Ecteinascidin derivative and use thereof

Abstract

An ecteinascidin compound as represented by formula (I), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt, prodrug, hydrate, solvate or isotopically labeled analog thereof, or a pharmaceutical composition thereof, and the use thereof in the treatment of cancer.

Description

A class of seaspinin derivatives and their uses

[0001] Cross-reference to related applications

[0002] This application claims priority and benefit to Chinese Patent Application No. 202510366578.7, filed with the China National Intellectual Property Administration on March 26, 2025, and Chinese Patent Application No. 202511977563.0, filed with the China National Intellectual Property Administration on December 25, 2025, the disclosures of which are incorporated herein by reference in their entirety. Technical Field

[0003] This disclosure belongs to the technical field of pharmaceuticals and their preparation and application, specifically relating to seasqualin derivatives and their preparation methods, and their application in the preparation of antitumor drugs. Background Technology

[0004] Sea tunicates are a class of marine natural alkaloids that exhibit significant biological activity against various tumor cells. At micromolar concentrations, low concentrations of sea tunicates inhibit the number of DNA-binding proteins, while at certain high concentrations they activate the synthesis of topoisomerase-mediated cleavage complexes and disrupt microtubule alignment.

[0005] Trabectedin, developed by the Spanish company PharmaMar, was the first marine natural product approved for clinical treatment. It was approved for marketing in the European Union in 2007, primarily for soft tissue sarcoma, leiomyosarcoma, and liposarcoma. Trabectedin contains three tetrahydroisoquinoline (THIQ) structures, A, B, and C. The fully functionalized isoquinoline structures A and B are important structures promoting DNA alkylation, while C interacts with DNA-binding proteins. These isoquinoline structural units are a key reason for trabectedin's antitumor activity. Studies have shown that trabectedin's mechanism of action involves binding to the small grooves of DNA, promoting DNA alkylation and forming DNA adducts. The presence of these adducts widens the small grooves of the target DNA and causes the DNA to bend towards larger grooves, resulting in abnormal DNA double helix structure. This disrupts the cell cycle, leading to apoptosis.

[0006] Rubitidine is a seasqualin derivative. Compared to trabectedine, it adds a β-carboline structure at the C-ring position, resulting in a similar mechanism of action. The tetrahydro-β-carboline moiety of rubitidine's C-ring interacts with the minor groove of DNA, affecting DNA transcription and inducing tumor cell apoptosis. The DNA adducts of these two drugs can interfere with nucleotide excision repair (NER) mechanisms and cells. Studies have shown increased NER in cisplatin-resistant cells, suggesting its potential for combination therapy with cisplatin-based drugs. Rubitidine was approved by the FDA in 2020, primarily for the treatment of small cell lung cancer, and research on its use in ovarian cancer has entered phase III trials.

[0007] More seaweed extract derivatives with excellent antitumor activity are still needed to meet clinical needs. Summary of the Invention

[0008] On the one hand, this disclosure provides seasqualin derivatives or their tautomers, stereoisomers, and their pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs as shown in formula (I):

[0009] in,

[0010] R 1 Selected from hydroxyl and cyano groups;

[0011] X is selected from O and NR. 2 and S, where R 2 Selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, and optionally substituted C6-C10 aryl;

[0012] Y is selected from hydrogen or Y1 is selected from optionally substituted C1-C6 alkylene, optionally substituted C3-C6 cycloalkylene, optionally substituted 3-8-membered heterocyclic group, optionally substituted 2-6-membered heteroalkylene, optionally substituted C6-C14 arylene and optionally substituted 5-12-membered heterocyclic group; and when the C1-C6 alkylene is substituted, the two substituents on the C1-C6 alkylene can form an optionally substituted C3-C6 cycloalkyl or an optionally substituted 4-8-membered heterocyclic group together with the same carbon atom attached thereto;

[0013] R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 ;

[0014] R 4 Selected from hydrogen and C1-C6 alkyl groups; and

[0015] n1 and n2 are each independently selected from integers from 0 to 2 (e.g., 0, 1, and 2);

[0016] The heteroalkyl, heteroaryl, heterocyclic, and heterocyclic groups contain 1-3 heteroatoms selected from N, O, or S; and

[0017] The term "optionally substituted" means that the hydrogen at the substituted site of the group is not substituted, or is substituted by one or more substituents selected from the group consisting of: deuterium, halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, or 5-14 heteroaryl.

[0018] In some embodiments, this disclosure provides saginata derivatives or tautomers, stereoisomers or pharmaceutical salts, prodrugs, hydrates, solvates or isotopically labeled analogs as shown in formula (I):

[0019] in,

[0020] R 1 Selected from hydroxyl and cyano groups;

[0021] X is selected from O and NR 2 , where R 2 Selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, and optionally substituted C6-C10 aryl;

[0022] Y is selected from hydrogen or Y1 is selected from optionally substituted C1-C6 alkylene, optionally substituted C3-C6 cycloalkylene, optionally substituted 3-8-membered heterocyclic group, optionally substituted 2-6-membered heteroalkylene, optionally substituted C6-C14 arylene and optionally substituted 5-12-membered heterocyclic group; and when the C1-C6 alkylene is substituted, the two substituents on the C1-C6 alkylene can form an optionally substituted C3-C6 cycloalkyl or an optionally substituted 4-8-membered heterocyclic group together with the same carbon atom attached thereto;

[0023] R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 ;

[0024] R 4 Selected from hydrogen and C1-C6 alkyl groups; and

[0025] n1 and n2 are each independently selected from integers from 0 to 2 (e.g., 0, 1, and 2);

[0026] The heteroalkyl, heteroaryl, heterocyclic, and heterocyclic groups contain 1-3 heteroatoms selected from N, O, or S; and

[0027] The term "optionally substituted" means that the hydrogen at the substituted site of the group is not substituted, or is substituted by one or more substituents selected from the group consisting of: deuterium, halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, or 5-14 heteroaryl.

[0028] In some implementation schemes, R 1 Selected from hydroxyl groups.

[0029] In some implementation schemes, R 1 Selected from cyano.

[0030] In some implementations, X is selected from O.

[0031] In some implementations, X is selected from NR 2 , where R 2 It is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl, each of which is optionally substituted.

[0032] In some implementations, X is selected from NR 2 , where R 2 Selected from hydrogen, methyl, CD3, CF3, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl.

[0033] In some implementations, X is selected from NR 2 , where R 2 Selected from hydrogen, methyl, and CD3.

[0034] In some implementations, X is selected from NR 2 , where R 2 X is selected from hydrogen and methyl. In some embodiments, X is selected from NR. 2 , where R 2 Selected from methyl and CD3.

[0035] In some implementations, X is selected from NR 2 , where R 2 Selected from methyl.

[0036] In some implementations, X is selected from S.

[0037] In some implementations, X is selected from O, NR 2 and S, and R 2 X is selected from hydrogen, methyl, and CD3. In some embodiments, X is selected from O, NR. 2 and S, and R 2 X is selected from hydrogen and methyl. In some embodiments, X is selected from O, NR. 2 and S, and R 2 X is selected from methyl and CD3. In some embodiments, X is selected from O, NR. 2 and S, and R 2 X is methyl. In some embodiments, X is selected from O and NR. 2 And R 2 It is a methyl group.

[0038] In some implementations, Y is selected from hydrogen.

[0039] In some implementation schemes, Y is selected from Wherein Y1 is selected from optionally substituted C1-C4 alkylene, optionally substituted C3-C6 cycloalkylene, optionally substituted 4-8-membered heterocyclic, optionally substituted 3-6-membered heteroalkylene, optionally substituted C6-C10 arylene, and optionally substituted 5-10-membered heteroarylene; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 , and R 4 Selected from hydrogen and C1-C6 alkyl groups.

[0040] In some implementation schemes, Y is selected from Wherein Y1 is selected from optionally substituted C1-C4 alkylene groups, optionally substituted C3-C6 cycloalkylene groups, and optionally substituted 3-6 heteroalkylene groups; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 , and R 4 Selected from hydrogen and C1-C6 alkyl groups.

[0041] In some embodiments, Y1 is selected from methylene, ethylene, n-propylene, isopropylene, n-butylene, isobutylene, tert-butylene, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, phenylene, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2- and -OCH2CH2CH2CH2-, each of which is optionally substituted; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 , and R 4 It is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, and n-butyl.

[0042] In some embodiments, Y1 is selected from optionally substituted C1-C4 alkylene, optionally substituted C4-C6 cycloalkylene, optionally substituted 4-8-membered heterocyclic, optionally substituted 3-6-membered heteroalkylene, optionally substituted C6-C10 arylene, and optionally substituted 5-10-membered heteroarylene; and R 3 Selected from -OH.

[0043] In some embodiments, Y1 is selected from methylene, ethylene, n-propylene, isopropylene, n-butylene, isobutylene, tert-butylene, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, and phenylene, each of which is optionally substituted; and R 3 Selected from -OH.

[0044] In some embodiments, Y1 is selected from methylene, -CD2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 ; and R 4 Selected from hydrogen and methyl.

[0045] In some embodiments, Y1 is selected from methylene, -CD2-, -CH2CH2-, -CH2CH2CH2-, and R 3 Selected from -OH.

[0046] In some implementations, Y1 is selected from methylene, and R 3 Selected from -OH.

[0047] In some embodiments, Y1 is selected from methylene; and R 3 Selected from -OH. In some embodiments, -Y1-R 3 Selected from -CH2OH, -CD2OH, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, -OCH2CH2OH, -OCH2CH2CH2OH, -OCH2CH2CH2CH2OH, -NHCH2CH2OH, -NHCH2CH2CH2OH, and -NHCH2CH2CH2CH2OH.

[0048] In some implementations, -Y1-R 3 It is selected from optionally substituted -C1-C4 alkylene-OH, optionally substituted -C3-C6 cycloalkylene-OH and optionally substituted -3-6 heteroalkylene-OH.

[0049] In some embodiments, Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, -OCH2CH2CH2CH2-, -SCH2CH2-, -SCH2CH2CH2-, and -SCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ; and R 4 Selected from hydrogen and methyl.

[0050] In some embodiments, Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ; and R 4 Selected from hydrogen and methyl.

[0051] In some embodiments, Y1 is selected from methylene, ethylene, n-propylene, n-butylene, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ; and R 4 It is hydrogen.

[0052] In some implementations, -Y1-R 3 Selected from -CH2OH, -OCH2CH2OH, and -NHCH2CH2OH.

[0053] In some implementations, n1 is selected from 0, 1, and 2, and n2 is selected from 0 and 1. In some implementations, n1 is selected from 0, 1, and 2, and n2 is 0.

[0054] In some implementation schemes, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, C1-C3 alkyl groups, and CD3; Y is selected from hydrogen or... Y1 is selected from C1-C4 alkylene groups and 3-6 heteroalkylene groups containing one heteroatom selected from N, O or S, R 3 Selected from -OH, -SH and -NHR 4 ;R 4 The n1 is selected from hydrogen and C1-C4 alkyl; and n1 is selected from 0, 1 and 2, and n2 is selected from 0 and 1.

[0055] In some implementation schemes, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, C1-C3 alkyl groups, and CD3; Y is selected from hydrogen or... Wherein Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, -OCH2CH2CH2CH2-, -SCH2CH2-, -SCH2CH2CH2- and -SCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 The n1 is selected from hydrogen and C1-C4 alkyl; and n1 is selected from 0, 1 and 2, and n2 is selected from 0 and 1.

[0056] In some implementation schemes, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, methyl, and CD3; Y is selected from hydrogen or Wherein Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, -OCH2CH2CH2CH2-, -SCH2CH2-, -SCH2CH2CH2- and -SCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 The n1 is selected from hydrogen and methyl; and n1 is selected from 0, 1 and 2, and n2 is selected from 0 and 1.

[0057] In some implementation schemes, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, methyl, and CD3; Y is selected from hydrogen or Wherein Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 The form is hydrogen; and n1 is selected from 0, 1, and 2, and n2 is selected from 0 and 1.

[0058] In some implementation schemes, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, methyl, and CD3; Y is selected from hydrogen or Where Y1 is selected from C1-C4 alkylene groups, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 The form is hydrogen; and n1 is selected from 0, 1, and 2, and n2 is selected from 0 and 1.

[0059] In some implementation schemes, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 And R 2 Selected from hydrogen, methyl, and CD3; Y is selected from hydrogen or Where Y1 is selected from methylene, ethylene, n-propylene, n-butylene, -OCH2CH2-, -OCH2CH2CH2- and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 The form is hydrogen; and n1 is selected from 0, 1, and 2, and n2 is selected from 0 and 1.

[0060] In some implementation schemes, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 And R 2 Selected from methyl and CD3; Y is selected from hydrogen or Where Y1 is selected from methylene, ethylene, n-propylene, -OCH2CH2- and -OCH2CH2CH2-; R 3 The values ​​are selected from -OH and -SH; and n1 is selected from 0, 1 and 2, and n2 is selected from 0 and 1.

[0061] In some implementation schemes, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 And R 2 Selected from methyl and CD3; Y is selected from hydrogen or Where Y1 is selected from methylene and -OCH2CH2-; R 3 The value is -OH; and n1 is selected from 0, 1 and 2, and n2 is 0.

[0062] In some embodiments, the compound of formula (I) is a compound of formula (II):

[0063] Among them, R 1 X, n1, and n2 are as described in equation (I);

[0064] R 5 and R 6Each of the following is independently selected from hydrogen, deuterium, optionally substituted C1-C3 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted 5-6 membered heterocyclic, optionally substituted C1-C3 haloalkyl, and optionally substituted C6-C14 aryl, or R 5 and R 6 Together with the carbon atom attached thereto, it forms an optionally substituted C3-C6 cycloalkyl group or an optionally substituted 5-6 membered heterocyclic group.

[0065] In some implementation schemes, R 5 and R 6 Each of the following is independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or phenyl, and each of these is optionally substituted, or R 5 and R 6 Together with the carbon atoms attached to it, it forms cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, each of which is optionally substituted.

[0066] In some implementation schemes, R 5 and R 6 Independently hydrogen or deuterium. In some implementations, R 5 and R 6 Both are hydrogen.

[0067] In some embodiments, the sucrose derivative or its tautomers, stereoisomers, and their pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs include one or more of the following structures:

[0068] In some embodiments, the sucrose derivative or its tautomers, stereoisomers, and their pharmaceutical salts, hydrates, solvates, or isotopically labeled analogs include the following structures:

[0069] In some embodiments of this disclosure, hydrogen at any position in the compounds having the structure of formula (I) or (II) may be substituted with one or more deuterium.

[0070] On the other hand, this disclosure provides pharmaceutical compositions comprising a compound having a structure of formula (I) or (II) or a tautomer, stereoisomer or pharmaceutical salt thereof, prodrug, hydrate, solvate or isotopically labeled analog thereof, and one or more pharmaceutically acceptable excipients.

[0071] In some embodiments, the pharmaceutical composition is used to treat cancer.

[0072] In another aspect, this disclosure provides a method for treating cancer, comprising administering to an individual in need an effective amount of the compound having the structure of formula (I) or (II) or a tautomer, stereoisomer or pharmaceutical salt, prodrug, hydrate, solvate or isotopically labeled analog or pharmaceutical composition thereof.

[0073] In another aspect, this disclosure provides the use of the compound having the structure of formula (I) or (II) or its tautomers, stereoisomers or pharmaceutical salts, prodrugs, hydrates, solvates or isotopically labeled analogs or pharmaceutical compositions thereof in the preparation of a medicament for treating cancer.

[0074] In another aspect, this disclosure provides compounds having the structure of formula (I) or (II) for the treatment of cancer, or their tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof.

[0075] In another aspect, this disclosure provides the use of the compound having the structure of formula (I) or (II) or its tautomer stereoisomers or its pharmaceutical salts, prodrugs, hydrates, solvates or isotopically labeled analogs or pharmaceutical compositions thereof for the treatment of cancer.

[0076] In some implementations, the cancers include liver cancer, kidney cancer, lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), stomach cancer, esophageal cancer, urethral cancer, bladder cancer, colon cancer, rectal cancer, prostate cancer, breast cancer, ovarian cancer, pancreatic cancer, melanoma, hematologic malignancies or gliomas, lymphomas (e.g., Hodgkin lymphoma, non-Hodgkin lymphoma, or relapsed anaplastic large cell lymphoma), cervical cancer, uterine cancer, endometrial cancer, salivary gland cancer, glioma, neuroblastoma, sarcoma, colorectal cancer, leukemia (e.g., acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia), bone cancer, skin cancer, thyroid cancer, etc.

[0077] In some embodiments, the cancer includes breast cancer and lung cancer (e.g., small cell lung cancer and non-small cell lung cancer). In some embodiments, the cancer includes breast cancer, non-small cell lung cancer, and small cell lung cancer. In some embodiments, the cancer includes breast cancer and lung adenocarcinoma.

[0078] The present invention also provides a method for synthesizing the compound shown in formula (I), using the following synthesis method:

[0079] General formulas I-1 and I-2 undergo a coupling reaction (when X is NR) 2 The reaction proceeds as follows: (when X is O) or substitution reaction (when X is O) yields the compound represented by general formula I-3. General formula I-3 then undergoes a protecting group removal reaction to yield the compound represented by general formula I-4. General formulas I-4 and I-5 then undergo a Pictet-Spengler reaction to yield the compound represented by general formula IA. General formula IA undergoes a condensation reaction to yield the compound represented by general formula IB. General formulas IA and I-6 undergo an addition reaction to yield the compound represented by general formula I-7. General formula I-7 then undergoes a protecting group removal reaction to yield the compound represented by general formula IC. General formulas IA and I-8 undergo a substitution reaction to yield the compound represented by general formula I-9. General formula I-9 then undergoes a protecting group removal reaction to yield the compound represented by general formula ID. General formulas IA, IB, IC, and ID each undergo hydrolysis reactions to yield the corresponding compounds represented by general formulas I-A', I-B', I-C', and I-D'. Wherein, R... 1 R 2 X, Y, n1, n2 are as defined in general formula I, and T is selected from OH, halogens, preferably OH, Cl, Br or I.

[0080] Terms and Definitions

[0081] In this disclosure, unless otherwise stated, scientific and technical terms used have the meanings commonly understood by those skilled in the art. When trademark names are used herein, unless otherwise indicated, a trademark name includes the product formulation, generic drug, and active ingredient of the product bearing that trademark name.

[0082] The term "alkyl" refers to an organic group consisting of a saturated, straight-chain or branched aliphatic hydrocarbon group containing only carbon and hydrogen atoms. Alkyl groups can have 1, 2, 3, 4, 5, or 6 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2, 3-Dimethylpentyl, 2,4-Dimethylpentyl, 2,2-Dimethylpentyl, 3,3-Dimethylpentyl, 2-Ethylpentyl, 3-Ethylpentyl, n-Octyl, 2,3-Dimethylhexyl, 2,4-Dimethylhexyl, 2,5-Dimethylhexyl, 2,2-Dimethylhexyl, 3,3-Dimethylhexyl, 4,4-Dimethylhexyl, 2-Ethylhexyl, 3-Ethylhexyl, 4-Ethylhexyl, 2-Methyl-2-Ethylpentyl, 2-Methyl-3-Ethylpentyl, n-Nonyl, 2-Methyl-2-Ethylhexyl, 2-Methyl-3-Ethylhexyl, 2,2-Diethylpentyl, n-Decyl, 3,3-Diethylhexyl, 2,2-Ethylhexyl, and their various branched isomers, etc.

[0083] The term "substituted alkyl" refers to an organic group in which the hydrogen in a saturated chain alkyl group as defined above is replaced by one or more substituents selected from the D atom, halogen, alkoxy, haloalkyl, haloalkoxy, cycloalkyl, cycloalkoxy, heteroatom-containing cycloalkoxy, hydroxyl, cyano, amino, nitro, mercapto, heteroatom-containing cycloalkyl, aryl, and heteroatom-containing aryl.

[0084] The term "cycloalkyl" refers to a fully saturated carbon ring that can exist as a monocyclic, bridged, or spirocyclic ring. Cycloalkyl groups contain only carbon and hydrogen atoms and have 3, 4, 5, 6, 7, or 8 carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, methylcyclopropane, 2-ethyl-cyclopentane, dimethylcyclobutane, norbornyl (bicyclo[2.2.1]heptyl), bicyclo[2.2.2]octyl, adamantyl, etc.

[0085] The term "halogen" refers to F, Cl, Br, and I.

[0086] The term "haloalkyl" refers to an alkyl group as defined above in which one, two, or more hydrogen atoms, or all hydrogen atoms, are replaced by a halogen. Representative examples of haloalkyl groups include, but are not limited to, CCl3, CHCl2, CH2Cl, CF3, CHF2, CH2F, CBr3, CHBr2, CH2Br, CI3, CHI2, CH2I, CH2CF3, CF2CF3, etc.

[0087] The term "heteroalkyl" refers to an alkyl residue in which one or more carbon atoms (and associated hydrogen atoms) are substituted by heteroatoms, such as nitrogen, oxygen, or sulfur. The alkyl group is defined as above, i.e., containing 1-20 carbon atoms, preferably 1-10 carbon atoms, more preferably 1-8 carbon atoms, and more preferably 1-6 carbon atoms (specifically 1, 2, 3, 4, 5, or 6). Heteroalkyl groups can be 2, 3, 4, 5, or 6-membered heteroalkyl groups, each containing 2, 3, 4, 5, or 6 members. For example, oxaalkyl groups include "alkoxy" and "alkoxyalkyl," examples of which include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, tert-butoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, methoxypropyl, etc. Thio-alkyl refers to a heteroalkyl group in which the oxygen in the above-mentioned "oxo-alkyl" is replaced with sulfur.

[0088] The term "heteroalkylene" refers to a divalent heteroalkyl group as defined above. Examples of heteroalkylene include, but are not limited to, -O-alkylene, -S-alkylene and -NH-alkylene, wherein the alkylene is a saturated straight-chain or branched alkylene that may have 1, 2, 3, 4, 5 or 6 carbon atoms.

[0089] The term "aryl" refers to a monocyclic, bicyclic, or tricyclic aromatic carbocyclic system containing 6-16 carbon atoms, or 6-14 carbon atoms, or 6-12 carbon atoms, or 6-10 carbon atoms, preferably 6-10 carbon atoms. Examples of aryl groups may include, but are not limited to, phenyl, naphthyl, anthracene, phenanthryl, or pyrene.

[0090] The term "heteroaryl" refers to an aromatic monocyclic or polycyclic cyclic system containing a 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14-membered structure, or preferably a 5, 6, 7, 8, 9, or 10-membered structure, or more preferably a 5, 6, 7, or 8-membered structure, and more preferably a 5-6-membered structure, wherein one, two, three, or more ring atoms are heteroatoms and the remaining atoms are carbon atoms, the heteroatoms being independently selected from O, N, or S, and the number of heteroatoms is preferably one, two, or three. Examples of heteroaryl groups include, but are not limited to, furanyl, thiophene, oxazolyl, thiazolyl, isoxazolyl, oxadiazolyl, thiazolyl, pyrroleyl, pyrazolyl, imidazoleyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, thiodiazolyl, triazinyl, phthalazinyl, quinolinyl, isoquinolinyl, pteridinyl, purine, indoleyl, isoindoleyl, indazoleyl, benzofuranyl, benzothiophene, benzopyridyl, benzopyrimidinyl, and benzo[] Pyrazinyl, benzimidazolyl, benziphthalazolyl, pyrrolo[2,3-b]pyridyl, imidazo[1,2-a]pyridyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl, [1,2,4]triazolo[1,5-a]pyridyl, etc.

[0091] The term "heterocyclic group" refers to a non-aromatic ring that is fully saturated or partially unsaturated (not fully unsaturated heteroaromatic) and can exist as a monocyclic, fused, bridged, or spirocyclic ring. Unless otherwise indicated, the heterocyclic group is typically a 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12-membered ring containing one, two, or three heteroatoms independently selected from sulfur, oxygen, and / or nitrogen (preferably one or two heteroatoms, but excluding -OO-, -OS-, or -SS- portions). Non-limiting examples of heterocyclic groups include, but are not limited to, ethylene oxide, tetrahydrofuranyl, dihydrofuranyl, pyrrolyl, N-methylpyrrolyl, dihydropyrrolyl, piperidinyl, piperazinyl, pyrazolyl, 4H-pyranyl, morpholinyl, thiomorpholinyl, tetrahydrothiophene, etc.

[0092] The term "optionally substituted" means that the hydrogen at the substituted site of the group is not substituted, or is substituted by one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, or 5-14 heteroaryl. "Multiple" refers to 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, preferably 2, 3, or 4.

[0093] The compounds disclosed herein can exist in specific stereoisomer forms; the term "stereoisomer" refers to isomers with the same structure but different atomic arrangements. These include cis and trans (or Z and E) isomers, (-)- and (+)- isomers, (R)- and (S)- enantiomers, diastereomers, (D)- and (L)- isomers, tautomers, blocked isomers, conformational isomers, and mixtures thereof (such as racemic mixtures and mixtures of diastereomers).

[0094] In the structure of the compounds disclosed herein, the bonds... This indicates that no configuration has been specified, and two chiral isomers exist, which can be: It may be a mixture of the two configurations.

[0095] The term "derivative" as used in this article refers to a substance that has a similar chemical structure to the compound but has different chemical groups.

[0096] The terms "pharmaceutically acceptable salt" and "medicinal salt" both refer to salts that can be obtained by adding a pharmaceutically acceptable acid or base to a compound. When a compound contains an acidic functional group, an acceptable base can be added to form a salt; when a compound contains a basic functional group, an acceptable acid can be added to form a salt. Examples of salts include, but are not limited to: sulfates, trifluoroacetates, citrates, acetates, oxalates, chlorides, bromides, iodides, nitrates, hydrogen sulfates, phosphates, acid phosphates, isonicotinates, lactates, salicylates, acid citrates, tartrates, oleates, tannates, pantothenates, hydrogen tartrates, ascorbic acid salts, formates, benzoates, glutamates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, potassium salts, sodium salts, etc.

[0097] Unless otherwise specified, the term "isotopically labeled analogue" means that the compounds of this disclosure can exist in an isotopically labeled, traced, or enriched form, containing one or more atoms whose atomic weights or mass numbers differ from the atomic weights or mass numbers of the most abundant atoms found in nature. The isotope can be radioactive or non-radioactive. Commonly used isotopes for isotopic labeling are: hydrogen isotopes, 2 H and 3 H; Carbon isotopes: 13 C and 14 C; Chlorine isotopes: 35 Cl and 37 Cl; Fluorine isotopes: 18 F; Iodine isotopes: 123 I and 125 I; Nitrogen isotopes: 13 N and 15 N; oxygen isotopes: 15 O, 17O and 18 O and sulfur isotopes 35 S. These isotope-labeled compounds can be used to study the distribution of pharmaceutical molecules in tissues. Especially 2 H and 13 C, because they are easy to label and convenient to detect, are more widely used. Some heavy isotopes, such as deuterium (… 2 Substitution with H can enhance metabolic stability and prolong the half-life, thereby achieving the goal of reducing dosage and providing therapeutic advantages. Isotope-labeled compounds are generally synthesized from labeled starting materials using known synthetic techniques, just like non-isotope-labeled compounds.

[0098] Unless otherwise specified, the terms "solvate" or "solvent" refer to the physical association of the disclosed compound with one or more solvent molecules (organic or inorganic). This physical association includes hydrogen bonding. In some cases, such as when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid, the solvate can be separated. The solvent molecules in the solvate may be present in a regular and / or disordered arrangement. The solvate may contain stoichiometric or non-stoichiometric solvent molecules. "Solvate" encompasses both solvates in the solution phase and separable solvates. When the solvent molecule is water, the solvate may be referred to as a hydrate. Exemplary solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Solvation methods are well known in the art.

[0099] Unless otherwise specified, the term "prodrug" refers to a drug that is converted into a parent drug in vivo. Prodrugs are generally useful because they can improve certain, undesirable physical or biological properties. Physical properties are generally related to solubility (excessive or insufficient lipid or water solubility) or stability, while problematic biological properties include metabolism that is too rapid or poor bioavailability, which may itself be related to physicochemical properties. For example, they can be bioavailable orally, whereas the parent drug cannot. Prodrugs also have improved solubility in pharmaceutical compositions compared to the parent drug. An example of a prodrug, but not limited to, is any compound of this disclosure that is administered as an ester ("prodrug") to facilitate transmembrane transport, where water solubility is detrimental to migration but beneficial once inside the cell, and is subsequently metabolized and hydrolyzed into a carboxylic acid, the active entity. Another example of a prodrug can be a short peptide (polyamino acid) bound to an acid group, where the peptide is metabolized to exhibit the active moiety.

[0100] The present disclosure will be further described in detail below with reference to specific embodiments. Except for the content specifically mentioned below, the processes, conditions, and experimental methods for implementing the present invention are all common knowledge and general knowledge in the art, and the present disclosure does not impose any particular limitations.

[0101] Explanation of Abbreviations Example

[0102] The following specific embodiments illustrate the implementation of this disclosure. Those skilled in the art can easily understand other advantages and effects of this disclosure from the content disclosed in this specification.

[0103] Test methods in the following examples, unless otherwise specified, are generally performed under standard conditions or as recommended by the manufacturer. Unless otherwise stated, all percentages, proportions, ratios, or parts are by weight.

[0104] Commercial reagents were purchased from Adamas, Aldrich, TCI, Titan, Energy Chemical, and J&K Chemical and used directly without any pretreatment. Unless otherwise stated, all reactions were carried out in dry glassware under a nitrogen atmosphere. Unless otherwise specified in the examples, products were purified by silica gel flash phase chromatography. Unless otherwise stated, solutions refer to aqueous solutions. Unless otherwise stated, the reaction temperature was room temperature, ranging from 20°C to 30°C.

[0105] Example 1: Synthesis of compounds D1-1 and D17-1

[0106] To a mixture of compound 1 (2.5 g) and triethylamine (1.43 g) dissolved in tetrahydrofuran (30 mL), di-tert-butyl dicarbonate (3.09 g) was added, and the reaction mixture was stirred at 25 °C for 1 hour. After the reaction was complete, the reaction mixture was extracted with dichloromethane (200 mL × 3). The organic phases were dried over anhydrous sodium sulfate, combined, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to give compound 2 (2.80 g, 89.7%). LCMS: m / z [M-56+H] + =221.4.

[0107] Compound 3 (1.22 g) was added to a mixture of compound 2 (1.40 g) and CMBP (6.12 g) dissolved in toluene (20 mL), and the reaction mixture was stirred at 110 °C for 18 hours. After the reaction was complete, the reaction mixture was extracted with ethyl acetate. The organic phases were dried over anhydrous sodium sulfate, combined, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to give the desired compound 4 (300 mg, 13.0%). LCMS: m / z [M-56+H] + =404.4.

[0108] A solution of dioxane in hydrochloric acid (4M, 2 mL) was added to a mixture of compound 4 (300 mg) dissolved in dioxane (1 mL). The reaction mixture was stirred at 25 °C for 1 hour. After the reaction was complete as determined by LCMS, the reaction mixture was filtered and concentrated to give compound 5 (220 mg, crude product). LCMS: m / z [M+H] + =260.4.

[0109] Compound 5 (167 mg) was added to a mixture of compound 6 (200 mg) dissolved in acetic acid (3 mL) at 25 °C under a nitrogen atmosphere. The mixture was stirred at 45 °C for 24 hours. After the reaction was complete as determined by LCMS, the reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D17-1 (250 mg, 86%). LCMS: m / z [M+H] + =863.2.

[0110] Silver nitrate (548 mg) was added to a mixture of compound D17-1 (70.0 mg) dissolved in acetonitrile (1.2 mL) and water (0.8 mL), and the mixture was stirred at 25 °C for 1 hour. After the reaction was complete, the reaction mixture was concentrated to obtain a residue, which was purified by Pre-HPLC (Xtimate C18, 21.2*250 mm, 5 μm, 10-40% aqueous acetonitrile solution) to obtain compound D1-1 (20.6 mg, 29.8%). LCMS: m / z [M+H] = 854.2.

[0111] Example 2: Synthesis of compounds D1-2 and D17-2

[0112] Compound 7 (1.22 g) was added to a mixture of compound 2 (1.40 g) and CMBP (6.12 g) dissolved in toluene (20 mL), and the reaction mixture was stirred at 110 °C for 18 hours. After the reaction was complete, the reaction mixture was extracted with ethyl acetate. The organic phases were dried over anhydrous sodium sulfate, combined, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to give the desired compound 8 (396 mg, 16.8%). LCMS: m / z [M-56+H] + =404.4.

[0113] A solution of dioxane hydrochloride (4M, 2 mL) was added to a mixture of compound 8 (396 mg) dissolved in dioxane (1 mL). The reaction mixture was stirred at 25 °C for 1 hour. After the reaction was completed as determined by LCMS, the reaction mixture was filtered and concentrated to give compound 9 (214 mg, 96%). LCMS: m / z [M+H] +=260.4.

[0114] Compound 9 (167 mg) was added to a mixture of compound 6 (200 mg) dissolved in acetic acid (3 mL) at 25 °C under a nitrogen atmosphere. The mixture was stirred at 45 °C for 24 hours. After the reaction was complete as determined by LCMS, the reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D17-2 (184 mg, 66%). LCMS: m / z [M+H] + =863.2.

[0115] Silver nitrate (661 mg) was added to a mixture of compound D17-2 (84.0 mg) dissolved in acetonitrile (1.2 mL) and water (0.8 mL), and the mixture was stirred at 25 °C for 1 hour. After the reaction was complete, the reaction mixture was concentrated to obtain a residue, which was purified by Pre-HPLC (Xtimate C18, 21.2*250 mm, 5 μm, 10-40% aqueous acetonitrile solution) to obtain compound D1-2 (20.0 mg, 24%). LCMS: m / z [M+H] = 854.2.

[0116] Example 3: Synthesis of compounds D2-1 and D18-1

[0117] Compound 10 (10.0 g) was dissolved in dichloromethane (80 mL), and di-tert-butyl dicarbonate (36.5 g), DMAP (0.51 g), and triethylamine (21.2 g) were added at 25 °C. The mixture was then stirred at room temperature for 12 hours. After the reaction was completed by LC-MS analysis, ethyl acetate was added to the reaction mixture, followed by extraction with water. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 10:1) to give compound 11 (16.0 g, 85%). LC-MS: [M+Na] + =461.0.

[0118] Compound 11 (5.0 g) was added to a reaction flask, dissolved in 100 mL of dioxane, followed by compound 12 (2.94 g), Brettphos Pd G2 (182 mg), Brettphos (245 mg), and cesium carbonate (7.42 g). The mixture was then stirred at 100 °C for 12 hours. After the reaction was complete as determined by LC-MS, the reaction mixture was filtered, ethyl acetate was added, and water was added for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound 13 (3.50 g, 55%). LC-MS: [M+H-56] + =503.4.

[0119] Compound 13 (1.10 g) was dissolved in 10 mL of acetonitrile in a 50 mL three-necked flask. Formaldehyde aqueous solution (37 wt%, 10 mL) was slowly added under ice bath conditions, followed by sodium cyanoborohydride (331 mg) and acetic acid (2 mL). The mixture was stirred at 0 °C for 1 hour under nitrogen atmosphere. After the reaction was complete as detected by LC-MS, 10 mL of ethyl acetate and 10 mL of water were added to the reaction mixture and extracted. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (acetonitrile:water = 1:1) to give compound 14 (700 mg, 62%). LC-MS: [M+H] + =573.4.

[0120] Compound 14 (700 mg) was added to a 50 mL three-necked flask with a 4 M dioxane solution (10 mL). The mixture was stirred at 25 °C for 2 hours under a nitrogen atmosphere. After the reaction was complete as detected by LC-MS, the reaction mixture was evaporated to dryness to give compound 15 (280 mg, 85%). LC-MS: [M+H] + =273.4.

[0121] Compound 15 (100 mg) was dissolved in 2 mL of acetic acid in a 10 mL single-necked flask. Compound 6 (228 mg) was added, and the mixture was stirred at 45 °C for 18 hours under a nitrogen atmosphere. After the reaction was completed as detected by LC-MS, the reaction mixture was evaporated to dryness. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D18-1 (320 mg, 98%). LC-MS: [M+H] + =876.2.

[0122] Compound D18-1 (50 mg) was dissolved in 2 mL of dimethyl sulfoxide and 2 mL of water. The temperature was lowered to 10 °C, and silver nitrate (48.5 mg) was added under a nitrogen atmosphere. After the reaction was completed as detected by LC-MS, the reaction mixture was concentrated to obtain the residue, which was purified by Pre-HPLC (Xtimate C18, 21.2*250 mm, 5 μm, 10-40% acetonitrile aqueous solution) to obtain compound D2-1 (24 mg, 49%). LC-MS: [M+H] + =867.3.

[0123] Example 4: Synthesis of compounds D2-2 and D18-2

[0124] Compound 11 (5.0 g) was added to a reaction flask, dissolved in 100 mL of dioxane, followed by compound 16 (2.94 g), Brettphos Pd G2 (182 mg), Brettphos (245 mg), and cesium carbonate (7.42 g). The mixture was then stirred at 100 °C for 12 hours. After the reaction was complete as determined by LC-MS, the reaction mixture was filtered, ethyl acetate was added, and water was added for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound 17 (3.0 g, 47%). LC-MS: [M+H-56] + =503.4.

[0125] Compound 17 (1.10 g) was dissolved in 10 mL of acetonitrile in a 50 mL three-necked flask. Formaldehyde aqueous solution (37 wt%, 10 mL) was slowly added under ice bath conditions, followed by sodium cyanoborohydride (331 mg) and acetic acid (2 mL). The mixture was stirred at 0 °C for 1 hour under nitrogen atmosphere. After the reaction was complete as detected by LC-MS, 10 mL of ethyl acetate and 10 mL of water were added to the reaction mixture and extracted. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (acetonitrile:water = 1:1) to give compound 18 (500 mg, 44%). LC-MS: [M+H] + =573.4.

[0126] Compound 18 (350 mg) was added to a 50 mL three-necked flask with dioxane hydrochloride solution (4 M, 10 mL). The mixture was stirred at 25 °C for 2 hours under a nitrogen atmosphere. After the reaction was complete as detected by LC-MS, the reaction mixture was evaporated to dryness to give compound 19 (150 mg, 94%). LC-MS: [M+H] + =273.4.

[0127] Compound 19 (100 mg) was dissolved in 2 mL of acetic acid in a 10 mL single-necked flask. Compound 6 (228 mg) was added, and the mixture was stirred at 45 °C for 18 hours under a nitrogen atmosphere. After the reaction was completed as detected by LC-MS, the reaction mixture was evaporated to dryness. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D18-2 (200 mg, 62%). LC-MS: [M+H] + =876.2.

[0128] Compound D18-2 (50 mg) was dissolved in 2 mL of dimethyl sulfoxide and 2 mL of water. The temperature was lowered to 10 °C, and silver nitrate (48.5 mg) was added under a nitrogen atmosphere with stirring. After the reaction was completed as detected by LC-MS, the reaction mixture was concentrated to obtain a residue, which was purified by Pre-HPLC (Xtimate C18, 21.2*250 mm, 5 μm, 10-40% acetonitrile aqueous solution) to obtain compound D2-2 (22 mg, 44%). LC-MS: [M+H] + =867.3.

[0129] Example 5: Synthesis of compounds D9-1 and D25-1

[0130] Compound D17-1 (80 mg) was dissolved in 2 mL of DMF in a 25 mL single-necked flask. Glycolic acid (14 mg), HATU (53 mg), and DIEA (24 mg) were added. The mixture was stirred at 25 °C for 12 hours under a nitrogen atmosphere. LC-MS showed that the starting material disappeared and a new product formed. Extraction was performed with 5 mL of ethyl acetate and 5 mL of water. The layers were separated, and the organic phase was collected and evaporated to dryness to remove the organic solvent. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D25-1 (50 mg, 59%). LC-MS: [M+Na] + =943.3.

[0131] Compound D25-1 (50 mg) was dissolved in 1 mL of acetonitrile and 1 mL of water. Silver nitrate (367 mg) was added under a nitrogen atmosphere at 25 °C. After reacting for 1 hour, the reaction mixture was filtered and purified by Pre-HPLC (Xtimate C18, 21.2*250 mm, 5 μm, 10-40% acetonitrile aqueous solution) to obtain compound D9-1 (20 mg, 40%). LC-MS: [M+H] + =912.2.

[0132] Example 6: Synthesis of compounds D9-2 and D25-2

[0133] Compound D17-2 (100 mg) was dissolved in 2 mL of DMF in a 25 mL single-necked flask. Glycolic acid (17.6 mg), HATU (66 mg), and DIEA (30 mg) were added. The mixture was stirred at 25 °C for 12 hours under a nitrogen atmosphere. LC-MS showed that the starting material disappeared and a new product formed. Extraction was performed with 5 mL of ethyl acetate and 5 mL of water. The layers were separated, and the organic phase was collected and evaporated to dryness to remove the organic solvent. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D25-2 (74 mg, 70%). LC-MS: [M+Na]+ =943.3.

[0134] Compound D25-2 (74 mg) was dissolved in 1 mL of acetonitrile and 1 mL of water. Silver nitrate (546 mg) was added under a nitrogen atmosphere at 25 °C. After reacting for 1 hour, the reaction mixture was filtered and purified by Pre-HPLC (Xtimate C18, 21.2*250 mm, 5 μm, 10-40% aqueous acetonitrile solution) to obtain compound D9-2 (23 mg, 31%). LC-MS: [M+H] + =912.2.

[0135] Example 7: Synthesis of compounds D10-1 and D26-1

[0136] Compound D18-1 (50 mg) was dissolved in 2 mL of DMF in a 25 mL single-necked flask. Glycolic acid (4.3 mg), HATU (43 mg), and DIEA (29 mg) were added. The mixture was stirred at 25 °C for 12 hours under a nitrogen atmosphere. LC-MS showed the starting material disappeared and a new product formed. Extraction was performed with 5 mL of ethyl acetate and 5 mL of water. The layers were separated, and the organic phase was collected and evaporated to dryness to remove the organic solvent. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D26-1 (51 mg, 95.8%). LC-MS: [M+H] + =934.2.

[0137] Compound D26-1 (50 mg) was dissolved in 2 mL of dimethyl sulfoxide and 2 mL of water. The temperature was lowered to 10 °C, and silver nitrate (54 mg) was added under a nitrogen atmosphere. The reaction progress was monitored by LC-MS. After the reaction was complete, the reaction mixture was filtered and purified by Pre-HPLC (Xtimate C18, 21.2*250 mm, 5 μm, 10-40% acetonitrile aqueous solution) to obtain compound D10-1 (21 mg, 48%). LC-MS: [M+H] + =925.2.

[0138] Example 8: Synthesis of compounds D10-2 and D26-2

[0139] Compound D18-2 (80 mg) was dissolved in 2 mL of DMF in a 25 mL single-necked flask. Glycolic acid (14 mg), HATU (53 mg), and DIEA (24 mg) were added. The mixture was stirred at 25 °C for 12 hours under a nitrogen atmosphere. LC-MS showed that the starting material disappeared and a new product formed. Extraction was performed with 5 mL of ethyl acetate and 5 mL of water. The layers were separated, and the organic phase was collected and evaporated to dryness to remove the organic solvent. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D26-2 (50 mg, 59%). LC-MS: [M+H] + =934.3.

[0140] Compound D26-2 (50 mg) was dissolved in 2 mL of dimethyl sulfoxide and 2 mL of water. The temperature was lowered to 10 °C, and silver nitrate (54 mg) was added under a nitrogen atmosphere. The reaction progress was monitored by LC-MS. After the reaction was complete, the reaction mixture was filtered and purified by Pre-HPLC (Xtimate C18, 21.2*250 mm, 5 μm, 10-40% acetonitrile aqueous solution) to obtain compound D10-2 (23 mg, 49%). LC-MS: [M+H] + =925.2.

[0141] Example 9: Synthesis of compound D21-1

[0142] Compound 20 (1.22 g) was added to a mixture of compound 2 (1.40 g) and CMBP (6.12 g) dissolved in toluene (20 mL), and the reaction mixture was stirred at 110 °C for 18 hours. After the reaction was complete, the reaction mixture was extracted with ethyl acetate. The organic phases were dried over anhydrous sodium sulfate, combined, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to give the desired compound 21 (376 mg, 17%). LCMS: m / z [M-56+H] + =390.2.

[0143] A 4M dioxane hydrochloride solution (2 mL) was added to a mixture of compound 21 (376 mg) dissolved in dioxane (1 mL). The reaction mixture was stirred at 25 °C for 1 hour. After the reaction was completed as determined by LCMS, the reaction mixture was filtered and concentrated to give compound 22 (200 mg, crude product). LCMS: m / z [M+H] + =246.4.

[0144] Compound 22 (200 mg) was added to a mixture of compound 6 (507 mg) dissolved in acetic acid (3 mL) at 25 °C under a nitrogen atmosphere. The mixture was stirred at 45 °C for 24 hours. After the reaction was complete as determined by LCMS, the reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D21-1 (245 mg, 34% in two steps). LCMS: m / z [M+H] + =849.4.

[0145] Example 10: Synthesis of compound D21-2

[0146] Compound 23 (1.22 g) was added to a mixture of compound 2 (1.40 g) and CMBP (6.12 g) dissolved in toluene (20 mL), and the reaction mixture was stirred at 110 °C for 18 hours. After the reaction was complete, the reaction mixture was extracted with ethyl acetate. The organic phases were dried over anhydrous sodium sulfate, combined, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to give the desired compound 24 (350 mg, 16%). LCMS: m / z [M-56+H] + =390.2.

[0147] A 4M dioxane hydrochloride solution (2 mL) was added to a mixture of compound 24 (350 mg) dissolved in dioxane (1 mL). The reaction mixture was stirred at 25 °C for 1 hour. After the reaction was complete as determined by LCMS, the reaction mixture was filtered and concentrated to give compound 25 (190 mg, crude product). LCMS: m / z [M+H] + =246.4.

[0148] Compound 25 (190 mg) was added to a mixture of compound 6 (482 mg) dissolved in acetic acid (3 mL) at 25 °C under a nitrogen atmosphere. The mixture was stirred at 45 °C for 24 hours. After the reaction was complete as determined by LCMS, the reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D21-2 (265 mg, 40% in two steps). LCMS: m / z [M+H] + =849.5.

[0149] Example 11: Synthesis of compound D23

[0150] Compound 26 (1.13 g) was added to a mixture of compound 2 (1.40 g) and CMBP (6.12 g) dissolved in toluene (20 mL), and the reaction mixture was stirred at 110 °C for 18 hours. After the reaction was complete, the reaction mixture was extracted with ethyl acetate. The organic phases were dried over anhydrous sodium sulfate, combined, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to give the desired compound 27 (373 mg, 17%). LCMS: m / z [M-56+H] + =376.0.

[0151] A 4M dioxane hydrochloride solution (2 mL) was added to a mixture of compound 27 (373 mg) dissolved in dioxane (1 mL). The reaction mixture was stirred at 25 °C for 1 hour. After the reaction was completed as determined by LCMS, the reaction mixture was filtered and concentrated to give compound 28 (200 mg, crude product). LCMS: m / z [M+H] + =232.3.

[0152] Compound 28 (200 mg) was added to a mixture of compound 6 (535 mg) dissolved in acetic acid (3 mL) at 25 °C under a nitrogen atmosphere. The mixture was stirred at 45 °C for 24 hours. After the reaction was complete as determined by LCMS, the reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D23 (363 mg, 50% in two steps). LCMS: m / z [M+H] + =835.4.

[0153] Example 12: Synthesis of compounds D17-2 and D33-2

[0154] Compound 29 (1.75 g), p-nitrobenzene chloroformate (3 g), and N,N-dimethylformamide (15 mL) were added to a reaction flask. The mixture was stirred, and N,N-diisopropylethylamine (2.32 g) was slowly added dropwise. The reaction was carried out at 25 °C for 4 hours. After the reaction was completed, the reaction mixture was evaporated to dryness. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 10:1) to give compound 30 (3.01 g, 82%). LC-MS: [M+H] + =318.0.

[0155] Compound 30 (33 mg), compound D17-2 (81 mg), and N,N-dimethylformamide (2 mL) were added to a reaction flask. The mixture was stirred, and triethylamine (21 mg) was slowly added dropwise. The reaction was carried out at 25 °C for 6 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane:methanol = 20:1) to give compound 31 (66 mg, 68%). LC-MS: [M+H] + =1041.1.

[0156] Compound 31 (66 mg), palladium on carbon (7 mg), and ethyl acetate (5 mL) were added to a reaction flask. The mixture was purged with hydrogen three times, and a hydrogen balloon was inserted. The reaction was carried out at 25°C for 6 hours. After the reaction was completed, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D33-2 (50 mg, 83%). LC-MS: [M+H] + =951.5.

[0157] Example 13: Synthesis of compound D41-2

[0158] Compound 32 (44 mg) was added to dichloromethane (1.5 mL) and saturated sodium bicarbonate aqueous solution (1.5 mL). Triphosgene (28 mg) was added under ice-water bath conditions. After stirring for 1.5 hours, the reaction was complete. Dichloromethane was added to the reaction mixture for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the solvent, yielding crude compound 33. Compound 33 was dissolved in dichloromethane (3 mL), and triethylamine (19 mg) and compound D17-2 (80 mg) were added sequentially. After stirring for 2 hours, the reaction was detected by LC-MS. After the reaction was complete, water (10 mL) was added to quench the reaction, and dichloromethane was added for extraction again. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 20:1) to give compound 34 (88 mg, 30%). LC-MS: [M+H] + =1040.0.

[0159] Compound 34 (88 mg), palladium on carbon (9 mg), and ethyl acetate (5 mL) were added to a reaction flask. The mixture was purged with hydrogen three times, and a hydrogen balloon was inserted. The reaction was carried out at 25°C for 6 hours. After the reaction was completed, the mixture was filtered, and the filtrate was concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to give compound D41-2 (76 mg, 95%). LC-MS: [M+H] + =950.3.

[0160] Example 14: Anti-tumor cell proliferation test of sucrose derivatives

[0161] This disclosure uses the CTG method to test the cell viability of atherosclerin-based compounds in human breast cancer cell lines MDA-MB-468 and SK-BR-3, and human lung adenocarcinoma cell line NCI-H1975. The cell sources used in this test were: MDA-MB-468 (gifted from Jushi Biosciences), SK-BR-3 (purchased from Kebai Biosciences), and NCI-H1975 (gifted from the Pharmacology Center). The culture medium for MDA-MB-468 was Advanced DMEM + 10% FBS, for SK-BR-3 it was McCoy's 5AMedium + 15% FBS, and for NCI-H1975 it was RPMI 1640 + 10% FBS.

[0162] Activity test:

[0163] Tumor cell lines were cultured to a confluence rate of 80%-90%, and cell viability was determined to be above 90% by trypan blue assay. Cell density was optimized, with MDA-MB-468 at 3000 cells / well, SK-BR-3 at 3000 cells / well, and NCI-H1975 at 1000 cells / well. 75 μL of each MDA-MB-468 / SK-BR-3 / NCI-H1975 cell suspension was seeded into Corning black clear-bottomed 96-well plates (catalog number: 3603) and incubated overnight at 37°C in a 5% CO2 cell culture incubator. The following day, after the MDA-MB-468 / SK-BR-3 / NCI-H1975 cells adhered and grew, 75 μL of the compound sample diluted with the corresponding culture medium for each cell type was added, controlling the final compound concentration to 1000 nM. A 5-fold serial dilution was performed, with a final DMSO concentration of 1‰. Cells were cultured at 37°C for 96 hours in a 5% CO2 incubator. Before the test, the CellTiter-GLOOR Luminescent Cell Viability Assay reagent was equilibrated to room temperature in the dark. Then, 50 μL of the CellTiter-GLOOR Luminescent Cell Viability Assay reagent (catalog number: G7573) was added to each well of a 96-well plate, and the plate was shaken at 300 rpm in the dark for 10 minutes to ensure complete cell lysis. After the reaction was complete, the chemiluminescence intensity was measured using a multi-mode microplate reader. The cell viability inhibition rate was determined by the chemiluminescence intensity, and a cell viability fitting curve was plotted and the IC50 was calculated. 50 The values ​​are shown in Table 1.

[0164] Table 1

[0165] This disclosure uses the CTG method to test the cell viability of sucrose compounds in human lung adenocarcinoma cell lines NCI-H446, SHP77, and NCI-H196. The cell sources used in this test were SHP77 and NCI-H446 provided by the Pharmacology Center, and NCI-H196 from Nanjing Kebai Biotechnology. The culture medium for NCI-H446, NCI-H96, and SHP77 was RPMI 1640 + 10% FBS.

[0166] Activity test:

[0167] Tumor cell lines were cultured to a confluence rate of 80%-90%, and cell viability was determined to be above 90% by trypan blue assay. Cell density was optimized, with NCI-H446 / SHP77 cell lines seeded at 2000 cells / well and NCI-H196 cell lines seeded at 1500 cells / well. 75 μL of each NCI-H446 / SHP77 / NCI-H196 cell suspension was seeded into Corning black clear-bottomed 96-well plates (catalog number: 3603) and incubated overnight at 37°C in a 5% CO2 incubator. The following day, after NCI-H446 / NCI-H196 cells adhered and SHP77 cells aggregated, 75 μL of the compound sample diluted with the corresponding culture medium was added, maintaining a final compound concentration of 1000 nM. The mixture was serially diluted 5-fold, with a final DMSO concentration of 1‰. The cells were then incubated at 37°C in a 5% CO2 incubator for 96 hours. Before the assay, the CellTiter-GLOOR Luminescent Cell Viability Assay reagent was equilibrated to room temperature in the dark. Then, 50 μL of the CellTiter-GLOOR Luminescent Cell Viability Assay reagent (catalog number: G7573) was added to each well of a 96-well plate, and the plate was shaken at 300 rpm in the dark for 10 minutes to ensure complete cell lysis. After the reaction was complete, the chemiluminescence intensity was measured using a multi-mode microplate reader. The cell viability inhibition rate was determined by the chemiluminescence intensity, and a cell viability curve was plotted using Graphpad Prism 8.0 to calculate the IC50. 50 The values ​​are shown in Table 2.

[0168] Table 2

[0169] As shown in Tables 1 and 2, the compounds disclosed herein exhibit good inhibitory activity against both breast cancer and lung adenocarcinoma.

Claims

1. A sucrose compound of formula (I) or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof: in, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, where R 2 Selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, and optionally substituted C6-C10 aryl; Y is selected from hydrogen or Y1 is selected from optionally substituted C1-C6 alkylene, optionally substituted C3-C6 cycloalkylene, optionally substituted 3-8-membered heterocyclic group, optionally substituted 2-6-membered heteroalkylene, optionally substituted C6-C14 arylene and optionally substituted 5-12-membered heterocyclic group; and when the C1-C6 alkylene is substituted, the two substituents on the C1-C6 alkylene can form an optionally substituted C3-C6 cycloalkyl or an optionally substituted 4-8-membered heterocyclic group together with the same carbon atom attached thereto; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 ; R 4 Selected from hydrogen and C1-C6 alkyl groups; and n1 and n2 are each independently selected from integers from 0 to 2 (e.g., 0, 1, and 2); The heteroalkyl, heteroaryl, heterocyclic, and heterocyclic groups contain 1-3 heteroatoms selected from N, O, or S; and The term "optionally substituted" means that the hydrogen at the substituted site of the group is not substituted, or is substituted by one or more substituents selected from the group consisting of: deuterium, halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, or 5-14 heteroaryl.

2. The sucrose compound as described in claim 1, or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, wherein: R 1 Selected from hydroxyl; or, R 1 Selected from cyano.

3. The sucrose compound as described in any one of claims 1-2, or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, wherein: X is selected from O and NR 2 , and R 2 Selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropane, cyclobutane, cyclopentane, cyclohexane, and phenyl, each of which may be optionally substituted, or R 2 Selected from hydrogen, methyl, CD3, CF3, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or, R 2 Selected from hydrogen, methyl, CD3, or R 2 Selected from hydrogen and methyl, or, R 2 Selected from methyl.

4. The succarpine compound as described in any one of claims 1-3, or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, wherein: Y is selected from hydrogen or Wherein Y1 is selected from optionally substituted C1-C4 alkylene, optionally substituted C3-C6 cycloalkylene, optionally substituted 4-8-membered heterocyclic, optionally substituted 3-6-membered heteroalkylene, optionally substituted C6-C10 arylene, and optionally substituted 5-10-membered heteroarylene; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 , and R 4 Selected from hydrogen and C1-C6 alkyl groups; Alternatively, Y1 is selected from optionally substituted C1-C4 alkylene groups, optionally substituted C3-C6 cycloalkylene groups, and optionally substituted 3-6 heteroalkylene groups; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 , and R 4 Selected from hydrogen and C1-C6 alkyl groups; Alternatively, Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, -OCH2CH2CH2CH2-, -SCH2CH2-, -SCH2CH2CH2-, and -SCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ; and R 4 Selected from hydrogen and methyl; Alternatively, Y1 is selected from methylene, ethylene, n-propylene, isopropylene, n-butylene, isobutylene, tert-butylene, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, phenylene, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-, each of which may be optionally substituted; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 , and R 4 Selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, and n-butyl; Alternatively, Y1 can be selected from methylene, -CD2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from hydrogen, halogens, -OH, -SH and -NHR 4 ; and R 4 Selected from hydrogen and methyl; Alternatively, Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ; and R 4 Selected from hydrogen and methyl; Or, -Y1-R 3 Selected from -CH2OH, -CD2OH, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, -OCH2CH2OH, -OCH2CH2CH2OH, -OCH2CH2CH2CH2OH, -NHCH2CH2OH, -NHCH2CH2CH2OH and -NHCH2CH2CH2CH2OH; Or, -Y1-R 3 Selected from -CH2OH, -OCH2CH2OH, and -NHCH2CH2OH.

5. The sucrose compound as described in any one of claims 1-4, or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, wherein: n1 is selected from 0, 1 and 2, and n2 is selected from 0 and 1, or n1 is selected from 0, 1 and 2, and n2 is 0.

6. The sucrose compound of claim 1, or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, wherein: R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, C1-C3 alkyl groups, and CD3; Y is selected from hydrogen or... Y1 is selected from C1-C4 alkylene groups and 3-6 heteroalkylene groups containing one heteroatom selected from N, O or S, R 3 Selected from -OH, -SH and -NHR 4 ;R 4 Selected from hydrogen and C1-C4 alkyl; and n1 selected from 0, 1 and 2, and n2 selected from 0 and 1; or, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, C1-C3 alkyl groups, and CD3; Y is selected from hydrogen or... Wherein Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, -OCH2CH2CH2CH2-, -SCH2CH2-, -SCH2CH2CH2- and -SCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 Selected from hydrogen and C1-C4 alkyl; and n1 selected from 0, 1 and 2, and n2 selected from 0 and 1; or, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, methyl, and CD3; Y is selected from hydrogen or Wherein Y1 is selected from C1-C4 alkylene groups, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 For hydrogen; and n1 is selected from 0, 1, and 2, and n2 is selected from 0 and 1; or, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 and S, and R 2 Selected from hydrogen, methyl, and CD3; Y is selected from hydrogen or Wherein Y1 is selected from C1-C4 alkylene groups, -OCH2CH2-, -OCH2CH2CH2-, and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 For hydrogen; and n1 is selected from 0, 1, and 2, and n2 is selected from 0 and 1; or, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 And R 2 Selected from hydrogen, methyl, and CD3; Y is selected from hydrogen or Where Y1 is selected from methylene, ethylene, n-propylene, n-butylene, -OCH2CH2-, -OCH2CH2CH2- and -OCH2CH2CH2CH2-; R 3 Selected from -OH, -SH and -NHR 4 ;R 4 For hydrogen; and n1 is selected from 0, 1, and 2, and n2 is selected from 0 and 1; or, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 And R 2 Selected from methyl and CD3; Y is selected from hydrogen or Where Y1 is selected from methylene, ethylene, n-propylene, -OCH2CH2- and -OCH2CH2CH2-; R 3 Selected from -OH and -SH; and n1 selected from 0, 1 and 2, and n2 selected from 0 and 1; or, R 1 Selected from hydroxyl and cyano groups; X is selected from O and NR. 2 And R 2 Selected from methyl and CD3; Y is selected from hydrogen or Where Y1 is selected from methylene and -OCH2CH2-; R 3 The value is -OH; and n1 is selected from 0, 1 and 2, and n2 is 0.

7. The sucrose compound of any one of claims 1, 3, and 5, or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, wherein the sucrose compound represented by formula (I) is the sucrose compound represented by formula (II): in, R 1 X, n1, and n2 are as defined in any one of claims 1, 3, and 5; R 5 and R 6 Each of the following is independently selected from hydrogen, deuterium, optionally substituted C1-C3 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted 5-6 membered heterocyclic, optionally substituted C1-C3 haloalkyl, and optionally substituted C6-C14 aryl, or R 5 and R 6 Together with the carbon atom to which it is attached, it forms an optionally substituted C3-C6 cycloalkyl group or an optionally substituted 5-6 membered heterocyclic group; or, R 5 and R 6 Each of the following is independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or phenyl, and each of these is optionally substituted, or R 5 and R 6 Together with the carbon atoms attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups, each of which is optionally substituted; or, R 5 and R 6 Independently hydrogen or deuterium; or, R 5 and R 6 Both are hydrogen.

8. The sucrose compound of claim 1, or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, wherein the compound is selected from one of the following compounds:

9. The sucrose compound of claim 1, or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, wherein the compound is selected from one of the following compounds:

10. A pharmaceutical composition comprising any of the saginata compounds of claims 1-9 or their tautomers, stereoisomers, pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, optionally further comprising a pharmaceutically acceptable carrier.

11. Use of any of the sucrose compounds of claims 1-9, or their tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, or the pharmaceutical composition of claim 10, in the preparation of a medicament for treating cancer.

12. A method for treating cancer, comprising administering to an individual in need a sucrose compound of any one of claims 1-9 or a tautomer, stereoisomer, or pharmaceutical salt, prodrug, hydrate, solvate, or isotopically labeled analogue thereof, or a pharmaceutical composition of claim 10.

13. The saginoid compound of any one of claims 1-9 or its tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, or the pharmaceutical composition of claim 10, for the treatment of cancer.

14. Use of any of the sucrose compounds of claims 1-9, or their tautomers, stereoisomers, or pharmaceutical salts, prodrugs, hydrates, solvates, or isotopically labeled analogs thereof, or the pharmaceutical composition of claim 10, in the treatment of cancer.

15. The use as described in claim 11 or 14, the method of claim 12, or the tunicate compound or its tautomer, stereoisomer, or pharmaceutical salt, prodrug, hydrate, solvate, or isotopically labeled analogue or pharmaceutical composition as described in claim 13, wherein, The cancers mentioned include liver cancer, kidney cancer, lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), stomach cancer, esophageal cancer, urethral cancer, bladder cancer, colon cancer, rectal cancer, prostate cancer, breast cancer, ovarian cancer, pancreatic cancer, melanoma, hematologic malignancies or gliomas, lymphomas (e.g., Hodgkin lymphoma, non-Hodgkin lymphoma, or relapsed anaplastic large cell lymphoma), cervical cancer, uterine cancer, endometrial cancer, salivary gland cancer, glioma, neuroblastoma, sarcoma, colorectal cancer, leukemia (e.g., acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia), bone cancer, skin cancer, thyroid cancer, etc.; or, the cancers include breast cancer and lung cancer; or, the cancers include breast cancer, small cell lung cancer, and non-small cell lung cancer; or, the cancers include breast cancer and lung adenocarcinoma.

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