,,    0 OH o rF^\Fr°> N A,"X -JU \ / N N^X—- 0= / NH ° / T0 F F C135 .    0 OH 0 Y"n^y\a nHzN'N\Nj °A NH F C136 ,,    O OH 0 Y^N^^N'N ,-V N        J N^AA <^>a 7 iT \= /  N  N^k^- 0= / NH V° F F C137 ,,    0 OH o r ^ASa N^° OA NH F C138 ,,    O OH o yF^a^ ,= a / nA \= / \|  N^k^- °= / NH O- °F F F C139 X' ? OH o y^n^yV yA / 1' N 'A' N A N'° \= / VAA^, 0=A NH cl °Co F F C140 <k 1A & A ’ >? NH °A° F F C141 / ,   9 OH o AfAA n^A^n^ An rvA j t n. a x= / n^A NH y F F C142 ,,     0 OH o v^’i^SrS^ AAnWNA n^n AA^nAnA^. 0= / NH °A° F F C143 ,,    0 OH 9 _y^ / N^ N^N \=^nAnA_, on NH Q x° F F C144 ,,    O OH 9 r^'i^Sr^n \ N^N / N^'NA„ °n NH °A° F F C145 ,    0 OH 9 nW __,  M A    J N^N /       / 7 N  V 0 A u 1 0= / NH A / °A° F F C146 ,,     0 OH □ AAA / aaAa n^n N^N^y^ °n NH °A° F F Pharmaceutical Composition and Treatment Method In some embodiments, the present disclosure provides a pharmaceutical composition comprising a prophylactically or therapeutically effective amount of the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof of the present disclosure, and one or more pharmaceutically acceptable carriers. The pharmaceutical composition is preferably a solid formulation, a semisolid formulation, a liquid formulation, or a gaseous formulation. In some embodiments, the pharmaceutical composition may further comprise one or more additional therapeutic agents. In some embodiments, the present disclosure provides use of the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof of the present disclosure, or of the pharmaceutical composition of the present disclosure in preparing a medicament as a WRN inhibitor. In some embodiments, the present disclosure provides the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof of the present disclosure, or the pharmaceutical composition of the present disclosure, for use as a WRN inhibitor. In some embodiments, the present disclosure provides a method for preventing or treating a cancer (preferably a cancer characterized by microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR)), comprising administering to a subject in need thereof an effective amount of the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof of the present disclosure, or the pharmaceutical composition of the present disclosure. In some embodiments, the cancer comprises colorectal cancer, gastric cancer, endometrial cancer, uterine cancer, adrenocortical carcinoma, cervical cancer, esophageal cancer, breast cancer, renal cancer, prostate cancer, and ovarian cancer. The term “pharmaceutically acceptable carrier” in the present disclosure refers to a diluent, an adjuvant, an excipient, or a vehicle administered together with a therapeutic agent, which is suitable, within the scope of sound medical judgment, for contact with the tissues of humans and / or other animals without undue toxicity, irritation, allergic response, or other problems or complications relative to a reasonable benefit / risk ratio. Unless otherwise stated, the term “treat”, “treating”, or “treatment” as used herein refers to reversing, alleviating, or inhibiting the progression of a disorder or condition to which such term applies or one or more symptoms of such a disorder or condition, or preventing such a disorder or condition or one or more symptoms of such a disorder or condition. As used herein, an “individual” includes a human or a non-human animal. Exemplary human individuals include human individuals suffering from a disease (e.g., a disease described herein), which are referred to as patients, or normal individuals. In the present disclosure, “non-human animals” include all vertebrates, e.g., non-mammals (e.g., birds, amphibians, and reptiles) and mammals, e.g., non-human primates, livestock, and / or domesticated animals (e.g., sheep, dogs, cats, cows, and pigs). In another type of embodiment, the pharmaceutical composition of the present disclosure may further comprise one or more additional therapeutic or prophylactic agents. The general synthetic route is as follows: Route I o Substitution reaction or coupling reaction Route II NH NH2 NH NH2 0 OH R1H R1H Alkylation reaction Oxidation reaction or R1B(OH)2 Cyclization reaction * Substitution reaction or coupling reaction Cyclization reaction or R1B(OH)2 * Substitution reaction or coupling reaction reaction Oxidation reaction OH R1H Substitution reaction or coupling reaction (R22) (R3)m - - Condensation reaction (R22) or R1B(OH)2 (R3)m Condensation reaction Halogenation reaction Substitution reaction or coupling reaction where in route I and route II, PG is a protecting group, m is 1 or 2, and the other groups are as defined herein. Examples The present disclosure is further described below with reference to examples, but these provided examples are not intended to limit the scope of the present disclosure. The abbreviations in the present disclosure have the following meanings: Abbreviation Full version ACN Acetonitrile AgBF4 Silver tetrafluoroborate Boc tert-Butyloxycarbonyl CMPI 2-Chloro-1 -methylpyridinium iodide DCE 1,2-Dichloroethane DCM Dichloromethane DIAD Diisopropyl azodicarboxylate DIEA / DIPEA N,N-diisopropylethylamine Diox / dioxane 1,4-Dioxane DMF N,N-dimethylformamide DMSO Dimethyl sulfoxide DPPA Diphenylphosphoryl azide EDCI 1 -Ethyl-(3 -dimethylaminopropyl)carbodiimide Et Ethyl Et3N / NEt3 Triethylamine EtOAc / EA Ethyl acetate EtOH Ethanol FA Formic acid h / hrs Hour HCl Hydrochloric acid Hex Hexane HOAt N-hydroxy-7-azabenzotriazole HOBT 1 -Hydroxybenzotriazole HPLC High-performance liquid chromatography K2CO3 Potassium carbonate LCMS Liquid chromatography-mass spectrometry LDA Lithium diisopropylamide MeOH Methanol min Minute NaOH Sodium hydroxide NBS N -bromosuccinimide NCS N-chlorosuccinimide n-BuLi n-Butyllithium O.N Overnight PE Petroleum ether p-TsOH p-Toluenesulfonic acid Pd(dppf)Cl2 [1,1 '-bis(diphenylphosphino)ferrocene]palladium(II) dichloride t-BuOH tert-Butanol TEA Triethylamine TEMPO 2,2,6,6-Tetramethylpiperidin-1 -oxyl TFA Trifluoroacetic acid THF Tetrahydrofuran TLC Thin-layer chromatography r.t. / rt Room temperature Example 1: (C87-P1-A, C87-P1-B, C87-P2-A, and C87-P2-B) C87-10 C87-P1-A + C87-P1-B C87-P2-A + C87-P2-B 1) Synthesis of intermediate C87-2: 5 Compound C87-1 (18.46 g, 128.2 mmol) was added to tetrahydrofuran (600 mL), and the mixture was cooled to 0 °C. Sodium hydride (5.12 g, 128.2 mmol) was slowly added, and the mixture was purged with nitrogen three times and stirred at 0 °C for 0.5 h. An n-butyllithium solution (80 mL, 128.2 mmol) was then slowly added dropwise, and the mixture was stirred at 0 °C for 0.5 h under nitrogen atmosphere. Subsequently, ethyl propionylacetate (25 g, 128.2 mmol) was added to the reaction liquid, 10 and the mixture was stirred at 0 °C for 0.5 h, then slowly warmed to room temperature, and allowed to react overnight. After the starting materials were substantially consumed completely as detected by TLC, the reaction liquid was quenched with a saturated ammonium chloride solution and extracted with ethyl acetate. The organic phase was washed with saturated brine, then dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (PE / EA = 90 / 10) to obtain C87-2 (11.96 g, yield: 36.2%) as a yellow oil. 1H NMR (400 MHz, CDCI3): 5 4.21-4.10 (m, 2H), 4.05-3.98 (m, 2H), 3.77 (s, 2H), 3.713.65 (m, 1H), 2.83-2.76 (m, 1H), 1.94-1.85 (m, 1H), 1.60-1.51 (m, 1H), 1.35 (s, 3H), 1.28 (m, 3H), 1.23 (t, J=9.6 Hz, 3H), 1.11 (d, J=9.6 Hz, 3H). 2) Synthesis of intermediate C87-4: Compounds C87-2 (11.96 g, 46.3 mmol), C87-3 (7.4 g, 46.3 mmol), and anhydrous p-toluenesulfonic acid (0.80 g, 4.63 mmol) were added to n-butanol (15 mL), and the reaction liquid was stirred at 140 °C for 16 h under nitrogen atmosphere. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was cooled and then concentrated under reduced pressure. The residue was purified by column chromatography (DCM / MeOH = 85 / 15) to obtain C87-4 (10.1 g, yield: 69.6%) as a white solid. LCMS (ESI) m / z: 315.0 [M+H]+. 3) Synthesis of intermediate C87-5: Compound C87-4 (10.1 g, 32.1 mmol) and triphenylphosphine (12.6 g, 48.2 mmol) were added to tetrahydrofuran (300 mL), and the mixture was cooled to 0 °C. DIAD (9.57 g, 48.2 mmol) was then slowly added dropwise, and the mixture was slowly warmed to room temperature under nitrogen atmosphere and stirred overnight. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was cooled and then concentrated under reduced pressure, and the residue was purified by column chromatography (DCM / MeOH = 85 / 15) to obtain C87-5 (7.46 g, yield: 78.3%) as a white solid. 1H NMR (400 MHz, DMSO-d6): 5 8.14-8.12 (m, 2H), 7.55-7.52 (m, 3H), 5.955.95 (m, 1H), 5.03-5.98 (m, 1H), 4.76-4.74 (m, 1H), 4.49-4.10 (m, 1H), 3.72-3.67 (m, 1H), 3.54-3.36 (m, 1H), 2.62-2.45 (m, 1H), 2.11-1.90 (m, 1H), 1.39-1.31 (m, 3H). 4) Synthesis of intermediate C87-6: TEMPO (0.83 g, 5.3 mmol) was added to an aqueous solution of NaH2PO4 (200 mL, 133.1 mmol, 0.67 M), a suspension of compound C87-5 (7.88 g, 26.6 mmol) in acetonitrile (50 mL) was then added, and finally an aqueous solution (40 mL) of NaClO2 (4.79 g, 53.2 mmol) and NaClO solution (0.8 mL) was added. The mixture was purged with nitrogen three times, then warmed to 50 °C, and stirred overnight under nitrogen atmosphere. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was cooled to room temperature and purified by reversed-phase column chromatography (H2O / ACN = 85 / 15) to obtain C87-6 (5.0 g, yield: 61.1%) as a white solid. 1H NMR (400 MHz, DMSO-d6): 5 8.15-8.12 (m, 2H), 7.58-7.53 (m, 3H), 7.31-7.05 (m, 2H), 5.97 (s, 1H), 4.844.80 (m, 1H), 2.83-2.73 (m, 1H), 2.02-1.97 (m, 1H), 1.34 (d, J=9.6 Hz, 3H). 5) Synthesis of intermediate C87-8: Compound C87-6 (500 mg, 1.61 mmol) and two drops of DMF were added to DCE (15 mL), and POCl3 (500 mg, 3.22 mmol) was slowly added dropwise. The mixture was purged with nitrogen three times, warmed to 80 °C, and stirred for 1 h under nitrogen atmosphere. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was cooled to room temperature, and a solution of compound C87-7 (1.58 g, 8.06 mmol) in pyridine (2 mL) was slowly added. The mixture was warmed to 80 °C and stirred for another 1 h under nitrogen atmosphere. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was cooled to room temperature, washed with a saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate. The organic phase was washed with saturated brine, then dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (PE / EA = 50 / 50) to obtain C87-8 (340 mg, yield: 43.3%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): 5 10.60 (s, 1H), 8.23-8.10 (m, 2H), 8.04-8.02 (m, 2H), 7.77-7.75 (m, 1H), 7.617.54 (m, 4H), 5.70 (d, J=10.8 Hz, 1H), 3.56-3.45 (m, 1H), 2.78-2.71 (m, 1H), 2.48-2.41 (m, 1H), 1.41 (d, J=9.2 Hz, 3H). 6) Synthesis of intermediate C87-9: Compound C87-8 (340 mg, 0.70 mmol) was added to chloroform (15 mL), and NBS (248 mg, 1.39 mmol) was slowly added at room temperature. The reaction liquid was purged with nitrogen three times, heated to 50 °C, and stirred overnight under nitrogen atmosphere. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was cooled to room temperature and concentrated under reduced pressure. The residue was purified by column chromatography (PE / EA = 65 / 35) to obtain C87-9 (360 mg, yield: 74.7%) as a yellow solid. LCMS (ESI) m / z: 566.0 [M+H]+. 7) Synthesis of intermediate C87-10: Compound C87-9 (218 mg, 0.38 mmol), piperazine (664 mg, 7.7 mmol), and AgBF4 (150 mg, 0.77 mmol) were added to DMSO (5 mL), and the reaction liquid was purged with nitrogen three times, heated to 120 °C, and stirred for 2 h under nitrogen atmosphere. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was cooled to room temperature, washed with water, and extracted with ethyl acetate. The organic phase was washed with saturated brine, then dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (DCM / MeOH = 85 / 15, 0.5% NH3.H2O) to obtain C87-10 (123 mg, yield: 55.9%) as a yellow solid. LCMS (ESI) m / z: 572.2 [M+H]+. 8) Synthesis of C87-P1 and C87-P2: Compound C87-11 (24 mg, 0.15 mmol) was added to DMF (2 mL), and HOBT (17 mg, 0.12 mmol) and EDCI (32 mg, 0.16 mmol) were added at room temperature. The mixture was stirred at room temperature for 2 h under nitrogen atmosphere. Subsequently, compound C87-10 (63 mg, 0.11 mmol) and DIEA (43 mg, 0.32 mmol) were added, and the mixture was purged with nitrogen three times and stirred at room temperature for 2 h under nitrogen atmosphere. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was concentrated under reduced pressure. The residue was purified by preparative high-performance liquid chromatography (RP-PREP-3 SunFire C18 5 mm 19 x 150 mm 18 min-55-65B, A: H2O (0.2% FA), B: ACN, UV: 214 nm, flow rate: 15 mL / min) to obtain C87-P1 (8.0 mg, yield: 10.2%, retention time: 10.79 min) and C87-P2 (10.2 mg, yield: 13.0%, retention time: 11.59 min). C87-P1 1H NMR (400 MHz, DMSO-d6): 5 10.56 (s, 1 H), 8.55 (s, 1 H), 8.08-8.06 (m, 2 H), 7.98-7.96 (m, 2 H), 7.74-7.72 (m, 1 H), 7.51-7.50 (m, 3 H), 5.71-5.67 (m, 1 H), 3.78-3.73 (m, 1 H), 3.38-3.10 (m, 9 H), 2.65-2.62 (m, 1 H), 2.44-2.41 (m, 4 H), 1.52 (d, J=7.2 Hz, 3 H). LCMS (ESI) m / z: 707.9 [M+H]+. C87-P2 1H NMR (400 MHz, DMSO-d6): 5 10.56 (s, 1 H), 8.55 (s, 1 H), 8.10-8.07 (m, 2 H), 7.98-7.94 (m, 2 H), 7.75-7.73 (m, 1 H), 7.52-7.50 (m, 3 H), 5.62-5.59 (m, 1 H), 3.77-3.73 (m, 1 H), 3.34-3.10 (m, 9 H), 3.07-2.99 (m, 1 H), 2.44 (s, 3 H), 2.15 (d, J=13.6 Hz, 1 H), 1.44 (d, J=7.2 Hz, 3 H). LCMS (ESI) m / z: 707.9 [M+H]+. 9) Synthesis of C87-P1-A, C87-P1-B, C87-P2-A, and C87-P2-B: Compound C87-P1 (8.0 mg) was subjected to chiral resolution (IBN, ACN:IPA:TFA = 90:10:0.3, 25 mL / min, 254 nm) to obtain C87-P1-A (2.8 mg, yield: 35.0%, retention time: 6.98 min) and C87-P1-B (2.6 mg, yield: 32.5%, retention time: 12.46 min). C87-P1-A 1H NMR (400 MHz, CD3OD): 5 8.75 (s, 1 H), 8.15 (s, 2 H), 8.08 (d, J=7.6 Hz, 1 H), 7.82 (s, 1 H), 7.60 (d, J=7.2 Hz, 1 H), 7.46 (s, 3 H), 5.70 (s, 1 H), 3.87 (s, 1 H), 3.87-3.31 (m, 4 H), 2.78 (s, 1 H), 2.78-2.61 (m, 3 H), 2.52 (s, 1 H), 1.99-1.65 (m, 4 H), 1.28 (s, 3 H). LCMS (ESI) m / z: 707.4 [M+H]+. C87-P1-B 1H NMR (400 MHz, CD3OD): 5 8.74 (s, 1 H), 8.14 (d, J=7.2 Hz, 2 H), 8.08 (d, J=8.4 Hz, 1 H), 7.82 (s, 1 H), 7.60 (d, J=8.0 Hz, 1 H), 7.46-7.44 (m, 3 H), 5.71-5.69 (m, 1 H), 3.86 (s, 1 H), 3.853.31 (m, 4 H), 2.77 (s, 1 H), 2.76-2.60 (m, 3 H), 2.52 (s, 1 H), 1.99-1.65 (m, 4 H), 1.29 (d, J=8.4 Hz, 3 H). LCMS (ESI) m / z: 707.4 [M+H]+. Compound C87-P2 (10.2 mg) was subjected to chiral resolution (IBN, ACN:IPA:TFA = 70:30:0.3, 25 mL / min, 254 nm) to obtain C87-P2-A (3.4 mg, yield: 33.3%, retention time: 6.02 min) and C87-P2-B (3.2 mg, yield: 31.3%, retention time: 12.52 min). C87-P2-A 1H NMR (400 MHz, CD3OD): 5 8.57 (s, 1 H), 8.17-8.16 (m, 2 H), 8.08 (d, J=8.4 Hz, 1 H), 7.82 (s, 1 H), 7.62 (d, J=8.4 Hz, 1 H), 7.47-7.46 (m, 3 H), 5.63 (d, J=8.8 Hz, 1 H), 3.87-3.84 (m, 1 H), 3.51-3.30 (m, 8 H), 3.13-3.08 (m, 1 H), 2.52 (s, 3 H), 2.32 (d, J=13.6 Hz, 1 H), 1.55 (d, J=7.2 Hz, 3 H). LCMS (ESI) m / z: 707.5 [M+H]+. C87-P2-B 1H NMR (400 MHz, CD3OD): 5 8.40 (s, 1 H), 8.08-8.06 (m, 2 H), 7.98 (d, J=8.4 Hz, 1 H), 7.73-7.72 (m, 1 H), 7.54-7.52 (m, 1 H), 7.37-7.35 (m, 3 H), 5.55-5.51 (m, 1 H), 3.78-3.74 (m, 1 H), 3.38-3.20 (m, 8 H), 3.06-2.98 (m, 1 H), 2.41 (s, 3 H), 2.24-2.20 (m, 1 H), 1.46 (d, J=7.6 Hz, 3 H). LCMS (ESI) m / z: 707.5 [M+H]+. Example 2: (C88-P1, C88-P2, and C88-P3) 1) Synthesis of intermediate C88-2: Compound C87-9 (35 mg, 0.062 mmol), compound C88-1 (104.07 mg, 0.93 mmol), and silver tetrafluoroborate (24.18 mg, 0.124 mmol) were added to dimethyl sulfoxide (4 mL), and the reaction liquid was heated to 120 °C and allowed to react for 2 h. After the starting materials were consumed completely as detected by LC-MS, an aqueous solution was added dropwise to quench the reaction, and the resulting mixture was extracted with ethyl acetate. The organic phase was then washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (DCM / MeOH = 10 / 1) to obtain compound C88-2 (15 mg, yield: 40%) as an off-white solid. LCMS (ESI) m / z = 598.1 [M+H]+. 2) Synthesis of C88-P1, C88-P2, and C88-P3: Compound C87-11 (8.78 mg, 0.06 mmol) was added to DMF (2 mL), and HOBT (5.94 mg, 0.044 mmol) and EDCI (11.52 mg, 0.06 mmol) were added at room temperature. The mixture was stirred at room temperature for 2 h under nitrogen atmosphere. Subsequently, compound C88-2 (25 mg, 0.04 mmol) and DIEA (15.48 mg, 0.12 mmol) were added to the reaction liquid, and the reaction liquid was stirred at room temperature for another 2 h. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was concentrated under reduced pressure. The residue was purified by preparative high-performance liquid chromatography (Waters-PREP-8 SunFire C18 5 Lim 19 x 150 mm 18 min-60-75B, A: H2O (0.2% FA), B: ACN, UV: 214 nm, flow rate: 15 mL / min) to obtain C88-P1 (1.3 mg, yield: 4.2%, retention time: 9.57 min), C88-P2 (3.0 mg, yield: 9.8%, retention time: 10.65 min), and C88-P3 (4.2 mg, yield: 13.7%, retention time: 11.27 min). C88-P1 and C88-P2 were both single-configuration compounds, and C88-P3 was a mixture of two diastereomers. C88-P1 (the configuration was confirmed based on crystal structure: C88-P1 is compound C10): LCMS (ESI) m / z= 734.2 [M+H]+. 1H NMR (400 MHz, CD3OD): 8 8.51 (s, 1H), 8.17-8.14 (m, 2H), 8.10 (d, J=8.4 Hz, 1H), 7.83 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.47-7.45 (m, 3H), 5.69-5.66 (m, 1H), 4.58-4.56 (m, 1H), 3.86-3.51 (m, 6H), 2.79-2.76 (m, 1H), 2.50 (s, 3H), 2.18-2.17 (m, 1 H), 1.62-1.59 (m, 7 H). C88-P2: LCMS (ESI) m / z = 734.2 [M+H]+. 1H NMR (400 MHz, CD3OD): 8 8.49 (s, 1H), 8.17-8.15 (m, 2H), 8.06 (d, J=8.8 Hz, 1H), 7.82 (s, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.47-7.43 (m, 3H), 5.59-5.56 (m, 1H), 4.74-4.60 (m, 1H), 3.96-3.59 (m, 6H), 3.13-3.05 (m, 1H), 2.49 (s, 3H), 2.34-2.30 (m, 1 H), 2.212.17 (m, 1 H), 1.56-1.53 (m, 6 H). C88-P3: LCMS (ESI) m / z=734.1 [M+H]+. 1H NMR (400 MHz, CD3OD): 8 8.53 (s, 1H), 8.18-8.14 (m, 2H), 8.10-8.07 (m, 1H), 7.82 (s, 1H), 7.64-7.59 (m, 1H), 7.47-7.44 (m, 3H), 4.76-4.60 (m, 1H), 5.70- 5.60 (m, 1H), 3.87-3.52 (m, 6H), 3.23-3.10 (m, 0.5H), 2.78-2.67 (m, 0.5H), 2.47 (s, 3H), 2.28-2.20 (m, 1H), 1.71-1.59 (m, 7H). Example 3: (C89-P1, C89-P2, and C89-P3) 1) n-BuLi 2) C2CI6 THF DPPA, DIEA t-BuOH, 80°C C89-3                     C89-4 C89-1                            C89-2 1) Synthesis of intermediate C89-2: C89-1 (9.0 g, 44.53 mmol) and anhydrous tetrahydrofuran (225 mL) were sequentially added to a 1000 mL three-necked flask, and the mixture was stirred at -70 °C to -75 °C under nitrogen atmosphere. A solution of n-butyllithium in n-hexane (2.5 mol / L, 48 mL, 120 mmol) was slowly added, and the mixture was stirred at -70 °C to -75 °C for 20 min, then slowly warmed to -5 °C to 0 °C, stirred at -5 °C to 0 °C for 70 min, and cooled to -70 °C to -75 °C. Hexachloroethane (31.6 g, 133.6 mmol) was then added at -70 °C to -75 °C, and the mixture was stirred at -70 °C to -75 °C for 40 min, then slowly warmed to room temperature, and stirred for another 40 min. The reaction was quenched with a 10% w / w aqueous citric acid solution, and the resulting mixture was extracted twice with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and subjected to column chromatography to obtain C89-2 (3.5 g, 33%). 2) Synthesis of intermediate C89-3: To a solution of C89-2 (3 g, 12.68 mmol) in anhydrous tert-butanol (30 mL) was added diphenylphosphoryl azide (4.08 g, 14.84 mmol). After the addition, N,N-diisopropylethylamine (1.92 g, 19.02 mmol) was added to the reaction liquid. The reaction liquid was warmed to 80 °C and stirred overnight. The reaction liquid was concentrated under reduced pressure, and a saturated sodium bicarbonate solution was added to the residue. The resulting mixture was extracted with ethyl acetate (3 x 50 mL). The organic phase was washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain compound C89-3 (2.8 g, 71%) as a white solid. 3) Synthesis of intermediate C89-4: C89-3 (450 mg, 1.46 mmol) was dissolved in a dichloromethane (3 mL) solution, and trifluoroacetic acid (1 mL) was added thereto. The reaction liquid was stirred at 25 °C for 2 h. After the reaction was completed as detected by LCMS, the reaction liquid was concentrated to obtain C89-4 (300 mg, mixture, yield: 98.8%) as a brown oil. LCMS (ESI) m / z = 208.1 [M+H]+. 4) Synthesis of intermediate C89-5: Compound C87-6 (240 mg, 0.77 mmol) was added to dichloromethane (10 mL), and CMPI (217.16 mg, 0.85 mmol), DIEA (299.61 mg, 2.32 mmol), and C89-4 (281.82 mg, 1.16 mmol) were added at 0 °C. The reaction liquid was heated to 50 °C and allowed to react for 2 h. After the starting materials were consumed completely as detected by LC-MS, an aqueous solution was slowly added dropwise to quench the reaction, and the resulting mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (DCM / MeOH = 100 / 1) to obtain compound C89-5 (180 mg, yield: 47%) as a yellow solid. LCMS (ESI) m / z = 500.1 [M+H]+. 5) Synthesis of intermediate C89-6: C89-5 (180 mg, 0.36 mmol) was added to dichloromethane (15 mL), and NBS (128.16 mg, 0.72 mmol) was added at 0 °C. The mixture was warmed to 50 °C and stirred overnight. After the starting materials were consumed completely as detected by LC-MS, an aqueous solution was added dropwise to quench the reaction, and the resulting mixture was extracted with ethyl acetate. The organic phase was then washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (DCM / MeOH = 100 / 1) to obtain compound C89-6 (160 mg, yield: 77%) as a pale yellow solid. LCMS (ESI) m / z = 579.8 [M+H]+. 6) Synthesis of intermediate C89-7: Compound C89-6 (160 mg, 0.28 mmol), compound C88-1 (464.25 mg, 4.15 mmol), and silver tetrafluoroborate (109.2 mg, 0.56 mmol) were added to dimethyl sulfoxide (4 mL), and the reaction liquid was heated to 120 °C and allowed to react for 2 h. After the starting materials were consumed completely as detected by LC-MS, an aqueous solution was added dropwise to quench the reaction, and the resulting mixture was extracted with ethyl acetate. The organic phase was then washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (DCM / MeOH / H2O.NH3 = 10 / 1 / 0.01) to obtain compound C89-7 (100 mg, yield: 59%) as an off-white solid. LCMS (ESI) m / z= 610.1 [M+H]+. 7) Synthesis of C89-P1, C89-P2, and C89-P3: Compound C87-11 (34.5 mg, 0.23 mmol) was added to DMF (5 mL), and HOBT (23.76 mg, 0.18 mmol) and EDCI (46.08 mg, 0.24 mmol) were added at room temperature. The mixture was stirred at room temperature for 2 h under nitrogen atmosphere. Subsequently, compound C89-7 (100 mg, 0.16 mmol) and DIEA (61.92 mg, 0.48 mmol) were added, and the mixture was purged with nitrogen three times and stirred at room temperature for 4 h under nitrogen atmosphere. After the starting materials were consumed completely as detected by LC-MS, the reaction liquid was concentrated under reduced pressure. The residue was purified by preparative high-performance liquid chromatography (RP-PREP-3 SunFire C18 5 mm 19 x 150 mm 18 min-55-70B, A: H2O (0.2% FA), B: ACN, UV: 214 nm, flow rate: 15 mL / min) to obtain C89-P1 (10.5 mg, yield: 8.6%, retention time: 10.52 min), C89-P2 (11.2 mg, yield: 9.2%, retention time: 11.31 min), and C89-P3 (16.6 mg, yield: 13.6%, retention time: 12.56 min) as white solids. C89-P1 and C89-P2 were both single-configuration compounds, and C89-P3 was a mixture of two diastereomers. C89-P1 (the configuration was confirmed based on crystal structure: C89-P1 is compound C2): LCMS (ESI) m / z = 744.1 [M-H]-. 1H NMR (400 MHz, DMSO_ d6): 5 10.49 (brs, 1H), 8.48 (s, 1H), 8.10-8.08 (m, 2H), 7.53-7.52 (m, 3H), 7.43 (d, J=8.8 Hz, 1H), 7.35 (d, J=8.8 Hz, 1H), 5.59-5.58 (m, 1H), 4.454.40 (m, 1H), 3.71-3.69 (m, 2H), 3.08-2.71 (m, 5H), 2.41 (s, 3H), 2.09-2.01 (m, 1H), 1.68-1.63 (m, 1H), 1.60-1.51 (m, 6H). C89-P2: LCMS (ESI) m / z = 744.1 [M-H]-. 1H NMR (400 MHz, DMSO_d6): 5 10.54 (brs, 1H), 8.54 (s, 1H), 8.11-8.09 (m, 2H), 7.54-7.53 (m, 3H), 7.44 (d, J=8.8 Hz, 1H), 7.35 (d, J=8.8 Hz, 1H), 5.485.46 (m, 1H), 4.43-4.39 (m, 1H), 3.72-3.71 (m, 2H), 3.08-3.05 (m, 5H), 2.43 (s, 3H), 2.02-1.96 (m, 1H), 1.68-1.61 (m, 1H), 1.60-1.51 (m, 6H). C89-P3: LCMS (ESI) m / z = 744.1 [M-H]-. 1H NMR (400 MHz, DMSO_d6): 5 10.53 (brs, 1H), 8.51 (s, 1H), 8.11-8.09 (m, 2H), 7.54-7.53 (m, 3H), 7.42 (d, J=8.8 Hz, 1H), 7.33 (d, J=8.8 Hz, 1H), 5.565.53 (m, 1H), 4.46-4.43 (m, 1H), 3.81-3.69 (m, 2H), 3.09-3.01 (m, 5H), 2.42 (s, 3H), 2.03-2.01 (m, 1H), 1.64-1.53 (m, 6H). Example 4: (C90-P1, C90-P2, and C90-P3) Referring to the synthetic method for compounds C87-P1 and C87-P2 in Example 1, C90 was obtained by replacing C87-7 with C89-4. C90 was subjected to chiral resolution (IBN, MeOH:EtOH:FA = 50:50:0.3, 25 mL / min, 254 nm) to obtain C90-P1 (2.0 mg, retention time: 9.55 min), C90-P2 (2.3 mg, retention time: 23.31 min), and C90-P3 (2.1 mg, retention time: 32.67 min). C90-P1 was a mixture of two diastereomers, and C90-P2 and C90-P3 were both single-configuration compounds. C90-P1: LCMS (ESI) m / z = 720.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 8 10.48 (brs, 1H), 8.56 (s, 1H), 8.12-8.08 (m, 2H), 7.55-7.52 (m, 3H), 7.44 (d, J=8.8 Hz, 1H), 7.36 (d, J=8.8 Hz, 1H), 5.485.46 (m, 1H), 3.77-3.73 (m, 1H), 3.08-3.02 (m, 6H), 2.51-2.50 (m, 1H), 2.46-2.44 (m, 4H), 2.01-1.99 (m, 2H), 1.53-1.44 (m, 3H). C90-P2: LCMS (ESI) m / z = 720.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 8 10.50 (brs, 1H), 8.49 (s, 1H), 8.33 (brs, 1H), 8.11-8.09 (m, 2H), 7.53-7.52 (m, 3H), 7.43 (d, J=8.8 Hz, 1H), 7.36 (d, J=8.8 Hz, 1H), 5.56-5.33 (m, 1H), 3.78-3.72 (m, 1H), 3.15-2.94 (m, 6H), 2.75-2.66 (m, 2H), 2.47 (s, 3H), 2.03-1.96 (m, 2H), 1.52-1.46 (m, 3H). C90-P3: LCMS (ESI) m / z = 720.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 8 10.49 (brs, 1H), 8.47 (s, 1H), 8.35 (brs, 1H), 8.12-8.10 (m, 2H), 7.54-7.53 (m, 3H), 7.44 (d, J=8.8 Hz, 1H), 7.34 (d, J=8.8 Hz, 1H), 5.49-5.47 (m, 1H), 3.77-3.75 (m, 1H), 3.08-2.97 (m, 6H), 2.53-2.49 (m, 2H), 2.41 (s, 3H), 2.03-1.96 (m, 2H), 1.46-1.44 (m, 3H). Example 5: (C93-P1, C93-P2, C93-P3, and C93-P4) Referring to the synthetic method in Example 4, C87-3 was replaced with C93-1, piperazine was replaced with C88-1, and the last step was purification by preparative high-performance liquid chromatography (Waters-PREP-8 SunFire C18 5 um 19 x 150 mm 18 min-45-55B, A: H2O (0.2% FA), B: ACN, UV: 214 nm, flow rate: 15 mL / min) to obtain C93-P1 (1.4 mg, yield: 2.9%, retention time: 9.83 min), C93-P2 (1.9 mg, yield: 3.9%, retention time: 10.70 min), C93-P3 (1.6 mg, yield: 3.3%, retention time: 11.57 min), and C93-P4 (1.2 mg, yield: 2.5%, retention time: 12.03 min). C93-P1: LCMS (ESI) m / z = 747.0 [M+H]+. 1H NMR (400 MHz, CD3OD): 8 8.69 (d, J=4.4 Hz, 1H), 8.53 (s, 1H), 8.30 (d, J=8.0 Hz, 1H), 8.00-7.96 (m, 1H), 7.55-7.48 (m, 2H), 7.18 (d, J=8.8 Hz, 1H), 5.64-5.61 (m, 1H), 5.35-5.33 (m, 1H), 3.35-3.33 (m, 7H), 2.80-2.76 (m, 1H), 2.53 (s, 3H), 2.03-2.01 (m, 1H), 1.79-1.65 (m, 6H). C93-P2: LCMS (ESI) m / z = 747.0 [M+H]+. 1H NMR (400 MHz, CD3OD): 8 8.69 (d, J=3.6 Hz, 1H), 8.48 (s, 1H), 8.30 (d, J=7.6 Hz, 1H), 8.00-7.96 (m, 1H), 7.55-7.52 (m, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.19 (d, J=8.8 Hz, 1H), 5.58-5.55 (m, 1H), 5.35-5.33 (m, 1H), 3.35-3.33 (m, 7H), 2.48 (s, 3H), 2.372.36 (m, 1H), 2.03-2.01 (m, 1H), 1.52-1.50 (m, 6H). C93-P3: LCMS (ESI) m / z = 747.0 [M+H]+. 1H NMR (400 MHz, CD3OD): 8 8.69 (d, J=4.4 Hz, 1H), 8.48 (s, 1H), 8.31 (d, J=8.0 Hz, 1H), 8.00-7.97 (m, 1H), 7.55-7.52 (m, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.20 (d, J=8.8 Hz, 1H), 5.61-5.58 (m, 1H), 5.35-5.33 (m, 1H), 3.32-3.31 (m, 7H), 2.49 (s, 3H), 2.342.31 (m, 1H), 2.03-1.97 (m, 1H), 1.58-1.56 (m, 6H). C93-P4: LCMS (ESI) m / z = 747.0 [M+H]+. 1H NMR (400 MHz, CD3OD): 8 8.60 (d, J=3.2 Hz, 1H), 8.43 (s, 1H), 8.21 (d, J=7.6 Hz, 1H), 7.91-7.87 (m, 1H), 7.45-7.42 (m, 1H), 7.38 (d, J=8.8 Hz, 1H), 7.07 (d, J=8.4 Hz, 1H), 5.55-5.52 (m, 1H), 5.25-5.23 (m, 1H), 3.32-3.31 (m, 7H), 2.66-2.69 (m, 1H), 2.41 (s, 3H), 1.94-1.92 (m, 1H), 1.57-1.49 (m, 6H). Example 6: (C43-P1, C43-P2, and C43-P3) Referring to the synthetic method in Example 3, C89-4 was replaced with C43-1, and the last step was purification by preparative high-performance liquid chromatography (Waters-PREP-8 SunFire C18 5 um 19 x 150 mm 18 min-42-78 B, A: H2O (0.2% FA), B: ACN, UV: 214 nm, flow rate: 15 mL / min) to obtain C43-P1 (11.1 mg, yield: 5.7%, retention time: 11.82 min), C43-P3 (14.1 mg, yield: 7.3%, retention time: 13.25 min), and a crude product of C43-P2 (30 mg, retention time: 12.82 min). The crude product of C43-P2 was purified by chiral resolution (IBN, Hex:EtOH:DEA = 50:50:0.3, 25 mL / min, 230 nm) to obtain C43-P2 (12 mg, yield: 6.2%, retention time: 7.997 min). C43-P1 (hydrochloride, single-configuration compound): 1H NMR (400 MHz, CD3OD): 8 8.80 (s, 1 H), 8.12-8.10 (m, 2 H), 7.68 (s, 1 H), 7.47-7.41 (m, 3 H), 7.31-7.28 (m, 1 H), 7.18-7.16 (m, 1 H), 5.505.47 (m, 1 H), 4.62-4.59 (m, 1 H), 4.00-3.44 (m, 6 H), 2.71-2.70 (m, 1 H), 2.64 (s, 3 H), 2.52-2.45 (m, 1 H), 1.83-1.62 (m, 6 H), 1.42-1.39 (m, 1 H). LCMS (ESI) m / z=712.1 [M+H]+. C43-P2 (free base, single-configuration compound): 1H NMR (400 MHz, DMSO-d6): 8 10.86 (s, 1 H), 8.54 (s, 1 H), 8.05-8.03 (m, 2 H), 7.74 (s, 1 H), 7.50-7.48 (m, 3 H), 7.41-7.39 (m, 1 H), 7.32-7.29 (m, 1 H), 5.36 (d, J=9.2 Hz, 1 H), 4.40-4.38 (m, 1 H), 3.71-3.70 (m, 2 H), 3.24-2.95 (m, 6 H), 2.43 (s, 3 H), 2.10 (d, J=13.6 Hz, 1 H), 1.75-1.34 (m, 6 H), 1.23-1.17 (m, 1 H). LCMS (ESI) m / z=712.1 [M+H]+. C43-P3 (hydrochloride, a mixture of two diastereomers): 1H NMR (400 MHz, CD3OD): 8 8.86 (s, 1 H), 8.13-8.10 (m, 2 H), 7.68-7.66 (m, 1 H), 7.47-7.41 (m, 3 H), 7.30-7.26 (m, 1 H), 7.18-7.15 (m, 1 H), 5.49-5.42 (m, 1 H), 4.71-4.68 (m, 1 H), 3.79-3.54 (m, 6 H), 3.13-3.03 (m, 1 H), 2.69 (s, 3 H), 2.502.43 (m, 1 H), 2.01-1.55 (m, 6 H), 1.40-1.37 (m, 1 H). LCMS (ESI) m / z=712.1 [M+H]+. Example 7: (C142-P1, C142-P2, C142-P3-A, and C142-P3-B) Pd(dppf)CI2,K2CO3,Diox.,H2O,80 °C 1) Synthesis of intermediate C142-2: Compound C142-1 (0.6 g, 2.38 mmol, prepared according to the synthetic method disclosed in patent application WO2008082484) and methylboronic acid (1.42 g, 23.8 mmol) were dissolved in a mixed solution of 1,4-dioxane (5 mL) and water (0.5 mL), and potassium carbonate (0.99 g, 7.14 mmol) was added under stirring. After the mixture was purged with a gas three times, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.17 g, 0.24 mmol) was added, and the mixture was stirred at 80 °C for 16 h. After the reaction was completed as detected by LCMS, the reaction liquid was concentrated and purified by column chromatography (ethyl acetate / petroleum ether) to obtain C142-2 (0.4 g, yield: 89.8%) as a white solid. m / z [M+H]+ = 188.1. 2) Synthesis of product: Referring to the synthetic method in Example 3, C89-4 was replaced with C142-2, and the last step was purification by preparative high-performance liquid chromatography (RP-PREP-3 SunFire C18 5 pm 19 x 150 mm 18 min-50-75B, A: H2O (0.2% FA), B: ACN, UV: 214 nm, flow rate: 15 mL / min) to obtain C142-P1 (33.6 mg, yield: 12.4%, retention time: 10.13 min), C142-P2 (25.2 mg, yield: 9.3%, retention time: 10.74 min), and C142-P3 (54.1 mg, yield: 19.9%, retention time: 11.53 min). C142-P1 and C142-P2 were both single-configuration compounds, and C142-P3 was a mixture of two diastereomers. C142-P3 was subjected to chiral resolution (IBN, Hex:EtOH:TFA = 50:50:0.2, 25 mL / min, 254 nm) to obtain C142-P3-A (10.7 mg, retention time: 11.1 min) and C142-P3-B (14.1 mg, retention time: 37.7 min). C142-P1: LCMS (ESI) m / z = 726.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 5 10.24 (s, 1H), 8.53 (s, 1H), 8.10-8.02 (m, 2H), 7.56-7.48 (m, 3H), 7.23 (d, J=8.8 Hz, 1H), 7.10 (d, J=8.8 Hz, 1H), 5.49- 5.45 (m, 1H), 4.40-4.38 (m, 1H), 3.76-3.73 (m, 2H), 3.35-3.17 (m, 4H), 2.67-2.52 (m, 1H), 2.51-2.47 (m, 1H), 2.45 (s, 3 H), 2.22 (s, 3 H), 1.67-1.66 (m, 1H), 1.65-1.57 (m, 3H), 1.49-1.42 (m, 2H), 1.231.22 (m, 2H). C142-P2: LCMS (ESI) m / z = 726.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 5 10.28 (s, 1H), 8.50 (s, 1H), 8.10-8.08 (m, 2H), 7.54-7.52 (m, 3H), 7.24 (d, J=8.4 Hz, 1H), 7.10 (d, J=8.4 Hz, 1H), 5.415.38 (m, 1H), 4.40-4.38 (m, 1H), 3.74-3.72 (m, 2H), 3.31-3.23 (m, 4H), 3.04-3.01 (m, 1H), 2.42 (s, 3 H), 2.23 (s, 3 H), 2.41-2.11 (m, 1H), 1.68-1.66 (m, 1H), 1.51-1.40 (m, 5H), 1.23-1.22 (m, 2H). C142-P3-A: LCMS (ESI) m / z = 726.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 5 10.28 (s, 1H), 8.56 (s, 1H), 8.12-8.05 (m, 2H), 7.58-7.50 (m, 3H), 7.25-7.21 (m, 1H), 7.11 (d, J=8.4 Hz, 1H), 5.50-5.45 (m, 1H), 4.45-4.42 (m, 1H), 3.76-3.71 (m, 1H), 3.61-3.45 (m, 5H), 2.63-2.58 (m, 1H), 2.50-2.35 (m, 4H), 2.21 (s, 3H), 1.66-1.63 (m, 1H), 1.49 (d, J=6.8 Hz, 3H), 1.44-1.16 (m, 4H). C142-P3-B (the configuration was confirmed by crystal structure analysis, and C142-P3-B was compound C100): 1H NMR (400 MHz, DMSO_d6): 5 10.26 (s, 1H), 8.56 (s, 1H), 8.12-8.05 (m, 2H), 7.58-7.50 (m, 3H), 7.24 (d, J=8.4 Hz, 1H), 7.08 (d, J=8.4 Hz, 1H), 5.41 (d, J=8.4 Hz, 1H), 4.47-4.42 (m, 1H), 3.80-3.73 (m, 2H), 3.61-3.45 (m, 4H), 3.10-3.02 (m, 1H), 2.44 (s, 3H), 2.22 (s, 3H), 2.10 (d, J=13.6 Hz, 1H), 1.68-1.63 (m, 1H), 1.48 (d, J=6.8 Hz, 3H), 1.44-1.16 (m, 4H). Example 8: (C143-P1, C143-P2, C143-P3, and C143-P4) Referring to the synthetic method in Example 5, C89-4 was replaced with C142-2, and the last step was purification by preparative high-performance liquid chromatography (Waters-PREP-8 SunFire C18 5 um 19 x 150 mm 18 min-45-50B, A: H2O (0.2% FA), B: ACN, UV: 214 nm, flow rate: 15 mL / min) to obtain C143-P1 (2.4 mg, yield: 3%, retention time: 9.88 min), C143-P2 (2.1 mg, yield: 2.6%, retention time: 10.25 min), C143-P3 (3.6 mg, yield: 4.5%, retention time: 12.07 min), and C143-P4 (3.6 mg, yield: 4.5%, retention time: 12.55 min). C143-P1: LCMS (ESI) m / z=727.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 5 10.28 (s, 1H), 8.73 (d, J=4.0 Hz, 1H), 8.48 (s, 1H), 8.14 (d, J=8.0 Hz, 1H), 8.01-7.97 (m, 1H), 7.55-7.52 (m, 1H), 7.23-7.20 (m, 1H), 7.16-7.13 (m, 1H), 5.51-5.47 (m, 1H), 4.48-4.46 (m, 1H), 3.76-3.64 (m, 2H), 2.99-2.96 (m, 4H), 2.67-2.58 (m, 1H), 2.33 (s, 3H), 2.21 (s, 3H), 2.03-1.97 (m, 1H), 1.55-1.35 (m, 7H). C143-P2: LCMS (ESI) m / z=727.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 5 10.33 (s, 1H), 8.72 (d, J=4.0 Hz, 1H), 8.47 (s, 1H), 8.14 (d, J=8.0 Hz, 1H), 8.01-7.96 (m, 1H), 7.54-7.51 (m, 1H), 7.24-7.20 (m, 1H), 7.16-7.12 (m, 1H), 5.50-5.44 (m, 1H), 4.41-4.40 (m, 1H), 3.73-3.64 (m, 2H), 3.17-3.05 (m, 4H), 2.44 (s, 3H), 2.40-2.39 (m, 1H), 2.27 (s, 3H), 2.03-1.89 (m, 1H), 1.59-1.45 (m, 7H). C143-P3: LCMS (ESI) m / z=727.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 5 10.32 (s, 1H), 8.73 (d, J=4.4 Hz, 1H), 8.43 (s, 1H), 8.15 (d, J=8.0 Hz, 1H), 8.00-7.96 (m, 1H), 7.55-7.52 (m, 1H), 7.25-7.23 (m, 1H), 7.15-7.11 (m, 1H), 5.46-5.44 (m, 1H), 4.45-4.40 (m, 1H), 3.80-3.64 (m, 2H), 3.17-3.01 (m, 4H), 2.46-2.44 (m, 1H), 2.34 (s, 3H), 2.21 (s, 3H), 2.03-1.90 (m, 1H), 1.53-1.40 (m, 7H). C143-P4: LCMS (ESI) m / z=727.1 [M+H]+. 1H NMR (400 MHz, DMSO_d6): 5 10.28 (s, 1H), 8.74 (d, J=4.0 Hz, 1H), 8.49 (s, 1H), 8.14 (d, J=8.0 Hz, 1H), 8.01-7.97 (m, 1H), 7.55-7.52 (m, 1H), 7.23-7.20 (m, 1H), 7.16-7.13 (m, 1H), 5.51-5.47 (m, 1H), 4.45-4.43 (m, 1H), 3.76-3.67 (m, 2H), 3.10-2.93 (m, 4H), 2.64-2.59 (m, 1H), 2.41 (s, 3H), 2.20 (s, 3H), 2.03-1.97 (m, 1H), 1.56-1.34 (m, 7H). Example 9: (C144-P1, C144-P2, C144-P3-A, and C144-P3-B) NaHCO3, KBr TEMPO, NaOCI C142-2 C88-1 CMPI, DIEA, DCM C144-6                                 C144-7 DIPA, DMSO, AgBF4 HOAT, EDCI, DIEA, ACN C144 C144-P1 C144-P2 C144-P3-A C144-P3-B 1) Synthesis of intermediate C144-2: Compound C144-1 (50 g, 341.9 mmol) was added to acetonitrile (500 mL), and a 2 mol / L solution of dimethylamine in tetrahydrofuran (200 mL) was then added. The mixture was allowed to react at 50 °C for 4 h. Hydrazine hydrate (51.35 g, 820.6 mmol) was then added, and the mixture was allowed to react at reflux overnight. After the reaction was completed as detected by LCMS, the reaction liquid was allowed to return to room temperature and concentrated under reduced pressure to a volume of 230 mL, and a solid was precipitated. The resulting mixture was filtered to obtain a filter cake, and the filter cake was dried to obtain C144-2 (39 g, yield: 89.7%). m / z [M+H]+ = 128.0. 2) Synthesis of intermediate C144-3: Compound C144-2 (32 g, 251.7 mmol) was added to acetic acid (210 mL), and methyl propionylacetate (39.3 g, 302.0 mmol) was then added. The mixture was allowed to react at 90 °C overnight. After the reaction was completed as detected by LCMS, the reaction liquid was allowed to return to room temperature and concentrated under reduced pressure to remove the acetic acid, and ethyl acetate (180 mL) and petroleum ether (110 mL) were then added. The resulting mixture was ground and stirred for 1 h, and filtered to obtain a filter cake, and the filter cake was dried to obtain C144-3 (50 g, yield: 95.9%). m / z [M+H]+ = 208.1. 3) Synthesis of intermediate C144-4: Compound C144-3 (4.5 g, 21.72 mmol) was added to tetrahydrofuran (110 mL) and 1,4-dioxane (110 mL), and LDA (2 M, 14 mL) was added under nitrogen atmosphere. The mixture was allowed to react at room temperature for 30 min. LDA (2 M, 14 mL) was added again at 0 °C, and the mixture was stirred at 0 °C for 30 min and then stirred at room temperature for another 30 min. S-epichlorohydrin (5.22 g, 56.47 mmol) was added at room temperature, and the mixture was stirred at room temperature overnight. After the reaction was completed as detected by LCMS, the reaction liquid was added to an aqueous ammonium chloride solution, and the liquid was separated to obtain an organic phase. The aqueous phase was then extracted twice with dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and subjected to column chromatography to obtain C144-4 (4 g, yield: 69.96%). m / z [M+H]+ = 264.2. 4) Synthesis of intermediate C144-5: Compound C144-4 (3.5 g, 13.29 mmol) was added to dichloromethane (40 mL), and NBS (2.60 g, 14.62 mmol) was added at 0 °C. The mixture was allowed to react at room temperature for 6 h. After the reaction was completed as detected by LCMS, the reaction liquid was diluted with dichloromethane, a 10% sodium sulfite solution was added, and the resulting mixture was subjected to liquid-liquid extraction. The aqueous phase was extracted twice with dichloromethane, and the organic phases were combined, and then washed twice with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain C144-5 (4 g, yield: 87.94%). m / z [M+H]+ = 342.1. 5) Synthesis of intermediate C144-6: Compound C144-5 (4 g, 11.69 mmol) was added to dichloromethane (80 mL), and an aqueous solution (100 mL) of sodium bicarbonate (9.82 g, 116.90 mmol), potassium bromide (0.14 g, 1.17 mmol), trioctylmethylammonium chloride (0.24 g, 0.58 mmol), and TEMPO (0.091 g, 0.58 mmol) were added. A 10% (by mass) aqueous sodium hypochlorite solution (43.51 g, 58.45 mmol) was added at 0 °C, and the mixture was allowed to react at room temperature for 2.5 h. After the reaction was completed as detected by LCMS, dichloromethane was added to the reaction liquid, and extraction and liquid separation were performed to obtain an aqueous phase. Dichloromethane was added to the aqueous phase, and extraction and liquid separation were performed. The organic phases were combined, a 10% aqueous sodium bicarbonate solution was added to the combined organic phase, and extraction and liquid separation were performed to obtain an aqueous phase. The two aqueous phases were combined, and dichloromethane was added to the combined aqueous phase. The aqueous phase was adjusted to pH 3-4 with diluted hydrochloric acid and extracted three times with dichloromethane. The dichloromethane phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to obtain C144-6 (2.5 g, yield: 60.05%). m / z [M+H]+ = 356.1. 6) Synthesis of intermediate C144-7: Compound C144-6 (2.15 g, 6.04 mmol) was added to dichloromethane (40 mL), and 2-chloro-1-methylpyridinium iodide (1.70 g, 6.64 mmol), DIEA (3.51 g, 27.18 mmol), and C142-2 (1.76 g, 7.85 mmol) were then added. The mixture was stirred at room temperature for 4 h. After the reaction was completed as detected by LCMS, dichloromethane and water were added to the reaction liquid, and the resulting mixture was subjected to liquid-liquid extraction. The aqueous phase was extracted twice with dichloromethane, and the organic phases were combined, washed twice with diluted hydrochloric acid, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure and subjected to column chromatography to obtain C144-7 (2.6 g, yield: 82.0%). m / z [M+H]+ = 525.1. 7) Synthesis of intermediate C144-8: Compound C144-7 (700 mg, 1.33 mmol) was added to DMSO (3 mL), and C88-1 (0.75 g, 6.65 mmol) and DIPA (0.67 g, 6.65 mmol) were then added. Under nitrogen atmosphere, silver tetrafluoroborate (0.39 g, 2.00 mmol) was added, and the mixture was allowed to react at 105 °C under microwave irradiation for 2 h under nitrogen atmosphere. After the reaction was completed as detected by LCMS, the reaction liquid was allowed to return to room temperature, diluted with dichloromethane, and filtered, and the filtrate was concentrated under reduced pressure and purified by reversed-phase column chromatography to obtain C144-8 (270 mg, yield: 36.41%). m / z [M+H]+ = 557.2 8) Synthesis of product C144: Compound C144-8 (0.10 g, 0.66 mmol) and HOAT (0.10 g, 0.76 mmol) were added to acetonitrile (3 mL), and EDCI (0.19 g, 0.98 mmol) was added. The mixture was stirred at room temperature for 1 h. C87-11 (270 mg, 0.49 mmol) and DIEA (0.22 g, 1.71 mmol) were then added, and the mixture was stirred at room temperature for 30 min. After the reaction was completed as detected by LCMS, the reaction liquid was filtered, and the filtrate was purified by reversed-phase column chromatography to obtain C144 (110 mg, yield: 32.74%). C144 was purified by preparative high-performance liquid chromatography (SHIMADZU LC 20, Agilent 10 Prep-C18, 250 x 21.2 mm, 10 gm, A: H2O (0.1% FA), B: ACN, UV: 214 nm, flow rate: 20 mL / min) to obtain C144-P1 (19.8 mg, yield: 4.3%, retention time: 13.1 min), C144-P2 (7.3 mg, yield: 1.6%, retention time: 14.0 min), and C144-P3 (retention time: 16.2 min). C144-P1 and C144-P2 were both single-configuration compounds, and C144-P3 was a mixture of two diastereomers. C144-P3 was subjected to chiral resolution (Waters SFC-150 mgm, Daicel OJ, 30 x 250 mm, 10 gm, CO2 / MEOH = 75 / 25, 50 mL / min, 254 nm) to obtain C144-P3-A (8 mg, retention time: 12.01 min) and C144-P3-B (19.7 mg, retention time: 16.19 min). C144-P1: LCMS m / z [M+H]+ = 693.3. 1H NMR (400 MHz, CDCI3-d) 5 11.46 (s, 1H), 8.69 (s, 1H), 8.59 (s, 1H), 7.24 (s, 1H), 6.87 (d, J = 8.5 Hz, 1H), 5.20 (d, J = 8.2 Hz, 1H), 4.66 (s, 1H), 4.12 (d, J = 66.5 Hz, 2H), 3.70 (dd, J = 15.7, 6.7 Hz, 2H), 3.08 (s, 6H), 3.06 - 2.98 (m, 1H), 2.54 (s, 3H), 2.43 - 2.27 (m, 1H), 2.24 - 2.16 (m, 1H), 2.14 (s, 3H), 2.07 - 1.95 (m, 1H), 1.68 - 1.57 (m, 1H), 1.55 - 1.38 (m, 4H), 1.37 - 1.28 (m, 1H), 1.20 - 1.09 (m, J = 9.7 Hz, 1H). C144-P2: LCMS m / z [M+H]+ = 693.3. 1H NMR (400 MHz, CDCl3-d) 5 11.46 (s, 1H), 8.69 (s, 1H), 8.59 (s, 1H), 7.24 (s, 1H), 6.87 (d, J = 8.5 Hz, 1H), 5.20 (d, J = 8.2 Hz, 1H), 4.66 (s, 1H), 4.12 (d, J = 66.5 Hz, 2H), 3.70 (dd, J = 15.7, 6.7 Hz, 2H), 3.08 (s, 6H), 3.06 - 2.98 (m, 1H), 2.54 (s, 3H), 2.43 - 2.27 (m, 1H), 2.24 - 2.16 (m, 1H), 2.14 (s, 3H), 2.07 - 1.95 (m, 1H), 1.68 - 1.57 (m, 1H), 1.55 - 1.38 (m, 4H), 1.37 - 1.28 (m, 1H), 1.20 - 1.09 (m, J = 9.7 Hz, 1H). C144-P3-A: LCMS m / z [M+H]+ = 693.3. 1H (400 MHz, CDCl3-d) 5 11.49 (s, 1H), 9.20 (s, 1H), 8.59 (s, 1H), 7.22 (d, J = 8.6 Hz, 1H), 6.88 (d, J = 8.5 Hz, 1H), 5.23 (d, J = 9.1 Hz, 1H), 4.71 (s, 1H), 4.09 (s, 2H), 3.74 - 3.50 (m, 2H), 3.10 (s, 6H), 2.81 (d, J = 13.1 Hz, 1H), 2.68 (dd, J = 20.1, 8.8 Hz, 1H), 2.54 (s, 3H), 2.35 (q, J = 9.6 Hz, 1H), 2.16 (s, 3H), 2.06 - 1.97 (m, 1H), 1.68 - 1.57 (m, 1H), 1.55 -1.38 (m, 4H), 1.37 - 1.28 (m, 1H), 1.20 - 1.09 (m, J = 9.7 Hz, 1H). C144-P3-B: LCMS m / z [M+H]+ = 693.3. 1H (400 MHz, CDCl3-d) 5 11.49 (s, 1H), 9.20 (s, 1H), 8.59 (s, 1H), 7.22 (d, J = 8.6 Hz, 1H), 6.88 (d, J = 8.5 Hz, 1H), 5.23 (d, J = 9.1 Hz, 1H), 4.71 (s, 1H), 4.09 (s, 2H), 3.74 - 3.50 (m, 2H), 3.10 (s, 6H), 2.81 (d, J = 13.1 Hz, 1H), 2.68 (dd, J = 20.1, 8.8 Hz, 1H), 2.54 (s, 3H), 2.35 (q, J = 9.6 Hz, 1H), 2.16 (s, 3H), 2.06 - 1.97 (m, 1H), 1.68 - 1.57 (m, 1H), 1.55 -1.38 (m, 4H), 1.37 - 1.28 (m, 1H), 1.20 - 1.09 (m, J = 9.7 Hz, 1H). Example 10: (C146-P1, C146-P2, C146-P3-A, and C146-P3-B) Referring to the synthetic method in Example 9, dimethylamine hydrochloride was replaced with tetrahydropyrrole in step 1, and the last step was purification by preparative high-performance liquid chromatography (SHIMADZU LC 20, Agilent 10 Prep-C18, 250 x 21.2 mm, 10 ^m, A: H2O (0.1% FA), B: ACN, UV: 214 nm, flow rate: 20 mL / min) to obtain C146-P1 (retention time: 10.5 min), C146-P2 (retention time: 11.3 min), and C146-P3 (retention time: 12.6 min). C146-P1 and C146-P2 were both single-configuration compounds, and C146-P3 was a mixture of two diastereomers. C146-P3 was subjected to chiral resolution (Waters SFC-150 mgm, Daicel OD, 30 x 250 mm, 10 Lim, CO2 / MEOH = 65 / 35, 50 mL / min, 214 nm) to obtain C146-P3-A (5.81 min) and C146-P3-B (11.14 min). C146-P1: LCMS m / z [M+H]+ = 719.3, 1H NMR (400 MHz, DMSO-d6) 8 10.17 (s, 1H), 8.54 (s, 1H), 7.23 (d, J = 8.5 Hz, 1H), 7.07 (d, J = 8.6 Hz, 1H), 5.30 (dq, J = 8.3, 5.0 Hz, 1H), 4.36 (d, J = 13.0 Hz, 1H), 3.65 (dq, J = 22.0, 7.2 Hz, 3H), 3.54 - 3.43 (m, 4H), 3.25 - 3.10 (m, 3H), 2.96 (dt, J = 13.5, 9.9 Hz, 1H), 2.42 (s, 3H), 2.35 (ddd, J = 12.6, 8.1, 5.9 Hz, 1H), 2.19 (s, 3H), 1.99 (dt, J = 13.0, 7.0 Hz, 1H), 1.90 (t, J = 5.9 Hz, 4H), 1.61 (d, J = 8.5 Hz, 1H), 1.51 (d, J = 7.1 Hz, 1H), 1.39 (dd, J = 20.7, 10.2 Hz, 3H), 1.15 (t, J = 8.9 Hz, 1H). C146-P2: LCMS m / z [M+H]+ = 719.3, 1H NMR (400 MHz, DMSO-d6) 8 10.17 (s, 1H), 8.54 (s, 1H), 7.23 (dd, J = 8.6, 1.9 Hz, 1H), 7.06 (dd, J = 11.0, 8.6 Hz, 1H), 5.31 - 5.22 (m, 1H), 4.38 (t, J = 16.1 Hz, 1H), 3.65 (dq, J = 22.0, 7.2 Hz, 3H), 3.54 - 3.43 (m, 4H), 3.25 - 3.10 (m, 3H), 2.96 (dt, J = 13.5, 9.9 Hz, 1H), 2.42 (s, 3H), 2.35 (ddd, J = 13.2, 8.8, 6.2 Hz, 1H), 2.19 (s, 3H), 2.01 (d, J = 13.7 Hz, 1H), 1.93 - 1.86 (m, 4H), 1.61 (d, J = 8.5 Hz, 1H), 1.51 (d, J = 7.1 Hz, 1H), 1.39 (dd, J = 20.7, 10.2 Hz, 3H), 1.15 (t, J = 8.9 Hz, 1H) C146-P3-A: LCMS m / z [M+H]+ = 719.3, 1H NMR (400 MHz, DMSO-d6) 8 10.19 (s, 1H), 8.55 (s, 1H), 7.22 (d, J = 8.5 Hz, 1H), 7.07 (d, J = 8.6 Hz, 1H), 5.31 (dt, J = 9.0, 5.1 Hz, 1H), 4.47 - 4.29 (m, 1H), 3.66 - 3.57 (m, 3H), 3.54 - 3.43 (m, 4H), 3.25 - 3.10 (m, 3H), 2.96 (dt, J = 13.5, 9.9 Hz, 1H), 2.42 (s, 3H), 2.35 (ddd, J = 13.2, 8.8, 6.2 Hz, 1H), 2.19 (s, 3H), 1.99 (dt, J = 13.0, 6.8 Hz, 1H), 1.93 -1.86 (m, 4H), 1.61 (d, J = 8.5 Hz, 1H), 1.51 (d, J = 7.1 Hz, 1H), 1.39 (dd, J = 20.7, 10.2 Hz, 3H), 1.15 (t, J = 8.9 Hz, 1H) C146-P3-B: LCMS m / z [M+H]+ = 719.3, 1H NMR (400 MHz, DMSO-d6) 8 10.18 (s, 1H), 8.55 (s, 1H), 7.24 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 8.6 Hz, 1H), 5.24 (d, J = 9.8 Hz, 1H), 4.42 (d, J = 9.1 Hz, 1H), 3.75 - 3.48 (m, 3H), 3.54 - 3.43 (m, 4H), 3.27 - 3.12 (m, 3H), 3.09 - 2.90 (m, 1H), 2.43 (s, 3H), 2.19 (s, 3H), 2.04 - 1.98 (m, 1H), 1.90 (t, J = 6.5 Hz, 4H), 1.62 (dd, J = 15.1, 7.2 Hz, 1H), 1.52 - 1.47 (m, 1H), 1.42 (d, J = 7.3 Hz, 3H), 1.34 (d, J = 8.4 Hz, 1H), 1.16 (t, J = 8.6 Hz, 1H) Example 11: (C145, C145-P1, and C145-P2) 1) Synthesis of intermediate C145-2: Compound C145-1 (0.1 g, 0.19 mmol, prepared according to the synthetic method disclosed in patent application WO2024079623) was added to dichloromethane (2 mL), and 2-chloro-1-methylpyridinium iodide (0.053 g, 0.21 mmol), DIEA (0.11 g, 0.85 mmol), and C142-2 (0.55 g, 0.25 mmol) were then added. The mixture was stirred at room temperature for 4 h. After the reaction was completed as detected by LCMS, dichloromethane and water were added to the reaction liquid, and the resulting mixture was subjected to liquid-liquid extraction. The aqueous phase was extracted twice with dichloromethane, and the organic phases were combined, washed twice with diluted hydrochloric acid, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure and subjected to column chromatography to obtain C145-2 (70 mg, yield: 54.0%). m / z [M+H]+ = 696.1. 2) Synthesis of intermediate C145-3: Compound C145-2 (0.7 g, 0.1 mmol) was dissolved in a dichloromethane (1 mL) solution, and trifluoroacetic acid (1 mL) was added dropwise. The reaction liquid was stirred at 25 °C for 1 h. After the reaction was completed as detected by LCMS, the reaction liquid was filtered and concentrated to obtain a crude product of C145-3 (100 mg, trifluoroacetate, yield: 100%) as a yellow oil. m / z [M+H]+ = 596.3. 3) Synthesis of product C145: Compound C87-11 (23 mg, 0.15 mmol) and HOAT (22 mg, 0.16 mmol) were added to DMF (1 mL), and EDCI (35 mg, 0.18 mmol) was added. The mixture was stirred at room temperature for 1 h. C145-3 (0.10 g, crude product, 0.1 mmol) and DIEA (39 mg, 0.3 mmol) were then added, and the mixture was stirred at room temperature for 30 min. After the reaction was completed as detected by LCMS, the reaction liquid was filtered, and the filtrate was purified by reversed-phase column chromatography to obtain C145 (40 mg, yield: 54.5%). LCMS m / z [M+H]+ = 732.4. 1H NMR (400 MHz, DMSO-d6) 5 10.18 (d, J = 8.7 Hz, 1H), 8.55 (s, 1H), 7.27 - 7.19 (m, 1H), 7.06 (d, J = 8.3 Hz, 1H), 6.80 (dd, J = 4.6, 2.6 Hz, 1H), 5.35 (ddd, J = 21.9, 9.5, 4.3 Hz, 1H), 4.40 (t, J = 15.3 Hz, 1H), 4.26 (q, J = 2.9 Hz, 2H), 3.86 - 3.65 (m, 4H), 3.55 - 3.43 (m, 2H), 3.17 (s, 2H), 3.05 - 2.94 (m, 1H), 2.54 - 2.50 (m, 1H), 2.43 (s, 3H), 2.42 - 2.38 (m, 1H), 2.18 (s, 3H), 2.06 (dt, J = 12.9, 2.6 Hz, 1H), 1.62 (d, J = 9.9 Hz, 1H), 1.53 (d, J = 6.7 Hz, 1H), 1.45 (d, J = 7.0 Hz, 3H), 1.37-1.30 (m, 1H), 1.21-1.11 (m, 1H). 4) Synthesis of products C145-P1 and C145-P2: C145 was purified by preparative high-performance liquid chromatography (SHIMADZU LC 20, Agilent 10 Prep-C18, 250 x 21.2 mm, 10 pm, A: H2O (0.1% FA), B: ACN, UV: 214 nm, flow rate: 20 mL / min) to obtain C145-P1 (8 mg, retention time: 10.675 min) and C145-P2 (18 mg, retention time: 11.147 min). C145-P1: LCMS m / z [M+H]+ = 732.4. 1H NMR (400 MHz, DMSO-d6) 5 10.16 (s, 1H), 8.55 (s, 1H), 7.23 (d, J = 8.6 Hz, 1H), 7.08 (d, J = 8.6 Hz, 1H), 6.85 - 6.72 (m, 1H), 5.38 (dd, J = 8.5, 5.7 Hz, 1H), 4.37 (d, J = 11.3 Hz, 1H), 4.31 - 4.22 (m, 2H), 3.81 (t, J = 5.7 Hz, 2H), 3.74 - 3.65 (m, 2H), 3.56 -3.45 (m, 2H), 3.35 - 3.15 (m, 4H), 2.58 (q, J = 7.2 Hz, 1H), 2.43 (s, 3H), 2.38 (dd, J = 8.0, 5.3 Hz, 1H), 2.18 (s, 3H), 2.00 (dq, J = 13.0, 6.1 Hz, 1H), 1.71 - 1.60 (m, 1H), 1.54 (d, J = 7.0 Hz, 3H), 1.48 - 1.40 (m, 1H), 1.21 - 1.12 (m, 1H). C145-P2: LCMS m / z [M+H]+ = 732.4. 1H NMR (400 MHz, DMSO-d6) 5 10.22 (s, 1H), 8.48 (s, 1H), 7.24 (d, J = 8.5 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.80 (s, 1H), 5.33 (d, J = 9.8 Hz, 1H), 4.40 (d, J = 13.1 Hz, 1H), 4.26 (d, J = 3.1 Hz, 2H), 3.85 - 3.65 (m, 4H), 3.51 (dd, J = 16.8, 7.4 Hz, 2H), 3.20 -3.10 (m, 4H), 3.07 - 2.93 (m, 1H), 2.54 - 2.50 (m, 1H), 2.41 (s, 3H), 2.18 (s, 3H), 2.06 (d, J = 13.5 Hz, 1H), 1.63 (q, J = 6.6, 5.4 Hz, 1H), 1.45 (d, J = 7.2 Hz, 3H), 1.40 - 1.27 (m, 1H), 1.19 - 1.10 (m, 1H). Example 12: (C147) C142-5 HOAT, EDCI DMF ho'1^'n Compound    " (100 mg, 0.88 mmol) and HOAT (100 mg, 0.73 mmol) were added to DMF (1 mL), and EDCI (150 mg, 0.78 mmol) was added. The mixture was stirred at room temperature for 1 h. C142-5 (0.08 g, 0.14 mmol) and DIEA (78 mg, 0.6 mmol) were then added, and the mixture was stirred at room temperature for 30 min. After the reaction was completed as detected by LCMS, the reaction liquid was filtered, and the filtrate was purified by reversed-phase column chromatography to obtain C147 (25 mg, yield: 26.5%). LCMS m / z [M+H]+ = 698.4. 1H NMR (400 MHz, DMSO-d6) 8 10.30 (d, J = 9.2 Hz, 1H), 8.21 - 8.03 (m, 3H), 7.71 (d, J = 5.6 Hz, 1H), 7.57 (dd, J = 5.2, 2.0 Hz, 3H), 7.30 (dd, J = 23.9, 8.6 Hz, 1H), 7.14 (dd, J = 23.1, 8.6 Hz, 1H), 5.56 - 5.33 (m, 1H), 4.47 (t, J = 7.4 Hz, 1H), 3.89 (s, 3H), 3.80 - 3.69 (m, 1H), 3.65 - 3.49 (m, 2H), 3.43 (d, J = 5.3 Hz, 1H), 3.08 (dt, J = 13.3, 9.8 Hz, 1H), 2.25 (s, 3H), 2.15 (s, 3H), 2.11 (t, J = 2.6 Hz, 1H), 1.60 (d, J = 7.0 Hz, 1H), 1.50 (d, J = 7.2 Hz, 3H), 1.46 - 1.36 (m, 1H), 1.21 — 1.11 (m, 1H). Biological Assay Section Experimental Example 1: Biological Activity Assay ATPase activity assay of WRN helicase The ADP content generated by ATP hydrolysis catalyzed by WRN helicase was measured using a commercial ADP-Glo assay kit (Promega, #V9102), and the measured ADP level could reflect the ATPase activity of WRN helicase. The 45 nt oligonucleotide single-stranded DNA FLAP26 (TTTTTTTTTTTTTTTTTTTTTTCCAAGTAAAACGACGGCCAGTGC) was synthesized by Azenta. Reference was made, for example, to Brosh RM Jr et al., J Biol Chem, 2002 Jun;277(26):23236-45. A reaction buffer (30 mM Tris pH 7.5, 2 mM MgCl2, 0.02% BSA, 50 mM NaCl, 0.1% pluronic F127) was prepared. To a 384-well clear plate were sequentially added 5 liL of 3X test compound (which was diluted in the reaction buffer to contain 0.5% DMSO, with a final initial concentration of 10 gM and subjected to 1:3 serial dilution to obtain a total of 9 concentration gradients), 5 uL of 3X WRN recombinant protein, and 3X ATP substrate solution (diluted in the reaction buffer, with final concentrations of WRN and ATP being 10 nM and 300 ^M, respectively). The resulting mixture was mixed well by shaking and incubated at 37 °C for 3 h. Subsequently, a 3X FLAP26 solution was prepared using the reaction buffer, and 5 gL of the solution (with a final FLAP26 concentration of 0.4 nM) was added to the 384-well clear plate. The mixture was mixed well by shaking to initiate the enzymatic reaction, and then incubated at room temperature for 30 min. 5 gL of the above mixture was transferred to a 384-well white plate, and 5 gL of ADP-Glo reagent was added. The mixture was mixed well by shaking, and incubated at room temperature in the dark for 40 min. 10 gL of kinase detection reagent was added to the above solution. The mixture was mixed well by shaking and incubated at room temperature in the dark for 30 min, and then chemiluminescence readings were recorded. The inhibition rate of the compound on the enzyme activity was calculated, and the inhibition rate value and the logarithm value of the compound concentration were fitted using non-linear regression (dose response-variable slope) to obtain the IC50 value of the test compound. Table 1. WRN ATPase activity data of compounds in the examples of the present application Compound WRN ATPase activity inhibition IC50 (gM) C89-P1 0.001 C89-P2 0.273 C89-P3 0.003 C88-P1 0.002 C88-P2 0.134 C88-P3 0.011 C87-P1-B 0.02 C87-P2-B 0.006 C90-P2 0.01 C90-P3 0.013 C93-P1 0.009 C93-P3 0.009 C43-P1 0.004 C43-P3 0.004 C142-P1 0.001 C142-P3-B 0.001 C143-P1 0.014 C143-P3 0.017 C144-P1 0.022 C144-P3-B 0.005 C145 0.002 C145-P1 0.007 C145-P2 0.005 C147 0.001 As can be seen from Table 1, the compounds of the present application exhibited good inhibitory activity against the ATPase activity of WRN protein. Inhibitory activity assay for tumor cell proliferation Cell line Catalog No. Manufacturer HCT116 CBP60028 Nanjing Cobioer SW48 FH0526 Fuheng DLD1 FH0017 Fuheng A DLD1-WRN-KO cell line was constructed by stably knocking out the WRN gene in DLD1 cells using CRISPR / Cas9 technology, and the constructed cell line was used to evaluate potential off-target effects of the compounds. Human colonic adenocarcinoma SW48 cells were cultured in monolayer in vitro under the following conditions: DMEM medium containing 10% fetal bovine serum and 1% penicillin and streptomycin, at 37 °C with 5% CO2. Human colonic adenocarcinoma HCT116 cells were cultured in monolayer in vitro under the following conditions: McCOY's5A medium containing 10% fetal bovine serum and 1% penicillin and streptomycin, at 37 °C with 5% CO2. DLD1-WRN-KO cells were cultured in monolayer in vitro under the following conditions: 1640 medium containing 10% fetal bovine serum and 1% penicillin and streptomycin, at 37 °C with 5% CO2. The cells were digested with trypsin twice a week for passaging. After treatment of SW48 cell lines and HCT116 cell lines with microsatellite instability and the control DLD1-WRN-KO cell line using the test compounds for 4 days, ATP levels were measured using a CellCounting-Lite kit from Vazyme to evaluate inhibitory effects of the test compounds on the growth of tumor cell lines. In the present application, the SW48 cell line, the HCT116 cell line, and the DLD1-WRN-KO cell line were seeded into a 96-well cell culture plate at an appropriate cell density. After 24 h, the cells were treated with the test compounds at the highest concentration of 10 ^M, followed by 1:3 serial dilution to obtain 9 concentration gradients, and a DMSO treatment group was set up separately. The cells were cultured in an incubator at 37 °C with 5% CO2 for 4 days. To evaluate inhibitory effects of the test compounds on tumor cell proliferation, the cells were equilibrated at room temperature for 30 min, and then 100 gL of a cell proliferation detection reagent, CellCounting-Lite (CCL), was added to each well. The plate was shaken for 5 min and then incubated in the dark for 10 min. Chemiluminescence values were read using a Thermo Varioskan LUX-3020 multifunctional microplate reader for conversion to proliferation indices to calculate the inhibition rate of the compound on tumor cell proliferation, and the inhibition rate value and the logarithm value of the compound concentration were fitted using nonlinear regression (dose response-variable slope) to obtain the IC50 value of the compound. Table 2. Inhibitory activity data of compounds in the examples of the present application against 5                                             tumor cell proliferation Compound SW48 Proliferation inhibition IC50 (gM) HCT116 Proliferation inhibition IC50 (gM) DLD1-WRN-KO Proliferation inhibition IC50 (gM) C89-P1 0.0002 >10 C89-P2 0.24 >10 C89-P3 0.0002 >10 C88-P1 0.0004 >10 C88-P2 0.087 >10 C88-P3 0.002 >10 C87-P1-B 0.109 >10 C87-P2-B 0.001 >10 C90-P2 0.148 >10 C90-P3 0.029 >10 C93-P1 0.010 0.019 >10 C93-P3 0.0042 0.0054 >10 C43-P1 0.010 0.009 >10 C43-P3 0.011 0.004 >10 C142-P1 0.001 0.0025 >10 C142-P3-B 0.0002 0.0001 >10 C143-P1 0.012 0.0097 >10 C143-P3 0.0027 0.0072 >10 C144-P1 0.018 >10 C144-P3-B 0.006 >10 C146-P1 0.011 >10 C146-P3-B 0.008 >10 C145 0.014 >10 C145-P1 0.018 0.015 >10 C145-P2 0.012 0.007 >10 C147 0.2 0.11 >10 As can be seen from Table 2, the compounds of the present application exhibited good proliferation inhibition activity on SW48 cells and HCT116 cells with microsatellite instability, while no significant proliferation inhibition activity was observed against WRN knockout DLD1 cells, indicating good selectivity. Experimental Example 2: Stability Assay in Liver Microsomes Phase I metabolic stability of the test compounds in liver microsomes of CD-1 mice, Sprague-Dawley rats, beagle dogs, cynomolgus monkeys, and humans was assessed. Experimental system: The animal and human liver microsomes used in the assay system were purchased from Xenotech, Corning, or other qualified suppliers and stored in a freezer at a temperature below -60 °C prior to use. Brief introduction of the experiment: The test samples and control compounds were separately incubated with animal and human liver microsomes at 37±1 °C for a period of incubation time up to 60 min. The samples were removed at the indicated time points, and the reaction was stopped with acetonitrile or another organic solvent containing an internal standard. After centrifugation, the resulting supernatants were assayed by the liquid chromatography-tandem mass spectrometry (LC-MS / MS) method. Experimental method: 1. Preparation of buffer 73.21 g of dipotassium hydrogen phosphate trihydrate and 10.78 g of potassium dihydrogen phosphate were dissolved in 4000 mL of ultrapure water. The solution was adjusted to pH 7.40±0.10 with 10% phosphoric acid or 1 M potassium hydroxide to make a final concentration of 100 mM. 2. Preparation of working solutions The test sample powder was prepared into a stock solution at a certain concentration with DMSO or another organic solvent, which was then further diluted with a suitable organic solvent. The reference compounds testosterone, diclofenac, and propafenone were each prepared into a 10 mM stock solution with DMSO, which was then further diluted with a suitable organic solvent. 3. Preparation of liver microsome solution Microsomes of each species were diluted into a 2x working solution with a 100 mM potassium phosphate buffer. The final concentration of the microsomes in the reaction system was 0.5 mg / mL. 4. Preparation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) regeneration system An appropriate amount of nicotinamide adenine dinucleotide phosphate (NADP) and isocitric acid (ISO) powder was weighed out, dissolved in a magnesium chloride solution, and mixed well by shaking. An appropriate amount of isocitrate dehydrogenase (IDH) was added, and the mixture was mixed well by gently turning upside down. The final concentrations in the reaction system were: 1 mM NADP, 1 mM magnesium chloride, 6 mM ISO, and 1 unit / mL IDH. 5. Preparation of stop solution The stop solution was prepared with acetonitrile or another organic solvent containing an internal standard (tolbutamide or another suitable compound). The prepared stop solution was stored in a freezer at 2-8 °C. 6. Incubation process Incubation was performed in a 96-well plate. Eight incubation plates were prepared and designated T0, T5, T15, T30, T45, T60, Blank60, and NCF60, respectively. The first 6 plates corresponded to reaction time points of 0 min, 5 min, 15 min, 30 min, 45 min, and 60 min, respectively. No test sample or reference compound was added to the Blank60 plate, and samples were taken after 60 min of incubation. In the NCF60 plate, incubation was performed for 60 min using the potassium phosphate buffer instead of the NADPH regeneration system solution. Three replicates were made for samples in all conditions. The microsomes and the test sample or reference compound were mixed, and then the incubation plates Blank60, T5, T15, T30, T45, and T60 except for T0 and NCF60 were placed in a 37 °C water bath for pre-incubation for about 10 min. In the incubation plate T0, a stop solution was first added, followed by the addition of the NADPH regeneration system working solution, and 98 liL of the potassium phosphate buffer was added to each sample well of the incubation plate NCF60 to initiate the reaction. After the pre-incubation of the incubation plates Blank60, T5, T15, T30, T45, and T60 was completed, 98 uL of the NADPH regeneration system working solution was added to each sample well to initiate the reaction. The reaction temperature was 37±1 °C, the final volume of the reaction was 200 liL, and the reaction system included 0.5 mg / mL microsomes, 1.0 uM substrate, 1 mM NADP, 6 mM ISO, and 1 unit / mL IDH. At 5 min, 15 min, 30 min, 45 min, and 60 min, a cold stop solution containing an internal standard was added to the reaction plate to stop the reaction. All the reaction plates after the reaction was stopped were shaken well and centrifuged at 3220^ g at 4 °C for 20 min. After the supernatant was diluted at a certain ratio, LC-MS / MS analysis was performed. Sample analysis Sample analysis was performed by the liquid chromatography-tandem mass spectrometry (LC-MS / MS) method without standard curves and quality control samples. Semi-quantitative determination was performed according to the ratio of the analyte peak area to the internal standard peak area. The retention times of the analyte and internal standard, the chromatogram acquisition, and chromatogram 5 integration were processed using the Analyst software (Sciex, Framingham, Massachusetts, USA). The CV for the internal standard peak area in each matrix in each analysis batch should be within 20%. Data analysis The in vitro elimination rate constant ke of the compound was obtained by converting the ratio of the peak area of the compound to the internal standard peak area in the following formula into the 10 remaining rate: Peak area ratio of compound to internal standard at any time Remaining rate (%) =                            point                            x 100 Peak area ratio of compound to internal standard at 0 min Ct C0 • e-ke •t when C T1 / 2 = 1 C 2  0 Ln2    0.693 ke ke 15 CLint (mic) = 0.693 / T1 / 2 / microsome protein content (microsome concentration during incubation in mg / mL) CLint (liver) = CLint (mic) x microsome protein amount in liver (mg / g) x liver-to-body weight ratio According to the well stir model, the hepatic intrinsic clearance and hepatic clearance can be converted through the following formula. CL(liver) = (CLint (liver) x Qh) / (CLint (liver) + Qh) Parameters in the formula are shown in the table below. Parameters in the data analysis formula Liver-to-body    weight Liver blood flow volume Microsome       protein Species ratio (Qh) amount (g / kg body weight) (mL / min / kg) (mg / g liver weight) Mouse 88 90.0 Rat 40 55.2 45 Dog 32 30.9 Monkey 30 43.6 Human 20 20.7 Experimental Example 3: Metabolic Stability Assay in Hepatocytes This experimental example was used to assay the metabolic stability of the compounds in hepatocytes. A suspension of hepatocytes was prepared at 0.5 x 106 / mL with a pre-heated medium, then 198 liL of the pre-heated cell suspension was added to a 96-well plate. To each well of the 96-well plate, 2 liL of the test compound was added so that the final concentration was 1 lM, and 2 replicate wells were set. For the T = 0 min sample, the compound was mixed well with the cells for 1 min, then 25 lL of the sample was immediately added to 125 lL of a stop solution (an acetonitrile solution containing 200 ng / mL tolbutamide and 200 ng / mL labetalol) in an ice bath, and the mixture was mixed well. At the same time, all the plates were placed in an incubator at 37 °C with 5% CO2, with the shaker set at 600 rpm. The sample was mixed well at 15, 30, 60, and 90 min of incubation, separately. 25 lL of the sample was added to 125 lL of a stop solution (an acetonitrile solution containing 200 ng / mL tolbutamide and 200 ng / mL labetalol) in an ice bath, and the mixture was mixed well and shaken at 500 rpm for 10 min. Subsequently, the plate was centrifuged for 20 min at 3220x g at 4 °C. After the centrifugation was completed, 80 lL of the supernatant from each well was transferred to another 96-well plate containing 240 lL of ultrapure water. Subsequently, analysis was carried out using LC-MS / MS, and intrinsic clearance (CLint) and half-life (T1 / 2) were calculated. Experimental Example 4: Pharmacokinetic Study in Rats In this experimental example, the pharmacokinetic profile of the compounds after administration by intravenous injection (IV) and oral gavage (PO) in SD rats was evaluated. On the day of administration, rats were weighed for actual body weight, and the administration volume was calculated. Each compound was tested in two groups with 3 rats in each group; one group was subjected to administration by single intravenous injection, and the other group was subjected to administration by single oral gavage. Whole blood samples were collected via the jugular vein at prescribed time points (0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, and 24 h after administration). After the blood sample collection, the samples were immediately transferred to labeled commercial sample tubes containing K2-EDTA (0.85-1.15 mg), followed by centrifugation (3200x g, 4 °C, 10 min) and plasma collection. The plasma was transferred to a pre-cooled centrifuge tube, frozen in dry ice, and then stored in an ultra-low temperature freezer at -60 °C or lower until the LC-MS / MS analysis was performed. Plasma concentrations were determined by the LC-MS / MS method. Plasma drug concentration data for the compounds were processed using a non-compartmental model in the WinNonlin Version 6.3 (Pharsight, Mountain View, CA) pharmacokinetic software. The relevant pharmacokinetic parameters were calculated by a linear-log trapezoidal method. Experimental Example 5: Pharmacokinetic Study in Mice In this experimental example, the pharmacokinetic profile of the compounds after administration by intravenous injection (IV) and oral gavage (PO) in BALB / c mice was evaluated. On the day of administration, mice were weighed for actual body weight, and the administration volume was calculated. Each compound was tested in two groups with 9 mice in each group; one group was subjected to administration by single intravenous injection, and the other group of mice was subjected to administration by single oral gavage. Whole blood samples were collected via the orbit at prescribed time points (0.083 h, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, and 24 h after administration). After the blood sample collection, the samples were immediately transferred to labeled commercial sample tubes containing K2-EDTA (0.85-1.15 mg), followed by centrifugation (3200x g, 4 °C, 10 min) and plasma collection. The plasma was transferred to a pre-cooled centrifuge tube, frozen in dry ice, and then stored in an ultra-low temperature freezer at -60 °C or lower until the LC-MS / MS analysis was performed. Plasma concentrations were determined by the LC-MS / MS method. Plasma drug concentration data for the compounds were processed using a non-compartmental model in the WinNonlin Version 6.3 (Pharsight, Mountain View, CA) pharmacokinetic software. The relevant pharmacokinetic parameters were calculated by a linear-log trapezoidal method. Compound No. Route of administration Administration dose (mg / kg) AUCc-t (ngx h / mL) IV C0h or PO Cmax (ng / mL) T1 / 2 (h) C142-P3-B IV 2 9224 2360 5.6 PO 10 55042 6096 6.5 C146-P3-B IV 2 4530 2013 3.5 PO 10 28222 5299 4.1 Experimental Example 6: hERG Inhibition Assay HEK293 cells were cultured in a DMEM medium containing 10% fetal bovine serum and 0.8 mg / mL G418 at 37 °C with 5% CO2. The cells were digested by TrypLE™ Express and then centrifuged. The cell density was adjusted to 2 x 106 cells / mL. The cells were then gently mixed for 15 to 20 min using a shaker equilibrated at room temperature, and subjected to a patch clamp assay on a machine. The medium of the prepared cells was replaced with extracellular fluid. The intracellular fluid and the extracellular fluid were taken from the fluid pool and added to the intracellular fluid pool and the cell and test substance pool of the QPlate chip, respectively. The voltage stimulation of the whole-cell hERG potassium current was recorded by the whole-cell patch clamp, and the experimental data were collected and stored by Qpatch. The compound was subjected to a 3-fold dilution starting from 30 liM to obtain 6 concentration points, each for two administrations over a period of at least 5 min. The current detected in compound-free extracellular fluid for each cell served as its own control group, and the detection was repeated twice independently using at least two cells per concentration. All electrophysiological experiments were performed at room temperature. For data analysis, the current after the action of each drug concentration and the current of the blank control were standardized (Peak tail current compound), and then the inhibition rate corresponding to each drug Peak tail currentvehicle concentration was calculated (1- Peak tail.currentcompound). The mean and standard error were calculated for Peak tail currentvehicle each concentration, and the half maximal inhibitory concentration of each compound was calculated: Y = Bottom + Top - Bottom 1 + 10A((LogIC5Q- C) x HillSlope) . The dose-dependent effect was fitted non-linearly using the above equation, where Y represents the inhibition rate, C represents the concentration of the test substance, IC50 is the half maximal inhibitory concentration, and HillSlope represents the Hill coefficient. Curve fitting and calculation of IC50 were performed using Graphpad software. Experimental Example 7: Cytochrome Oxidase P450 Inhibition Assay 1) Preparation of buffer: 100 mM K-Buffer: 9.5 mL of stock solution A was mixed with 40.5 mL of stock solution B, the total volume was adjusted to 500 mL with ultrapure water, and the buffer was titrated to pH 7.4 with KOH or H3PO4. Starting material A (1 M potassium dihydrogen phosphate): 136.5 g of potassium dihydrogen phosphate in 1 L of water; stock B (1 M potassium dihydrogen phosphate): 174.2 g of potassium dihydrogen phosphate in 1 L of water. 2) Preparation of test substance The test substance powder was prepared into a stock solution at a certain concentration with DMSO or another organic solvent, which was then further diluted with a suitable organic solvent. 3) In vitro incubation The liver microsomal in vitro incubation system for the CYP450 enzyme metabolism phenotype study was a biochemical reaction of the prepared liver microsomes supplemented with a redox coenzyme and an enzyme-specific selective inhibitor under simulated physiological temperature and physiological environment conditions. 4) Detection of parent drug or metabolite The concentration of the parent drug or a metabolite thereof in the incubation solution was determined by LC-MS / MS. Experimental Example 8: Pharmacodynamic Model of Mouse Tumor In this experimental example, the in vivo efficacy of the compound in a mouse xenograft tumor model after administration by oral gavage (PO) was studied. Human colonic adenocarcinoma SW48 cells were cultured in monolayer in vitro under the following conditions: DMEM medium containing 10% fetal bovine serum and 1% penicillin and streptomycin, at 37 °C with 5% CO2. The cells were digested with trypsin twice a week for passaging. When the saturation degree of the cells was 80% to 90%, the cells were collected, counted, and inoculated. 0.1 mL (107 cells) of SW48 cells were subcutaneously inoculated on the right back of each mouse. On day 14 after inoculation of the cells, the mean tumor volume reached about 200 mm3. The mice were randomly grouped for administration and intragastrically dosed once daily. Changes in body weight and tumor volume were recorded. After a certain number of days of administration, the experiment was ended. Tumor volume changes and mouse body weight changes were counted and analyzed. The results showed that the compound of the present application exhibited excellent tumor inhibition effects. Experimental Example 9: PXR Activation Assay In this experimental example, the compound was assayed for PXR activation. 100 uL of stably transfected DPX2 cells were seeded to each well of a 96-well cell culture plate (4.5 x 105 cells / mL in Puracyp medium), and the 96-well plate was then placed in a 37 °C incubator. After 24 h, the 96-well plate was taken out from the incubator, the medium was replaced with 100 liL of the test compound (at a final concentration of 10 liM and 30 liM), positive control compound rifampicin (at a final concentration of 10 lM), and the DMSO treatment group (at a final concentration of 0.1%), and 3 replicate wells were set. The test plate was placed back into the incubator. After 24 h, the medium was replaced with the freshly prepared test compound and rifampicin solution, and the test plate was placed into the incubator again. After the compound was treated for 48 h, the test plate was taken out from the incubator. The medium in the wells was discarded, and the plate was washed twice with PBS. 50 lL of a medium containing 1x CellTiter-Fluor™ cell viability assay reagent was added, and the mixture was incubated at 37 °C for 30 min. The test plate was taken out and equilibrated to room temperature, and the fluorescence signal under the conditions of 400 nm excitation light / 505 nm emission light was detected by a microplate reader. Subsequently, 50 lL of a medium containing ONE-Glo assay reagent was added to each well, and the plate was mixed well by shaking and then incubated at room temperature for 5 min. Chemiluminescence was detected by a microplate reader. The data was analyzed to evaluate activation effect of the test compound on PXR. The results showed that the compound of the present application did not exhibit significant PXR activation activity. Experimental Example 10: Test of Saturation Solubility of Samples in FaSSIF Solution 1. Experimental procedure 1.1 Preparation of FaSSIF solution Preparation of buffer (pH 6.5): About 0.21 g of sodium hydroxide, about 2.24 g of sodium dihydrogen phosphate dihydrate, and 3.09 g of sodium chloride were weighed out and dissolved in 500 mL of water, and after dissolution, the pH was adjusted to 6.5 with 1 N sodium hydroxide or 1 N hydrochloric acid. 112 mg of FaSSIF solid was weighed out and placed in a 50 mL volumetric flask, and the buffer described above was added for dissolution. The resulting solution was diluted to volume, mixed well, and left to stand at room temperature for 2 h or more. 1.2 Preparation of sample 5 Test sample: About 1 mg of the test sample was taken, and 1 mL of FaSSIF solution was added. The mixture was stirred at room temperature overnight and centrifuged, and the supernatant was collected for analysis. Reference sample solution: About 1.5 mg of the test sample was precisely weighed out and placed in a 50 mL volumetric flask, and DMF was added for dissolution. The resulting solution was diluted to 10 volume and mixed well to obtain the reference sample solution. 1.3 Preparation of mobile phase Mobile phase A: 1000 mL of purified water was accurately measured, 1 mL of formic acid was added, and the mixture was mixed well and degassed by ultrasonication to obtain mobile phase A. Mobile phase B: Acetonitrile. 15    1.4 Chromatographic conditions Instrument HPLC Chromatographic column Waters XBridge C18, 4.6 x 50 mm 3.5 Lim Sample tray (°C) off Column temperature (°C) 30 UV wavelength (nm) 254 Needle washing solution MeOH Flow rate (mL / min) 1.0 Run time (min) 6 Gradient elution table Time (min) Mobile phase A (%) Mobile phase B (%) 0 90 10 0.5 90 10 6 10 90 7 10 90 7.1 90 10 10 90 10 Experimental Example 11:Co-crystallization of Small Molecules with WRN Protein The purified recombinant WRN (500-945) protein (storage buffer: 50 mM HEPES, 500 mM NaCl, 0.5 mM TCEP, pH 7.5, 5% glycerol) was concentrated to 7 mg / mL and mixed with the corresponding compound dissolved in 100% DMSO to obtain a final compound concentration of 2 mM. Subsequently, the mixture was incubated at 4 °C for 2 h, and then centrifuged at 12,000 rpm for 10 min at 4 °C using a benchtop refrigerated centrifuge (eppendorf 5418 R). Crystallization was then performed using a Mosquito Xtal3 or Formulatrix NT8 liquid handling robot. Kits used for crystallization were commercially available kits, such as Crystal Screen / Crystal Screen 2, Index, PEG / Ion, and PEGRx HT from Hampton Research. The obtained initial crystals were optimized based on the corresponding conditions. Finally, diffraction-quality crystals were obtained under the following conditions: 0.1 M sodium citrate (pH 5.0) with 8-12% w / v PEG 6000, or 0.2 M potassium sodium tartrate with 0.1 M BIS-TRIS (pH 6.5) with 8-12% w / v PEG 10,000, or 0.1 M sodium citrate (pH 5.0) with 16-20% w / v PEG 20,000. The crystals were cryoprotected under the crystallization conditions supplemented with 20%-25% glycerol, then flash-frozen in liquid nitrogen, and sent to a synchrotron radiation source for data collection. Experimental Example 12: CYP Induction Assay 1)Preparation and plating of human hepatocytes Preparation of media The following media were prepared in a biosafety cabinet and stored at 4 °C before use: Hepatocyte thawing medium (prepared by mixing the following components: Williams E medium, isotonic Percoll, DPBS, glutamine, HEPES, fetal bovine serum, recombinant human insulin, and dexamethasone). Plating medium (prepared by mixing the following components: Williams E medium, fetal bovine serum, dexamethasone, penicillin / streptomycin, recombinant human insulin, glutamine, and HEPES). Incubation medium (prepared by mixing the following components: Williams E medium, dexamethasone, ITS, penicillin / streptomycin, glutamine, and HEPES, serum-free). Thawing and treatment of hepatocytes A vial of cryopreserved human hepatocytes was thawed in a water bath at 37 °C for 2 min. The vial was wiped with 70% ethanol in a biosafety cabinet. The hepatocytes were transferred to 50 mL of prewarmed hepatocyte thawing medium using a wide-bore pipette tip. About 500 liL of hepatocyte thawing medium was added to rinse the vial thoroughly, the cap was closed, and the vial was inverted several times. The cells were centrifuged at 150 g at room temperature for 10 min. The supernatant was carefully pipetted, and the cells were diluted with the plating medium to a seeding density of 0.55 x 106 cells / mL. 100 lL of the cell suspension was transferred to each well of a collagen I-coated 96-well plate. The plate was placed in an incubator and incubated at 37 °C under an atmosphere of 5% CO2 / 95% air and 95% relative humidity for 4-6 h. Subsequent treatment After incubation, the cell morphology was observed under a microscope. The plate was gently shaken to loosen debris, and 125 liL of medium was replaced with 0.25 mg / mL Matrigel diluted in the incubation medium. The plate was placed back into the incubator and incubated for another 18 h. At this point, the cultures were ready for induction studies. 2) Co-incubation with test compounds Preparation of compounds The test compounds were prepared in DMSO at 1000^ the highest working concentration and were also prepared at the highest working concentration in the incubation medium, and the solubility of the compounds in both solutions was determined by visual inspection. Then, 1000^ stock solutions at the final concentrations of the test compounds, negative control, and positive control inducer were prepared in DMSO and diluted to their respective working concentrations using the incubation medium prewarmed to 37 °C. The negative control was prepared by adding 5 liL of DMSO to 5 mL of warm incubation medium. In some cases, the test compounds were prepared using a higher concentration of DMSO or were directly prepared at the final concentration in a medium containing 0.1% DMSO. The concentrations of the test compounds and the positive control inducer (rifampicin) were 10 liM. Treatment procedure The hepatocyte plates were removed from the incubator. The cell morphology was observed under a microscope. The medium in the corresponding wells was replaced with DMSO control, inducer, or test compound solutions, with three replicates set for each treatment. Incubation and medium exchange After 24 h and 48 h, the hepatocyte plates were removed from the incubator, and the cell morphology was observed under a microscope. The medium was replaced with freshly diluted test compounds from the DMSO stock solution. The plates were returned to the incubator. The total incubation time was 72 h. 3) mRNA preparation and RT-PCR mRNA preparation mRNA was prepared and measured using the Cells-to-Ct kit purchased from Life Technologies. The remaining CellTiter cell viability assay reagent was removed by pipetting, and the cell monolayer was washed twice with 125 lL of phosphate-buffered saline. The plate was then placed on ice. DNase was added to the lysis solution according to the instructions. 50 lL of lysis solution was added to each well of the hepatocyte plate, and the lysis reaction was mixed by pipetting up and down 5 times. The lysis reaction was performed by incubation at room temperature for 8 min, followed by addition of 5 liL of stop solution to each lysis reaction and mixing by pipetting up and down 5 times. The mixture was incubated at room temperature for another 2 min. The lysates could be stored at -20 °C or -80 °C for up to 5 months prior to the RT reaction. Reverse transcription reaction The QPCR system was programmed for reverse transcription as follows: reverse transcription (hold), 1 cycle, 37 °C for 60 min; RT inactivation (hold), 1 cycle, 95 °C for 5 min; hold, 1 cycle, 4 °C indefinitely. A mixture for 106 reactions was prepared in a 15 mL tube and then distributed into the corresponding wells of a 96-well PCR plate. One tube of mixture was prepared per plate. Reverse transcriptase master mix: 2x RT buffer, 25 liL for each reaction; 20x RT enzyme mixture, 2.5 oL for each reaction; nuclease-free water, 7.5 lL for each reaction; final volume of reverse transcription master mix: 35 lL. 15 lL of sample lysate was added to each aliquot of the reverse transcription master mix to obtain a final reaction volume of 50 lL. The negative control (NC) was prepared by adding 15 lL of the mixture from the previous step (not incubated with cells). After assembly, the reactions were gently mixed and briefly centrifuged to collect the contents at the bottom of the reaction vessels. The samples were incubated at 37 °C for 60 min using the QPCR system, followed by incubation at 95 °C for 5 min to inactivate the RT enzyme. The prepared RT samples were stored at -20 °C until QPCR analysis. Real-time PCR cycling The QPCR system was programmed for real-time PCR cycling as follows: enzyme activation (hold), 1 cycle, 95 °C for 5 min; PCR (cycling), 45 cycles, 95 °C for 15 s and 60 °C for 1 min. A separate PCR cocktail was prepared for CYP3A4, and each cocktail contained a CYP-specific probe set and an ACTB probe set as an endogenous control gene. PCR cocktail: Taqman gene expression master mix (2x), 10 liL per reaction; Taqman gene expression detection probe (20x, CYP3A4, FAM-labeled), 1 liL per reaction; Taqman gene expression detection probe (20x, ACTB, VIC-labeled), 1 liL per reaction; nuclease-free water, 4 liL per reaction; final volume of PCR cocktail, 16 lL. The PCR cocktail was distributed into the wells of a real-time PCR plate at room temperature. The cDNA samples were diluted 3-fold with nuclease-free water. 4 lL of the diluted cDNA sample was added to each aliquot of the PCR cocktail to obtain a final volume of 20 lL. The plate was sealed and gently mixed. Centrifugation was then briefly performed to collect the contents at the bottom of the wells. For each PCR plate, 4 lL of RT mixture without cell lysate was added to the PCR cocktail in 2 wells as a negative control. The standard curve template was prepared by 3-fold serial dilutions of a mixture of cDNA samples from corresponding rifampicin-induced samples, with the undiluted sample serving as the highest concentration. The reactions were placed in the QPCR system, and the real-time PCR cycling program was used to initiate the process. 4) Data analysis: determination of mRNA Levels All calculations were performed using Microsoft Excel. The mRNA level in each vial was expressed as 2Ct (ACTB)-Ct (CYP). The induction fold of mRNA levels was determined according to the following formula: induction fold = mRNA (induced) / mRNA (solvent control). The results showed that the compound of the present application did not exhibit significant CYP induction activity. Experimental Example 13: Caco-2 Permeability Assay 1) Cell culture: Caco-2 cells used in the study were cultured in DMEM basal culture solution at 37 °C with 5% CO2. The DMEM basal culture solution contained 10% fetal bovine serum, penicillin-streptomycin solution (100 U / mL and 0.1 mg / mL), 1% MEM non-essential amino acids, and 25 liM HEPES. The cells were seeded into a Transwell-24-well plate at a density of 1.00 x 105 cells / mL. The cells were cultured in a CO2 incubator for 21 days prior to use in transport experiments, during which the medium was replaced every three days. 2) Preparation of solutions: The donor solutions were a high-efflux control substance roxithromycin solution, a high-permeability control substance metoprolol solution, a low-permeability control substance atenolol solution, and a test compound solution. HBSS was used to prepare both donor and receiver solutions. Solutions for apical to basal (A-B) transport experiments were prepared as follows: the 10 lM donor solution at the apical side contained 5 lM lucifer yellow and 0.4% DMSO; the receiver solution at the basal side contained 0.4% DMSO. Solutions for basal to apical (B-A) transport experiments were prepared as follows: the receiver solution at the apical side contained 5 lM lucifer yellow and 0.4% DMSO; the 10 lM donor solution at the basal side contained 0.4% DMSO. 3) Incubation procedures: ® Quality control experiment prior to permeability assay: Before the assay, the transepithelial electrical resistance of the cells was measured using a resistance meter, and the apparent transmembrane resistance of the monolayer membrane was calculated. ® Permeability assay: Before the experiment, the cell culture in the culture plate was aspirated, and the cells were then washed three times (both apical and basal sides) with HBSS buffer pre-warmed to 37 °C. A-B transport experiment: The buffer in the plate was removed by pipetting, and 800 lL of HBSS buffer pre-warmed to 37 °C was added to the basal side. 600 lL of each of roxithromycin solution, metoprolol solution, atenolol solution, and test compound solution pre-warmed to 37 °C was separately added to the apical side. 100 lL of solution was withdrawn from the apical side as the 0-minute apical-side sample and stored at -20 °C for analysis. B-A transport experiment: The buffer in the plate was removed by pipetting, and 500 ^L of HBSS buffer pre-warmed to 37 °C was added to the apical side. 900 ^L of each of roxithromycin solution, metoprolol solution, atenolol solution, and test compound solution pre-warmed to 37 °C was separately added to the basal side. 100 ^L of solution was withdrawn from the basal side as the 0-minute basal-side sample and stored at -20 °C for analysis. The culture plate was incubated in a cell incubator for 90 min. After incubation, 100 uL of solution was collected from both the apical and basal sides of all samples as the 90-minute samples and stored at -20 °C for analysis. Standard curves were prepared for roxithromycin, metoprolol, atenolol, and the test compound. All samples were mixed with acetonitrile containing an internal standard and analyzed by LC-MS / MS. ® Quality control experiment of permeability assay (assessment of the integrity of cell membrane): At 0 min, 100 uL of solution was taken from the apical side of both A-B and B-A experiments and transferred into a black 96-well plate. After 90 min of incubation, 100 uL of solution was taken from the basal side of both A-B and B-A experiments and transferred into a black 96-well plate. Fluorescence intensity was measured using a fluorescence microplate reader at an excitation wavelength of 485 nm and an emission wavelength of 527 nm. 4) Data analysis Permeability: Apparent permeability coefficient (Papp) = (volume of receiver end solution / (membrane surface area x time)) x (drug concentration at receiver end at 90 min x dilution factor) / (drug concentration at donor end at 0 min x dilution factor), where the time represented the total transport time in seconds. Recovery rate: Recovery rate% = 100 x (drug concentration at receiver end at 90 min x volume of receiver end solution x dilution factor + drug concentration at donor end at 90 min x volume of donor end solution x dilution factor) / (drug concentration at donor end at 0 min x volume of donor end solution x dilution factor). Efflux ratio (ER) = apparent permeability coefficient from B-A direction (Papp) / apparent permeability coefficient from A-B (Papp) Various modifications of the present disclosure in addition to those described herein will be apparent to those skilled in the art on the basis of the aforementioned description. Such modifications are also intended to fall within the scope of the appended claims. References (including all patents, patent applications, journal articles, books, and any other publications) cited in the present application are all incorporated herein by reference in their entirety.

Claims

1. A compound, or a pharmaceutically acceptable salt, an ester, a stereoisomer, an atropisomer, a tautomer, a polymorph, a solvate, a metabolite, an isotopically labeled compound, or a prodrug thereof,wherein the compound has a structure of formula (I):(I)wherein:--- represents a single bond or a double bond, with the proviso that two double bonds are not directlyconnected;W1, W2, W3, and W4 are each independently C or N, with the proviso that C is attached to one double bond; preferably, at least one of W1 and W2 is N, and / or at least one of W3 and W4 is N;is selected fromandR1, R3, R21, and R22, at each occurrence, are each independently selected from H, a deuterium atom,halogen, -OH, -NH2, -CN, -NO2, -SF5, =CH2, C1-6 alkyl, deuterated C1-6 alkyl, C1-6 haloalkyl, C2-6alkenyl, C2-6 alkynyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14membered heteroaryl, C6-12 aralkyl, -C(=O)Ra, -OC(=O)Ra, -C(=O)ORa, -ORa, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRaRb, -S(=O)(=NRa)Rb, -NRaRb, -C(=O)NRaRb, -NRa-C(=O)Rb, -NRa-C(=O)ORb, -NRa-S(=O)2-Rb, -NRa-C(=O)-NRaRb, -P(=O)RaRb, -C1-6 alkylene-Ra, -C1-6 alkylene-ORa, -C1-6alkylene-NRaRb,   -O-C1-6   alkylene-NRaRb, (-C3-6   cyclohydrocarbylene)-CN, and (-C3-6cyclohydrocarbylene)-C1-6 alkyl;when m is greater than 1, two R3 located at the same ring atom or adjacent ring atoms, together with the group to which they are attached, optionally form a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, or a 5- to 14-membered heteroaromatic ring;R4 is;L2 is selected from -O-, -C(=O)-, -NRC(=O)-, -S-, -S(=O)-, -S(=O)2-, C1-6 alkylene, and -O-(C1-6alkylene)-;R41 is selected from a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring;R, Ra, and Rb, at each occurrence, are each independently selected from H, C1-6 alkyl, C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and C6-12 aralkyl;ring B, ring X, and ring Z are each independently selected from a C3-6 hydrocarbon ring, a 3- to 10membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring;ring Y is absent or selected from a C3-6 hydrocarbon ring, a 3- to 10-membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring; when ring Y is absent, R22 is also absent; the alkylene, the alkyl, the alkenyl, the alkynyl, the cyclohydrocarbylene, the cyclohydrocarbyl, the hydrocarbon ring, the heterocyclyl, the heterocyclic ring, the aryl, the aromatic ring, the heteroaryl, the heteroaromatic ring, and the aralkyl described above, at each occurrence, are each optionally substituted with one or more substituents independently selected from the following: a deuterium atom, halogen, -OH, =O, -NH2, -CN, -NO2, =CH2, C1-6 alkyl, deuterated C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, -C(=O)Rc, -OC(=O)Rc, -C(=O)ORc, -ORc, -SRc, -S(=O)Rc, -S(=O)2Rc, -S(=O)2NRcRd, -NRcRd, -C(=O)NRcRd, -NRc-C(=O)Rd, -NRc-C(=O)ORd, -NRc-S(=O)2-Rd, -NRc-C(=O)-NRcRd, -C1-6 alkylene-ORc, -C1-6 alkylene-NRcRd, and -O-C1-6 alkylene-NRcRd; the alkylene, the alkyl, the alkenyl, =CH2, the alkynyl, the cyclohydrocarbyl, the heterocyclyl, the aryl, the heteroaryl, and the aralkyl are each further optionally substituted with one or more substituents independently selected from the following: halogen, -OH, =O, -C(=O)O-tert-butyl, -NH2, -CN, -NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, -C1-6 alkylene-C3-6 cyclohydrocarbyl, -O-C1-6 alkyl, and -C1-6 alkylene-O-C1-6 alkyl;Rc and Rd, at each occurrence, are each independently selected from: H, C1-6 alkyl, C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and C6-12 aralkyl, wherein the alkyl, the cyclohydrocarbyl, the heterocyclyl, the aryl, the heteroaryl, and the aralkyl are further optionally substituted with one or more substituents independently selected from the following: halogen, -OH, =O, -C(=O)O-tert-butyl, -NH2, -CN, -NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, and -C1-6 alkylene-O-C1-6 alkyl; andp, q, and m are each independently an integer selected from 1, 2, or 3.

2. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to claim 1, wherein the compound has structures of the following formulas:(III)(II)(IV)(R22)q(R22)(V)(VI)(VII)(VIII)(IX)(X)(XI).

3. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to claim 1, wherein:ring B is a C3-6 hydrocarbon ring or a 3- to 10-membered heterocyclic ring;preferably, ring B is a cyclopentene ring, a cyclohexene ring, a pyrrolidine ring, an oxazolidine ring, a piperidine ring, a morpholine ring, or an azepane ring.

4. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 3, wherein:R1, at each occurrence, is each independently selected from H, halogen, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, -S(=O)2Ra, -ORa, and -NRaRb, and Ra and Rb, at each occurrence, are each independently selected from H, C1-6 alkyl, C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and C6-12 aralkyl; preferably, R1, at each occurrence, is each independently selected from 3-to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, and -NRaRb, wherein the alkyl, the cyclohydrocarbyl, the heterocyclyl, the aryl, and the heteroaryl are each optionally substituted withone or more substituents independently selected from the following: halogen, -S(=O)2Rc, C1-6 alkyl, C2-6 alkenyl, =CH2, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, and 5- to 14membered heteroaryl; the alkyl, the alkenyl, =CH2, the cyclohydrocarbyl, the heterocyclyl, the aryl, and the heteroaryl are each further optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-memberedheterocyclyl, and -C1-6 alkylene-C3-6 cyclohydrocarbyl;preferably, R1, at each occurrence, is each independently C6-10 aryl or -NRaRb;preferably, R1 is H, methyl, halogen, methoxy,more preferablymost preferably, R1 isor5. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 4, wherein ring X is a benzene ring, a 5- to 6membered heterocyclic ring, or a 5- to 6-membered heteroaromatic ring, and ring Y is absent; or ring X is a benzene ring, and ring Y is a 5- to 6-membered heterocyclic ring or a 5- to 6-membered heteroaromatic ring;preferably,, more preferably6. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 5, wherein R21 and R22, at each occurrence, are each independently selected from H, halogen, -SF5, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10membered heterocyclyl, -O-(C1-6 alkyl), -S(=O)2-(C1-6 alkyl), -S(=O)2-(C3-6 cyclohydrocarbyl), -S(=O)(=NRa)Rb,    -P(=O)(C1-6    alkyl)2,    (-C3-6 cyclohydrocarbylene)-CN, and   (-C3-6cyclohydrocarbylene)-C1-6 alkyl, the alkyl, the cyclohydrocarbylene, the cyclohydrocarbyl, and the heterocyclyl being each optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, and C1-6 haloalkyl;preferably, R21 and R22, at each occurrence, are each independently selected from H, halogen, -SF5, C1-6 alkyl, C3-6 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, and -O-(C1-6 alkyl), the alkyl, the cyclohydrocarbyl, and the heterocyclyl being each optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, and C1-6 haloalkyl.

7. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer,the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or theprodrug thereof according to any one of claims 1 to 6, whereinis selected from8. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 7, wherein R3 is H, C1-6 alkyl, -ORa, or -SRa; preferably, R3 is H or C1-6 alkyl;more preferably, R3 is H, methyl, ethyl, -O-CH3, or -S-CH3; most preferably, R3 is H or methyl;when m is greater than 1, two R3 located at a same ring atom or adjacent ring atoms, together with the group to which they are attached, optionally form a C3-6 hydrocarbon ring (preferably a cyclopropyl ring), the hydrocarbon ring being optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, and C1-6 haloalkyl.

9. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or theprodrug thereof according to any one of claims 1 to 8, wherein ring Z is a 3- to 10-membered heterocyclic ring or a benzene ring, preferably a 5- to 10-membered heterocyclic ring, and more preferably a 5- to 6-membered heterocyclic ring; andthe heterocyclic ring and the benzene ring, at each occurrence, are each optionally substituted with one or more substituents independently selected from the following: halogen, C1-6 alkyl, and C1-6 haloalkyl;preferably, ring Z isor10. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 9, wherein L2 is -C(=O)-, C1-6 alkylene, or -NRC(=O)-, R being H or C1-6 alkyl;preferably, L2 is -C(=O)-, -CH2-, or -CD2-.

11. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 10, wherein R41 is selected from a 3- to 10membered heterocyclic ring, a C6-10 aromatic ring, and a 5- to 14-membered heteroaromatic ring, and the heterocyclic ring, the aromatic ring, and the heteroaromatic ring are each optionally substituted with one or more substituents independently selected from the following: halogen, -OH, C1-6 alkyl, -O-C1-6 alkyl, and -S-C1-6 alkyl, preferably, the heterocyclic ring, the aromatic ring, and the heteroaromatic ring at least being substituted with -OH or -O-C1-6 alkyl;0 OH      O OH       O OH       O OHpreferably, -L2-R41OHO OHO OH,12. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 11, wherein R41 is a 5- to 6-membered heteroaromatic ring, preferably a 6-membered heteroaromatic ring, and more preferably a pyridine ring or a pyrimidine ring, being at least substituted with one -OH;O OH O OH       O OHpreferably, -L2-R41 is,,13. The compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the atropisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 12, wherein the compound is selected from:Compound No. Structure Compound No. StructureC1 ,    0 OH 9 / --K   N         J N^N N N0..... oy NH ^^-01 °Co F F C3 ,    0 OH 9 V? W ,—v n A ,n, > n ^n - \= / n^n a_ Oy''’ NH O'O :? C5 ,,    0 OH 9 fyy'N^r^ N^ \=N  N^n^x oy NH ^Xci ° / ° F F C7 / ,   0 OH 9 Sy^V ,,S  N,O, / N / N / N Qi oo jf OO NH C^ci :rC2 / ,   0 OH 9 / / N"N^N^ N\^N \= / N^N^y- 0=A NH LzOd °Co F F C4 ,,    O OH o y ...... °o NH yya °Co F F C6 ,,    0 OH 9 / S  N.nAzNJ N / N O=:L NH Cl °Co F F C8 ,,    O OH 0 n-^n ^N N*^nA^ oy NH Lyci °y° F FC9 ,,     0 OH o ..... 0=^ NH Vy-01 f~7 / ~~~^ F F C10 .,    0 OH 0 Y"^ ,--, M A ^N, J N.^N AXJ Y |T \=^ n^nA^-. °A NH ci VA F F C11 ,,    0 OH 9 / ^X\ ,n'nV^ N^N \= / N^N^y— 0= / NH L>Ci F-A F F C12 ,,    O OH o V^W / FA,”        N^N \= /  N^m^X.,,^ 0= / NH Ka^~ci F F C17 ., o OH o 0=^’ NH k5^ci F F C18 .,    0 OH °Y NH CY F-tY^7 F F C19 O OH o ,--. n A ,N J N..N YY iY w N O..... 0^' NH L>Ci F~?\~^ F F C20 0 OH ? oW ,--. N X.N. > N-.N N^n^X^. °A NH Y / ~ci FX\ F FC21 0 OH ° ,__k N A     J N.^N iA A / N^NA_- oA NH V^Z cl F-A"^ F F C22 .,    0 OH 9 v?Vv \ N^N °A' NH C^^c| F F C23 .    0 OH \n a ir N^N nAA °A NH CA F-A^^ F F C24 .,    0 OH ? f^x An       N^N f>An^nAn1 °A NH A / Z Cl FA F F C25 .,    O OH 9 , n^n n^nA- 0¾^ NH A / Cl F-A~~^ F F C26 O OH ? oW fy_^AN^ N^N N O..... °A NH A / / Cl A F F C27 0 OH ° an^\t^a n^n \= / \anA °A NH A / ~ci °A F F C28 0 OH ? oAV fuAnJ n-n N' N0 °A NH Az Cl °A° F FC29 .,    0 OH o^ NH O~ci ¥ C31 .,    0 OH ? Sy^V N^N \=N N^NA 0¾^ NH ¥ C33 .    0 OH ? nW .rnW N^~ N w 0^'' NH W / Cl ¥ C35 .,    0 OH o Vn\V N^N / nVy. °¥ NH jCwci °Co F FC30 .,    O OH ? nW nnW N-N ■“^0 °¥ NH ty-ci °Co F F C32 .,    O OH o ¥W onn¥J N^N N' O °¥'~ NH 'W / C| °¥° F F C34 .,    0 OH ° i^w^y N^N v^ / °W NH W / Cl °Co F F C36 .    o OH ;n W......... °¥ NH yzn~ci °¥° F FC37 .     0 OH o Vn W N          n^n >mYa 0^" NH yA ci A C39 ,,    0 OH 9 / zN^N^yN^ N^N \=N  N'^n^X^ 0==^ NH Y / ci V F F C41 ,,    0 OH ? \N^N / n^n^xZ OjZ NH YYci ¥ C43 ,,    0 OH o .--, N A ,N, J N^N \= / N^NA_ o=z NH 0 °yO F FC38 ,,    0 OH O .__. M A ^N. J N.^N A k N= /  N^^n^X^ °A NH Y / ci °Co F F C40 ,,    0 OH nxn \=N N^^N^AA °A NH A^z Cl °A° F F C42 ,,    O OH 9 \n_A'n^n^ n^n /  n^'n^'A °A NH a :? C44 ,,    0 OH 9 .--. N A ,N. J N.^N fY 1 1 N tr °A NH 0-F °yO F FC45 ,,    0 OH N^N 0=X NH °v F F C46 ,,    0 OH 9 a^n-nW^ N^N \=N  N^n^X^- °A NH °y0 F F C47 ,,    0 OH 9 .--, N A ,N. J N.^N fY \=N N^nA^ 0==X NH ^F <Co F F C48 ,,    0 OH 9 f^N'N\NJ N^N \=N  N^n^V_- O^x' NH °3) F F C49 ,,    O OH 9 \ An^n^ N^N / n^nA_ 0^-' NH o- C50 .    0 OH 9 v^-W n-nA-^ N-^N F^^ N^nA_ °0 NH °yO F F C51 ,    0 OH 9 nW 0^NnyJ n-^n n^nA^ 0^ NH Cn O / C° F F C52 ,,    0 OH o AAV oAAiY^ n^n n <y 0=^'' NH °v F FC53 ,,    0 OH / ^X            N,^ \=N N^N )<7 0==^ NH °v F F C54 ,,    0 OH 9 N^N \=N            ,- 0=A NH °Co F F C55 ,,    0 OH 9 \ / NArN^ N^N / N 0-::^ NH O- C56 ,    0 OH 9 X-W F\nN zh      N^N nAnCX 0=~'' NH €x °Co F F C57 ,    0 OH 9 nVv 0^N / nX n-^n X^ 0¾^ NH X-v F F C58 ,,    O OH 9 o-xnAn^ n^n N <K 0=a' NH X F F C59 ,,    0 OH 9 X^V x n^XX n^n / n^nA^ 0=^'' NH X~ C60 .    0 OH 9 xVv F\y^N n-n^n^ n^n O^'‘ NH °yO F FC61 .,    0 OH 9 N^N NH 0 :- C62 ,   0 OH o X-w n-n o^' NH oy-° F F C63 ,   0 OH 9 N^N 0^'' NH O-°A> F F C64 ,   0 OH 9 N^N n= / VAA---' 0=^''' NH °A F F C65 .    0 OH o Vn\V n         J n.^n 0¾^ NH AAi X C66 .,    O OH 9 N X,N, J N.,N F. / \   / / N Y X N—1  0 H N^Nyx °x NH Kv Cl °X° F F C67 ,   0 OH ? \x^0N^ N^N / 0==^ NH C0 F-X F F C68 ,   0 OH o n^n / n^nA / °A NH Cl F FC69 ,    o OH o W-w F X--7 N 'NAyf 0=-'" NH l / AI F F C70 ,    o OH o nv< 0^'' NH CXci V~7\~^ F F C71 ,    0 OH o Vn W N / N o=z NH fj~ci F^ / ^ F F C72 ,,    0 OH ? W^W , n.n^n^ n^n °A NH V^Aci F'7\'^ F F C73 ,,    O OH o ^n^Sr^n P^ZnA^ N^ an nanA^ °A NH V / Ai F-Z"^ F F C74 ,,    0 OH ° i^N>n^n .—,   N J-L,N, ) N.,N Jt if \=N   N'^'N'^'Z °n NH n^Aci F“n F F C75 ,    0 OH 9 nW .—v n Z,N / n,n 1 1 NZ N^'V'Z o^n NH W~ci F F C76 ,,    0 OH o yZVv ^nn n"n °Z NH A / Cl f^Z F FC77 ,,    0 OH „ vx-w vV o^' NH (^ci F~V^ F F C78 ,,    0 OH o y-w oyyV^ N-N vV n^nA^ O^''' NH £^ci F'7\^^ F F C79 ,,    0 OH n^n o^' NH (^ci F~V^ F F C80 ,,    0 OH o y-j-W N^N N^r£yC 0;y' NH \yy~a F F C81 ,,    O OH o m:ANj N"N O~ NH L>Ci f- / F F C82 ,,    0 OH o y-W n"n '=N O:y NH k / Cl F F C83 ,,    0 OH 0 \y-N^Y^ N^N / n^nA O'Y NH €^d f‘7\ F F C84 ,,    O OH 9 v?Vv \ / / N'N^N^ N-*N / n^nA °^\' NH °Co F FC85 ,,    0 OH yy ( / N'N^N^ n^n 0= / NH V / ~CI °Co fa F C86 ,,    O OH 0 Y^N iiY ,--\ N A ^N. J N.=N rwi i \=N   N^^N^A. oy' NH Y / c| °\=° 4 C87 0 OH 0 N^N \= / fANA, oV NH Cj-ci F-y / ’’’’’’’^ F F C88 ,,    0 OH 0 l^N>llY .--. m A     J N.=N ? if 0= / NH Yj / ci F F C89 ,,    0 OH 9 / Y^\ >y^ n^n YNY 0= / NH / = / Cl °\,o Y C90 0 OH 0 ,--. N A ^N, J N,=N AXJ i H o= / NH VAc| °Co FA C91 0 OH N>N OY NH s / ,6 F F C92 O OH 9 r^AV = N A,N=I N = N nA^ 0= / NH O- A^o FAC93 ,,    O OH ? nA fyn / A N"N 0: / NH / / -01 °\,0 a C94 ,,    0 OH 9 >-N X / Nk > N^N A if \=N °0 NH ^Xci °Co F F C95 ,,    0 OH \ N^N !  n^n^X^- oy NH O / ° C96 ,,    0 OH 9 \ n^n ' ..... °A NH 0~~ °A° F F C97 ,,    0 OH 9 r\ / N'N^n^ an L / A a A N -Nxy °A NH °y F F C98 ,,    O OH 9 :> sXr ■- °A NH ¢0 / ° C99 ,,    0 OH yy / -x^yN"   N xN N^NAy. oy NH o- °Ao F F C100 ,,    0 OH 9 .--. N A ,N. J N.^N N O..... °A NH 0^ 0 F FC101 ,,    0 OH 9 Y^^V / ^YN'Z N^N \=N 0= / NH O- A C102 ,,    0 OH 9 YF^V n^n Yn nAnA..... 0= / NH A F F C103 .,    O OH 0 I N iiF n=>YJ N^N —N N—<( p—j || NH F C104 .,    0 OH ? A Vy / ,,,5  N,nA,N^> N^N °. Ti yxz / I 0= / NH CF °F F F C105 .,    0 OH 0 i^n>FAY rV / ^-NV^ N^N rNv 0 \ Y A 1 o ^=7 N NH F C106 ,,    O OH 9 rY „n yj n^n °F NH Y F / F F C107 .    0 OH 9 zta / 'n |fN^ N^N Y / nAnJ\__ 0= / NH a fa \A F F C108 ,,    0 OH 9 YY^V ,--i   N A, ,N, J N, .N oYh n aaYYnA_. 0= / NH Y F / \=A F FC109 ,,    0 OH o / YY 0= / NH F F C110 ,,    0 OH ? Y^YY „N YN- / \= / N N^V— 0= / NH F F S C111 / ,    0 OH 8 nVr / ■ / Y^ n^<nA_ NH CXci F F C112 / -, 0 0H 0 l^N TiY' / / / nYn^ n^n —N \ N— / \1 |J ^=7 n^n / Y NH % C113 ,,    0 OH / --9    / --9    N           J N^N / \ YY\ Y'N y ^N N-C / --(z 1 |l N^n-^x- NH F C114 0 OH NH F C115 ,,    0 OH 9 N / .N \= /  N^N^k^- 0= / NH °F F F C116 ,,    0 OH 9 yyY'n^n^ n^n 0= / NH °Y° F FC117 ,,    0 OH 9 Y?^V [hY n'''A^ 0= / NH °Co F F C118 ,,    0 OH 9 Y^^V / / nA / n    N xN °\ A A N^N^y- °A NH O~- °y° F F C119 .    0 OH 9 Y Y n^n N o..... °Y NH % C120 ,,    0 OH 9 P^n-n^^ N^N \= / |An^Z °A NH Y~ Y F F C121 ,         OH ° YnYV AnJ n^n \= /  N'^'N^y- oy NH Y^ °y-° F F C122 ,,    O OH ? A-SS .--, N A ,N, J N A ? if \= / n" n^A— 0= / NH Y~~ Y F F C123 ? aav ^'nYn^ n~n ^iAn'V, oY NH X v° F F C124 9 Yv ,--\ N A ,N, J N= / Yw jYt \= / N^nA_ °Y NH FC125 OH 9 N^N O= / NH V / ~CI F-. / F F C126 ,         OH 0 r^^FiT^ J / x / xV^ N^M NH CF C127 ,„ o OH 0 N if / 0 / -> N JF^N.J N. / N II / TA / / N T -s / 7—<z । I o    N^nA_ 0¾^ NH F C128 / , o OH Vn-Vv x 0  ,__. N ^k / N^ > N^ / N \ " O / / n Y VsY yY J 11 /  \= / N^nA_- 0== / NH F C129 ,,    0 OH 0 r^N iFn 0 ,—< N A / N^ J N. / N a^ / j • / NH F C130 / ,    0 OH ? YyW N^N 6^= / ^N^N'xy-0= / NH £Fci F>\ F F C131 ,,    0 OH 0 r^'iiF n-n —N N^    ( 2 |l v_ / \= / NANA, »A NH KT"01 F A F F C132 ,. o OH ? / / l] / x / Y <v \_ / \.^k A      X-N NH o~~ °v° F FC133 ,    0 OH AAAA- 0^0 NH C134 ,,    O OH u i0^A7r°> O / i'A AA   n A^ 0= / NH 0~~ °A° F F C135 ,    0 OH o Y^NJiY\^> A / ^nAnA_ oA NH °A0 F F C136 ,,    O OH o y '' NJl ^ 7-N A.,nA N^AA AVA'? if AA   NA_ 0= / NH 0 F F C137 ,--- 0 OH o r ^0AA A^AA, OcA NH F C138 ,,    O OH o rA^03 N \ AA n^ n A^- 0= / NH f0 0 F F C139 ,,      ii     OH 0 pN'YV <OH / / N'NAfN^ N~° A nAnA_ oA NH o-0 F F C140 <= A I" c><yA NH C0 0 F FC141 / , 9 OH O ryA j T   n. > O= / NH 0- F F C142 ,,     0 OH 0   [ ^AN-nW^ n^n An\AN / k 0= / NH °Co F F C143 ,    0 OH 9 nW =N N==^  N^N / 7 \\____( / 7 l| A= / 0== / NH O" °v F F C144 ,,    O OH 9 \ nNAr^ N^N / N nAnA. 0= / NH 0" °yO F F C145 ,,    0 OH 9 W^V AW N^N °\ / A A on NH F F C146 ,,     0 OH 0 c^N,n n^n N^N^y- 0= / NH °yO F F C147 9 S^n^nn „„ A,n,> ln-\= / n" NA, 0= / NH °A° F F C148 o / —<z ।    |                x '  n^” N>y 0= / NH 0- A14. A pharmaceutical composition, comprising a prophylactically or therapeutically effective amount of the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 13, and a pharmaceutically acceptable carrier.

15. Use of the compound, or the pharmaceutically acceptable salt, the ester, the stereoisomer, the tautomer, the polymorph, the solvate, the metabolite, the isotopically labeled compound, or the prodrug thereof according to any one of claims 1 to 13, or the pharmaceutical composition according to claim 14 in preparing a medicament as a WRN inhibitor, wherein preferably, the medicament is used for preventing or treating a cancer (preferably, the cancer is characterized by microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR)); preferably, the cancer is selected from colorectal cancer, gastric cancer, endometrial cancer, uterine cancer, adrenocortical carcinoma, cervical cancer, esophageal cancer, breast cancer, renal cancer, prostate cancer, and ovarian cancer.