Taxane drug conjugate, and preparation method therefor and use thereof

Abstract

Disclosed in the present invention are a taxane drug conjugate, and a preparation method therefor and the use thereof. Provided in the present invention is a compound as shown in formula I or a pharmaceutically acceptable salt thereof, which compound has an anti-tumor activity.

Description

Taxane conjugate drug and its preparation method and use

[0001] This application claims priority to Chinese Patent Application No. 2024101763916, filed on February 7, 2024, and Chinese Patent Application No. 2025101134124, filed on January 23, 2025. The entire text of the above-mentioned Chinese patent application is incorporated herein by reference. Technical Field

[0002] The present invention relates to a taxane conjugate drug and a preparation method and application thereof. Background Art

[0003] Chemotherapy is a mainstay of treatment for many cancers, using drugs to inhibit or kill rapidly proliferating cancer cells. However, it also presents challenges and side effects. Traditional cytotoxic chemotherapy drugs often affect normal cells, leading to a range of side effects such as nausea, vomiting, fatigue, hair loss, digestive problems, and immune system impairment. These side effects can impact patient quality of life and treatment compliance. Some tumor cells may develop resistance to chemotherapy, resulting in diminished or ineffective treatment. This may require switching or adjusting drug combinations or employing alternative treatment approaches. The effects of chemotherapy drugs on normal cells are a significant concern in treatment. To mitigate these effects, the pharmaceutical industry has adopted a number of strategies and technologies to improve the safety and efficacy of chemotherapy, including prodrugs and peptides or antibodies that bind to specific receptors or antigens. For example, enzyme-activated prodrugs are designed to render a drug inactive until activated under specific conditions. This is achieved through the action of enzymes in the body, which are often highly expressed in tumor tissue. This approach reduces the drug's impact on normal cells because the drug is activated only in the vicinity of cancer cells.

[0004] Patent US20050187147A1 describes a novel conjugate comprising a drug component and a protein kinase or lipid kinase substrate (typically a polypeptide having a sequence of seven or more amino acids). In preparing this conjugate, the document discloses a compound, PA-1, in which the hydrogen of the hydroxyl group at the 2' position of the carbon-13 side chain of paclitaxel is replaced by a benzyloxycarbonyl group (see Table 1).

[0005] CN102378626A discloses a polymer-drug conjugate, including a compound PA-2 (see Table 2) in which the hydrogen of the hydroxyl group at the 2' position of the carbon-13 side chain of docetaxel is replaced by a benzyloxycarbonyl group.

[0006] CN101374856A discloses a novel class of peptide-conjugated drug molecules that target the tumor-specific protease Legumain in the tumor microenvironment. Legumain is a cysteine ​​protease specifically expressed in tumor cells and tumor-associated macrophages that recognizes and cleaves peptides containing asparagine (Asn) peptide bonds.

[0007] CN109420179A discloses a polyene taxane polypeptide-coupled targeted prodrug, which is covalently coupled to a polypeptide via a degradable bridging group, wherein the polypeptide is a substrate of matrix metalloproteinase MMP-7, cysteine ​​protease B, and fibroblast activation protein α, and the polypeptide is an octapeptide containing asparagine.

[0008] CN109422799A also discloses a polypeptide-based targeted prodrug of polyene taxanes, which covalently binds the polyene taxane drug to the polypeptide via a degradable bridging group. The polypeptide is an octapeptide containing asparagine, which serves as a recognition substrate for matrix metalloproteinases MMP-2 and MMP-9.

[0009] CN102413842A discloses a paclitaxel conjugate containing an albumin-bound carrier cleaved by prostate-specific antigen. The two amino acids adjacent to the active moiety are leucine (Leu) and serine (Ser), respectively. Two compounds, PA-3 and PA-4, are disclosed (see Table 1).

[0010] Patent WO2017093719A1 discloses a membrane-type matrix metalloproteinase (MT-MMP)-sensitive paclitaxel peptide-conjugated prodrug. One of the amino acid sequences of the peptide is -Arg-Ser-Cit (guanine)-Gly-Hof (phenylbutyric acid)-Tyr-Leu-, where the two amino acids adjacent to the active moiety are leucine (Leu) and tyrosine (Tyr). Compound PA-5 is disclosed (see Table 1).

[0011] CN106715457A discloses a peptide-coupled compound with targeted activation and improved solubility properties. The peptide containing asparagine is coupled to a cleavable linker. In the tumor microenvironment, the linker can be selectively recognized and cleaved by asparagine endopeptidase, thereby releasing a drug with novel targeting, activation, and metabolic characteristics.

[0012] Patent CN107847607A discloses a conjugate of a nucleic acid aptamer coupled to paclitaxel, and involves the use of compound PA-6 (see Table 1) to prepare such a conjugate.

[0013] CN101935336A discloses a class of polyethylene glycol-modified, highly water-soluble peptide-drug conjugates that can be recognized by cathepsin B and release the active ingredient. The study discloses the tolerability and efficacy of the prodrug PTX in MCF-7 and HeLa cell lines and animal studies, but does not disclose the prodrug's stability in human or mouse serum and plasma. Two compounds, PA-7 and PA-8, are also disclosed (see Table 1).

[0014] WO2015136545A1 discloses a polymer, wherein compound PA-9 (see Table 1) is involved in the preparation process.

[0015] The document "El Alaoui A, Schmidt F, Monneret C, et al. Protecting groups for glucuronic acid: application to the synthesis of new paclitaxel (taxol) derivatives [J]. The Journal of Organic Chemistry, 2006, 71(26): 9628-9636" discloses a paclitaxel glucuronide prodrug, which aims to achieve tumor-specific activation using a tumor-activated prodrug (TAP) strategy. It discloses compound PA-10 (see Table 1).

[0016] The paper "Meng X, Lian X, Li X, et al. Synthesis of 2′-paclitaxel 2-deoxy-2-fluoro-glucopyranosyl carbonate for specific targeted delivery to cancer cells [J]. Carbohydrate Research, 2020, 493: 108034" describes a novel fluorinated glucuronide prodrug. The introduction of fluorine into drug compounds can modulate their properties, thereby affecting their pharmacodynamics and pharmacokinetics. The publicly disclosed compounds include PA-11 and PA-12 (see Table 1).

[0017] CN103641925A discloses a covalent polymer of a water-soluble polysaccharide and a taxane compound. One of the compounds involved in the preparation of the polymer is PA-13 (see Table 1).

[0018] The document "Gropeanu RA, Baumann H, Ritz S, Mailander V, Surrey T, del Campo A. Phototriggerable 2′,7-caged paclitaxel. PLoS One. 2012; 7(9): e43657" discloses a photoactivated paclitaxel prodrug, one of the compounds involved being PA-14 (see Table 1). Related content is also disclosed in EP2565188A1. Studies have shown that derivatization at C1 has little effect on the activity of paclitaxel, while esterification at C7 or C2′ results in a loss of microtubule assembly activity in vitro but does not affect cytotoxicity.

[0019] The document "Damen EWP, Nevalainen TJ, van den Bergh TJM, et al. Synthesis of novel paclitaxel prodrugs designed for bioreductive activation in hypoxic tumor tissue [J]. Bioorganic & Medicinal Chemistry, 2002, 10(1): 71-77" discloses a method for reducing paclitaxel toxicity by esterification at the C2' end. Using the reduction of an aromatic nitro compound as a trigger, the researchers developed a low-toxic paclitaxel prodrug that is selectively activated in hypoxic tissue. The disclosed compound includes PA-15 (see Table 1).

[0020] Patent CN101328159A discloses a class of taxane prodrugs that are activated by reduction in cancer cells under hypoxic conditions, and the disclosed compound includes PA-16 (see Table 1).

[0021] WO2020069488A1 discloses a bioorthogonal prodrug system. The patent reveals a series of prodrug molecules, one of which is PA-17 (see Table 1).

[0022] There is evidence that polyethylene glycol (PEG) can trigger immunogenic responses, especially when conjugated to other materials such as proteins and nanocarriers. Certain PEG-modified compounds induce additional anti-PEG antibodies that may adversely affect the efficacy and safety of drugs. Accelerated blood clearance (known as the "ABC phenomenon") is an unexpected immunogenic reaction observed with PEG conjugates, resulting in rapid clearance of PEGylated nanocarriers. The ABC phenomenon has been widely observed after repeated dosing and reduces the effectiveness of PEG conjugates and nanocarriers. Another unexpected immune response is a hypersensitivity reaction known as CARPA, which significantly reduces the safety of PEGylated nanocarriers and has been associated with reduced effectiveness of PEGylated therapies in clinical trials. The CARPA phenomenon has been classified as a non-IgE-mediated pseudoallergic reaction caused by activation of the complement system. (Chen BM, Cheng TL, Roffler S R.Polyethylene glycol immunogenicity: theoretical, clinical, and practical aspects of anti-polyethylene glycol antibodies[J]. ACS nano, 2021, 15(9): 14022-14048.)

[0023] The document Wu W, Luo Y, Sun C, et al. Targeting cell-impermeable prodrug activation to tumor microenvironment eradicates multiple drug-resistant neoplasms [J]. Cancer research, 2006, 66(2): 970-980. discloses a class of polypeptide conjugates that are specifically hydrolyzed by the asparagine endopeptidase Legubicin. The study investigated the efficacy of three compounds (LEG-2 / 3 / 4) in tumor-bearing mice. The document states that "LEG-4 is not cleaved by Legubicin and has no antitumor activity, while LEG-2 and LEG-3, which are converted from Legubicin, exhibit antitumor effects in vivo." It can be seen that the structures of the three compounds are similar, with LEG-4 lacking one amino acid compared to LEG-2 / 3. This suggests that due to the specificity of the enzyme, compounds with structural differences have poor predictability.

[0024] As mentioned above, a variety of prodrug design strategies for taxanes have been disclosed, including: (1) targeting peptides; (2) polymers; (3) specific enzyme recognition; (4) dedicated transporters; (5) photoactivation methods; (6) hypoxia activation strategies; (7) bioorthogonal prodrugs; (8) or a combination of multiple strategies. To date, strategies for specific enzyme recognition activation of drug release have been challenged in terms of enzyme diversity and specificity. Achieving good efficacy and / or reducing side effects and / or enhancing enzyme selectivity and / or controlling tissue distribution and / or ensuring good pharmacokinetics and / or enzyme kinetics and / or prodrug activity and / or tolerable dose and / or cell permeability and / or efficacy against specific tumor cells and / or prodrugs with high activity and / or stability in systemic circulation and / or targeting and / or good stability in plasma and serum are still areas lacking clear guidance. Therefore, comprehensive research and development are urgently needed to create new cytotoxic prodrugs.

[0025] Table 1 Similar compounds disclosed in the prior art Summary of the Invention

[0026] The present invention provides a taxane-based drug conjugate, a preparation method, and a use thereof, which has anti-tumor activity. In a first aspect, the present invention provides a compound as shown in Formula I or a pharmaceutically acceptable salt thereof,

[0027] T is Formula A, Formula B or Formula C:

[0028] Z is O or NH;

[0029] m is 0, 1, 2, 3, 4 or 5;

[0030] o is 0, 1, 2, 3, 4, or 5;

[0031] n is 0, 1, 2, 3, 4 or 5;

[0032] Each R 1 are independently hydrogen, deuterium, halogen, nitro, cyano, -OR 1-1 、-SR 1-1 、-NR 1-1 R 1-1 、-C(=O)R 1-1 、-S(=O)2R 1- 1 、-S(=O)R 1-1 、-P(=O)R 1-1 R 1-1 、C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20 cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 an aromatic hydrocarbon group or a 5-20 membered heteroaromatic hydrocarbon group; the C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20 cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 The aromatic hydrocarbon group and the 5-20 membered heteroaromatic hydrocarbon group are optionally replaced by one or more R 1-1 replace;

[0033] Each R 1-1 are independently hydrogen, deuterium, halogen, nitro, cyano, -OR 1-1-1 、-SR 1-1-1 、-NR 1-1-1 R 1-1-1 、-C(=O)R 1-1-1 、-S(=O)2R 1-1-1 、-S(=O)R 1-1-1 、-P(=O)R 1-1-1 R 1-1-1 、C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20 cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 an aromatic hydrocarbon group or a 5-20 membered heteroaromatic hydrocarbon group; the C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 The aromatic hydrocarbon group and the 5-20 membered heteroaromatic hydrocarbon group are optionally replaced by one or more R 1-1-1 replace;

[0034] Each R 1-1-1 are independently hydrogen, deuterium, halogen, nitro, cyano, -OR 1-1 - 1- 1. -SR 1-1-1-1 、-NR 1-1-1-1 R 1-1-1-1 、-C(=O)R 1- 1-1-1 、-S(=O)2R 1-1-1-1 、-S(=O)R 1-1-1-1 、-P(=O)R 1-1-1-1 R 1-1-1-1 、C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20 cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 an aromatic hydrocarbon group or a 5-20 membered heteroaromatic hydrocarbon group; the C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20 cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 The aromatic hydrocarbon group and the 5-20 membered heteroaromatic hydrocarbon group are optionally replaced by one or more R 1-1-1-1 replace;

[0035] Each R 1-1-1-1 are independently hydrogen, deuterium, halogen, nitro, cyano, -OR 1-1-1-1-1 、-SR 1-1-1-1-1 、-NR 1-1-1-1-1 R 1-1-1-1-1 、-C(=O)R 1-1-1-1-1 、-S(=O)2R 1-1-1-1-1 、-S(=O)R1-1-1-1-1 、-P(=O)R 1-1-1-1-1 R 1-1-1-1-1 、C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20 cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 an aromatic hydrocarbon group or a 5-20 membered heteroaromatic hydrocarbon group; the C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20 cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 The aromatic hydrocarbon group and the 5-20 membered heteroaromatic hydrocarbon group are optionally replaced by one or more R 1-1-1-1-1 replace;

[0036] Each R 1-1-1-1-1 are independently hydrogen, deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2OH, -S(=O)2NH2, -S(=O)OH, -S(=O)NH2, -P(=O)(OH)2, -P(=O)NH2(OH), -P(=O)(NH2)2, -PH(=O)OH, -PH(=O)NH2, -PH2(=O), C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 20 Cycloalkyl, C3-C 20 Cycloalkenyl, C3-C 20 cycloalkynyl, 3-20 membered heteroalkyl, 4-20 membered heteroalkenyl, 4-20 membered heteroalkynyl, 3-20 membered heterocycloalkyl, 3-20 membered heterocycloalkenyl, 3-20 membered heterocycloalkynyl, C6-C 20 An aromatic hydrocarbon group or a 5-20 membered heteroaromatic hydrocarbon group;

[0037] The heteroatoms are independently selected from 1, 2, 3 or 4 of O, P, S and N; the number of heteroatoms is independently 1, 2, 3 or 4;

[0038] R as above 1 defined;

[0039] R c -NR e -XY;

[0040] R e As above R 1 defined;

[0041] X is an amino acid residue or a peptide chain formed by 2-10 amino acids;

[0042] Y is -C(=O)R b 、-S(=O)2R b 、-S(=O)R b 、-P(=O)R b R b ;

[0043] R b As above R 1 defined;

[0044] R d are independently -NR d-0 Y d-1 OR d-2 ;

[0045] R d-0 As above R 1 defined;

[0046] R d-2 As above R 1 defined;

[0047] Y d-1 -C(=O)R d-1 、-S(=O)2R d-1 、-S(=O)R d-1 、-P(=O)R d-1 R d-1 ;

[0048] R d-1 As above R 1 defined.

[0049] In some embodiments, in the compound of Formula I or a pharmaceutically acceptable salt thereof, certain groups have the following definitions, and the definitions of the groups not mentioned are as described in any embodiment of the present invention (hereinafter referred to as "in some embodiments"):

[0050] T is Formula A, Formula B or Formula C;

[0051] n is 0, 1, 2, 3, 4 or 5;

[0052] m is 0, 1, 2, 3, 4 or 5;

[0053] o is 0, 1, 2, 3, 4, or 5;

[0054] Each R 1 are independently hydrogen, deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, -OR 1-1 、-SR 1-1 、-NR 1-1 R 1-1 , nitro, cyano, -C(=O)R 1-1 、-C(=O)OR 1-1 、-C(=O)NR 1-1 R 1-1 、-S(=O)2NR 1-1 R 1-1 、-S(=O)OR 1-1 、-S(=O)2OR 1-1 , optionally by multiple R 1-1 Substituted C1-C 20 Alkyl, optionally replaced by one or more R 1-1 Substituted C2-C 20 The alkenyl group, optionally substituted by one or more R 1-1 Substituted C2-C 20 Alkynyl, optionally substituted by one or more R 1-1 substituted 3-10 membered heteroalkenyl, optionally substituted by one or more R 1-1 substituted 3-10 membered heteroalkynyl or optionally substituted with multiple R 1-1 substituted 3-20 membered heteroalkyl;

[0055] Each R 1-1 are independently hydrogen, deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, nitro, cyano, C1-C 20 Alkyl or 3-20 membered heteroalkyl; the -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, C1-C 20 The alkyl and 3-20 membered heteroalkyl groups are optionally substituted with any substituent;

[0056] Each R is independently deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, -OR a 、-SR a 、-NR a R a , nitro, cyano, -C(=O)R a 、-C(=O)OR a 、-C(=O)NR a R a 、-S(=O)2NR a R a 、-S(=O)R a 、-S(=O)2OR a , nitro, cyano, optionally replaced by one or more R a Substituted C1-C 20 Alkyl, optionally replaced by one or more R a Substituted C1-C 20 Alkoxy, C2-C 20 The alkenyl group, optionally substituted by one or more R a Substituted C2-C 20 Alkynyl, optionally substituted by one or more R a substituted 3-10 membered heteroalkenyl, optionally substituted by one or more R a The substituted 3-10 membered heteroalkynyl group is unsubstituted or optionally substituted with multiple R a substituted 3-20 membered heteroalkyl; each R a are independently hydrogen, deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, nitro, cyano, C1-C 20 Alkyl or 3-20 membered heteroalkyl; the -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, C1-C 20 The alkyl and 3-20 membered heteroalkyl groups are optionally substituted with any substituent;

[0057] Each R d As defined above for R;

[0058] R c is -NH-XY;

[0059] X is an amino acid residue or a peptide chain formed by 2-4 amino acids;

[0060] Y is -C(=O)OR b 、-C(=O)R b 、-C(=O)NR b R b 、-S(=O)2NR b R b 、-S(=O)2OR b 、-S(=O)2R b 、-S(=O)R b 、-S(=O)NR b R b 、-S(=O)OR b 、-P(=O)(OR b )2、-P(=O)NR b R b (OR b ),-P(=O)(NR b R b )2、-PH(=O)OR b 、-PH(=O)NR b R b or -PH(=O)R b ; R b are independently hydrogen, -C(=O)OH, C1-C 20 Alkyl, C1-C 20 Alkoxy, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 aryl, 3-20 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the C1-C 20 Alkyl, C1-C 20 Alkoxy, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 aryl, 3-20 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl and 5-12 membered heteroaryl are optionally substituted with any substituent;

[0061] The heteroatoms are independently selected from one, two, three or four of O, P, S and N, and the number of heteroatoms is independently one, two, three or four.

[0062] In some embodiments, the heteroatom is not attached to a halogen, nitro, or cyano group.

[0063] In some embodiments, the heteroatoms are independently selected from one, two, three or four of O, P, S and N; and the number of heteroatoms is independently one, two, three or four.

[0064] In some embodiments, two heteroatoms are not connected by a single bond unless one heteroatom is oxo-substituted.

[0065] In some embodiments, the compound represented by Formula I is a compound represented by Formula IA:

[0066] In some embodiments, the compound represented by Formula I is a compound represented by Formula IB:

[0067] In some embodiments, the compound represented by Formula I is a compound represented by Formula IC:

[0068] In some embodiments, the compound represented by Formula I is a compound represented by Formula ID:

[0069] In some embodiments, the compound represented by Formula I is a compound represented by Formula IE:

[0070] In some embodiments, the compound represented by Formula I is a compound represented by Formula IF:

[0071] In some embodiments, the compound represented by formula I is a compound represented by formula IG:

[0072] In some embodiments, the compound represented by formula IG is a compound represented by formula IGA:

[0073] In some embodiments, the compound represented by formula IG is a compound represented by formula IGB:

[0074] In some embodiments, the compound represented by Formula I is a compound represented by Formula IH:

[0075] In some embodiments, the compound represented by formula I is a compound represented by formula II:

[0076] In some embodiments, the compound represented by Formula I is a compound represented by Formula IJ:

[0077] In some embodiments, the compound represented by Formula I is a compound represented by Formula IK:

[0078] In some embodiments, the compound represented by Formula I is a compound represented by Formula IL:

[0079] In some embodiments, the compound represented by formula I is a compound represented by formula IM:

[0080] In some embodiments, the compound represented by Formula I is a compound represented by Formula IN:

[0081] In some embodiments, the compound represented by Formula I is a compound represented by Formula IO:

[0082] In some embodiments, the compound represented by Formula I is a compound represented by Formula IP:

[0083] In some embodiments, R 1 are independently hydrogen, deuterium, halogen, or C1-C4 alkyl.

[0084] In some embodiments, R 1 are independently hydrogen.

[0085] In some embodiments, n is 0, o is 0, and m is 1.

[0086] In some embodiments, m is 0, n is 0, and o is 1 or 2.

[0087] In some embodiments, n is an integer from 1 to 5, o is 0, and m is 1.

[0088] In some embodiments, m is 1.

[0089] In some embodiments, n is 0, 1, 2, 3, 4, or 5.

[0090] In some embodiments, o is 1 or 2.

[0091] In some embodiments, m=n=o=0.

[0092] In some embodiments, m is 0, n is an integer from 1 to 5, and o is 1.

[0093] In some embodiments, m is 0, n is an integer from 1 to 4, and o is 2.

[0094] In some embodiments, R eare independently hydrogen, deuterium, or a C1-C4 alkyl group.

[0095] In some embodiments, R e are independently hydrogen.

[0096] In some embodiments, R d-0 are independently hydrogen, deuterium, or a C1-C4 alkyl group.

[0097] In some embodiments, R d-0 are independently hydrogen.

[0098] In some embodiments, n is 0.

[0099] In some embodiments, Y is -C(=O)R b 、S(=O)2R b or -S(=O)R b , the R b -OH, -NH2, -NHR b-1 、-NR b-1 R b-1 、-C(=O)R b-1 、S(=O)2R b-1 、-S(=O)R b-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is 1, 2 or 3.

[0100] In some embodiments, each R b-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1 、-NR b-1-1 R b-1-1 、-C(=O)R b-1-1 、S(=O)2Rb-1-1 、-S(=O)R b-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0101] In some embodiments, each R b-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1-1 、-NR b-1-1-1 R b-1-1-1 、-C(=O)R b-1-1-1 、S(=O)2R b-1-1-1 、-S(=O)R b-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0102] In some embodiments, each Rb-1-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1-1-1 、-NR b-1-1-1-1 R b-1-1-1-1 、-C(=O)R b-1-1-1-1 、S(=O)2R b-1-1-1-1 、-S(=O)R b-1-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 an aromatic hydrocarbon group, a 5-10 membered heteroaromatic hydrocarbon group or a 5-10 membered heteroaromatic hydrocarbon group; said R b-1-1-1-1 Substituted C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0103] In some embodiments, each R b-1-1-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkylNH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylNH-, (3-8 membered heteroalkyl)(3-8 membered heteroalkyl)N-, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkylNH-, (3-8 membered heterocycloalkyl)(3-8 membered heterocycloalkyl)N-, C3-C8 cycloalkyloxy, 3-8 membered heterocycloalkyloxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group or the 5-10 membered heteroaromatic hydrocarbon group; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0104] In some embodiments, two heteroatoms are not connected by a single bond unless one of the heteroatoms is oxo-substituted, and the heteroatoms are independently selected from 1, 2, or 3 of O, S, and N; and the number of the heteroatoms is independently 1, 2, or 3.

[0105] In some embodiments, Y is -C(=O)R b 、S(=O)2R b or -S(=O)R b , the R b N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy or C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkylamino group; the N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino group, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino group, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C6-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy and C5-C 10The 3-8 membered heteroalkylamino group of the aromatic heteroalkyl group is optionally substituted by one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2 or -C(=O)OH; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0106] In some embodiments, Y is -C(=O)R b 、S(=O)2R b or -S(=O)R b , the R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkoxy, 1-3 halogen-substituted C1-C6 alkylamino, 3-8 membered heterocycloalkyl C1-C6 alkyl, 3-8 membered heterocycloalkyl C1-C6 alkoxy, 3-8 membered heterocycloalkyl C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group, 1-3 halogen-substituted C6-C 10 Aromatic oxy, 1-3 halogen-substituted C6-C 10 C(=O)OH C0-C6 alkyl, C(=O)OH C0-C6 alkoxy, C(=O)OH C0-C6 alkylamino, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkoxy, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkylamino group, C(=O)OH 3-8 membered heteroalkyl group, C(=O)OH 3-8 membered heteroalkoxy group or C(=O)OH 3-8 membered heteroalkylamino group; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of heteroatoms is independently 1, 2 or 3.

[0107] In some embodiments, Y is -C(=O)R b 、S(=O)2Rb or -S(=O)R b , the R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OHC0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0108] In some embodiments, Y is -C(=O)R b .

[0109] In some embodiments, R b N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy or C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkylamino group; the N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino group, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino group, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy and C5-C 10 The 3-8 membered heteroalkylamino group of the aromatic heteroalkyl group is optionally substituted by one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0110] In some embodiments, R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkoxy, 1-3 halogen-substituted C1-C6 alkylamino, 3-8 membered heterocycloalkyl C1-C6 alkyl, 3-8 membered heterocycloalkyl C1-C6 alkoxy, 3-8 membered heterocycloalkyl C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group, 1-3 halogen-substituted C6-C 10 Aromatic oxy, 1-3 halogen-substituted C6-C 10 Aromatic amino, C(=O)OH C0-C6 alkyl, C(=O)OH C0-C6 alkoxy, C(=O)OH C0-C6 alkylamino, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10Aromatic C1-C6 alkoxy, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkylamino group, C(=O)OH 3-8 membered heteroalkyl group, C(=O)OH 3-8 membered heteroalkoxy group or C(=O)OH 3-8 membered heteroalkylamino group; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of heteroatoms is independently 1, 2 or 3.

[0111] In some embodiments, R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OH C0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group: C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl.

[0112] In some embodiments, Y d-1 -C(=O)R d-1 、-S(=O)2R d-1 or -S(=O)R d-1 , the R d-1 -OH, -NHR d-1-1 、-NR d-1-1 R d-1-1 、-C(=O)R d-1-1 、S(=O)2R d-1-1 、-S(=O)R d-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R d-1-1Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0113] In some embodiments, each R d-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR d-1-1-1 、-NR d-1-1-1 R d-1-1-1 、-C(=O)R d-1-1-1 、S(=O)2R d-1-1-1 、-S(=O)R d-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R d-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0114] In some embodiments, each R d-1-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR d-1-1-1-1 、-NR d-1-1-1-1 R d-1-1-1-1 、-C(=O)R d-1-1-1-1 、S(=O)2R d-1-1-1-1 、-S(=O)R d-1-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R d-1-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0115] In some embodiments, each R d-1-1-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR d-1-1-1-1-1 、-NR d-1-1-1-1-1 R d-1-1-1-1-1 、-C(=O)R d-1-1-1-1-1 、S(=O)2R d-1-1-1-1-1 、-S(=O)R d-1-1-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 an aromatic hydrocarbon group, a 5-10 membered heteroaromatic hydrocarbon group or a 5-10 membered heteroaromatic hydrocarbon group; said R d-1-1-1-1-1 Substituted C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R d-1-1-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0116] In some embodiments, each R d-1-1-1-1-1are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkylNH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylNH-, (3-8 membered heteroalkyl)(3-8 membered heteroalkyl)N-, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkylNH-, (3-8 membered heterocycloalkyl)(3-8 membered heterocycloalkyl)N-, C3-C8 cycloalkyloxy, 3-8 membered heterocycloalkyloxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group or the 5-10 membered heteroaromatic hydrocarbon group; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0117] In some embodiments, Y d-1 -C(=O)R d-1 、S(=O)2R d-1 or -S(=O)R d-1 , the R d-1 N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy or C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkylamino group; the N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino group, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino group, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy and C5-C 10 The 3-8 membered heteroalkylamino group of the aromatic heteroalkyl group is optionally substituted by one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2 or -C(=O)OH; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0118] In some embodiments, Y d-1 -C(=O)R d-1 、S(=O)2R d-1 or -S(=O)R d-1 , the R d-1 N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkoxy, 1-3 halogen-substituted C1-C6 alkylamino, 3-8 membered heterocycloalkyl C1-C6 alkyl, 3-8 membered heterocycloalkyl C1-C6 alkoxy, 3-8 membered heterocycloalkyl C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group, 1-3 halogen-substituted C6-C 10 Aromatic oxy, 1-3 halogen-substituted C6-C 10 Aromatic amino, C(=O)OH C0-C6 alkyl, C(=O)OH C0-C6 alkoxy, C(=O)OH C0-C6 alkylamino, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10Aromatic C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkoxy, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkylamino group, C(=O)OH 3-8 membered heteroalkyl group, C(=O)OH 3-8 membered heteroalkoxy group or C(=O)OH 3-8 membered heteroalkylamino group; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of heteroatoms is independently 1, 2 or 3.

[0119] In some embodiments, Y d-1 -C(=O)R d-1 、S(=O)2R d-1 or -S(=O)R d-1 , the R d-1 N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OH C0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0120] In some embodiments, Y d-1 -C(=O)R d-1 .

[0121] In some embodiments, R d-1 N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy or C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkylamino group; the N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino group, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino group, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy and C5-C 10 The 3-8 membered heteroalkylamino group of the aromatic heteroalkyl group is optionally substituted by one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2 or -C(=O)OH; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0122] In some embodiments, R d-1 N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10alkylamino, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkoxy, 1-3 halogen-substituted C1-C6 alkylamino, 3-8 membered heterocycloalkyl C1-C6 alkyl, 3-8 membered heterocycloalkyl C1-C6 alkoxy, 3-8 membered heterocycloalkyl C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group, 1-3 halogen-substituted C6-C 10 Aromatic oxy, 1-3 halogen-substituted C6-C 10 Aromatic amino, C(=O)OH C0-C6 alkyl, C(=O)OH C0-C6 alkoxy, C(=O)OH C0-C6 alkylamino, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkoxy, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkylamino group, C(=O)OH 3-8 membered heteroalkyl group, C(=O)OH 3-8 membered heteroalkoxy group or C(=O)OH 3-8 membered heteroalkylamino group; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of heteroatoms is independently 1, 2 or 3.

[0123] In some embodiments, R d-1 N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OH C0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group: C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl.

[0124] In some embodiments, two heteroatoms are not connected by a single bond unless one of the heteroatoms is oxo, where the heteroatom is O, S, or N.

[0125] In some embodiments, R d-2C1-C6 alkyl, 3-8 membered heteroalkyl, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C6-C 10 The aromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl group, 3-8 membered heteroalkyl group, C3-C8 cycloalkyl group, 3-8 membered heterocycloalkyl group, C6-C 10 The aromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally replaced by one or more R d-2-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0126] In some embodiments, each R d-2-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR d-2-1-1 、-NR d-2-1-1 R d-2-1-1 、-C(=O)R d-2-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R d-2-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0127] In some embodiments, each R d-2-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR d-2-1-1-1 、-NR d-2-1-1-1 R d-2-1-1-1 、-C(=O)R d-2-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R d-2-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0128] In some embodiments, each R d-2-1-1-1 and independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkylNH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylNH-, (3-8 membered heteroalkyl)(3-8 membered heteroalkyl)N-, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkylNH-, (3-8 membered heterocycloalkyl)(3-8 membered heterocycloalkyl)N-, C3-C8 cycloalkyloxy, C3-C8 cycloalkylNH-, (C3-C8 cycloalkyl)(C3-C8 cycloalkyl)N-, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 Aromatic oxy, C6-C 10 The aromatic hydrocarbon group NH-, a 5-10 membered heteroaromatic hydrocarbon group, a 5-10 membered heteroaromatic hydrocarbon oxy group or a 5-10 membered heteroaromatic hydrocarbon group NH-; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0129] In some embodiments, R d-2 It is a C1-C6 alkyl group.

[0130] In some embodiments, R d-2 It is a methyl group.

[0131] In some embodiments, R is deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR a 、-NR a R a 、-C(=O)R a, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R a Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0132] In some embodiments, each R a are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR a-1 、-NR a-1 R a-1 、-C(=O)R a-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R a- 1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0133] In some embodiments, each R a-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRa-1-1 、-NR a-1-1 R a-1-1 、-C(=O)R a-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R a-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0134] In some embodiments, each R a-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR a-1-1-1 、-NR a-1-1-1 R a-1-1-1 、-C(=O)R a-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R a-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0135] In some embodiments, each R a-1-1-1are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR a-1-1-1-1 、-NR a-1-1-1-1 R a-1-1-1-1 、-C(=O)R a-1-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R a-1-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0136] In some embodiments, each R a-1-1-1-1 Each is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkylNH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylNH-, (3-8 membered heteroalkyl)(3-8 membered heteroalkyl)N-, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkylNH-, (3-8 membered heterocycloalkyl)(3-8 membered heterocycloalkyl)N-, C3-C8 cycloalkyloxy, C3-C8 cycloalkylNH-, (C3-C8 cycloalkyl)(C3-C8 cycloalkyl)N-, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 Aromatic oxy, C6-C 10 The aromatic hydrocarbon group NH-, a 5-10 membered heteroaromatic hydrocarbon group, a 5-10 membered heteroaromatic hydrocarbon oxy group or a 5-10 membered heteroaromatic hydrocarbon group NH-; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0137] In some embodiments, each R is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, N(C0-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C0-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C0-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino, N(C0-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C0-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C0-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy or C5-C 10Aromatic heteroalkyl 3-8 membered heteroalkylamino group; the N(C0-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C0-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C0-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino group, N(C0-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C0-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C0-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino group, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy and C5-C 10The 3-8 membered heteroalkylamino group of the aromatic heteroalkyl group is optionally substituted by deuterium, halogen, nitro, cyano, -OH, -SH, -NH2 or -C(=O)OH; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0138] In some embodiments, each R is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 alkylamino, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkoxy, 1-3 halogen-substituted C1-C6 alkylamino, 3-8 membered heterocycloalkyl C1-C6 alkyl, 3-8 membered heterocycloalkyl C1-C6 alkoxy, 3-8 membered heterocycloalkyl C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group, 1-3 halogen-substituted C6-C 10 Aromatic oxy, 1-3 halogen-substituted C6-C 10 Aromatic amino, C(=O)OH C0-C6 alkyl, C(=O)OH C0-C6 alkoxy, C(=O)OH C0-C6 alkylamino, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, 1-3 halogen-substituted C56C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkoxy, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkylamino group, C(=O)OH 3-8 membered heteroalkyl group, C(=O)OH 3-8 membered heteroalkoxy group or C(=O)OH 3-8 membered heteroalkylamino group; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of heteroatoms is independently 1, 2 or 3.

[0139] In some embodiments, each R is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkylNH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylNH-, (3-8 membered heteroalkyl)(3-8 membered heteroalkyl)N-, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkylNH-, (3-8 membered heterocycloalkyl)(3-8 membered heterocycloalkyl)N-, C3-C8 cycloalkyloxy, C3-C8 cycloalkylNH-, (C3-C8 cycloalkyl)(C3-C8 cycloalkyl)N-, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 Aromatic oxy, C6-C 10 The aromatic hydrocarbon group NH-, a 5-10 membered heteroaromatic hydrocarbon group, a 5-10 membered heteroaromatic hydrocarbon oxy group or a 5-10 membered heteroaromatic hydrocarbon group NH-; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0140] In some embodiments, each R is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OH C0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0141] In some embodiments, R is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, 3-6 membered heteroalkyl, 3-6 membered heteroalkoxy or 3-6 membered heteroalkylamino; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of heteroatoms is independently 1, 2 or 3.

[0142] In some embodiments, each R is independently H.

[0143] In some embodiments, T is represented by Formula C.

[0144] In some embodiments, X is selected from

[0145] 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of X may be the same or different; preferably 1, 2, 3 or 4, more preferably 2.

[0146] In some embodiments, X is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of X may be the same or different; preferably 1, 2, 3 or 4, more preferably 2.

[0147] In some embodiments, X is X1, X2-X3 or X4-X5-X6-X7;

[0148] X1 is X2 is X3 is X4 is X5 is X6 X7 is

[0149] In some embodiments, X1 is

[0150] In some embodiments, X2 is

[0151] In some embodiments, X2 is

[0152] In some embodiments, X3 is

[0153] In some embodiments, X3 is

[0154] In some embodiments, X4 is

[0155] In some embodiments, X5 is

[0156] In some embodiments, X6 is

[0157] In some embodiments, X7 is

[0158] In some embodiments, X is

[0159] In some embodiments, X is

[0160] In some embodiments, Y is -C(=O)OR b 、-C(=O)R b 、-C(=O)NR b R b 、-S(=O)2NR b R b 、-S(=O)2OR b 、-S(=O)2R b 、-S(=O)R b 、-S(=O)NR b R b 、-S(=O)OR b 、-P(=O)(OR b )2、-P(=O)NR b R b (OR b ),-P(=O)(NR b R b )2、-PH(=O)OR b 、-PH(=O)NR b R b or -PH(=O)R b ; R b are independently hydrogen, -C(=O)OH, C1-C 20 Alkyl, C1-C 20 Alkoxy, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the C1-C 20 Alkyl, C1-C 20 Alkoxy, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10Aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl and 5-12 membered heteroaryl are optionally substituted with one or more R b-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0161] In some embodiments, each R b-1 are independently deuterium, halogen, hydroxyl, -NR f R f 、C1-C 20 Alkoxy, C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl, 5-12 membered heteroaryl, -C(=O)OR f 、-C(=O)R f 、-C(=O)NR f R f 、-S(=O)2NR f R f 、-S(=O)2OR f 、-S(=O)2R f 、-S(=O)R f 、-P(=O)R f R f or -PH(=O)R f ; the C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 Aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl and 5-12 membered heteroaryl are optionally substituted with one or more R b-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0162] In some embodiments, each R b-1-1 are independently deuterium, halogen, hydroxyl, amino, C1-C 20 Alkoxy, C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl, 5-12 membered heteroaryl, -C(=O)OH, -C(=O)H, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, -S(=O)2H, -S(=O)R f or -P(=O)2(OH)2; the heteroatoms are independently selected from one, two or three of O, S and N; the number of the heteroatoms is independently one, two or three.

[0163] In some embodiments, R f are independently hydrogen, C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 Aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl and 5-12 membered heteroaryl are optionally substituted with one or more R f-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0164] In some embodiments, each R f-1 are independently deuterium, halogen, hydroxyl, amino, C1-C 20 Alkoxy, C1-C 20 Alkyl, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10Aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl, -C(=O)OH, -C(=O)H, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, -S(=O)2H or -P(=O)2(OH)2; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of heteroatoms is independently 1, 2 or 3.

[0165] In some embodiments, Y is -C(=O)OR b or -C(=O)R b ; R b Independently C1-C 20 Alkyl, C6-C 10 Aryl C(=O)OR f ; the C1-C 20 Alkyl and C6-C 10 The aryl group is optionally substituted with one or more R b-1 replace.

[0166] In some embodiments, each R b-1 are independently halogen, -NR f R f 、C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 10 Aryl, 3-10 membered heterocycloalkyl or -C(=O)OR f ; the C1-C 20 Alkyl, C6-C 10 Aryl and 3-10 membered heterocycloalkyl are optionally substituted by one or more R b-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0167] In some embodiments, each R b-1-1 are independently halogen or -C(=O)OH.

[0168] In some embodiments, R f are independently hydrogen or C1-C 20 of alkyl.

[0169] In some embodiments, Y is -C(=O)R b ; R b Independently C1-C 20 Alkyl, C1-C 20 Alkoxy, 3-8 membered heteroalkyl, -COOH or C6-C 10Aryl; the C1-C 20 Alkyl, C1-C 20 Alkoxy, 3-8 membered heteroalkyl and C6-C 10 The aryl group is optionally substituted with one or more R b-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0170] In some embodiments, each R b-1 are independently halogen, -NR f R f , 3-10 membered heterocycloalkyl, C6-C 10 Aryl or -C(=O)OH; the C6-C 10 The aryl group is optionally substituted with one or more R b-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0171] In some embodiments, each R b-1-1 are independently halogen.

[0172] In some embodiments, R f Independently C1-C 20 of alkyl.

[0173] In some embodiments, the halogen is not attached to a heteroatom.

[0174] In some embodiments, Y is

[0175] In some embodiments, each R is independently deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, -OR a 、-SR a 、-NR a R a , nitro, cyano, -C(=O)R a 、-C(=O)OR a 、-C(=O)NR a R a 、-S(=O)2NR a R a 、-S(=O)2R a 、-S(=O)2OR a , nitro, cyano, optionally replaced by one or more R a Substituted C1-C20 Alkyl, optionally replaced by one or more R a Substituted C1-C 20 The alkoxy group, optionally with one or more R a Substituted C2-C 20 The alkenyl group, optionally substituted by one or more R a Substituted C2-C 20 Alkynyl, optionally substituted by one or more R a substituted 3-8 membered heteroalkyl, optionally substituted by one or more R a substituted 3-10 membered heteroalkenyl or optionally substituted by one or more R a substituted 3-10 membered heteroalkynyl; each R a are independently hydrogen, deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, nitro, cyano, C1-C 20 Alkyl or 3-20 membered heteroalkyl; the -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, C1-C 20 The alkyl and 3-20 membered heteroalkyl groups are optionally replaced by one or more R a-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0176] In some embodiments, each R a-1 Independently C1-C 20 Alkyl, C1-C 20 Alkoxy, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the C1-C 20 Alkyl, C1-C 20 Alkoxy, C2-C 20 Alkenyl, C2-C 20 Alkynyl, C3-C 10 Cycloalkyl, C6-C 10 Aryl, 3-8 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl, 3-10 membered heterocycloalkyl and 5-12 membered heteroaryl are optionally substituted with one or more R a-1Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0177] In some embodiments, each R a-1-1 are independently deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, nitro, cyano, C1-C 20 Alkyl, C6-C 10 Aryl or 3-20 membered heteroalkyl; the C6-C 10 Aryl, C1-C 20 The alkyl and 3-20 membered heteroalkyl groups are optionally replaced by one or more R a-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0178] In some embodiments, each R a-1-1-1 are independently halogen.

[0179] In some embodiments, each R d Independently -NHY d-1 or C1-C 20 of alkoxy.

[0180] In some embodiments, each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl, C1-C 20 Alkoxy or C6-C 10 Aryl; the C1-C 20 Alkyl, C1-C 20 Alkoxy and C6-C 10 The aryl group is optionally substituted with one or more R d-1-1 replace.

[0181] In some embodiments, each R d-1-1 are independently halogen, C6-C 10 Aryl or C1-C 20 The alkyl group of C6-C 10 Aryl and C1-C 20 The alkyl group is optionally replaced by one or more R d-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0182] In some embodiments, each R d-1-1-1 are independently halogen.

[0183] In some embodiments, R d NHY d-1 .

[0184] In some embodiments, Y d-1 -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl, C1-C 20 Alkoxy or C6-C 10 Aryl; the C1-C 20 Alkyl, C1-C 20 Alkoxy and C6-C 10 The aryl group is optionally substituted with one or more R d-1-1 replace.

[0185] In some embodiments, each R d-1-1 are independently halogen, C6-C 10 Aryl or C1-C 20 The alkyl group of C6-C 10 Aryl and C1-C 20 The alkyl group is optionally replaced by one or more R d-1-1-1 Substitution; the heteroatoms are independently selected from 1, 2 or 3 of O, S and N; the number of the heteroatoms is independently 1, 2 or 3.

[0186] In some embodiments, each R d-1-1-1 are independently halogen.

[0187] In some embodiments, R d C1-C 20 of alkoxy.

[0188] In some embodiments, each Y d-1 Independently

[0189] In some embodiments, R d-0 For H.

[0190] In some embodiments, R d-2 It is a methyl group.

[0191] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-1 to I-12:

[0192] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-13 to I-24:

[0193] In some embodiments, the compound of Formula I is a compound of Formula Ia, Ib, or Ic:

[0194] In some embodiments, the compound represented by Formula Ia is a compound represented by Formula Ia-1, a compound represented by Formula Ia-2, a compound represented by Formula Ia-3, a compound represented by Formula Ia-4, or a compound represented by Formula Ia-5.

[0195] In some embodiments, in the compound represented by Formula Ia-1, R c is -NH-XY; X is X1, X2-X3 or X4-X5-X6-X7; X1 is

[0196] X2 is

[0197] X3 is

[0198] X4 is X5 is X6 X7 is

[0199] Y is -C(=O)OR b or -C(=O)R b ; R b Independently C1-C 20 Alkyl, C6-C 10 Aryl or C(=O)OR f ; the C1-C 20 Alkyl and C6-C 10 The aryl group is optionally substituted with one or more R b-1 Replace; each R b-1 are independently halogen, -NR f R f 、C1-C 20 Alkoxy, C1-C 20 Alkyl, C6-C 10 Aryl, 3-10 membered heterocycloalkyl or -C(=O)OR f ; the C1-C 20 Alkoxy, C1-C 20 Alkyl, C6-C10 Aryl and 3-10 membered heterocycloalkyl are optionally substituted by one or more R b-1-1 Replace; each R b-1-1 are independently halogen or -C(=O)OH; R f are independently hydrogen or C1-C 20 The heteroatoms of the heterocycloalkyl group are N and / or O, and the number of heteroatoms is 1 or 2.

[0200] In some embodiments, Y is -C(=O)R b , the R b is the R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OH C0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group: C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl.

[0201] In some embodiments, in the compound represented by Formula Ia-2, R d NHY d-1 or optionally one or more R d-1 Substituted C1-C 20 Alkoxy; each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl, C1-C 20 Alkoxy or C6-C 10 Aryl; the C1-C 20 Alkyl, C1-C 20 Alkoxy and C6-C 10 The aryl group is optionally substituted with one or more R d-1-1 Replace; each R d-1-1 are independently halogen, C6-C 10 Aryl or C1-C 20 The alkyl group of C6-C 10 Aryl and C1-C 20 The alkyl group is optionally replaced by one or more R d-1-1-1 Replace; each R d-1-1-1 are independently halogen.

[0202] In some embodiments, R d NHY d-1 , the Y d-1 -C(=O)R d-1 , the R d-1 C1-C 10 Alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group or C1-C 10 of alkoxy.

[0203] In some embodiments, in the compound represented by formula Ia-3, R d NHY d-1 or optionally one or more R d-1 Substituted C1-C 20 Alkoxy; each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl or C1-C 20 of alkoxy.

[0204] In some embodiments, in the compound represented by Formula Ia-4, each R d Independently -NHY d-1 or optionally one or more R d-1 Substituted C1-C 20 Alkoxy; each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl or C1-C 20 of alkoxy.

[0205] In some embodiments, in the compound represented by Formula Ia-5, R c is -NH-XY; X is X1; X1 is Y is -C(=O)R b ; R b Independently C1-C 20 The C1-C 20 The alkyl group is optionally replaced by one or more R b-1 Replace; each R b-1 are independently -C(=O)OR d ; R d are independently hydrogen.

[0206] In some embodiments, the compound represented by Formula Ib is a compound represented by Formula Ib-1, a compound represented by Formula Ib-2, or a compound represented by Formula Ib-3.

[0207] In some embodiments, in the compound represented by Formula Ib-1, R c is -NH-XY; X is X2-X3;

[0208] X2 is

[0209] X3 is

[0210] Y is -C(=O)R b ; R b C1-C 20 Alkyl or -NR f R f ; R f are independently hydrogen or C1-C 20 of alkyl.

[0211] In some embodiments, Y is -C(=O)R b , the R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C 10 of alkoxy.

[0212] In some embodiments, in the compound represented by formula Ib-2, R d NHY d-1 ; Each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 of alkoxy.

[0213] In some embodiments, in the compound represented by formula Ib-3, R d It is a C1-C6 alkoxy group.

[0214] In some embodiments, the compound represented by formula Ic is a compound represented by formula Ic-1

[0215] In some embodiments, in the compound represented by formula Ic-1, R c is -NH-XY; X is X2-X3; X2 is X3 is Y is -C(=O)R b ; R b C1-C 20 The alkyl group is preferably a C1-C8 alkyl group.

[0216] In some embodiments, X is X1 or X2-X3;

[0217] X1 is X2 is X3 is

[0218] Y is -C(=O)OR b or -C(=O)R b ; R b Independently C1-C 20 Alkyl or C6-C 10 Aryl; the C1-C 20 Alkyl and C6-C 10 The aryl group is optionally substituted with one or more R b-1 Replace; each R b-1 are independently halogen, -NR f R f , 3-10 membered heterocycloalkyl or -C(=O)OR f ; R f are independently hydrogen or C1-C 20 Alkyl (for example, Y is ).

[0219] In some embodiments, Y is -C(=O)R b ; R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 aromatic hydrocarbon group, C(=O)OH C2-C6 alkyl group or C1-C 10 of alkoxy.

[0220] In some embodiments, Y is -C(=O)R b ; R b It is not an electron-withdrawing group, such as -C(=O)OH.

[0221] In some embodiments, each R d Independently -NHY d-1 or C1-C 20 Alkoxy; each Y d-1are independently -C(=O)R d- 1 ; Each R d-1 Independently C1-C 20 Alkyl or C1-C 20 Alkoxy groups (e.g., each R d Independently or methoxy; each Y d-1 Independently ).

[0222] In some embodiments, X is X1 or X2-X3;

[0223] X1 is X2 is X3 is

[0224] Y is -C(=O)OR b or -C(=O)R b ; R b Independently C1-C 20 The C1-C 20 The alkyl group is optionally replaced by one or more R b-1 Replace; each R b-1 are independently halogen or -NR f R f ; R f are independently hydrogen or C1-C 20 Alkyl (for example, Y is ).

[0225] In some embodiments, Y is -C(=O)R b ; R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl or C1-C 10 of alkoxy.

[0226] In some embodiments, each R d Independently -NHY d-1 or C1-C 20 Alkoxy; each Y d-1 are independently -C(=O)R d- 1 ; Each R d-1 Independently C1-C 20 Alkyl or C1-C 20 Alkoxy groups (e.g., each R d Independently or methoxy, each Y d-1 Independently ).

[0227] In some embodiments, X is X2-X3;

[0228] X2 is X3 is

[0229] Y is -C(=O)OR b or -C(=O)R b ; R b Independently C1-C 20 Alkyl or C6-C 10 Aryl; the C1-C 20 Alkyl and C6-C 10 The aryl group is optionally substituted with one or more R b-1 Replace; each R b-1 are independently halogen, -NR f R f , 3-10 membered heterocycloalkyl or -C(=O)OR f ; R f are independently hydrogen or C1-C 20 Alkyl (for example, Y is ).

[0230] In some embodiments, Y is -C(=O)R b ; R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl or C1-C 10 of alkoxy.

[0231] In some embodiments, each R d are independently -NH-Y d-1 or optionally one or more R d-1 Substituted C1-C 20 Alkoxy; each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl or C1-C 20 Alkoxy groups (e.g., each R d Independently or methoxy, each Y d-1 Independently ).

[0232] In some embodiments,

[0233] X is X1 or X2-X3;

[0234] X1 is X2 is X3 is

[0235] Y is -C(=O)R b ; R b Independently C1-C 20 Alkyl or C6-C 10 Aryl; the C1-C 20 Alkyl and C6-C 10 The aryl group is optionally substituted with one or more R b-1 Replace; each R b-1 are independently halogen, -NR f R f , 3-10 membered heterocycloalkyl or -C(=O)OR f ; R f are independently hydrogen or C1-C 20 Alkyl (for example, Y is ).

[0236] In some embodiments, Y is -C(=O)R b ; R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 aromatic hydrocarbon group, C(=O)OH C2-C6 alkyl group or C1-C 10 of alkoxy.

[0237] In some embodiments, each R d Independently -NHY d-1 or optionally one or more R d-1 Replace C1-C 20 Alkoxy; each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl or C1-C 20 Alkoxy groups (e.g., each R d Independently or methoxy; each Y d-1 Independently ).

[0238] In some embodiments,

[0239] X is X2-X3;

[0240] X2 is X3 is

[0241] Y is -C(=O)OR b or -C(=O)R b ; R b Independently C1-C 20 Alkyl or C6-C 10 Aryl; the C1-C 20 Alkyl and C6-C 10 The aryl group is optionally substituted with one or more R b-1 Replace; each R b-1 are independently -NR f R f or a 3-10 membered heterocycloalkyl group; R f are independently hydrogen or C1-C 20 Alkyl (for example, Y is ).

[0242] In some embodiments, Y is -C(=O)R b ; R b It is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl or 3-8 membered heterocycloalkylC1-C6 alkyl.

[0243] In some embodiments, each R d Independently -NHY d-1 ; Each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 The alkyl groups (e.g. each R d Independently Each Y d-1 Independently ).

[0244] In some embodiments,

[0245] X is X2-X3;

[0246] X2 is X3 is

[0247] Y is -C(=O)R b ; R b Independently C1-C 20The C1-C 20 The alkyl group is optionally replaced by one or more R b-1 Replace; each R b-1 are independently -NR f R f ; R f are independently hydrogen or C1-C 20 Alkyl (for example, Y is );

[0248] In some embodiments, Y is -C(=O)R b ; R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl or C1-C 10 of alkyl.

[0249] In some embodiments,

[0250] Each R d Independently -NHY d-1 ; Each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl or C1-C 20 Alkoxy (e.g., each R is independently Each Y d-1 Independently ).

[0251] In some embodiments,

[0252] X is X2-X3;

[0253] X2 is X3 is

[0254] Y is -C(=O)R b ; R b Independently C1-C 20 The C1-C 20 The alkyl group is optionally replaced by one or more R b-1 Replace; each R b-1 are independently -NR f R f or -C(=O)OR f ; R f are independently hydrogen or C1-C 20 Alkyl (for example, Y is ).

[0255] In some embodiments, Y is -C(=O)R b ; R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 or C(=O)OH C2-C6 alkyl.

[0256] In some embodiments, each R d Independently -NHY d-1 ; Each Y d-1 are independently -C(=O)R d-1 ; Each R d-1 Independently C1-C 20 Alkyl or C1-C 20 Alkoxy (e.g., each R is independently Each Y d-1 Independently ).

[0257] In some embodiments, Y is -C(=O)R b ; R b are independently C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C 10 Aromatic hydrocarbon group or C6-C 10 The aromatic hydrocarbon group; the C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C 10 Aromatic hydrocarbon groups and C6-C 10 The aromatic hydrocarbon group is optionally replaced by R b-1 Substituted; said R b- 1 -C(=O)OH, halogen, C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C 10 Aromatic hydrocarbon group or C6-C 10 of aromatic hydrocarbon radicals.

[0258] In some embodiments, Y d-1 -C(=O)R d-1 ; R d-1 are independently C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C 10 Aromatic hydrocarbon group or C6-C 10 The aromatic hydrocarbon group; the C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C 10 Aromatic hydrocarbon groups and C6-C10 The aromatic hydrocarbon group is optionally replaced by R d-1 Substituted; said R d-1 -C(=O)OH, halogen, C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C 10 Aromatic hydrocarbon group or C6-C 10 of aromatic hydrocarbon radicals.

[0259] In some embodiments, R d-2 is a C1-C8 alkyl, a C3-C8 cycloalkyl or a C6-C 10 The C1-C8 alkyl, C3-C8 cycloalkyl and C6-C 10 The aromatic hydrocarbon group is optionally replaced by R d-2-1 Substituted; said R d-2-1 -C(=O)OH, halogen, C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C 10 Aromatic hydrocarbon group or C6-C 10 of aromatic hydrocarbon radicals.

[0260] In some embodiments, the compound of formula I does not include any compound of PA-1 to PA-16, or an optical isomer of any compound of PA-1 to PA-16.

[0261] In some embodiments, R d-1 or R b Does not contain polyethylene glycol segments ( n-1 is an integer ≥ 2), a 6-membered oxoheterocyclic group substituted by a hydroxy group, or a (C═O)OHC1-C6 alkylOC1-C6 alkyl group.

[0262] In some embodiments, the amino acid residues involved in chirality are all L-type amino acid residues.

[0263] In some embodiments, the amino terminus of X is linked to Y, and the carbonyl terminus of X is linked to -NR e -connect.

[0264] In some embodiments, X is formed by two or more amino acids, and each amino acid is linked by an amide bond.

[0265] In some embodiments, R does not contain a nitro (—NO 2 ) or amino (—NH 2 ) group.

[0266] In some embodiments, R d-2 Excluding R'NHC(=O)C1-C6 alkyl, R' is an arbitrary substituent.

[0267] In some embodiments, Y is -C(=O)C2-C4 linear alkyl b 、-S(=O)2C2-C4 linear alkyl R b 、-S(=O)C2-C4 linear alkyl R b 、-P(=O)(C2-C4 linear alkyl R b )R b .

[0268] In some embodiments, Y d-1 -C(=O)C2-C4 straight chain alkyl R d-1 、-S(=O)2C2-C4 linear alkyl R d-1 、-S(=O)C2-C4 linear alkyl R d-1 、-P(=O)(C2-C4 linear alkyl R d-1 )R d-1 .

[0269] In some embodiments, Y d-1 Middle R d-1 For electron donating groups.

[0270] In some embodiments, Y d-1 -C(=O)CF3 is not included.

[0271] In some embodiments, -OR d-2 At the para position of the benzyloxycarbonyl group, R d-2 For electron donating groups.

[0272] In some embodiments, R c In the para position of the benzyloxycarbonyl group.

[0273] In some embodiments, the compound represented by Formula I is a compound represented by Formula II-1, II-2 or II-3,

[0274] X2 or X3 are each independently selected from an alanine residue, a guanine residue, a valine residue, a glycine residue, a phenylalanine residue, a leucine residue, a cysteine ​​residue, an aspartic acid residue, a glutamic acid residue, a histidine residue, an isoleucine residue, a lysine residue, a methionine residue, an asparagine residue, a proline residue, a glutamine residue, an arginine residue, a serine residue, a threonine residue, a tryptophan residue or a tyrosine residue;

[0275] In some embodiments, Y is -C(=O)R b 、S(=O)2R b or -S(=O)R b ;

[0276] In some embodiments, Rb NHR b-1 、-NR b-1 R b-1 、-C(=O)R b-1 、-OR b-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1 replace;

[0277] In some embodiments, each R b-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1 、-NR b-1-1 R b-1-1 、-OR b-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1 replace.

[0278] In some embodiments, each R b-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1-1 、-NRb-1-1-1 R b-1-1-1 、-OR b-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1-1 replace.

[0279] In some embodiments, each R b-1-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1-1-1 、-NR b-1-1-1-1 R b-1-1-1-1 、-OR b-1-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 an aromatic hydrocarbon group, a 5-10 membered heteroaromatic hydrocarbon group or a 5-10 membered heteroaromatic hydrocarbon group; said R b-1-1-1-1 Substituted C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1-1-1 replace.

[0280] In some embodiments, each R b-1-1-1-1are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkylNH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylNH-, (3-8 membered heteroalkyl)(3-8 membered heteroalkyl)N-, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkylNH-, (3-8 membered heterocycloalkyl)(3-8 membered heterocycloalkyl)N-, C3-C8 cycloalkyloxy, 3-8 membered heterocycloalkyloxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 aryloxy, 5-10 membered heteroaryloxy or 5-10 membered heteroaryloxy.

[0281] In some embodiments, two heteroatoms are not connected by a single bond unless one of the heteroatoms is oxo, where the heteroatom is O, S, or N.

[0282] In some embodiments, R b Does not contain polyethylene glycol segments ( n-1 is an integer ≥ 2), a 6-membered oxoheterocyclic group substituted by a hydroxy group, or a (C═O)OHC1-C6 alkylOC1-C6 alkyl group.

[0283] In some embodiments, X2 is an L-guanidine residue or an L-alanine residue, and X3 is an L-valine residue; the X2-X3 are preferably

[0284] In some embodiments, Y is -C(=O)R b 、S(=O)2R b or -S(=O)R b , the R b N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy or C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkylamino group; the N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)C1-C6 alkylamino group, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3-8 membered heteroalkylamino group, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10alkylamino, 3-8 membered heteroalkyl, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylamino, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkoxy, 3-8 membered heterocycloalkylamino, 3-8 membered heterocycloalkylC1-C6 alkyl, 3-8 membered heterocycloalkylC1-C6 alkoxy, 3-8 membered heterocycloalkylC1-C6 alkylamino, 3-8 membered heterocycloalkyl3-8 membered heteroalkyl, 3-8 membered heterocycloalkyl3-8 membered heteroalkoxy, 3-8 membered heterocycloalkyl3-8 membered heteroalkylamino, -C(=O)OH, C6-C 10 Aromatic hydrocarbon group, C6-C 10 Aromatic oxy, C6-C 10 Aromatic amine, C5-C 10 Aromatic heteroalkyl, C5-C 10 Aromatic heteroalkyloxy, C5-C 10 Aromatic heteroalkylamine, C6-C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, C6-C 10 Aromatic 3-8 membered heteroalkyl, C6-C 10 Aromatic 3-8 membered heteroalkoxy, C6-C 10 Aromatic 3-8 membered heteroalkylamino, C5-C 10 Aromatic heteroalkyl C1-C6 alkyl, C5-C 10 Aromatic heteroalkyl C1-C6 alkoxy, C5-C 10 Aromatic heteroalkyl C1-C6 alkylamino, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkyl, C5-C 10 Aromatic heteroalkyl 3-8 membered heteroalkoxy and C5-C 10 The aromatic heteroalkyl 3-8 membered heteroalkylamino group is optionally substituted with one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH or unsubstituted.

[0285] In some embodiments, Y is -C(=O)R b 、S(=O)2R b or -S(=O)R b , the R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkoxy, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkylamino, C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10alkylamino, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkoxy, 1-3 halogen-substituted C1-C6 alkylamino, 3-8 membered heterocycloalkyl C1-C6 alkyl, 3-8 membered heterocycloalkyl C1-C6 alkoxy, 3-8 membered heterocycloalkyl C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group, 1-3 halogen-substituted C6-C 10 Aromatic oxy, 1-3 halogen-substituted C6-C 10 Aromatic amino, C(=O)OH C0-C6 alkyl, C(=O)OH C0-C6 alkoxy, C(=O)OH C0-C6 alkylamino, C6C 10 Aromatic C1-C6 alkyl, C6-C 10 Aromatic C1-C6 alkoxy, C6-C 10 Aromatic C1-C6 alkylamino, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic C1-C6 alkoxy, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkylamino group, C(=O)OH 3-8 membered heteroalkyl group, C(=O)OH 3-8 membered heteroalkoxy group or C(=O)OH 3-8 membered heteroalkylamino group.

[0286] In some embodiments, Y is -C(=O)R b 、S(=O)2R b or -S(=O)R b , the R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OH C0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group: C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl.

[0287] In some embodiments, Y is -C(=O)R b .

[0288] In some embodiments, R b is a C1-C6 alkyl, a C1-C6 alkoxy, -ORb-1 、C6-C 10 aromatic hydrocarbon group, -C(=O)OH or 3-8 membered heteroalkyl group; the C1-C6 alkyl group, C1-C6 alkoxy group, C6-C 10 The aromatic hydrocarbon group and the 3-8 membered heteroalkyl group are optionally replaced by one or more R b-1 replace.

[0289] In some embodiments, each R b-1 are independently C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, halogens, -NR f R f , 3-8 membered heterocycloalkyl or -C(=O)OH; the C1-C6 alkyl, C6-C 10 The aromatic hydrocarbon group and the 3-8 membered heterocycloalkyl group are optionally replaced by one or more R b- 1-1 replace.

[0290] In some embodiments, each R f are independently C1-C6 alkyl.

[0291] In some embodiments, each R b-1-1 are independently halogen.

[0292] In some embodiments, R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OHC0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group: C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl.

[0293] In some embodiments, the compound of formula II-1 is a compound represented by formula II-1-1, formula II-1-2, formula II-1-3 or formula II-1-4:

[0294] In some embodiments, R b As defined in the compound portion of formula II-1, II-2 or II-3.

[0295] In some embodiments, R bis a C1-C6 alkyl, a C1-C6 alkoxy, -OR b-1 or C6-C 10 The C1-C6 alkyl, C1-C6 alkoxy and C6-C 10 The aromatic hydrocarbon group is optionally replaced by one or more R b-1 replace.

[0296] In some embodiments, each R b-1 are independently -NR f R f , halogen, 3-8 membered heterocycloalkyl, -C(=O)OH or C1-C6 alkyl.

[0297] In some embodiments, each R f are independently C1-C6 alkyl.

[0298] In some embodiments, R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C8 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C8 alkyl substituted with 1-3 halogens 10 an aromatic hydrocarbon group, a C(=O)OHC0-C6 alkyl group or a C1-C8 alkoxy group.

[0299] In some embodiments, each R b-1 are independently -NR f R f , halogen, 3-8 membered heterocycloalkyl, -C(=O)OH, C6-C 10 An aromatic hydrocarbon group or a C1-C6 alkyl group; the C6-C 10 The aromatic hydrocarbon group is optionally replaced by one or more R b-1-1 replace.

[0300] In some embodiments, each R b-1-1 are independently halogen.

[0301] In some embodiments, R b C1-C 10 Alkyl, 3-8 membered heterocycloalkyl C1-C6 alkyl, 1-3 halogen substituted C6-C 10 Aromatic hydrocarbon groups, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkyl, C1-C6 alkyl substituted with 1-3 halogens, N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C(=O)OH C1-C6 alkyl or C1-C 10of alkoxy.

[0302] In some embodiments, the compound of formula II-2 is a compound represented by formula II-2-1, formula II-2-2, formula II-2-3 or formula II-2-4:

[0303] In some embodiments, R b As defined in the compound portion of Formula II-1-1, Formula II-1-2, Formula II-1-3 or Formula II-1-4.

[0304] In some embodiments, R b is a C1-C6 alkyl group; the C1-C6 alkyl group is optionally replaced by one or more R b-1 replace.

[0305] In some embodiments, each R b-1 are independently -NR f R f .

[0306] In some embodiments, each R f are independently C1-C6 alkyl.

[0307] In some embodiments, R b It is a C1-C6 alkyl group.

[0308] In some embodiments, R b It is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl.

[0309] In some embodiments, the compound of formula II-3 is a compound represented by formula II-3-1, formula II-3-2, formula II-3-3 or formula II-3-4:

[0310] In some embodiments, R b As defined in the compound portion of Formula II-2-1, Formula II-2-2, Formula II-2-3 or Formula II-2-4.

[0311] In some embodiments, R b It is a C1-C8 alkyl group.

[0312] In some embodiments, the compound represented by Formula I is a compound represented by Formula II-4, II-5 or II-6,

[0313] X1 is an amino acid residue, preferably an α-amino acid residue, preferably an alanine residue, a guanine residue, a valine residue, a glycine residue, a phenylalanine residue, a leucine residue, a cysteine ​​residue, an aspartic acid residue, a glutamic acid residue, a histidine residue, an isoleucine residue, a lysine residue, a methionine residue, an asparagine residue, a proline residue, a glutamine residue, an arginine residue, a serine residue, a threonine residue, a tryptophan residue, or a tyrosine residue, more preferably an L-alanine residue, an L-guanine residue, an L-valine residue, a glycine residue, an L-phenylalanine residue, an L-leucine residue, an L-cysteine ​​residue, an L-aspartic acid residue, an L-glutamic acid residue, an L-histidine residue, an L-isoleucine residue, an L-lysine residue, an L-methionine residue, an L-asparagine residue, an L-proline residue, an L-glutamine residue, an L-arginine residue, an L-serine residue, an L-threonine residue, an L-tryptophan residue, or an L-tyrosine residue;

[0314] Y is -C(=O)R b 、S(=O)2R b or -S(=O)R b In some embodiments, Y is -C(=O)R b .

[0315] In some embodiments, R b As defined in the compound portion of Formula II-3-1, Formula II-3-2, Formula II-3-3 or Formula II-3-4.

[0316] In some embodiments, R b is C1-C6 alkyl, -C(=O)OH or 3-8 membered heteroalkyl; the C1-C6 alkyl and 3-8 membered heteroalkyl are optionally replaced by one or more R b-1 replace.

[0317] In some embodiments, each R b-1 is independently -C(=O)OH.

[0318] In some embodiments, R b It is C(=O)OH C0-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl.

[0319] In some embodiments, the compound of formula II-4 is a compound represented by formula II-4-1, formula II-4-2, formula II-4-3, formula II-4-4, formula II-4-5, formula II-4-6, formula II-4-7, formula II-4-8, formula II-4-9, formula II-4-10, formula II-4-11 or formula II-4-12:

[0320] In some embodiments, R b As defined in the compound portion of formula II-4, II-5 or II-6.

[0321] In some embodiments, R b is a C1-C6 alkyl group; the C1-C6 alkyl group is optionally replaced by one or more R b-1 replace.

[0322] In some embodiments, R b is a C1-C6 alkyl group or -C(=O)OH; the C1-C6 alkyl group is optionally replaced by one or more R b-1 replace.

[0323] In some embodiments, each R b-1 is independently -C(=O)OH.

[0324] In some embodiments, R b It is C(=O)OH C1-C6 alkyl.

[0325] In some embodiments, R b It is a C(=O)OH C0-C6 alkyl group.

[0326] In some embodiments, the compound of formula II-5 is a compound represented by formula II-5-1, formula II-5-2, formula II-5-3, formula II-5-4, formula II-5-5, formula II-5-6, formula II-5-7, formula II-5-8, formula II-5-9, formula II-5-10, formula II-5-11 or formula II-5-12:

[0327] In some embodiments, R b As defined in part by the compound shown in Formula II-4-1, Formula II-4-2, Formula II-4-3, Formula II-4-4, Formula II-4-5, Formula II-4-6, Formula II-4-7, Formula II-4-8, Formula II-4-9, Formula II-4-10, Formula II-4-11 or Formula II-4-12.

[0328] In some embodiments, the compound of formula II-6 is a compound represented by formula II-6-1, formula II-6-2, formula II-6-3, formula II-6-4, formula II-6-5, formula II-6-6, formula II-6-7, formula II-6-8, formula II-6-9, formula II-6-10, formula II-6-11 or formula II-6-12:

[0329] In some embodiments, R b As defined in part by the compound shown in Formula II-4-1, Formula II-4-2, Formula II-4-3, Formula II-4-4, Formula II-4-5, Formula II-4-6, Formula II-4-7, Formula II-4-8, Formula II-4-9, Formula II-4-10, Formula II-4-11 or Formula II-4-12.

[0330] In some embodiments, the compound represented by formula I is a compound represented by formula II-7, II-8, II-9, II-10, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-19, II-20 or II-21,

[0331] In some embodiments, Y d-1 -C(=O)R d-1 、S(=O)2R d-1 or -S(=O)R d-1 .

[0332] In some embodiments, Y d-1 -C(=O)R d-1 .

[0333] In some embodiments, R d-1 The compound part R represented by formula II-4-1, formula II-4-2, formula II-4-3, formula II-4-4, formula II-4-5, formula II-4-6, formula II-4-7, formula II-4-8, formula II-4-9, formula II-4-10, formula II-4-11 or formula II-4-12 b defined.

[0334] In some embodiments, R d-1 C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon group, C1-C6 alkoxy group or -OR d-1-1 The C1-C6 alkyl, C6-C 10 The aromatic hydrocarbon group and the C1-C6 alkoxy group are optionally replaced by one or more R d-1-1 replace.

[0335] In some embodiments, each R d-1-1 are independently C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon group or halogen; the C1-C6 alkyl and C6-C 10 The aromatic hydrocarbon group is optionally replaced by one or more R d-1-1-1 replace.

[0336] In some embodiments, each R d-1-1-1 are independently halogen.

[0337] In some embodiments, R d-2 It is a C1-C6 alkyl group.

[0338] In some embodiments, R d-2 It is a C1-C3 alkyl group.

[0339] In some embodiments, R d-2 It is a methyl group.

[0340] In some embodiments, R d-1 is a C1-C6 alkyl group or a C1-C6 alkoxy group; R d-2 It is a C1-C6 alkyl group.

[0341] In some embodiments, R d-1 C1-C 10 Alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group or C1-C 10 of alkoxy.

[0342] In some embodiments, R d-1 C1-C 10 Alkyl or C1-C 10 Alkoxy; R d-2 It is a C1-C6 alkyl group.

[0343] In some embodiments, the compound of formula II-7 is a compound represented by formula II-7-1 or II-7-2:

[0344] In some embodiments, R d-1 As defined in part by the compound represented by formula II-7, II-8, II-9, II-10, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-19, II-20 or II-21.

[0345] In some embodiments, the compound of formula II-8 is a compound represented by formula II-8-1 or II-8-2:

[0346] In some embodiments, R d-1As defined in the compound portion of formula II-7-1 or II-7-2.

[0347] In some embodiments, R d-1 is a C1-C6 alkyl group, a C1-C6 alkoxy group or -OR d-1-1 .

[0348] In some embodiments, each R d-1-1 are independently C1-C6 alkyl.

[0349] In some embodiments, R d-1 It is a C1-C6 alkyl group or a C1-C6 alkoxy group.

[0350] In some embodiments, the compound of formula II-9 is a compound represented by formula II-9-1 or II-9-2:

[0351] In some embodiments, R d-1 As defined in the compound portion of formula II-8-1 or II-8-2.

[0352] In some embodiments, R d-1 is a C1-C6 alkoxy group; R d-2 It is a C1-C6 alkyl group.

[0353] In some embodiments, the compound of formula II-10 is a compound represented by formula II-10-1 or II-10-2:

[0354] In some embodiments, R d-1 and R d-2 As defined in the compound portion of formula II-9-1 or II-9-2.

[0355] In some embodiments, R d-1 is a C1-C6 alkoxy group; R d-2 It is a C1-C6 alkyl group.

[0356] In some embodiments, the compound of formula II-12 is a compound represented by formula II-12-1 or II-12-2:

[0357] In some embodiments, R d-1 As defined in the compound portion of formula II-8-1 or II-8-2.

[0358] In some embodiments, R d-1 is a C1-C6 alkoxy group or -OR d-1-1 .

[0359] In some embodiments, each R d-1-1 are independently C1-C6 alkyl.

[0360] In some embodiments, R d-1 It is a C1-C6 alkoxy group.

[0361] Another aspect of the present invention provides a compound or a pharmaceutically acceptable salt thereof, wherein the compound is any one of the following compounds:

[0362] Another aspect of the present invention provides a compound or a pharmaceutically acceptable salt thereof, wherein the compound is any one of the following compounds:

[0363] In some embodiments, the amino group of the amino acid in X is linked to Y.

[0364] In some embodiments, the halogen may be fluorine, chlorine, bromine, or iodine, for example, fluorine or chlorine.

[0365] In some embodiments, the C1-C 20 The alkyl group can be C1-C 10 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0366] In some embodiments, the C2-C 20 Alkenyl can be C2-C 10 Alkenyl, the C2-C 20 An alkenyl group may contain 1, 2, or 3 carbon-carbon double bonds; for example, ethenyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, or 4-methyl-3-pentenyl.

[0367] In some embodiments, the C2-C 20 Alkynyl can be C2-C 10 Alkynyl, the C2-C 20Alkynyl groups may contain 1, 2, or 3 carbon-carbon triple bonds; for example, ethynyl, 1-propynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, or 5-hexynyl.

[0368] In some embodiments, the C3-C 20 The cycloalkyl group may be C3-C 10 Cycloalkyl, may also be C3-C8 cycloalkyl; the C3-C 20 A cycloalkyl group may be monocyclic or polycyclic; for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0369] In some embodiments, the C3-C 20 Cycloalkenyl can be C3-C 10 Cycloalkenyl; the C3-C 20 The cycloalkenyl group may be monocyclic or polycyclic; 20 A cycloalkenyl group may contain 1, 2 or 3 carbon-carbon double bonds; for example, cyclopropenyl, cyclobutenyl, cyclopentenyl or cyclohexenyl.

[0370] In some embodiments, the C3-C 20 The cycloalkynyl group can be C3-C 10 Cycloalkynyl; the C3-C 20 The cycloalkynyl group may be monocyclic or polycyclic; the C3-C 20 A cycloalkynyl group may contain 1, 2 or 3 carbon-carbon triple bonds; for example, cyclopropynyl, cyclobutynyl, cyclopentynyl or cyclohexynyl.

[0371] In some embodiments, the 3-20 membered heteroalkyl group may be a 3-10 membered heteroalkyl group, or may be a 3-8 membered heteroalkyl group; the heteroatoms of the 3-20 membered heteroalkyl group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2).

[0372] In some embodiments, the 4-20 membered heteroalkenyl group may be a 4-10 membered heteroalkenyl group; the heteroatoms of the 4-20 membered heteroalkenyl group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 4-20 membered heteroalkenyl group may contain 1, 2 or 3 carbon-carbon double bonds.

[0373] In some embodiments, the 4-20 membered heteroalkynyl group may be a 4-10 membered heteroalkynyl group; the heteroatoms of the 4-20 membered heteroalkynyl group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 4-20 membered heteroalkynyl group may contain 1, 2 or 3 carbon-carbon triple bonds.

[0374] In some embodiments, the 3-20 membered heterocycloalkyl group may be a 3-10 membered heterocycloalkyl group; the heteroatoms of the 3-20 membered heterocycloalkyl group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); for example, an oxirane group, an epoxyalkyl group, an epoxybutyl group, a pyrrolidinyl group, a tetrahydrofuranyl group, a piperidinyl group, a piperazinyl group, a tetrahydropyranyl group or a homopiperazinyl group.

[0375] In some embodiments, the 3-20 membered heterocycloalkenyl group may be a 3-10 membered heterocycloalkenyl group; the heteroatoms of the 3-20 membered heterocycloalkenyl group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-20 membered heterocycloalkenyl group may contain 1, 2 or 3 carbon-carbon double bonds.

[0376] In some embodiments, the 3-20 membered heterocycloalkynyl group may be a 3-10 membered heterocycloalkynyl group; the heteroatoms of the 3-20 membered heterocycloalkynyl group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-20 membered heterocycloalkynyl group may contain 1, 2 or 3 carbon-carbon double bonds.

[0377] In some embodiments, the C6-C 20 The aromatic hydrocarbon group can be C6-C 10 an aromatic hydrocarbon group; for example, a phenyl group or a naphthyl group.

[0378] In some embodiments, the 5-20 membered heteroaromatic hydrocarbon group may be a 5-10 membered heteroaromatic hydrocarbon group; the heteroatoms of the 5-20 membered heteroaromatic hydrocarbon group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably 1, 2 or 3 of N, O and S, and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1, 2 or 3); for example, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl or indolyl.

[0379] In some embodiments, the C1-C6 alkoxy group may be methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, neopentyloxy, or n-hexyloxy.

[0380] In some embodiments, the 3-8 membered heteroalkoxy group is a 3-8 membered heteroalkane group connected via oxygen, and the definition of the 3-8 membered heteroalkane group is the same as that of the 3-8 membered heteroalkyl group.

[0381] In some embodiments, the C3-C8 cycloalkoxy group may be cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, or cyclohexyloxy.

[0382] In some embodiments, the 3-8 membered heterocycloalkoxy group is a 3-8 membered heterocycloalkane connected via oxygen, and the definition of the 3-8 membered heterocycloalkane is the same as that of the 3-8 membered heterocycloalkyl group.

[0383] In some embodiments, the C6-C 10 The aryloxy group may be -O-phenyl or -O-naphthyl.

[0384] In some embodiments, the 5-10 membered heteroareneoxy group is a 5-10 membered heteroarene linked via oxygen, and the definition of the 5-10 membered heteroarene group is the same as that of the 5-10 membered heteroarene group.

[0385] In some embodiments, the C6-C 10 The aromatic amine group may be -NH-phenyl or -NH-naphthyl.

[0386] In some embodiments, the 3-8 membered heteroalkylamine group is a 3-8 membered heteroalkane connected via an amine group, and the definition of the 3-8 membered heteroalkane is the same as that of the 3-8 membered heteroalkyl group.

[0387] In some embodiments, the C5-C 10 The aromatic heteroalkylamine group is a 5-10 membered heteroarene linked via an amine group, and the definition of the 5-10 membered heteroarene is the same as that of the 5-10 membered heteroarene group.

[0388] In some embodiments, R b In the C1-C 20 The alkyl group can be C1-C 10 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0389] In some embodiments, R b In the C6-C 10 Aryl may be phenyl or naphthyl, for example phenyl.

[0390] In some embodiments, R b-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine, for example fluorine or chlorine.

[0391] In some embodiments, R b-1 In the C1-C 20 The alkyl group can be C1-C 10 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0392] In some embodiments, R b-1 In the C6-C 10 Aryl may be phenyl or naphthyl, for example phenyl.

[0393] In some embodiments, R b-1 In the 3-10 membered heterocycloalkyl group, the heteroatoms may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-10 membered heterocycloalkyl group is preferably a 3-6 membered heterocycloalkyl group, such as a pyrrolidinyl group.

[0394] In some embodiments, R b-1-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine, for example fluorine or chlorine.

[0395] In some embodiments, R f In the C1-C 20 The alkyl group can be C1-C 10 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0396] In some embodiments, in R, the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine or chlorine.

[0397] In some embodiments, in R, the C1-C 20 The alkyl group can be C1-C 10 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0398] In some embodiments, in R, the C1-C 20 The alkoxy group can be C1-C 10 The alkoxy group is preferably a C1-C6 alkoxy group, such as methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, neopentyloxy or n-hexyloxy.

[0399] In some embodiments, in R, the C2-C 20 The alkenyl group can be C2-C 10 Alkenyl, the C2-C 20 An alkenyl group may contain 1, 2, or 3 carbon-carbon double bonds; for example, ethenyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, or 4-methyl-3-pentenyl.

[0400] In some embodiments, in R, the C2-C 20 The alkynyl group can be C2-C 10 Alkynyl, the C2-C 20 Alkynyl groups may contain 1, 2, or 3 carbon-carbon triple bonds; for example, ethynyl, 1-propynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, or 5-hexynyl.

[0401] In some embodiments, in R, the heteroatoms of the 3-8 membered heteroalkyl group may be selected from 1, 2, 3 or 4 types (preferably N and / or O) of N, O, P and S, and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the heteroatoms of the 3-8 membered heteroalkyl group are not at both ends of the substituent group.

[0402] In some embodiments, in R, the heteroatoms of the 3-10 membered heteroalkenyl group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-10 membered heteroalkenyl group may contain 1, 2 or 3 carbon-carbon double bonds; the 3-10 membered heteroalkenyl group may be a 3-6 membered heteroalkenyl group.

[0403] In some embodiments, in R, the heteroatoms of the 3-10 membered heteroalkynyl group may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-10 membered heteroalkynyl group may contain 1, 2 or 3 carbon-carbon triple bonds; the 3-10 membered heteroalkenyl group may be a 3-6 membered heteroalkynyl group.

[0404] In some embodiments, R a In the above, the halogen may be fluorine, chlorine, bromine or iodine, for example fluorine or chlorine.

[0405] In some embodiments, R aIn the 3-20 membered heteroalkyl group, the heteroatoms may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-20 membered heteroalkyl group may be a 2-6 membered heteroalkyl group.

[0406] In some embodiments, R a-1 In the C1-C 20 The alkyl group can be C1-C 10 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0407] In some embodiments, R a-1 In the C1-C 20 The alkoxy group can be C1-C 10 The alkoxy group is preferably a C1-C6 alkoxy group, such as methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, neopentyloxy or n-hexyloxy.

[0408] In some embodiments, R a-1 In the C2-C 20 The alkenyl group can be C2-C 10 Alkenyl, the C2-C 20 An alkenyl group may contain 1, 2, or 3 carbon-carbon double bonds; for example, ethenyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, or 4-methyl-3-pentenyl.

[0409] In some embodiments, R a-1 In the C2-C 20 The alkynyl group can be C2-C 10 Alkynyl, the C2-C 20 Alkynyl groups may contain 1, 2, or 3 carbon-carbon triple bonds; for example, ethynyl, 1-propynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, or 5-hexynyl.

[0410] In some embodiments, R a-1 In the C3-C 10 The cycloalkyl group may be a C3-C8 cycloalkyl group; the C3-C 10 A cycloalkyl group may be monocyclic or polycyclic; for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0411] In some embodiments, R a-1 In the C6-C 10 Aryl may be phenyl or naphthyl, for example phenyl.

[0412] In some embodiments, R a-1 In the 3-8 membered heteroalkyl group, the heteroatoms can be selected from 1, 2, 3 or 4 types (preferably N and / or O) of N, O, P and S, and the number of heteroatoms can be 1, 2, 3 or 4 (preferably 1 or 2).

[0413] In some embodiments, R a-1 In the embodiment, the heteroatoms of the 3-10 membered heteroalkenyl group may be selected from 1, 2, 3 or 4 types (preferably N and / or O) of N, O, P and S, the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2), and the 3-10 membered heteroalkenyl group may contain 1, 2 or 3 carbon-carbon double bonds; the 3-10 membered heteroalkenyl group may be a 3-6 membered heteroalkenyl group.

[0414] In some embodiments, R a-1 In the 3-10 membered heteroalkynyl group, the heteroatoms may be selected from 1, 2, 3 or 4 types (preferably N and / or O) of N, O, P and S, and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-10 membered heteroalkynyl group may contain 1, 2 or 3 carbon-carbon triple bonds.

[0415] In some embodiments, R a-1 In the 3-10 membered heterocycloalkyl group, the heteroatoms may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-10 membered heterocycloalkyl group is preferably a 3-6 membered heterocycloalkyl group, such as a pyrrolidinyl group.

[0416] In some embodiments, R a-1 In the above, the 5-12 membered heteroaryl group may be selected from 1, 2, 3 or 4 heteroatoms of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2). The 5-12 membered heteroaryl group may be a 5-6 membered heteroaryl group, such as a thienyl group, a furyl group, a pyrrolyl group, an oxazolyl group, a thiazolyl group, an imidazolyl group, a pyrazolyl group, a pyridyl group, a pyrazinyl group, an isoxazolyl group, an isothiazolyl group, an oxadiazolyl group, a triazolyl group, a thiadiazolyl group or an indolyl group.

[0417] In some embodiments, R a-1-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine, for example fluorine or chlorine.

[0418] In some embodiments, Ra-1-1 In the C1-C 20 The alkyl group can be C1-C 10 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0419] In some embodiments, R a-1-1 In the C6-C 10 Aryl may be phenyl or naphthyl, for example phenyl.

[0420] In some embodiments, R a-1-1 In the 3-20 membered heteroalkyl group, the heteroatoms may be selected from 1, 2, 3 or 4 of N, O, P and S (preferably N and / or O), and the number of heteroatoms may be 1, 2, 3 or 4 (preferably 1 or 2); the 3-20 membered heteroalkyl group may be a 2-6 membered heteroalkyl group.

[0421] In some embodiments, R a-1-1-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine, for example fluorine or chlorine.

[0422] In some embodiments, R d In the C1-C 20 The alkoxy group can be C1-C 10 The alkoxy group is preferably a C1-C6 alkoxy group, such as methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, neopentyloxy or n-hexyloxy.

[0423] In some embodiments, R d-1 In the C1-C 20 The alkyl group can be C1-C 10 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0424] In some embodiments, R d-1 In the C1-C 20 The alkoxy group can be C1-C 10 The alkoxy group is preferably a C1-C6 alkoxy group, such as methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, neopentyloxy or n-hexyloxy.

[0425] In some embodiments, R d-1 In the C6-C 10 Aryl may be phenyl or naphthyl, for example phenyl.

[0426] Another aspect of the present invention provides a pharmaceutical composition comprising the compound as described herein or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0427] Another aspect of the present invention provides use of a compound in preparing a medicament, wherein the compound is a compound as described herein or a pharmaceutically acceptable salt thereof, and the medicament is used for treating and / or preventing cancer.

[0428] Another aspect of the present invention provides use of a composition in preparing a medicament, wherein the composition is the pharmaceutical composition as described herein, and the medicament is used for treating and / or preventing cancer.

[0429] Another aspect of the present invention provides a compound for use as a medicament, which is a compound as described herein or a pharmaceutically acceptable salt thereof.

[0430] Another aspect of the present invention provides a composition for use as a medicine, which is the pharmaceutical composition described herein.

[0431] Another aspect of the present invention provides a compound for treating and / or preventing cancer, wherein the compound is a compound as described herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein.

[0432] Another aspect of the present invention provides a composition for treating and / or preventing cancer, wherein the composition is the pharmaceutical composition as described herein.

[0433] Another aspect of the present invention provides a method for treating and / or preventing cancer, comprising administering to a subject an effective amount of the compound as described herein or a pharmaceutically acceptable salt thereof.

[0434] Another aspect of the present invention provides a method for treating and / or preventing cancer, comprising administering to a subject an effective amount of the pharmaceutical composition described herein.

[0435] In some embodiments, the cancer is selected from a solid tumor or a hematological tumor. In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is a hematological tumor.

[0436] Another aspect of the present invention provides a method for preparing the compound as described herein, wherein the preparation method is method 1, method 2, method 3 or method 4;

[0437] Method 1:

[0438] The method 1 comprises the following steps: in a solvent, in the presence of a catalyst, a compound represented by formula a and a compound represented by formula a' undergo an exchange reaction as shown in the following formula to obtain the compound represented by formula I;

[0439] Each substituent is as defined in the first aspect.

[0440] In some embodiments, Z is O.

[0441] In some embodiments, a' is

[0442] In some embodiments, the solvent is an organic solvent, such as a mixed solvent of N,N-dimethylformamide and dichloromethane, or a mixed solvent of dichloromethane, N,N-dimethylformamide, tetrahydrofuran, and dichloromethane.

[0443] In some embodiments, the catalyst is 4-dimethylaminopyridine.

[0444] In some embodiments, the exchange reaction is carried out under the protection of an inert gas, such as nitrogen or argon.

[0445] In some embodiments, the exchange reaction is carried out at room temperature.

[0446] In some embodiments, the temperature when the compound represented by formula a and the compound represented by formula a' are mixed is 0-5°C.

[0447] Method 2:

[0448] The method 2 comprises the following steps: in a solvent, in the presence of a base, a compound represented by formula b and b' undergo a condensation reaction as shown below to obtain a compound represented by formula I;

[0449] Where b' is anhydride, WC(=O)R b 、WC(=O)R b 、WC(=O)NR b R b 、WS(=O)2NR b R b WS(=O)2OR b 、WS(=O)2R b 、WS(=O)R b 、WS(=O)NR b R b 、WS(=O)OR b 、WP(=O)(OR b )2、WP(=O)NR b R b (OR b ), WP(=O)(NR b Rb )2、W-PH(=O)OR b 、W-PH(=O)NR b R b or W-PH(=O)R b ; W is halogen or hydroxy; each substituent is as defined in the first aspect.

[0450] In some embodiments, b' is succinic anhydride, oxalyl chloride,

[0451] In some embodiments, b is

[0452] In some embodiments, Z is O.

[0453] In some embodiments, the temperature of the mixture of the compound of formula b and formula b' is 0-5°C.

[0454] In some embodiments, the solvent is an organic solvent, such as dichloromethane or tetrahydrofuran.

[0455] In some embodiments, the base is an organic base, such as pyridine or triethylamine.

[0456] In some embodiments, the condensation reaction is carried out at room temperature.

[0457] In some embodiments, the condensation reaction is carried out under the protection of an inert gas, such as nitrogen or argon.

[0458] Method 3

[0459] The method 3 comprises the following steps: in a solvent, in the presence of a catalyst, a compound represented by formula c and a compound represented by formula c' undergo an exchange reaction as shown in the following formula to obtain the compound represented by formula I;

[0460] Each substituent is as defined in the first aspect.

[0461] In some embodiments, Z is O.

[0462] In some embodiments, the compound shown in formula c is

[0463] In some embodiments, the solvent is an organic solvent, such as dichloromethane.

[0464] In some embodiments, the exchange reaction is carried out at room temperature.

[0465] In some embodiments, the exchange reaction is carried out under the protection of an inert gas, preferably nitrogen or argon.

[0466] In some embodiments, the temperature of the mixture of the compound represented by Formula Ic and the compound represented by Formula I-c' is 0-5°C.

[0467] In some embodiments, the catalyst is 4-dimethylaminopyridine.

[0468] In some embodiments, the exchange reaction is carried out in the presence of a base; the base is an organic base, such as pyridine or triethylamine.

[0469] Method 4

[0470] The method 4 comprises the following steps: in a solvent, in the presence of a catalyst, the compound represented by formula d and the compound represented by formula c' undergo an exchange reaction as shown in the following formula to obtain the compound represented by formula I;

[0471] Each substituent is as defined in the first aspect, and Hal is chlorine, bromine or iodine.

[0472] In some embodiments, Z is O.

[0473] In some embodiments, the compound shown in formula d is

[0474] In some embodiments, the solvent is an organic solvent, such as dichloromethane.

[0475] In some embodiments, the exchange reaction is carried out at room temperature.

[0476] In some embodiments, the exchange reaction is carried out under the protection of an inert gas, preferably nitrogen or argon.

[0477] In some embodiments, the temperature of the mixture of the compound represented by formula d and c' is 0-5°C.

[0478] In some embodiments, the catalyst is 4-dimethylaminopyridine.

[0479] In some embodiments, the exchange reaction is carried out in the presence of a base; the base is preferably an organic base, such as pyridine, triethylamine or N,N-diisopropylethylamine.

[0480] Unless otherwise specified in this application, the relevant terms are defined as follows.

[0481] In this application, the term "pharmaceutically acceptable carrier" refers to excipients and additives used in the production of drugs and the preparation of prescriptions. It refers to substances other than active ingredients that have been reasonably evaluated for safety and are included in pharmaceutical preparations. In addition to shaping, acting as carriers, and improving stability, pharmaceutical excipients also have important functions such as solubilization, solubilization, and sustained-release. They are important ingredients that may affect the quality, safety, and effectiveness of drugs. Based on their source, they can be divided into natural, semi-synthetic, and fully synthetic. According to their functions and uses, they can be divided into: solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, antioxidants, chelating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoaming agents, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, release retardants, etc. According to their route of administration, they can be divided into oral, parenteral, mucosal, transdermal or topical administration, nasal or oral inhalation administration, and ocular administration, etc. The same pharmaceutical excipient can be used in pharmaceutical preparations for different routes of administration and have different functions and uses.

[0482] In this application, the term "pharmaceutical composition" refers to various dosage forms that can be prepared according to the route of administration, such as tablets, capsules, granules, oral solutions, oral suspensions, oral emulsions, powders, tinctures, syrups, injections, suppositories, ointments, creams, pastes, ophthalmic preparations, pills, implants, aerosols, powder sprays, sprays, etc.

[0483] In the present application, the term "pharmaceutically acceptable salt" or "pharmaceutically acceptable salt" generally refers to a salt of a compound of the present application, or a salt of a compound described in the present application. Such salts may be safe and / or effective when used in mammals and may have the desired biological activity. The compounds of the present application may form salts with acids or bases. Non-limiting examples of pharmaceutically acceptable salts include: hydrochloride, hydrobromide, hydroiodide, sulfate, bisulfate, citrate, acetate, succinate, ascorbate, oxalate, nitrate, sorbate, hydrogen phosphate, dihydrogen phosphate, salicylate, hydrogen citrate, tartrate, maleate, fumarate, formate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, lithium salt, sodium salt, potassium salt, calcium salt, aluminum salt, magnesium salt, zinc salt, bismuth salt, ammonium salt, and diethanolamine salt.

[0484] The compounds of the present invention may exist in the form of solvates (e.g., hydrates), wherein the compounds of the present invention contain a polar solvent as a structural element of the crystal lattice of the compound, in particular water, methanol or ethanol. The amount of polar solvent, in particular water, may be present in a stoichiometric or non-stoichiometric ratio.

[0485] The term "subject" refers to any animal including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses or primates, and most preferably humans.

[0486] In this application, the term "alkyl" refers to a saturated straight or branched hydrocarbon group. 1-20 "Alkyl" refers to a saturated straight or branched hydrocarbon group having 1 to 20 carbon atoms (e.g., 1, 2, 3, 4, 5, or 6 carbon atoms). 1-6 The "alkyl" group is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl.

[0487] In this application, the term "heteroalkyl" refers to an alkyl group containing at least one heteroatom selected from N, O, P and S. Preferably, the number of the heteroatoms is 1, 2, 3 or 4. and "Alkyl" is as defined above.

[0488] In the present application, the term "alkoxy" refers to an alkyl group attached to another group through oxygen. "Alkyl" is as defined above.

[0489] In this application, the term "alkenyl" refers to a straight-chain or branched aliphatic hydrocarbon group having one or more carbon-carbon double bonds. 2-20 The term "alkenyl" refers to an alkenyl group having 2 to 20 carbon atoms and one, two or three (preferably one) carbon-carbon double bonds (e.g., ethenyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl, etc.).

[0490] In the present application, the term "heteroalkenyl" refers to an alkyl group containing at least one heteroatom selected from N, O, P and S. Preferably, the number of the heteroatoms is 1, 2, 3 or 4. The definition of "alkenyl" is as described above.

[0491] In this application, the term "alkynyl" refers to a straight-chain or branched aliphatic hydrocarbon group having one or more carbon-carbon triple bonds. 2-20The term "alkynyl" refers to an alkynyl group having 2 to 20 carbon atoms and one, two or three (preferably one) carbon-carbon triple bonds (e.g., ethynyl, 1-propynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, etc.).

[0492] In the present application, the term "heteroalkynyl" refers to an alkyl group containing at least one heteroatom selected from N, O, P and S. Preferably, the number of the heteroatoms is 1, 2, 3 or 4. "Alkynyl" is as defined above.

[0493] The term "heterocycloalkyl" refers to a saturated or partially saturated non-aromatic cyclic group containing at least one heteroatom selected from N, O, P, and S. Preferably, the number of heteroatoms is 1, 2, 3, or 4. Examples include 3-20-membered, 3-12-membered, 3-8-membered, and 3-6-membered heterocycloalkyl groups. Specific examples include, but are not limited to, oxiranyl, oxiranyl, oxiranyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, and homopiperazinyl groups.

[0494] The term "heterocycloalkenyl" refers to a heterocycloalkyl group containing one or more double bonds, and "heterocycloalkyl" has the same meaning as described above.

[0495] The term "heterocycloalkynyl" is a heterocycloalkyl group containing one or more triple bonds, and "heterocycloalkyl" has the same meaning as described above.

[0496] In this application, the term "aryl", "aromatic hydrocarbon" or "aromatic ring" refers to a monocyclic or polycyclic ring system containing one or more conjugated π electron systems. For example, C6-C 20 An aromatic hydrocarbon group, preferably C6-C 10 , such as phenyl or naphthyl.

[0497] As used herein, the terms "heteroaryl," "heteroaralkyl," or "heteroaromatic ring" refer to monocyclic and fused heterocyclic ring systems containing one or more conjugated π-electron systems, wherein one or more (e.g., 1, 2, or 3) ring atoms are heteroatoms selected from N, O, P, and S, and the remaining ring atoms are C. A heteroaryl or heteroaromatic ring can be characterized by the number of ring atoms. For example, a 5-12 membered heteroaryl group can contain 5-12 (e.g., 5, 6, 7, 8, 9, 10, 11, or 12) ring atoms, particularly 5, 6, 9, or 10 ring atoms. Examples of heteroaryl groups include thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrazinyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, indolyl, and the like.

[0498] In this application, the term "cycloalkyl" refers to a saturated or partially saturated, monocyclic or polycyclic (such as bicyclic) non-aromatic hydrocarbon group. For example, "C 3-12 "Cycloalkyl" or "3-12 membered cycloalkyl" refers to a cycloalkyl group having 3-12 ring carbon atoms (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12). Common cycloalkyl groups include, but are not limited to, monocyclic cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutene, cyclopentene, cyclohexene, etc.; or bicyclic cycloalkyl groups, including cyclic, bridged or spirocyclic groups, such as bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, bicyclo[3.2.1]octyl, bicyclo[5.2.0]nonyl, decahydronaphthyl, etc.

[0499] The term "heteroalkoxy" refers to a heteroalkyl group attached to another group through an oxygen radical. "Heteroalkyl" is as defined above.

[0500] The term "cycloalkoxy" refers to a cycloalkyl group attached to another group through an oxygen radical. "Cycloalkyl" is as defined above.

[0501] The term "heterocycloalkoxy" refers to a heterocycloalkane group connected to another group through an oxygen radical. "Heterocycloalkane" is as defined above.

[0502] The term "areneoxy" refers to an aromatic hydrocarbon linked to another group via an oxygen. "Aromatic hydrocarbon" is as defined above.

[0503] The term "heteroareneoxy" refers to a heteroarene attached to another group via oxygen. "Heteroarene" is as defined above.

[0504] The term "heteroalkylamino" refers to a heteroalkyl group connected to another group through -NH-. "Heteroalkyl" is as defined above.

[0505] The term "cycloalkylamino" refers to a cycloalkyl group connected to another group through -NH-. "Cycloalkyl" is as defined above.

[0506] The term "heterocycloalkoxy" refers to a heterocycloalkane group connected to another group through -NH-. "Heterocycloalkane" is as defined above.

[0507] The term "aryloxy" refers to an aromatic hydrocarbon group connected to another group through -NH-. "Aromatic hydrocarbon" is as defined above.

[0508] The term "heteroareneoxy" refers to a heteroarene linked to another group via -NH-. "Heteroarene" is as defined above.

[0509] The term "N(w)(C0-C6 alkyl)q" means that "w", "q" and "C0-C6 alkyl" are respectively connected to N; when the number of C in "C0-C6 alkyl" is 0, "C0-C6 alkyl" is hydrogen; in "N(w)(C0-C6 alkyl)q", q is connected to other groups.

[0510] The term "amino acid residue" refers to a natural amino acid or a non-natural amino acid residue, such as an α-amino acid residue, preferably an alanine residue, a guanine residue, a valine residue, a glycine residue, a phenylalanine residue, a leucine residue, a cysteine ​​residue, an aspartic acid residue, a glutamic acid residue, a histidine residue, an isoleucine residue, a lysine residue, a methionine residue, an asparagine residue, a proline residue, a glutamine residue, an arginine residue, a serine residue, a threonine residue, a tryptophan residue, a tyrosine residue, more preferably an L-alanine residue, an L-guanidine residue, The term "residue" refers to an amino acid residue, an L-valine residue, a glycine residue, an L-phenylalanine residue, an L-leucine residue, an L-cysteine ​​residue, an L-aspartic acid residue, an L-glutamic acid residue, an L-histidine residue, an L-isoleucine residue, an L-lysine residue, an L-methionine residue, an L-asparagine residue, an L-proline residue, an L-glutamine residue, an L-arginine residue, an L-serine residue, an L-threonine residue, an L-tryptophan residue or an L-tyrosine residue, wherein the residue means a residue with one less H on the amino group and one less OH on the carboxyl group.

[0511] The term "electron-donating group" refers to a group that increases the electron cloud density on the benzene ring when a substituent replaces a hydrogen on the benzene ring.

[0512] The term "cycloalkenyl" refers to a cycloalkyl group containing one or more double bonds, and "cycloalkyl" has the same meaning as described above.

[0513] The term "cycloalkynyl" refers to a cycloalkyl group containing one or more triple bonds, and "cycloalkyl" has the same meaning as described above.

[0514] In the present application, the term "halogen" generally refers to fluorine, chlorine, bromine or iodine, for example, it can be fluorine, chlorine, or fluorine.

[0515] In this application, "C(=O)OH-f" generally means that C(=O)OH is indirectly on f, and f is connected to other groups in the molecule. If f does not exist, such as C0, then C(=O)OH is directly connected to other groups in the molecule.

[0516] In this application, the term "each independently" means that at least two groups (or fragments) present in a structure with the same or similar value ranges may have the same or different meanings in specific circumstances. For example, if substituent X and substituent Y are each independently hydrogen, halogen, hydroxyl, cyano, alkyl, or aryl, then when substituent X is hydrogen, substituent Y may be either hydrogen, or halogen, hydroxyl, cyano, alkyl, or aryl; similarly, when substituent Y is hydrogen, substituent X may be either hydrogen, or halogen, hydroxyl, cyano, alkyl, or aryl.

[0517] In this application, the term "optional" or "optionally" generally means that the subsequently described event or circumstance can but need not occur, and the description includes instances where the event or circumstance occurs or does not occur. For example, "a heterocyclic group optionally substituted with an alkyl group" means that the alkyl group can but need not be present, and the description includes instances where the heterocyclic group is substituted with an alkyl group and instances where the heterocyclic group is not substituted with an alkyl group.

[0518] In this application, the term "substituted" generally refers to one or more hydrogen atoms in a group, for example up to 5, for example 1 to 3 hydrogen atoms, which are independently replaced by a corresponding number of substituents. The substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) whether substitution is possible or not without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (e.g., olefinic) bond.

[0519] In the present application, one or more hydrogen atoms in a group, for example up to 5, for example 1 to 3 hydrogen atoms, are independently replaced by a corresponding number of substituents. The substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) whether substitution is possible or not without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (e.g., olefinic) bond.

[0520] The term "oxo," as used herein alone or in combination with other groups, refers to =0.

[0521] In this application, the term "comprising" generally refers to including the features specified but not excluding other elements. The terms "above" and "below" generally refer to including the number.

[0522] In the present application, the term "arbitrary substituent" means a group substituted by any group, such as deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, nitro, cyano, C1-C 20 Alkyl, C1-C20 Alkoxy, C2-C 20 Alkenyl, C2-C 20 alkynyl, 3-20 membered heteroalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkynyl or unsubstituted, 3-10 membered heterocycloalkyl, C6-C 10 Aryl, 5-12 membered heteroaryl.

[0523] Unless otherwise indicated, the structures described herein may also include compounds that differ only in the presence or absence of one or more isotopically enriched atoms. For example, compounds identical to the structures described herein except for the replacement of a hydrogen atom by deuterium or tritium, or the replacement of a carbon atom by carbon-13 or carbon-14, are within the scope of this application.

[0524] The terms "active ingredient," "therapeutic agent," "active substance," or "active agent" refer to a chemical entity that is effective in treating one or more symptoms of a target disorder or condition.

[0525] As used herein, the term "effective amount" (e.g., "therapeutically effective amount" or "prophylactically effective amount") refers to an amount of active ingredient that, after administration, will achieve the desired effect to some extent, such as alleviating one or more symptoms of the condition being treated or preventing the appearance of the condition or its symptoms.

[0526] As used herein, unless otherwise indicated, the terms "treat," ...

[0527] All substituent descriptions can be selected from 1 to N-1 types, where N is the number of substituent types. For example, the substituents are A, B, C, and D, then N is 4, which can be expressed as in some embodiments, the substituent is A; in some embodiments, the substituent is B; in some embodiments, the substituent is C; in some embodiments, the substituent is D; in some embodiments, the substituents are A and B; in some embodiments, the substituents are A and C; in some embodiments, the substituents are A and D; in some embodiments, the substituents are B and C; in some embodiments, the substituents are B and D; in some embodiments, the substituents are C and D; in some embodiments, the substituents are A, B, and C; in some embodiments, the substituents are A, B, and D; in some embodiments, the substituents are A, C, and D; in some embodiments, the substituents are B, C, and D; although these contents are not written out, they are also the contents of this article.

[0528] Unless otherwise specified, the expression of the numerical range is "In some embodiments, the range includes the range between any integers", such as in some embodiments, 3-6 membered cycloalkyl, which also means that in some embodiments, it is 3-4 membered cycloalkyl; in some embodiments, it is 3-5 membered cycloalkyl; in some embodiments, it is 4-5 membered cycloalkyl; in some embodiments, it is 4-6 membered cycloalkyl; in some embodiments, it is 5-6 membered cycloalkyl. Although these contents are not written out, they are also the contents of this article.

[0529] The description of substituent matching is based on the principle of the least substitution layer and the principle of the most atoms on the matching chain. When the nearest layer substitution cannot be matched, the next outer layer substitution matching is performed, and the subsequent layers are matched in turn.

[0530] The general formula of this application does not include any compounds disclosed in the prior art.

[0531] Unless otherwise specified, the connection mode of amino acid residues or peptide chains is that the carbonyl end is connected to the amino group, and the amino end is connected to the substituent Y.

[0532] The structural formula of CBTX-PNP or PNP-CBTX is as follows:

[0533] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0534] The reagents and raw materials used in the present invention are commercially available.

[0535] The positive progress effect of the present invention is:

[0536] The compounds of the present application have the following effects: high in vitro antitumor biological activity, with a half-maximal inhibitory concentration (IC50) lower than 1 μM / L, preferably below 500 nM / L, preferably below 200 nM / L, more preferably below 100 nM / L, more preferably below 50 nM / L, below 20 nM / L, below 10 nM / L, and below 5 nM / L. BRIEF DESCRIPTION OF THE DRAWINGS

[0537] Figure 1 is a curve showing changes in body weight of experimental animals after the start of treatment.

[0538] FIG2 shows the growth curve of the DU145 subcutaneous xenograft tumor model after treatment initiation.

[0539] Figure 3 is a curve showing changes in body weight of experimental animals after the start of treatment.

[0540] FIG4 shows the growth curve of the human prostate cancer PC-3 subcutaneous xenograft tumor model after treatment initiation.

[0541] FIG5 is a curve showing changes in body weight of experimental animals after the start of treatment.

[0542] FIG6 shows the growth curve of the human breast cancer MDA-MB-231 subcutaneous xenograft tumor model after treatment initiation.

[0543] FIG7 is a curve showing changes in body weight of experimental animals after the start of treatment.

[0544] FIG8 shows the growth curve of the human pancreatic cancer Capan-1 subcutaneous xenograft tumor model after treatment initiation.

[0545] mpk means mg / kg; QW means once a week; wks means weeks; BIW means twice a week. DETAILED DESCRIPTION

[0546] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0547] The preparation method of the compound represented by formula I of the present invention is prepared by referring to the following general method:

[0548] (1) Some compounds were prepared using route a-1-A or a-1-B:

[0549] A1, A2 are benzyl, methyl, hydrogen, isobutyl, butyl, R2 is a C1-C4 alkyl group, preferably a methyl group; other substituents are as defined in the first aspect.

[0550] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0551] (2) Some compounds were prepared using the a-2-A route or a-2-B route.

[0552] A1, A2 are benzyl, methyl, hydrogen, isobutyl, butyl, R2 is a C1-C4 alkyl group, preferably a methyl group, and R4 is the same as R in the first aspect. b Other substituents are as defined in the first aspect.

[0553] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0554] (3) Some compounds were prepared using route a-3.

[0555] A1, A2 are benzyl, methyl, hydrogen, isobutyl, butyl, R2 is a C1-C4 alkyl group, preferably a methyl group; p is 1, 2, 3, 4, 5 or 6; Set1 is selected from Set2 is selected from R3 is independently hydrogen, deuterium, or C1-C4 alkyl; Y is O, S, N, or C; q and R are independently 0, 1, 2, or 3; Hal is chlorine, bromine, or iodine; and other substituents are as defined in the first aspect.

[0556] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0557] (4) Some compounds were prepared using the a-4-A route or the a-4-B route.

[0558] A1, A2 are benzyl, methyl, hydrogen, isobutyl, butyl, R2 is a C1-C4 alkyl group, preferably a methyl group; s is 1, 2, 3, 4, 5 or 6; Set1 is selected from Set2 is selected from Other substituents are as defined in the first aspect.

[0559] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0560] (5) Some compounds were prepared using route a-5.

[0561] A1, A2, A3 or A4 is benzyl, methyl, hydrogen, isobutyl, butyl or R2 is a C1-C4 alkyl group, preferably a methyl group; other substituents are as defined in the first aspect.

[0562] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0563] (6) Some compounds were prepared using route a-6.

[0564] A1, A2, A3 or A4 is benzyl, methyl, hydrogen, isobutyl, butyl, R2 is a C1-C4 alkyl group, preferably a methyl group, and R4 is the same as R in the first aspect. b Other substituents are as defined in the first aspect.

[0565] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0566] (7) Some compounds were prepared using route b-1, route b-2-A or route b-2-B.

[0567] A1, A2, A3 or A4 is benzyl, methyl, hydrogen, isobutyl, butyl, R2 is a C1-C4 alkyl group, preferably a methyl group; Set3 is C(=O)OHR d-1 、R d-1 When the terminal is -C(=O)OH, it is HalC(=O)R d-1 (C=O)Hal, or R d-1 When the terminal is -C(=O)OH, the lactone structure formed by the C(=O)OH connected to the other end Set 4 is as defined in the first aspect, wherein Y is -C(=O)R b ; Other substituents are as defined in the first aspect.

[0568] In some embodiments,

[0569] Set3 is selected from Set4 is selected from Hal is selected from Cl, Br, I; s is 1, 2, 3, 4 or 5; t is each independently 1, 2, 3, 4 or 5; u is 0, 1, 2, 3, 4, 5 or 6.

[0570] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0571] (8) Some compounds were prepared using route c-1.

[0572] Set5 is R d-1 (=O)O(=O)R d-1 or R d-1 (=O)OH;Set6 is R d-1 ; R d For-OR d-2 ; Other substituents are as defined in the first aspect.

[0573] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0574] (9) Some compounds were prepared using route c-2.

[0575] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0576] R d For-OR d-2 ; Other substituents are as defined in the first aspect.

[0577] (10) Some compounds were prepared using route c-3.

[0578] R d For-OR d-2 ; Hal is selected from Cl, Br, I; other substituents are as defined in the first aspect.

[0579] Unless otherwise specified, the reactions involved in the above routes can be prepared according to the conditions of similar reactions in the prior art. For details, please refer to the relevant reaction conditions in the examples.

[0580] HATU refers to 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0581] The amino acids used in this embodiment are all L-amino acids if they have chiral carbons.

[0582] Among them, Example 60 uses D-guanidine, Example 61 uses D-guanidine and D-valine, and Example 78 uses D-valine.

[0583] Example 1 Synthesis of Compound 1

[0584] 1b:

[0585] Thionyl chloride (12.8 ml, 176.96 mmol) was added dropwise to a solution of 1a (12.4 g, 70.78 mmol) in anhydrous methanol (100 ml) at 0-10°C. Stir for 10 minutes, then raise the temperature to 60°C and stir for 3 hours. Cool to room temperature, add dichloromethane (100 ml), and concentrate under reduced pressure to obtain 7b (15.9 g, 100% yield) as a light yellow oil.

[0586] 1c:

[0587] 2b (13.39 g, 59.33 mmol) was dissolved in N,N-dimethylformamide (15 ml), followed by the addition of dichloromethane (100 ml). The pH was adjusted to 9-10 with triethylamine, and the filtrate was filtered and set aside. Boc-L-valine (12.89 g, 59.33 mmol) was dissolved in dichloromethane (150 ml). Under nitrogen, the temperature was lowered to 5°C, 1-hydroxybenzotriazole (8.82 g, 65.27 mmol) was added, and N,N′-diisopropylcarbodiimide (10.11 ml, 65.27 mmol) was added dropwise. The temperature was raised to room temperature and stirred for 20 minutes. The prepared 7-M1 was then added dropwise to the reaction solution, and stirred at room temperature for 0.5 hour.

[0588] The product was washed with 0.3N hydrochloric acid (200 ml), washed twice with saturated sodium bicarbonate (100 ml), washed with saturated sodium chloride (100 ml), dried over anhydrous sodium sulfate, and concentrated to dryness. Column chromatography gave 7c as a white solid (25 g, yield: 92%).

[0589] 1d:

[0590] Dissolve 1c (8.0 g, 20.59 mmol) in dichloromethane (15 ml) and add trifluoroacetic acid (15 ml) dropwise at 5°C. Warm to room temperature and stir for 1.0 hour. Add dichloromethane (30 ml) and concentrate under reduced pressure. Column chromatography gives 8-M1 (6.20 g, yield: 74%) as a light yellow oil.

[0591] 1e:

[0592] At 0-10°C, under nitrogen protection, DIC (1.92 g, 15.2 mmol) was added dropwise to a dichloromethane (60 ml) solution of 3-chloropropionic acid (1.50 g, 13.8 mmol) and HOBt (2.05 g, 15.2 mmol), and the mixture was stirred and reacted for 30 minutes. 1d (5.01 g, 12.4 mmol) was added to a dichloromethane (40 ml) solution, and the pH value was adjusted to 9-10 with triethylamine under nitrogen protection at 0-10°C. After stirring for 5 minutes, the mixture was added to the 3-chloropropionic acid reaction solution, and the mixture was stirred and reacted for 30 minutes at 20-25°C. The solvent was removed by concentration, and the residue was purified by silica gel column chromatography [V DCM / V MeOH =8:1] separation and purification gave 3.00 g of a white solid with a yield of 57%.

[0593] 1f:

[0594] Lithium hydroxide monohydrate (664 mg, 15.8 mmol) was dissolved in water (8 ml) at 0-10°C and added dropwise to a solution of 1b (3.00 g, 7.92 mmol) in tetrahydrofuran (20 ml). The mixture was stirred at 15-25°C for 0.5 hours. The reaction solution was cooled to 0-5°C and the pH was adjusted to 3-4 by the addition of 6N hydrochloric acid. The solvent and water were removed by concentration. The residue was concentrated with tetrahydrofuran (30 ml x 2) to remove water and dried to obtain 2.89 g of a white foamy solid (yield: 100%).

[0595] 1g:

[0596] At room temperature, EEDQ (3.39 g, 13.7 mmol) and p-aminobenzyl alcohol (844 mg, 6.85 mmol) were added to a solution of 1c (2.50 g, 6.85 mmol) in dichloromethane (60 ml) / methanol (10 ml) in sequence, and the mixture was stirred at room temperature for 1 hour. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeoH =15:1] separation and purification gave 630 mg of a white solid, with a yield of 20%.

[0597] 1h:

[0598] At room temperature, diethylamine (467 mg, 6.38 mmol) and potassium iodide (424 mg, 2.55 mmol) were added to a 95% ethanol (20 ml) solution of 1d (600 mg, 1.28 mmol), and the mixture was heated to 60°C and stirred for 3 hours. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeoH =5:1] separation and purification gave 300 mg of an off-white solid with a yield of 46%.

[0599] 1j:

[0600] 1i (0.50 g, 5.98 mmol) was dissolved in dichloromethane (8 ml), and 4-dimethylaminopyridine (15 mg, 0.12 mmol) and diisopropylethylamine (0.23 g, 1.79 mmol) were added sequentially. The mixture was cooled to -5°C under nitrogen protection, and a dichloromethane solution (3 ml) of p-nitrophenyl chloroformate (0.24 g, 1.20 mmol) was added dropwise. The mixture was warmed to room temperature and stirred for 0.5 hour. Dichloromethane (80 ml) was added, and the mixture was washed twice with 0.3N hydrochloric acid (20 ml), then with saturated sodium bicarbonate (20 ml), and then with saturated sodium chloride (20 ml). The mixture was dried over anhydrous sodium sulfate, concentrated to dryness, and purified by column chromatography to obtain 1j (CBTX-PNP) as a white solid (0.55 g, yield: 92%).

[0601] 1H NMR (400MHz, DMSO-d6) δ (ppm) 8.40–8.30 (m, 2H), 8.00 (dd, J=18.2, 8.2Hz, 3H) , 7.72 (t, J = 7.3Hz, 1H), 7.64 (t, J = 7.5Hz, 2H), 7.55 (d, J = 9.1Hz, 2H), 7.45 (dt, J=14.8, 7.6Hz, 4H), 7.23 (t, J=7.0Hz, 1H), 5.88 (t, J=8.8Hz, 1H), 5.38 (d, J=7 .0Hz, 1H), 5.24 (d, J=7.6Hz, 1H), 5.14 (t, J=8.3Hz, 1H), 4.94 (d, J=9.6Hz, 1H), 4.68 (s, 1H), 4.54 (s, 1H), 4.02 (d, J=8.8Hz, 2H), 3.72 (dd, J=10.3, 6.7Hz, 1H) , 3.58(d, J=7.0Hz, 1H), 3.27(s, 3H), 3.18(s, 3H), 2.70–2.58(m, 1H), 2.25(s, 3 H), 1.85 (dd, J=15.3, 9.3Hz, 1H), 1.78 (s, 3H), 1.63 (dd, J=15.2, 9.1Hz, 1H), 1 .47(d, J=21.2Hz, 4H), 1.39(s, 8H), 1.25(d, J=10.3Hz, 1H), 1.03–0.95(m, 6H).

[0602] Synthesis of 1:

[0603] At 0-5°C under nitrogen protection, 1h (200 mg, 0.39 mmol) was dissolved in dichloromethane (12 ml) / N,N-dimethylformamide (2 mL), and 1j (395 mg, 0.39 mmol) and N,N-dimethylpyridine (48 mg, 0.39 mmol) were added in sequence. The mixture was stirred at 15-25°C for 2 hours. Dichloromethane (50 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (30 ml × 2) and saturated sodium chloride aqueous solution (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =6:1] separation and purification gave 220 mg of a white solid with a yield of 46% and a HPLC purity of 96.26%.

[0604] LC-MS: 1368.6941 [M+H + ]

[0605] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.15 (s, 1H), 8.34–8.18 (m, 2H), 7.95 (dd, J=20.3, 8.2Hz, 3H), 7.7 3 (t, J=7.3Hz, 1H), 7.65 (t, J=7.7Hz, 4H), 7.42 (t, J=7.6Hz, 2H), 7.39–7.28 (m, 4H), 7.18 (t, J=7. 2Hz, 1H), 6.10 (s, 1H), 5.82 (t, J=8.7Hz, 1H), 5.45 (s, 2H), 5.37 (d, J=7.1Hz, 1H), 5.14 (s, 2H), 5. 10–4.91 (m, 3H), 4.70 (s, 1H), 4.50 (s, 1H), 4.41 (dd, J=13.3, 8.2Hz, 1H), 4.24 (dd, J=8.4, 6.7Hz, 1H), 4.02(s, 2H), 3.75(dd, J=10.2, 6.8Hz, 1H), 3.69–3.61(m, 1H), 3.59(d, J=6.5Hz, 1H), 3.29(s , 3H), 3.22 (s, 3H), 2.99 (ddd, J=24.1, 13.1, 6.4Hz, 6H), 2.71–2.62 (m, 2H), 2.24 (s, 3H), 2.01 (td , J=13.5, 6.9Hz, 1H), 1.79(d, J=12.8Hz, 4H), 1.75–1.67(m, 1H), 1.66–1.59(m, 1H), 1.57–1.43(m , 6H), 1.29 (d, J=43.8Hz, 12H), 1.15 (s, 6H), 0.98 (d, J=7.5Hz, 6H), 0.87 (dd, J=11.9, 6.8Hz, 6H).

[0606] Example 2 Synthesis of Compound 2

[0607] 2b:

[0608] Acetic acid (1.0 g, 16.65 mmol) was dissolved in dichloromethane (20 ml). Under nitrogen protection, the temperature was lowered to 5°C, 1-hydroxybenzotriazole (2.48 g, 18.32 mmol) was added, and N, N'-diisopropylcarbodiimide (2.31 g, 18.32 mmol) was added dropwise. The temperature was raised to room temperature and stirred for 30 minutes. 1d (4.80 g, 11.93 mmol) was dissolved in dichloromethane (30 ml) and N, N-diisopropylethylamine was adjusted to pH = 9. The mixture was added dropwise to the above reaction solution and stirred at room temperature for 30 minutes. The mixture was directly concentrated to dryness. Column chromatography gave 2-M1 (3.58 g, yield: 65%) as a white solid.

[0609] 2c:

[0610] 2b (3.58 g, 10.84 mmol) was dissolved in tetrahydrofuran (40 mL), and an aqueous solution of lithium hydroxide monohydrate (0.91 g, 21.67 mmol) was added. The mixture was stirred at room temperature for 30 minutes. Tetrahydrofuran (40 mL) was added, and the pH was adjusted to 5 with 6N hydrochloric acid at -5°C. The mixture was concentrated to dryness to obtain a light yellow oil 2-M2 (3.4 g, yield: 99%).

[0611] 2d:

[0612] Dissolve 2c (3.4 g, 10.75 mmol) in methanol (10 ml) and dichloromethane (100 ml). Add p-aminobenzyl alcohol (1.32 g, 10.75 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (5.32 g, 21.49 mmol). Stir at room temperature for 1.5 hours. Concentrate under reduced pressure and perform column chromatography to obtain a light yellow solid 2-M3 (1.25 g, yield: 28%).

[0613] 1 H NMR (400MHz, DMSO-d6) δ9.93 (ppm) (s, 1H), 8.12 (d, J = 7.7Hz, 1H), 7.92 (d, J = 8.6Hz, 1H), 7.56 (d, J = 8.5Hz, 2 H), 7.23 (d, J=8.5Hz, 2H), 6.06 (dd, J=18.9, 13.4Hz, 1H), 5.43 (s, 2H), 5.11 (s, 1H), 4.53–4.32 (m, 3H), 2.98 (ddt, J=19.3, 13.1, 6.5Hz, 2H), 1.97 (dt, J=13.4, 6.7Hz, 1H), 1.90 (d, J=8.5Hz, 3H), 1.70 (dd, J=13.9, 6.5H z, 1H), 1.60 (ddd, J=18.4, 9.1, 4.7Hz, 1H), 1.50–1.33 (m, 2H), 0.87 (d, J=6.8Hz, 3H), 0.84 (d, J=6.8Hz, 3H).

[0614] Synthesis of 2:

[0615] 2d (0.15 g, 0.36 mmol) and 1j (0.36 g, 0.36 mmol) were dissolved in tetrahydrofuran (4 ml), and 4-dimethylaminopyridine (48 mg, 0.39 mmol) was added. The mixture was stirred at room temperature for 2 hours. Water (20 ml) was added, and the mixture was extracted three times with dichloromethane (30 ml). The organic phases were combined and washed twice with 0.6N hydrochloric acid (30 ml), then washed with saturated sodium bicarbonate (20 ml), and then washed with saturated sodium chloride (20 ml). The mixture was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 2 as a white solid (0.16 g, yield: 35%, HPLC purity: 95.935%).

[0616] LC-MS: 1283.6118 [M+H + ]

[0617] 1 H NMR (400MHz, DMSOd-6) δ (ppm) 10.02 (s, 1H), 8.13 (d, J = 7.5Hz, 1H), 8.02–7.83 (m, 4H) , 7.77–7.57(m, 5H), 7.38(dt, J=13.4, 8.0Hz, 6H), 7.18(t, J=7.1Hz, 1H), 5.97(t, J=5. 9Hz, 1H), 5.82 (t, J=8.6Hz, 1H), 5.45–5.32 (m, 3H), 5.14 (s, 2H), 5.05 (dd, J=17.6, 8.3 Hz, 2H), 4.95 (d, J=9.9Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.39 (dd, J=13.2, 8.2Hz, 1H) , 4.19 (dd, J=8.4, 6.8Hz, 1H), 4.03–4.00 (m, 2H), 3.75 (dd, J=10.2, 6.8Hz, 1H), 3.59 (d , J=6.9Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 3.07–2.90 (m, 2H), 2.69 (d, J=15.4Hz, 1H), 2 .24(s, 3H), 2.08–1.92(m, 3H), 1.82(d, J=12.4Hz, 4H), 1.74–1.53(m, 3H), 1.53–1.37( m, 6H), 1.35 (s, 8H), 1.24 (s, 2H), 0.98 (d, J=7.4Hz, 6H), 0.86 (dd, J=11.0, 6.8Hz, 6H).

[0618] Example 3 Synthesis of Compound 3

[0619] Referring to the synthetic route of compound 2 in Example 2, trifluoroacetic acid was used instead of acetic acid to obtain compound 2 (0.23 g, yield: 45%, HPLC purity: 99.373%)

[0620] LC-MS: 1337.5764 [M+H + ]

[0621] 1 H NMR (400MHz, DMSOd-6) δ (ppm) 10.14 (s, 1H), 9.41 (d, J = 8.4Hz, 1H), 8.42 (d, J = 7.3Hz, 1H), 7.95 (dd, J=23.3, 8.1Hz, 3H), 7.73 (t, J=7.2Hz, 1H), 7.64 (dd, J=12.2, 8.1Hz, 4H ), 7.38 (dt, J=12.5, 8.1Hz, 6H), 7.18 (t, J=7.3Hz, 1H), 5.98 (t, J=5.7Hz, 1H), 5.82 (t , J=8.4Hz, 1H), 5.47–5.29 (m, 3H), 5.14 (s, 2H), 5.11–4.92 (m, 3H), 4.70 (s, 1H), 4.50 ( s, 1H), 4.40 (dd, J=13.4, 7.6Hz, 1H), 4.23 (t, J=8.4Hz, 1H), 4.03–4.00 (m, 2H), 3.75( dd, J=10.1, 6.9Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 3.08–2.92 (m , 2H), 2.67 (s, 1H), 2.24 (s, 3H), 2.09 (dd, J=14.9, 6.9Hz, 1H), 1.81 (s, 3H), 1.77–1.5 5(m, 3H), 1.48(d, J=18.3Hz, 5H), 1.42–1.29(m, 9H), 1.24(s, 2H), 1.05–0.78(m, 12H).

[0622] Example 4 Synthesis of Compound 4

[0623] Referring to the synthetic route of compound 1 in Example 1, tetrahydropyrrole was used to replace diethylamine to obtain compound 4 (165 mg, yield: 24%, HPLC purity: 94.76%)

[0624] LC-MS: 1319.5 [M-OH-OMe]

[0625] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.17 (s, 1H), 8.24 (t, J = 7.7Hz, 2H), 7.95 (dd, J = 19.9, 8.2Hz, 3H), 7.77–7.59 (m, 5H), 7.43 (t, J=7.6Hz, 2H), 7.38–7.26 (m, 4H), 7.18 (t, J=7 .2Hz, 1H), 6.12 (t, J=5.5Hz, 1H), 5.82 (t, J=8.7Hz, 1H), 5.46 (s, 2H), 5.37 (d, J=6.9H z, 1H), 5.15 (s, 2H), 5.10–4.92 (m, 3H), 4.70 (s, 1H), 4.50 (s, 1H), 4.41 (dd, J=13.2, 8. 3Hz, 1H), 4.24 (dd, J=8.3, 6.9Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J=10.1, 6.8Hz, 1H), 3.5 9(d, J=6.8Hz, 1H), 3.30–3.24(m, 6H), 3.22(s, 3H), 3.06–2.92(m, 3H), 2.77–2.62(m, 3 H), 2.24 (s, 3H), 2.05–1.86 (m, 5H), 1.79 (d, J=12.1Hz, 4H), 1.75–1.53 (m, 3H), 1.55– 1.40 (m, 6H), 1.40–1.19 (m, 11H), 0.98 (d, J=7.5Hz, 6H), 0.87 (dd, J=11.1, 6.8Hz, 6H).

[0626] Example 5 Synthesis of Compound 5

[0627] Referring to the synthesis of compound 2 in Example 2, acetic acid was replaced by p-fluorobenzoic acid to obtain compound 5 (350 mg, yield: 51%, HPLC purity: 99.03%)

[0628] LC-MS: 1363.6000 [M+H + ]

[0629] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.07 (s, 1H), 8.32 (d, J = 8.4Hz, 1H), 8.23 ​​(d, J = 7.5Hz, 1H), 7. 95 (ddd, J=16.4, 11.0, 7.4Hz, 5H), 7.73 (t, J=7.3Hz, 1H), 7.65 (t, J=8.3Hz, 4H), 7.42 (t, J=7. 6Hz, 2H), 7.38–7.27(m, 6H), 7.18(t, J=7.2Hz, 1H), 5.98(t, J=5.8Hz, 1H), 5.82(t, J=8.6Hz, 1H), 5.45–5.34(m, 3H), 5.15(s, 2H), 5.10–4.99(m, 2H), 4.95(d, J=10.1Hz, 1H), 4.70(s, 1H), 4.50 (s, 1H), 4.42 (dd, J=13.4, 7.9Hz, 1H), 4.35 (t, J=8.1Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J=1 0.3, 6.8Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 3.09–2.90 (m, 2H), 2.72–2. 61(m, 1H), 2.24(s, 3H), 2.14(dq, J=13.8, 6.8Hz, 1H), 1.86–1.75(m, 4H), 1.75–1.68(m, 1H), 1.63 (dd, J=9.1, 4.6Hz, 1H), 1.49 (d, J=17.7Hz, 5H), 1.44–1.21 (m, 11H), 1.03–0.89 (m, 12H).

[0630] Example 6 Synthesis of Compound 6

[0631] 6b:

[0632] p-Aminobenzyl alcohol (3.44 g, 27.7 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (9.33 g, 37.8 mmol) were added to a mixture of N-fluorenylmethyloxycarbonyl-L-citrulline (10.00 g, 25.2 mmol) in dichloromethane (100 mL) and methanol (60 mL). The mixture was stirred at room temperature for 3 h. The mixture was filtered, and the filter cake was washed with dichloromethane (10 mL). The filter cake was collected and dried to give 7.20 g of a white solid (yield: 57%).

[0633] 6c:

[0634] At 0-5°C under nitrogen protection, PNP-CBTX (1j) (2.99 g, 2.98 mmol) and 4-dimethylaminopyridine (243 mg, 1.99 mmol) were added to tetrahydrofuran (30 mL) of 6b (1.00 g, 1.99 mmol) and stirred at 40°C for 3 hours. Ethyl acetate (60 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (20 ml × 2) and saturated sodium chloride aqueous solution (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =25:1] separation and purification gave 2.56 g of a white solid with a yield of 94%.

[0635] 6d:

[0636] At 0-5°C under nitrogen, piperidine (820 mg, 9.75 mmol) was added dropwise to a solution of 6c (1.33 g, 0.97 mmol) in acetonitrile (100 mL), and the mixture was stirred at 5-10°C for 3 h. Ethyl acetate (100 mL) was added to the reaction solution, which was then washed with 5% aqueous citric acid solution (60 mL) and saturated aqueous sodium chloride solution (60 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [V DCM / V MeoH =10:1] separation and purification gave 0.95 g of a white solid with a yield of 85%.

[0637] 6e:

[0638] At 10-15°C, under nitrogen protection, 6d (700 mg, 0.61 mmol), (7-azobenzotriazole)-N,N,N′,N″-tetramethyluronium hexafluorophosphate (280 mg, 0.73 mmol) and diisopropylethylamine (159 mg, 1.23 mmol) were added to a solution of N-fluorenylmethoxycarbonyl-L-valine (250 mg, 25.2 mmol) in N,N-dimethylacetamide (10 mL) in sequence, and the mixture was stirred at room temperature for 0.5 h. Water (20 ml) was added dropwise at 10-15°C, solid precipitated, and the mixture was stirred for 30 minutes. The filter cake was collected by suction filtration and purified by silica gel column chromatography [V DCM / V MeOH =30:1] separation and purification gave 650 mg of a white solid with a yield of 72%.

[0639] 6f:

[0640] At 0-5°C under nitrogen, piperidine (189 mg, 2.22 mmol) was diluted with acetonitrile (4 mL) and then added dropwise to a solution of 6e (650 mg, 0.44 mmol) in acetonitrile (20 mL). The mixture was stirred at 5-10°C for 2.5 h. Ethyl acetate (50 mL) was added to the reaction solution, which was then washed with 5% aqueous citric acid solution (60 mL) and saturated aqueous sodium chloride solution (60 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [V DCM / V MeOH =5:1] separation and purification gave 240 mg of a white solid, yield: 43%.

[0641] 6:

[0642] At 0-5°C, under nitrogen protection, succinic anhydride (39 mg, 0.39 mmol) and pyridine (46 mg, 0.58 mmol) were added to a dichloromethane (5 mL) solution of 6e (240 mg, 0.19 mmol) in sequence and stirred at room temperature for 1 hour. Dichloromethane (20 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (15 ml × 2) and saturated sodium chloride aqueous solution (20 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =10:1] separation and purification gave 130 mg of a white solid with a yield of 50% and a HPLC purity of 98.73%.

[0643] LC-MS: 1341.6045 [M+H + ]

[0644] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 12.15 (s, 1H), 9.95 (s, 1H), 8.10 (d, J = 7.4Hz, 1H), 7.95 (dd, J=20.5, 7.8Hz, 4H), 7.80–7.53(m, 5H), 7.38 (dt, J=13.6, 7.9Hz, 6H), 7.18(t , J=7.1Hz, 1H), 6.04(s, 1H), 5.82(t, J=8.9Hz, 1H), 5.58–5.31(m, 3H), 5.14(s, 2H ), 5.10–4.90 (m, 3H), 4.71 (s, 1H), 4.50 (s, 1H), 4.36 (dd, J=13.5, 8.0Hz, 1H), 4.2 4–4.15 (m, 1H), 4.02 (s, 2H), 3.82–3.70 (m, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3H ), 3.22(s, 3H), 3.00(dtd, J=19.6, 13.2, 6.5Hz, 2H), 2.74–2.60(m, 1H), 2.44(s, 3 H), 2.41 (s, 1H), 2.24 (s, 3H), 2.00 (dq, J=13.1, 6.7Hz, 1H), 1.91–1.53 (m, 7H), 1. 56–1.39 (m, 6H), 1.35 (s, 9H), 0.98 (d, J=7.4Hz, 6H), 0.86 (dd, J=11.1, 6.8Hz, 6H).

[0645] Example 7 Synthesis of Compound 7

[0646] 7b:

[0647] Dissolve 1c (3.0 g, 7.72 mmol) in tetrahydrofuran (20 mL), add 8 mL of an aqueous solution of lithium hydroxide monohydrate (0.65 g, 15.45 mmol), and stir at room temperature for 1 hour. Adjust the pH to 5 with 1N hydrochloric acid at -5°C, add ethyl acetate (80 mL), and extract twice. Combine the organic phases, dry over anhydrous sodium sulfate, and concentrate to obtain 7d (2.7 g, 93% yield) as a white solid.

[0648] 7c:

[0649] 7b (2.70 g, 7.10 mmol) was dissolved in dichloromethane (50 ml) and methanol (5 ml). p-Aminobenzyl alcohol (0.92 g, 7.45 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (3.51 g, 14.20 mmol) were added and stirred at room temperature for 2 hours. The mixture was concentrated under reduced pressure and purified by column chromatography to obtain BH259e (3.0 g, 88% yield) as a white solid.

[0650] 1 H NMR (400MHz, DMSOd-6) δ (ppm) 9.97 (s, 1H), 7.97 (d, J = 7.7Hz, 1H), 7.54 (d, J = 8.5Hz, 2H), 7.24 (d, J =8.5Hz, 2H), 6.75 (d, J = 8.9Hz, 1H), 5.97 (t, J = 5.7Hz, 1H), 5.40 (s, 2H), 5.09 (t, J = 5.7Hz, 1H), 4.4 5 (t, J=8.2Hz, 3H), 3.95–3.73 (m, 1H), 3.12–2.87 (m, 2H), 2.51 (dt, J=3.5, 1.7Hz, 2H), 1.96 (dt, J= 13.4, 6.7Hz, 1H), 1.66 (ddd, J=18.3, 12.7, 6.9Hz, 2H), 1.39 (s, 9H), 0.85 (dd, J=15.8, 6.7Hz, 6H).

[0651] 7:

[0652] 7c (0.14 g, 0.29 mmol) and 1j (0.30 g, 0.30 mmol) were dissolved in a mixture of N,N-dimethylformamide (1 ml) and dichloromethane (10 ml). 4-Dimethylaminopyridine (39 mg, 0.32 mmol) was added and the mixture was stirred at reflux for 2 hours. Dichloromethane (40 ml) and water (20 ml) were added, and the mixture was separated. The aqueous phase was extracted with dichloromethane (40 ml). The organic phases were combined and washed twice with 0.3N hydrochloric acid (20 ml), then with saturated sodium bicarbonate (20 ml), and then with saturated sodium chloride (20 ml). The mixture was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 7 (0.17 g, yield: 43.4%, HPLC purity: 99.536%) as a white solid.

[0653] LC-MS: 1341.6259 [M+H + ]

[0654] 1H NMR (400MHz, DMSOd-6) δ (ppm) 10.17 (s, 1H), 8.13–7.91 (m, 4H), 7.83–7.64 (m, 5H) , 7.44 (dt, J=13.3, 8.0Hz, 6H), 7.24 (t, J=7.2Hz, 1H), 6.80 (d, J=8.8Hz, 1H), 6.02 ( t, J=5.8Hz, 1H), 5.88 (t, J=8.6Hz, 1H), 5.52–5.36 (m, 3H), 5.20 (s, 2H), 5.15–5.0 4(m, 2H), 5.01(d, J=10.0Hz, 1H), 4.76(s, 1H), 4.58–4.44(m, 2H), 4.07(s, 2H), 3.9 9–3.65 (m, 3H), 3.65–3.56 (m, 1H), 3.35 (s, 3H), 3.31–3.26 (m, 3H), 3.05 (ddt, J=3 1.4, 13.2, 6.6Hz, 2H), 2.30 (s, 3H), 2.02 (dd, J=13.6, 7.0Hz, 1H), 1.88 (d, J=12.5H z, 4H), 1.80–1.70 (m, 1H), 1.66 (dd, J=9.2, 4.7Hz, 1H), 1.54 (d, J=18.5Hz, 5H), 1.4 8–1.37 (m, 18H), 1.29 (s, 2H), 1.03 (d, J=7.3Hz, 6H), 0.90 (dd, J=16.0, 6.7Hz, 6H).

[0655] Example 8 Synthesis of Compound 8

[0656] 8b:

[0657] 1d (4.4 g, 15.40 mmol) was added to dichloromethane (30 ml), and the pH was adjusted to 9 with diisopropylethylamine for later use.

[0658] Dissolve pivalic acid (1.57 g, 15.40 mmol) in dichloromethane (50 ml) and cool to 5°C under nitrogen. Add 1-hydroxybenzotriazole (2.29 g, 16.94 mmol) and dropwise add N,N′-diisopropylcarbodiimide (2.14 g, 16.94 mmol). Warm to room temperature and stir for 20 minutes. Add the prepared 1d solution dropwise to the above reaction solution and stir at room temperature for 0.5 hour. Wash with 0.3N hydrochloric acid (20 ml), saturated sodium bicarbonate (20 ml), saturated sodium chloride (20 ml), dry over anhydrous sodium sulfate, and concentrate to dryness. Column chromatography afforded 8c (1.40 g, 24.4% yield) as a white solid.

[0659] 8c:

[0660] 8b (1.4 g, 3.76 mmol) was dissolved in tetrahydrofuran (20 mL), and 4 mL of an aqueous solution of lithium hydroxide monohydrate (0.32 g, 7.52 mmol) was added. The mixture was stirred at room temperature for 30 minutes. The pH was adjusted to 5 with 1N hydrochloric acid at -5°C, and the mixture was extracted twice with ethyl acetate (80 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain 8d (0.75 g, 55% yield) as a white solid.

[0661] 8d:

[0662] Dissolve 8c (0.75 g, 2.08 mmol) in dichloromethane (10 ml), add p-aminobenzyl alcohol (0.0.26 g, 2.08 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (1.03 g, 4.16 mmol), and stir at room temperature for 2 hours. Concentrate under reduced pressure and perform column chromatography to obtain 8e (0.45 g, 47% yield) as a white solid.

[0663] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 9.94 (s, 1H), 8.01 (d, J = 7.5Hz, 1H), 7.53 (d, J = 8.5Hz, 2H), 7.23 (d, J=8.5Hz, 2H), 7.13 (d, J=8.7Hz, 1H), 5.96 (t, J=5.7Hz, 1H), 5.40 (s, 2H), 5.08 (s, 1H), 4.47–4.35 (m, 3H), 4.21–4.11 (m, 1H), 3.09–2.88 (m, 2H), 2.04 (dt, J=13.7, 6.8Hz, 1H), 1.76–1.64 (m, 1H), 1 .58 (ddd, J=18.3, 8.9, 4.6Hz, 1H), 1.51–1.29 (m, 2H), 1.12 (s, 9H), 0.85 (dd, J=14.6, 6.7Hz, 6H).

[0664] Synthesis of 8

[0665] 8d (0.17 g, 0.37 mmol) and 1j (0.37 g, 0.37 mmol) were dissolved in N,N-dimethylformamide (2 ml) and dichloromethane (8 ml), and 4-dimethylaminopyridine (49 mg, 0.40 mmol) was added. The mixture was stirred at room temperature for 2 hours. Dichloromethane (40 ml) and water (20 ml) were added, and the mixture was separated. The aqueous phase was extracted with dichloromethane (40 ml). The organic phases were combined, washed twice with 0.3N hydrochloric acid (20 ml), washed sequentially with saturated sodium bicarbonate (20 ml), and washed with saturated sodium chloride (20 ml). The mixture was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 8 as a white solid (0.29 g, yield: 59.7%, HPLC purity: 98.95%).

[0666] LC-MS: 1325.6407 [M+H + ]

[0667] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 10.10 (s, 1H), 8.09–7.86 (m, 4H), 7.78–7.57 (m, 5 H), 7.38 (dt, J=13.5, 8.0Hz, 6H), 7.24–7.09 (m, 2H), 5.97 (t, J=5.7Hz, 1H), 5.8 2(t, J=8.9Hz, 1H), 5.44–5.30(m, 3H), 5.14(s, 2H), 5.09–4.91(m, 3H), 4.70(s, 1H), 4.50 (s, 1H), 4.40 (dd, J=13.3, 7.8Hz, 1H), 4.17 (t, J=8.1Hz, 1H), 4.02 (s, 1H), 3.75 (dd, J=10.1, 6.8Hz, 1H), 3.62–3.56 (m, 1H), 3.29 (s, 3H), 3.22 (s, 3H) , 3.08–2.89 (m, 2H), 2.73–2.63 (m, 1H), 2.24 (s, 3H), 2.05 (dd, J=13.9, 6.9Hz, 1 H), 1.88–1.73(m, 4H), 1.73–1.65(m, 1H), 1.64–1.41(m, 7H), 1.41–1.28(m, 9H) , 1.24 (s, 2H), 1.12 (s, 9H), 0.98 (d, J=7.5Hz, 6H), 0.85 (dd, J=15.1, 6.7Hz, 6H).

[0668] Example 9 Synthesis of Compound 9

[0669] 9b:

[0670] Compound 9a (25.00 g, 280.6 mmol) was dissolved in methanol (150 ml). Under nitrogen, the temperature was lowered to 0-10°C, and thionyl chloride (50 mL, 701.5 mmol) was added dropwise. The addition rate was controlled to keep the internal temperature below 25°C. After the addition was complete, the temperature was gradually increased to 60°C (10°C / 5 min) and the reaction was stirred for 3 hours. The solvent was removed by concentration, and dichloromethane (75 ml / time) was added to the residue. The mixture was concentrated and concentrated. This process was repeated twice to obtain 39.17 g of a white solid (100% yield).

[0671] 9c:

[0672] At 0-10°C, under nitrogen protection, DIC (38.96 g, 308.69 mmol) was added dropwise to a dichloromethane (250 ml) solution of Boc-L-valine (60.97 mg, 280.6 mmol) and HOBt (41.71 g, 308.7 mmol), and the mixture was stirred and heated for 30 minutes. Compound 9b (39.17 g, 280.6 mmol) was added to a dichloromethane (250 ml) solution, and the pH value was adjusted to 9-10 with diisopropylethylamine under nitrogen protection at 0-10°C. After stirring for 5 minutes, the mixture was filtered and the filtrate was added dropwise to the Boc-L-valine reaction solution. The mixture was stirred at 10-15°C for 30 minutes. The reaction solution was washed with 0.3 mol / L hydrochloric acid (300 ml), 50% sodium bicarbonate solution (300 ml) and saturated sodium chloride (300 ml), dried over anhydrous sodium sulfate, concentrated, and the residue was purified by [V PE / V EA =4:1, 250 mL] slurry was performed and dried to obtain 47.65 g of a white solid with a yield of 56%.

[0673] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 9.91 (s, 1H), 8.04 (d, J = 7.1Hz, 1H), 7.53 (d, J = 8.5Hz, 2H), 7.24 (d, J=8.5Hz, 2H), 6.72 (d, J=8.8Hz, 1H), 5.08 (t, J=5.7Hz, 1H ), 4.43 (t, J=5.3Hz, 3H), 3.91–3.74 (m, 1H), 1.96 (dq, J=13.3, 6.8Hz, 1H), 1.3 8 (s, 9H), 1.30 (d, J = 7.1Hz, 3H), 0.87 (d, J = 6.8Hz, 3H), 0.82 (d, J = 6.7Hz, 3H).

[0674] 9d:

[0675] Compound 9c (25.00 g, 82.68 mmol) was dissolved in dichloromethane (20 mL), cooled to 0-10°C, and trifluoroacetic acid (45 ml) was added dropwise under nitrogen protection. The temperature was raised to 30°C and stirred for 3 hours. The solvent and part of the trifluoroacetic acid were removed by concentration, and the residue was added with dichloromethane (125 mL / time) and concentrated. The operation was repeated twice. The residue was purified by silica gel column chromatography [V PE / V EA =1:1] separation and purification gave 12.20 g of a white solid with a yield of 47%.

[0676] 9e:

[0677] At 0-10°C, under nitrogen protection, DIC (1.95 g, 15.4 mmol) was added dropwise to a solution of trimethylacetic acid (1.50 g, 14.7 mmol) and HOBt (2.08 g, 15.4 mmol) in dichloromethane (25 ml), and the mixture was stirred at 10-15°C for 20 minutes. Compound 9d (5.11 g, 16.2 mmol) was added to a dichloromethane (25 ml) solution, and the pH value was adjusted to 9-10 with diisopropylethylamine at 0-10°C under nitrogen protection. The mixture was then added dropwise to the Boc-L-valine reaction solution, and the mixture was stirred at 10-15°C for 30 minutes. The reaction solution was washed with 50% sodium bicarbonate solution (30 ml × 2) and saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [V PE / V EA =1:1] separation and purification gave 2.50 g of a white solid with a yield of 59%.

[0678] 9f:

[0679] Lithium hydroxide monohydrate (916 mg, 21.8 mmol) was dissolved in water (6 ml) at 0°C and added dropwise to a solution of compound 9e (2.50 g, 8.72 mmol) in tetrahydrofuran (16 ml). The mixture was stirred at 15-25°C for 1 hour. The reaction solution was cooled to 0-5°C, and the pH was adjusted to 2-3 by dropwise addition of 6N hydrochloric acid. Ethyl acetate (80 ml) was added for extraction. The upper organic phase was collected, washed with saturated brine (50 ml), and dried over anhydrous sodium sulfate. The resulting mixture yielded 2.10 g of a white foamy solid (yield: 88%).

[0680] 9g:

[0681] At room temperature, EEDQ (3.81 g, 15.4 mmol) and p-aminobenzyl alcohol (950 mg, 7.71 mmol) were added to a solution of compound 9f (2.10 g, 7.71 mmol) in dichloromethane (40 ml) in sequence and stirred at room temperature for 1.5 hours. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeOH =70:1] separation and purification gave 1.56 g of a white solid with a yield of 54%.

[0682] 9h:

[0683] At 0-5°C, under nitrogen protection, 4-nitrophenyl chloroformate (662 mg, 15.4 mmol) was dissolved in dichloromethane (6 ml), and the compound 9g (950 mg, 7.71 mmol), diisopropylethylamine (2.10 g, 7.71 mmol), N, N-dimethylpyridine (2.10 g, 7.71 mmol) in dichloromethane (20 ml) were added dropwise. The mixture was stirred at room temperature for 30 minutes. Dichloromethane (30 ml) and water (30 ml) were added to the reaction solution, shaken and separated. The lower organic phase was taken and washed with 0.1N hydrochloric acid (30 ml) and saturated sodium chloride aqueous solution (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =60:1] separation and purification gave 850 mg of a white solid with a yield of 95%.

[0684] Synthesis of 9

[0685] At 0-5°C, under nitrogen protection, compound 9h (200 mg, 0.37 mmol) was dissolved in dichloromethane (20 ml), and under nitrogen protection, cabazitaxel (309 mg, 0.37 mmol), N,N-dimethylpyridine (14 mg, 0.11 mmol), and pyridine (146 mg, 0.18 mmol) were added in sequence, and the mixture was stirred at 15-25°C for 16 hours. Dichloromethane (30 ml) and water (30 ml) were added to the reaction solution, shaken well, and separated. The lower organic phase was taken and washed with 0.5N hydrochloric acid (25 ml × 2) and saturated sodium chloride aqueous solution (30 ml), respectively, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V PE / V EA =1:1] separation and purification gave 230 mg of a white solid with a yield of 95% and a HPLC purity of 99.725%.

[0686] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.05 (s, 1H), 8.15 (d, J = 6.7Hz, 1H), 7.98 (d, J = 7.4Hz, 2H), 7. 93 (d, J=9.0Hz, 1H), 7.74 (t, J=7.2Hz, 1H), 7.64 (dd, J=14.8, 8.0Hz, 4H), 7.43 (t, J=7.5Hz, 2 H), 7.39–7.28 (m, 4H), 7.19 (t, J=7.2Hz, 1H), 7.09 (d, J=8.6Hz, 1H), 5.83 (t, J=8.8Hz, 1H), 5 .38 (d, J=6.9Hz, 1H), 5.15 (s, 2H), 5.11–4.99 (m, 2H), 4.96 (d, J=9.7Hz, 1H), 4.71 (s, 1H), 4.5 0 (s, 1H), 4.40 (p, J=6.7Hz, 1H), 4.17 (t, J=8.0Hz, 1H), 4.03 (s, 2H), 3.76 (dd, J=10.0, 6.9Hz , 1H), 3.60 (d, J=6.8Hz, 1H), 3.30 (s, 3H), 3.23 (s, 3H), 2.68 (t, J=10.3Hz, 1H), 2.25 (s, 3H), 2 .05(dt, J=13.8, 6.7Hz, 1H), 1.81(s, 4H), 1.59–1.45(m, 5H), 1.38–1.29(m, 11H), 1.25(d, J= 9.1Hz, 2H), 1.13 (s, 9H), 0.98 (d, J=7.1Hz, 6H), 0.89 (d, J=6.7Hz, 3H), 0.84 (d, J=6.7Hz, 3H).

[0687] Example 10 Synthesis of Compound 10

[0688] 10b:

[0689] At 0-10°C under nitrogen, diisopropylethylamine (7.36 g, 56.9 mmol) was added dropwise to a solution of 9d (6.00 g, 19.0 mmol) in dichloromethane (30 ml). 3-Chloropropionyl chloride (4.82 g, 38.0 mmol) was diluted with dichloromethane (50 ml) and added dropwise to the reaction solution. After the addition was complete, the mixture was stirred at room temperature for 30 minutes. The system was cooled to 0°C and quenched with 0.1N hydrochloric acid (30 ml). The mixture was separated and the lower organic phase was removed and washed with 50% sodium bicarbonate solution (30 ml x 2) and saturated sodium chloride (30 ml), respectively. The mixture was dried over anhydrous sodium sulfate and concentrated to give 4.50 g of a white solid (yield: 81%).

[0690] 10c:

[0691] At 0°C, lithium hydroxide monohydrate (1.61 g, 38.4 mmol) was dissolved in water (10 ml) and added dropwise to a solution of 10b (4.50 g, 15.4 mmol) in tetrahydrofuran (30 ml). The mixture was stirred at 15-25°C for 0.5 hours. The reaction solution was cooled to 0-5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2-3. Ethyl acetate (50 ml) was added, and the upper organic phase was collected, washed with saturated brine (50 ml), and dried over anhydrous sodium sulfate. The resulting solution was concentrated to 4.00 g of a light yellow solid (yield: 93%).

[0692] 10d:

[0693] At room temperature, EEDQ (7.10 g, 28.7 mmol) and p-aminobenzyl alcohol (1.77 g, 14.4 mmol) were added to a mixed solution of 10c (4.00 g, 14.4 mmol) in dichloromethane (50 ml) and methanol (5 ml) in sequence, and the mixture was stirred at room temperature for 2 hours. The solvent was removed by concentration under reduced pressure, and the residue was purified by [V PE / V EA =5:1] slurry for 1 hour, filtered and dried to obtain 2.60 g of white solid, yield: 41%.

[0694] 10e:

[0695] 10d (1.0 g, 2.61 mmol) and morpholine (0.91 g, 10.45 mmol) were dissolved in ethanol (15 ml), and potassium iodide (0.865 g, 5.21 mmol) was added and stirred for 5 minutes. The temperature was raised to 50°C and stirred for 1.0 hour. The reaction solution was concentrated to dryness, and dichloromethane (30 mL) was added. The product was washed with saturated sodium bicarbonate aqueous solution (30 ml x 2), saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated to dryness, and column chromatography [V DCM / V MEOH =20:1] to obtain 0.76 g of light yellow foamy solid, yield: 67.14%.

[0696] 10:

[0697] 10e (0.13 g, 0.30 mmol) was dissolved in dichloromethane (8 mL) under nitrogen protection. CBTX-PNP (1j) (0.27 g, 0.27 mmol) and 4-dimethylaminopyridine (36 mg, 0.30 mmol) were added under ice-cooling. After the addition, the mixture was reacted at 30°C for 2.5 hours. The reaction solution was diluted with dichloromethane (30 mL), washed with 0.2 mol / L HCl aqueous solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography [V DCM / V MEOH=20:1] separation and purification gave 0.12 g of an off-white solid, with a yield of 35.6% and an HPLC rate of 99.56%.

[0698] HR-MS: 1296.6019 [M+H + ]

[0699] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 10.06 (s, 1H), 8.27 (dd, J = 10.1, 8.0Hz, 2H), 8.01 (dd, J = 23.8, 8.1Hz, 3H), 7.79 (t, J=7.4Hz, 1H), 7.70 (dd, J=10.2, 8.2Hz, 4H), 7.48 (t, J=7.6Hz, 2H), 7.43 –7.37 (m, 4H), 7.24 (t, J=7.1Hz, 1H), 5.88 (t, J=8.9Hz, 1H), 5.43 (d, J=6.9Hz, 1H), 5.21 (s, 2 H), 5.15–5.06 (m, 2H), 5.01 (d, J=9.9Hz, 1H), 4.76 (s, 1H), 4.56 (s, 1H), 4.47 (p, J=7.0Hz, 1H ), 4.30 (dd, J=8.6, 6.4Hz, 1H), 4.08 (s, 2H), 3.81 (dd, J=10.2, 6.8Hz, 1H), 3.62 (dd, J=9.8, 4 .8Hz, 5H), 3.35 (s, 3H), 3.28 (s, 3H), 2.77–2.71 (m, 1H), 2.62 (dd, J=12.3, 7.0Hz, 1H), 2.48– 2.38(m, 5H), 2.37–2.33(m, 1H), 2.30(s, 3H), 2.08–2.01(m, 1H), 1.86(s, 4H), 1.62–1.51(m, 5H), 1.44–1.35 (m, 12H), 1.04 (t, J=5.4Hz, 6H), 0.95 (d, J=6.8Hz, 3H), 0.91 (d, J=6.8Hz, 3H).

[0700] Example 11 Synthesis of Compound 11

[0701] 11b:

[0702] At 0-10°C, under nitrogen protection, DIC (3.70 g, 29.3 mmol) was added dropwise to a solution of acetic acid (1.60 g, 26.6 mmol) and HOBt (3.96 g, 29.3 mmol) in dichloromethane (30 ml), and the mixture was stirred and heated for 30 minutes. 9d (7.58 g, 24.0 mmol) was added to a solution of dichloromethane (40 ml), and the pH value was adjusted to 8-9 with triethylamine at 0-10°C under nitrogen protection. The mixture was stirred for 5 minutes, filtered, and the filtrate was added dropwise to the acetic acid reaction solution. The mixture was stirred and reacted for 30 minutes at 20-25°C. The reaction solution was washed with 50% sodium bicarbonate solution (50 ml) and saturated sodium chloride (50 ml × 2), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [V DCM / V MeoH =30:1] separation and purification gave 2.30 g of a white solid with a yield of 36%.

[0703] 11c:

[0704] Lithium hydroxide monohydrate (790 mg, 18.8 mmol) was dissolved in water (10 ml) at 0-10°C and added dropwise to a solution of 11b (2.30 g, 1.17 mmol) in tetrahydrofuran (20 ml). The mixture was stirred at 15-25°C for 1 hour. The reaction solution was cooled to 0-5°C and the pH was adjusted to 2-3 by adding 6N hydrochloric acid dropwise. The solvent was then concentrated to remove most of the residue. The residue was then added to tetrahydrofuran (20 ml x 2) and concentrated to afford 2.17 g of a yellow oil (yield: 100%).

[0705] 11d:

[0706] At room temperature, EEDQ (4.66 g, 18.8 mmol) and p-aminobenzyl alcohol (1.22 g, 9.90 mmol) were added sequentially to a solution of 11c (2.17 g, 9.90 mmol) in dichloromethane (15 ml) / methanol (1.5 ml). The mixture was stirred at room temperature for 1 hour. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeOH =12:1] separation and purification gave 800 mg of a white solid, yield: 25%.

[0707] 11:

[0708] At 0-5°C, under nitrogen protection, 11d (150 mg, 0.45 mmol) was dissolved in dichloromethane (10 ml) / N,N-dimethylformamide (1 mL). Under nitrogen protection, 1j (448 mg, 0.45 mmol) and N,N-dimethylpyridine (60 mg, 0.49 mmol) were added in sequence. The mixture was stirred at 20-25°C for 3 hours. Dichloromethane (50 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (30 ml × 2) and saturated sodium chloride aqueous solution (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =24:1] separation and purification gave 150 mg of a white solid with a yield of 28% and a HPLC purity of 98.03%.

[0709] HR-MS: 1197.5599[M+H + ]

[0710] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 9.96 (s, 1H), 8.20 (d, J = 7.0Hz, 1H), 8.02–7.84 (m, 4 H), 7.73(t, J=7.4Hz, 1H), 7.69–7.54(m, 4H), 7.42(t, J=7.6Hz, 2H), 7.38–7.25(m , 4H), 7.18 (t, J=7.3Hz, 1H), 5.82 (t, J=8.8Hz, 1H), 5.37 (d, J=7.0Hz, 1H), 5.14 (s , 2H), 5.10–4.90 (m, 3H), 4.70 (s, 1H), 4.50 (s, 1H), 4.39 (p, J=7.1Hz, 1H), 4.17 (dd , J=8.4, 6.9Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J=10.3, 6.7Hz, 1H), 3.59 (d, J=6.8Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (ddd, J=15.3, 9.8, 6.9Hz, 1H), 2.24 (s, 3H), 1. 97(dt, J=13.6, 6.8Hz, 1H), 1.88(s, 3H), 1.86–1.72(m, 4H), 1.60–1.43(m, 5H), 1. 30 (dd, J=25.5, 18.4Hz, 12H), 0.98 (d, J=7.2Hz, 6H), 0.86 (dd, J=14.0, 6.8Hz, 6H).

[0711] Example 12 Synthesis of Compound 12

[0712] Referring to the synthesis of compound 9 in Example 9, n-octanoic acid was used instead of trimethylacetic acid to obtain compound 12 (130 mg, yield: 24%, HPLC purity: 96.23%).

[0713] ESI-MS: 1281.6244 [M+H + ]

[0714] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 10.04 (s, 1H), 8.20 (d, J = 7.0Hz, 1H), 8.04 (d, J = 7.4Hz, 2H), 7. 98(d, J=9.0Hz, 1H), 7.86(d, J=8.5Hz, 1H), 7.79(t, J=7.2Hz, 1H), 7.76–7.66(m, 4H), 7.48(t , J=7.6Hz, 2H), 7.44–7.34(m, 4H), 7.24(t, J=7.1Hz, 1H), 5.88(t, J=8.7Hz, 1H), 5.43(d, J=7 .0Hz, 1H), 5.20 (s, 2H), 5.15–5.04 (m, 2H), 5.01 (d, J=9.6Hz, 1H), 4.76 (s, 1H), 4.56 (s, 1H), 4.49–4.38 (m, 1H), 4.26–4.20 (m, 1H), 4.08 (s, 2H), 3.81 (dd, J=10.2, 6.8Hz, 1H), 3.65 (d, J= 6.8Hz, 1H), 3.35 (s, 3H), 3.28 (s, 3H), 2.77–2.68 (m, 1H), 2.30 (s, 3H), 2.22 (ddd, J=18.3, 14 .1, 6.8 Hz, 2H), 2.03 (dd, J = 13.6, 6.8 Hz, 1H), 1.88 (d, J = 14.0 Hz, 4H), 1.57 (s, 7H), 1.45–1.35 (m, 11H), 1.30 (s, 9H), 1.03 (d, J = 7.2 Hz, 6H), 0.92 (dd, J = 13.9, 6.9 Hz, 9H). Synthesis of Compound 13 in Example 13

[0715] Example 13 Synthesis of Compound 13

[0716] Referring to the synthesis of compound 11 in Example 11, 4-fluorobenzoic acid was used instead of acetic acid to obtain compound 13 (180 mg, yield: 29%, HPLC purity: 96.242%).

[0717] HR-MS: 1277.5629[M+H + ]

[0718] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 10.01 (s, 1H), 8.31 (t, J = 7.6Hz, 2H), 7.97 (dd, J = 8.6, 5.6Hz, 5H), 7.73 (t, J=7.3Hz, 1H), 7.64 (dd, J=11.4, 8.2Hz, 4H), 7.42 (t, J =7.5Hz, 2H), 7.33 (dt, J = 17.8, 6.7Hz, 6H), 7.17 (dd, J = 16.8, 8.1Hz, 1H), 5.82 ( t, J=8.7Hz, 1H), 5.37(d, J=6.9Hz, 1H), 5.14(s, 2H), 5.10–4.99(m, 2H), 4.95(d, J=9.8Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.43 (t, J=7.0Hz, 1H), 4.34 (t, J=8.1H z, 1H), 4.02 (s, 2H), 3.75 (dd, J=10.2, 6.8Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 ( s, 3H), 3.22 (s, 3H), 2.67 (s, 1H), 2.23 (d, J=6.7Hz, 3H), 2.14 (td, J=13.6, 6.8H z, 1H), 1.80 (s, 4H), 1.58–1.46 (m, 5H), 1.35–1.23 (m, 12H), 1.02–0.90 (m, 12H).

[0719] Example 14 Synthesis of Compound 14

[0720] Referring to the synthesis of compound 11 in Example 11, phenylpropionic acid was used instead of acetic acid to obtain compound 14 (0.23 g, yield: 44.7%, HPLC: 99.785%).

[0721] HR-MS: 1287.5961[M+H + ]

[0722] 1H NMR (400MHz, DMSO-d6) δ (ppm) 9.98 (s, 1H), 8.19 (d, J = 6.9Hz, 1H), 7.98 (d, J = 7.4Hz, 2H), 7. 90 (dd, J=17.6, 8.8Hz, 2H), 7.73 (t, J=7.3Hz, 1H), 7.64 (t, J=8.4Hz, 4H), 7.42 (t, J=7.5Hz, 2 H), 7.37–7.32 (m, 4H), 7.26–7.16 (m, 6H), 5.82 (t, J=8.6Hz, 1H), 5.37 (d, J=6.9Hz, 1H), 5.14 (s, 2H), 5.05 (dd, J=17.6, 8.3Hz, 2H), 4.95 (d, J=9.8Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.38 (dd, J=13.9, 6.9Hz, 1H), 4.21–4.16 (m, 1H), 4.02 (s, 2H), 3.79–3.71 (m, 1H), 3.59 (d, J=6.9H z, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.82 (t, J=7.5Hz, 2H), 2.67 (s, 1H), 2.58–2.52 (m, 1H), 2.4 4 (dd, J=14.6, 7.9Hz, 1H), 2.24 (s, 3H), 1.94 (dd, J=13.4, 6.7Hz, 1H), 1.80 (s, 4H), 1.51 (s, 5 H), 1.37–1.30 (m, 12H), 0.98 (d, J = 6.6Hz, 6H), 0.84 (d, J = 6.7Hz, 3H), 0.80 (d, J = 6.7Hz, 3H).

[0723] Example 15 Synthesis of Compound 15

[0724] Referring to the synthesis of compound 11 in Example 11, 4-fluorophenylpropionic acid was used instead of acetic acid to obtain compound 15 (210 mg, yield: 36%, HPLC purity: 99.5879%).

[0725] HR-MS: 1305.5900[M+H + ]

[0726] 1H NMR (400MHz, DMSO-d6) δ (ppm) 9.99 (s, 1H), 8.19 (d, J = 6.8Hz, 1H), 8.02–7.79 (m, 4H ), 7.72(d, J=6.9Hz, 1H), 7.70–7.55(m, 4H), 7.50–7.27(m, 6H), 7.29–7.21(m, 2H), 7 .18 (t, J=7.1Hz, 1H), 7.07 (t, J=8.8Hz, 2H), 5.82 (t, J=8.9Hz, 1H), 5.37 (d, J=6.6H z, 1H), 5.14 (s, 2H), 5.10–4.92 (m, 3H), 4.70 (s, 1H), 4.50 (s, 1H), 4.44–4.35 (m, 1H) , 4.22–4.14(m, 1H), 4.02(s, 2H), 3.80–3.70(m, 1H), 3.59(d, J=6.9Hz, 1H), 3.29(s , 3H), 3.22 (s, 3H), 2.80 (t, J=7.6Hz, 2H), 2.66 (dd, J=19.2, 11.1Hz, 1H), 2.48–2.37 (m, 2H), 2.24 (s, 3H), 1.94 (dt, J=13.2, 6.5Hz, 1H), 1.82 (d, J=14.3Hz, 4H), 1.62–1. 42 (m, 5H), 1.41–1.15 (m, 12H), 0.97 (d, J = 6.6Hz, 6H), 0.80 (dd, J = 17.3, 6.7Hz, 6H).

[0727] Example 16 Synthesis of Compound 16

[0728] Referring to the synthesis of compound 11 in Example 11, 3,3,3-trimethylpropionic acid was used instead of acetic acid to obtain compound 16 (260 mg, yield: 41%, HPLC purity: 98.62%).

[0729] HR-MS: 1253.6158[M+H + ]

[0730] 1H NMR (400MHz, DMSO-d6) δ (ppm) 9.99 (s, 1H), 8.13 (d, J = 6.9Hz, 1H), 8.02–7.87 (m, 3 H), 7.78–7.68(m, 2H), 7.64(t, J=8.7Hz, 4H), 7.42(t, J=7.6Hz, 2H), 7.39–7.26(m , 4H), 7.18 (t, J=7.3Hz, 1H), 5.82 (t, J=8.8Hz, 1H), 5.37 (d, J=7.0Hz, 1H), 5.14 (s , 2H), 5.10–4.98 (m, 2H), 4.95 (d, J=9.9Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.39 (p, J=7.0Hz, 1H), 4.17 (dd, J=8.3, 7.0Hz, 1H), 4.02 (d, J=1.4Hz, 2H), 3.75 (dd, J=10. 3, 6.7Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.72–2.60 (m, 1H) , 2.24 (s, 3H), 2.02 (ddd, J=25.0, 20.3, 9.7Hz, 4H), 1.87–1.70 (m, 4H), 1.61–1.41 (m, 5H), 1.38–1.28 (m, 11H), 0.97 (d, J=9.6Hz, 15H), 0.87 (dd, J=12.3, 6.8Hz, 6H).

[0731] Example 17 Synthesis of Compound 17

[0732] Referring to the synthesis of compound 11 in Example 11, 3,3,3-trifluoropropionic acid was used instead of acetic acid to obtain compound 17 (210 mg, yield: 33%, HPLC purity: 96.29%).

[0733] HR-MS: 1255.6322[M+H + ]

[0734] 1H NMR (400MHz, DMSO-d6) δ (ppm) 9.99 (s, 1H), 8.27 (d, J = 6.6Hz, 1H), 8.17 (d, J = 8.7Hz, 1H), 7.95 (dd, J = 22.4, 8.1Hz, 3H), 7.72 (d, J = 6.9Hz, 1H), 7.64 (dd, J=12.6, 7.9Hz, 4H), 7.38 (dd, J=29.2, 7.4Hz, 6H), 7.19 (d, J=6.6Hz, 1H), 5. 82(t, J=8.8Hz, 1H), 5.37(d, J=6.5Hz, 1H), 5.14(s, 2H), 5.11–4.92(m, 3H), 4.70(s, 1H), 4.50(s, 1H), 4.45–4.34(m, 1H), 4.31–4.19(m, 1H), 4.02(s, 2H ), 3.79–3.71 (m, 1H), 3.60 (d, J = 10.7Hz, 3H), 3.29 (s, 3H), 3.22 (s, 3H), 2.6 7 (t, J=15.2Hz, 1H), 2.24 (s, 3H), 1.98 (td, J=13.0, 6.5Hz, 1H), 1.82 (d, J=1 3.4Hz, 4H), 1.61–1.43 (m, 5H), 1.33 (d, J=13.4Hz, 12H), 1.11–0.73 (m, 12H).

[0735] Example 18 Synthesis of Compound 18

[0736] Referring to the synthesis of compound 9 in Example 9, n-octanoic acid was used instead of trimethylacetic acid to obtain compound 18 (130 mg, yield: 24%, HPLC purity: 96.23%).

[0737] LC-MS: 1239.5839 [M+H + ]

[0738] 1H NMR (400MHz, DMSO-d6) δ (ppm) 9.98 (s, 1H), 8.15 (d, J = 6.9Hz, 1H), 7.95 (dd, J = 23.1, 8.2H z, 3H), 7.81 (d, J=8.6Hz, 1H), 7.73 (t, J=7.3Hz, 1H), 7.64 (t, J=8.7Hz, 4H), 7.42 (t, J=7.6 Hz, 2H), 7.37–7.27 (m, 4H), 7.18 (t, J=7.2Hz, 1H), 5.82 (t, J=8.9Hz, 1H), 5.37 (d, J=7.0H z, 1H), 5.14 (s, 2H), 5.10–4.99 (m, 2H), 4.95 (d, J=10.0Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.39 (p, J=7.0Hz, 1H), 4.17 (dd, J=8.4, 7.0Hz, 1H), 4.00 (s, 1H), 3.75 (dd, J=10.2, 6.8Hz , 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.66 (dd, J=17.6, 12.1Hz, 1H), 2.5 1(s, 1H), 2.23(d, J=8.0Hz, 3H), 2.21–2.10(m, 2H), 1.96(d, J=6.8Hz, 1H), 1.82(d, J=14.4 Hz, 4H), 1.59–1.43 (m, 7H), 1.36–1.23 (m, 14H), 0.98 (d, J=7.1Hz, 6H), 0.91–0.82 (m, 9H).

[0739] Example 19 Synthesis of Compound 19

[0740] 19b

[0741] At 0-10°C, under nitrogen protection, a solution of 9d (9.22 g, 29.1 mmol) in dichloromethane (50 ml) was adjusted to pH 9-10 with diisopropylethylamine, and acrylic acid (2.00 g, 27.7 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.98 g, 41.6 mmol), and N,N-lutidine (0.34 g, 2.78 mmol) were added in sequence. The mixture was stirred at 20-25°C for 1 hour. Dichloromethane (100 ml) was added to the reaction solution, and the reaction solution was washed with 50% aqueous ammonium chloride (50 ml), saturated aqueous sodium bicarbonate (50 ml), and saturated aqueous sodium chloride (50 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V PE / VEA =2:1] separation and purification gave 2.20 g of an off-white solid with a yield of 62%.

[0742] 19c

[0743] At 0-10°C, under nitrogen protection, diethylamine (2.85 g, 39 mmol) was added to a solution of 19b (2.00 g, 7.80 mmol) in tetrahydrofuran (50 ml), and the temperature was raised to 60-65°C, and the mixture was stirred for 16 hours. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeOH =19:1] separation and purification gave 2.05 g of a light yellow solid, with a yield of 80%.

[0744] 19d

[0745] Lithium hydroxide monohydrate (637 mg, 15.2 mmol) was dissolved in water (6 ml) at 0°C and added dropwise to a solution of 19c (2.00 g, 6.07 mmol) in tetrahydrofuran (20 ml). The mixture was stirred at 15-25°C for 0.5 h. The reaction solution was cooled to 0-5°C, and the pH was adjusted to 2-3 by dropwise addition of 6N hydrochloric acid. Ethyl acetate (20 ml) and tetrahydrofuran (20 ml) were added for extraction. The upper organic phase was collected, and the aqueous phase was extracted with tetrahydrofuran (20 ml x 3). The combined organic phases were dried over anhydrous sodium sulfate, and concentrated to yield 1.91 g of a yellow solid (yield: 100%).

[0746] 19e

[0747] At room temperature, EEDQ (2.99 g, 12.1 mmol) and p-aminobenzyl alcohol (0.746 g, 6.05 mmol) were added to a mixed solution of 19d (1.91 g, 6.05 mmol) in tetrahydrofuran (30 ml) and methanol (4 ml) in sequence, and the mixture was stirred at room temperature for 17 hours. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeOH =20:1] separation and purification gave 350 mg of a white solid, yield: 14%.

[0748] 19f

[0749] At 0-5°C under nitrogen protection, 4-nitrophenyl chloroformate (396 mg, 1.95 mmol) was dissolved in dichloromethane (5 ml), and the mixture was added dropwise to a solution of 19e (330 mg, 0.78 mmol), diisopropylethylamine (304 mg, 2.35 mmol), and N,N-lutidine (29 mg, 0.23 mmol) in dichloromethane (15 ml). The mixture was stirred at room temperature for 40 minutes. Dichloromethane (50 ml) was added to the reaction solution, and the reaction solution was washed with 0.1N hydrochloric acid (40 ml) and saturated sodium chloride aqueous solution (30 ml × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =35:1] separation and purification gave 135 mg of a white solid, yield: 29%.

[0750] 19

[0751] At 0-5°C under nitrogen protection, 19f (130 mg, 0.22 mmol) was dissolved in dichloromethane (15 ml), and cabazitaxel (195 mg, 0.23 mmol) and N,N-dimethylpyridine (30 mg, 0.24 mmol) were added in sequence. The mixture was stirred at 20-25°C for 16 hours. Dichloromethane (30 ml) was added to the reaction solution, and the reaction solution was washed with 0.5N hydrochloric acid (25 ml × 2) and saturated sodium chloride aqueous solution (60 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =40:1] separation and purification gave 72 mg of an off-white solid with a yield of 24% and a HPLC purity of 99.62%.

[0752] 11H NMR (400 MHz, DMSO-d6) δ (ppm) 10.01 (s, 1H), 8.29 (d, J = 8.5 Hz, 1H), 8.21 (d, J = 6.3 Hz, 1H), 7.98 (d, J = 7.4 Hz, 2H), 7.92 (d, J = 8.9 Hz, 1H), 7.73 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.8 Hz, 4H), 7.42 (t, J = 7.5 Hz, 2H), 7.38–7.28 (m, 4H), 7.18 (t, J = 7.1 Hz, 1H), 5.82 (t, J = 8.6 Hz, 1H), 5.37 (d, J = 6.8 Hz, 1H), 5.15 (s, 2H), 5.08 (d, J = 7.9 Hz, 1H), 5.05–4.99 (m, 1H), 4.95 (d, J = 9.4 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 从4.45至4.35 (m, 1H), 从4.26至4.18 (m, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.0, 7.0 Hz, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (s, 7H), 2.42 (s, 2H), 2.24 (s, 3H), 2.00 (dt, J = 13.4, 6.5 Hz, 1H), 1.80 (s, 4H), 1.51 (s, 4H), 1.35 (s, 8H), 1.32 (d, J = 7.1 Hz, 3H), 1.24 (s, 1H), 1.18 (s, 1H), 1.03 (s, 6H), 0.98 (d, J = 7.0 Hz, 6H), 0.89 (d, J = 6.7 Hz, 3H), 0.85 (d, J = 6.8 Hz, 3H).

[0753] Synthesis of Compound 20 in Example 20

[0754] 20b:

[0755] Under nitrogen at 0-10°C, dissolve N,N'-dicyclohexylcarbodiimide (5.84 g, 28.3 mmol) in tetrahydrofuran (15 ml) and add dropwise to a solution of N-Fmoc-L-valine (8.00 g, 23.6 mmol) and succinimide (3.26 g, 28.3 mmol) in tetrahydrofuran (30 ml). Stir and react at 20-25°C for 40 minutes. Filter and collect the filtrate. Add the filtrate to a solution of sodium carbonate (2.00 g, 22.4 mmol) and L-alanine (2.00 g, 22.4 mmol) in water (30 ml) and stir at 20-25°C for 2.5 hours. The solvent tetrahydrofuran was removed by concentration, and dichloromethane (80 ml) was added for extraction. The mixture was washed with 0.6N hydrochloric acid (30 ml) and saturated aqueous sodium chloride solution (40 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by beating with petroleum ether (40 ml) to obtain 5.00 g of a white solid. The yield was 54%.

[0756] 20c:

[0757] EEDQ (6.00 g, 24.4 mmol) and p-aminobenzyl alcohol (1.70 g, 13.40 mmol) were added sequentially to a solution of 20b (5.00 g, 12.2 mmol) in dichloromethane (35 ml) / methanol (3.5 ml) at room temperature and stirred for 16 hours. Dichloromethane (50 ml) was added to the reaction solution, which was then washed with 0.6N hydrochloric acid (40 ml) and saturated sodium chloride solution (50 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by slurrying with petroleum ether (20 ml) to afford 1.50 g of a white solid (yield: 24%).

[0758] 20d:

[0759] At 10-15°C under nitrogen protection, PNP-CBTX (780 mg, 0.78 mmol) and 4-dimethylaminopyridine (105 mg, 0.85 mmol) were added to tetrahydrofuran (8 mL) of 20c (400 mg, 0.78 mmol) and stirred at 30°C for 5 hours. Dichloromethane (30 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (20 ml) and saturated sodium chloride aqueous solution (20 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =80:1] separation and purification gave 650 mg of a white solid with a yield of 61%.

[0760] 20e:

[0761] At 0-5°C under nitrogen protection, piperidine (377 mg, 4.43 mmol) was dissolved in dichloromethane (2 mL) and added dropwise to a dichloromethane (4 mL) solution of 20d (610 mg, 0.44 mmol). The mixture was stirred at 10-15°C for 1 hour. Dichloromethane (40 ml) was added to the reaction solution, and the mixture was washed with 0.1N hydrochloric acid (20 ml), saturated sodium bicarbonate aqueous solution (20 ml), and saturated sodium chloride aqueous solution (20 ml), respectively. The mixture was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =50:1] separation and purification gave 270 mg of a white solid, yield: 53%.

[0762] Synthesis of 20

[0763] At 0-5°C, under nitrogen protection, succinic anhydride (35 mg, 0.35 mmol) and pyridine (37 mg, 0.47 mmol) were added to a dichloromethane (12 mL) solution of 20e (270 mg, 0.23 mmol) in sequence, and the mixture was stirred at room temperature for 0.5 hours. Dichloromethane (30 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (20 ml × 2) and saturated sodium chloride aqueous solution (20 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =30:1] separation and purification gave 170 mg of a white solid with a yield of 58% and a HPLC purity of 97.34%.

[0764] LC-MS: 1255.5622 [M+H + ]

[0765] 1H NMR (400MHz, DMSO-d6) δ (ppm) 12.09 (s, 1H), 9.91 (s, 1H), 8.14 (d, J = 6.9Hz, 1H), 7. 95 (dd, J=21.8, 8.0Hz, 4H), 7.73 (t, J=7.1Hz, 1H), 7.64 (d, J=8.2Hz, 4H), 7.39 (dt, J =13.0, 7.8Hz, 6H), 7.18 (t, J = 7.0Hz, 1H), 5.82 (t, J = 8.5Hz, 1H), 5.37 (d, J = 6.7Hz, 1H), 5.15(s, 2H), 5.11–4.99(m, 2H), 4.95(d, J=9.6Hz, 1H), 4.71(s, 1H), 4.50(s, 1H ), 4.43–4.34(m, 1H), 4.22–4.12(m, 1H), 4.02(s, 2H), 3.83–3.70(m, 1H), 3.59(d, J =6.7Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (dt, J = 15.7, 7.9Hz, 1H), 2.43 (d, J = 8.0 Hz, 5H), 2.24 (s, 3H), 1.99 (dq, J=13.7, 6.9Hz, 1H), 1.82 (d, J=13.2Hz, 4H), 1.61–1. 42 (m, 5H), 1.41–1.26 (m, 11H), 0.98 (d, J = 6.9Hz, 6H), 0.87 (dd, J = 14.0, 6.7Hz, 6H).

[0766] Example 21 Synthesis of Compound 21

[0767] 21b:

[0768] Lithium hydroxide monohydrate (1.35 g, 33.1 mmol) was dissolved in water (10 ml) at 0°C and added dropwise to a solution of 21a (5.00 g, 16.5 mmol) in tetrahydrofuran (40 ml). The mixture was stirred at 15-25°C for 0.5 hours. The reaction solution was cooled to 0-5°C, and the pH was adjusted to 2-3 by dropwise addition of 6N hydrochloric acid. Ethyl acetate (100 ml x 2) was added for extraction. The organic phases were combined, washed with saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate, and concentrated to give 4.40 g of a white solid (yield: 92%).

[0769] 21c:

[0770] At room temperature, EEDQ (7.50 g, 30.6 mmol) and p-aminobenzyl alcohol (2.26 g, 18.3 mmol) were added sequentially to a solution of 21b (4.40 g, 15.3 mmol) in dichloromethane (50 ml) and methanol (5 ml). The mixture was stirred at room temperature for 2 hours. The solvent was removed by concentration under reduced pressure, and the residue was slurried in ethyl acetate / petroleum ether (v / v = 1:3, 400 ml) for 1 hour. The residue was filtered, and the filter cake was washed with petroleum ether (30 ml). The filter cake was collected and dried at 30°C to obtain 3.8 g of a white solid (yield: 63%).

[0771] 21d:

[0772] At 0-5°C, under nitrogen protection, 4-nitrophenyl chloroformate (645 mg, 3.20 mmol) was dissolved in dichloromethane (6 ml), and the mixture was added dropwise to a solution of 21c (630 mg, 1.60 mmol), diisopropylethylamine (621 mg, 4.80 mmol), and N,N-lutidine (39 mg, 0.32 mmol) in dichloromethane (20 ml). The mixture was stirred at room temperature for 30 minutes. Dichloromethane (50 ml) was added to the reaction solution, and the reaction solution was washed with 0.1N hydrochloric acid (40 ml) and saturated sodium chloride aqueous solution (30 ml × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V PE / V EA =1:1] separation and purification gave 820 mg of a white solid, yield: 91%.

[0773] Synthesis of 21:

[0774] At 0-5°C under nitrogen protection, 21d (220 mg, 0.39 mmol) was dissolved in dichloromethane (15 ml), and cabazitaxel (330 mg, 0.39 mmol) and N,N-dimethylpyridine (53 mg, 0.43 mmol) were added in sequence. The mixture was stirred at 20-25°C for 16 hours. Dichloromethane (40 ml) was added to the reaction solution, and the reaction solution was washed with 0.5N hydrochloric acid (25 ml × 2) and saturated sodium chloride aqueous solution (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V PE / V EA =1:1] separation and purification gave 270 mg of an off-white solid with a yield of 55% and a HPLC purity of 97.99%.

[0775] ESI-MS: 1255.5779[M+H + ]

[0776] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.06 (s, 1H), 8.07 (d, J = 6.9Hz, 1H), 7.95 (dd, J = 23.2, 8.1Hz, 3H), 7.73 (t, J=7.3Hz, 1H), 7.64 (dd, J=14.5, 8.0Hz, 4H), 7.42 (t, J=7.6Hz, 2H ), 7.38–7.28(m, 4H), 7.18(t, J=7.2Hz, 1H), 6.71(d, J=8.7Hz, 1H), 5.82(t, J=8.6Hz, 1H), 5.37 (d, J=7.0Hz, 1H), 5.14 (s, 2H), 5.10–4.98 (m, 2H), 4.95 (d, J=9.9Hz, 1H), 4.7 0 (s, 1H), 4.45 (dd, J=19.7, 12.9Hz, 2H), 4.02 (s, 2H), 3.82 (dd, J=20.5, 13.3Hz, 1H), 3.75(dd, J=10.4, 6.7Hz, 1H), 3.59(d, J=7.0Hz, 1H), 3.29(s, 3H), 3.22(s, 3H), 2.72–2 .60(m, 1H), 2.24(s, 3H), 1.98–1.91(m, 1H), 1.80(s, 4H), 1.51(m, 5H), 1.34(dd, J=22 .5, 11.6Hz, 21H), 0.98 (d, J=7.0Hz, 6H), 0.87 (d, J=6.7Hz, 3H), 0.82 (d, J=6.7Hz, 3H).

[0777] Example 22 Synthesis of Compound 22

[0778] Referring to the synthesis of compound 10 in Example 10, tetrahydropyrrole was used to replace morpholine to obtain compound 22 (0.18 g, yield: 50%, HPLC: 99.91%).

[0779] MS:1280.6056[M+H + ]

[0780] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.07 (s, 1H), 8.26 (d, J = 7.8Hz, 2H), 7.96 (dd, J = 20.7, 8.4Hz, 3H), 7.74 (t, J=7.5Hz, 1H), 7.65 (t, J=7.4Hz, 4H), 7.43 (t, J=7.5Hz, 2H), 7.35 ( t, J=6.4Hz, 4H), 7.18 (t, J=7.5Hz, 1H), 5.82 (t, J=9.2Hz, 1H), 5.38 (d, J=7.1Hz, 1H), 5 .15(s, 2H), 5.10–5.00(m, 2H), 4.96(d, J=9.4Hz, 1H), 4.71(s, 1H), 4.51(s, 1H), 4.42( t, J=7.1Hz, 1H), 4.23 (t, J=7.5Hz, 1H), 4.02 (s, 2H), 3.80–3.72 (m, 1H), 3.59 (d, J=7. 1Hz, 1H), 3.12 (s, 2H), 3.06–2.94 (m, 3H), 2.63 (q, J=10.4, 7.2Hz, 3H), 2.25 (s, 3H), 2. 01 (q, J=6.7Hz, 1H), 1.85 (s, 4H), 1.80 (s, 3H), 1.51 (s, 3H), 1.33 (d, J=14.0Hz, 12H), 1 .28–1.17 (m, 3H), 0.98 (d, J = 7.6Hz, 6H), 0.90 (d, J = 6.8Hz, 3H), 0.86 (d, J = 6.8Hz, 3H).

[0781] Example 23 Synthesis of Compound 23

[0782] 23b:

[0783] p-Aminobenzyl alcohol (1.30 g, 10.6 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (4.80 g, 19.3 mmol) were added to a solution of N-fluorenylmethoxycarbonyl-L-alanine (3.00 g, 9.64 mmol) in dichloromethane (40 mL) / methanol (5 mL) and stirred at room temperature for 2 h. The reaction solution was washed with aqueous sodium bicarbonate (30 mL), 0.3N hydrochloric acid (20 mL), and saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was slurried with petroleum ether / ethyl acetate (v / v = 4:1, 25 mL), filtered, and the filter cake was collected and dried to obtain 2.90 g of a white solid (yield: 72%).

[0784] 23c:

[0785] At 0-5°C under nitrogen protection, PNP-CBTX (800 mg, 0.80 mmol) and 4-dimethylaminopyridine (108 mg, 0.88 mmol) were added to tetrahydrofuran (5 mL) of 23b (330 mg, 0.79 mmol) and stirred at 25-30°C for 2 hours. Dichloromethane (30 ml x 2) was added to the reaction solution for extraction. The organic phases were combined and washed with 0.5N hydrochloric acid (20 ml x 2) and saturated sodium chloride aqueous solution (30 ml), respectively, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =85:1] separation and purification gave 640 mg of a white solid with a yield of 63%.

[0786] 1 H NMR (400 MHz, DMSO-d6) 1 H NMR (400MHz, DMSO) δ (ppm) 10.08 (s, 1H), 7.98 (d, J = 7.3Hz, 2H), 7.91 (s, 1H), 7.89 ( s, 1H), 7.75 (d, J=7.3Hz, 2H), 7.71 (s, 1H), 7.70–7.66 (m, 2H), 7.65 (s, 2H), 7.63 (s, 1H), 7.43(d, J=7.6Hz, 3H), 7.40(s, 1H), 7.38–7.31(m, 7H), 7.18(t, J=7.2Hz, 1H), 5 .83 (t, J=8.8Hz, 1H), 5.37 (d, J=7.0Hz, 1H), 5.15 (s, 2H), 5.04 (dd, J=17.0, 8.3Hz, 2 H), 4.95 (d, J = 10.2Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.29 (d, J = 6.1Hz, 2H), 4.22 ( dd, J=14.5, 7.2Hz, 2H), 4.02 (s, 2H), 3.76 (dd, J=10.4, 6.8Hz, 1H), 3.59 (d, J=7.0Hz , 1H), 3.29(s, 3H), 3.22(s, 3H), 2.71–2.63(m, 1H), 2.25(s, 3H), 1.81(s, 3H), 1.57( d, J=9.2Hz, 1H), 1.49 (d, J=17.2Hz, 5H), 1.35–1.31 (m, 12H), 0.98 (d, J=6.3Hz, 6H).

[0787] 23d:

[0788] At -1 to 3°C under nitrogen protection, 23b (600 mg, 0.47 mmol) was added to a 1% piperidine solution in N,N-dimethylformamide (0.1 ml piperidine dissolved in 9.9 ml N,N-dimethylformamide) and stirred at -1 to 3°C for 2 h. Dichloromethane (40 ml) was added to the reaction solution, and the solution was washed with saturated sodium bicarbonate aqueous solution (20 ml × 2), water (20 ml × 2), and saturated sodium chloride aqueous solution (20 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [V DCM / V MeOH =30:1] separation and purification gave 300 mg of a white solid, yield: 58%.

[0789] Synthesis of 23

[0790] At 0-5°C, under nitrogen protection, succinic anhydride (46 mg, 0.46 mmol) and pyridine (54 mg, 0.68 mmol) were added to a dichloromethane (5 mL) solution of 23d (250 mg, 0.23 mmol) in sequence and stirred at room temperature for 1 hour. Dichloromethane (30 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (15 ml × 2) and saturated sodium chloride aqueous solution (20 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =20:1] separation and purification gave 210 mg of a white solid with a yield of 77% and a HPLC purity of 99.39%.

[0791] MS:642.2583[M / 2+H + ]

[0792] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 12.10 (s, 1H), 9.96 (s, 1H), 8.22 (d, J = 7.2Hz, 1H), 7.95 (dd, J = 20.7, 8.2Hz, 3H), 7.77–7.56 (m, 5H), 7.39 (dt, J = 1 3.4, 8.0Hz, 6H), 7.18 (t, J=7.2Hz, 1H), 5.82 (t, J=8.8Hz, 1H), 5.37 (d, J=6.9Hz, 1H), 5.15 (s, 2H), 5.10–4.99 (m, 2H), 4.95 (d, J=9.8Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.40 (p, J=7.1Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J=10.2, 6.8Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H) ), 2.78–2.59(m, 1H), 2.46–2.37(m, 4H), 2.24(s, 3H), 1.82(d, J=14.6Hz, 4H), 1.61–1.43(m, 5H), 1.40–1.24(m, 12H), 0.98(d, J=7.1Hz, 6H).

[0793] Example 24 Synthesis of Compound 24

[0794] Reference Example 23: Synthesis of Compound 23: Using oxalyl chloride instead of succinic anhydride, Compound 24 (100 mg, yield: 37%, HPLC purity: 94.03%) was obtained.

[0795] MS:

[0796] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 12.10 (s, 1H), 10.18 (s, 1H), 8.72 (d, J = 7.5Hz, 1H), 7.95 (dd, J = 20.3, 8.2Hz, 3H), 7.73 (t, J = 7.3Hz, 1H), 7.64 (dd, J=11.3, 8.2Hz, 4H), 7.46–7.32 (m, 6H), 7.18 (t, J=7.3Hz, 1H), 5.82 (t, J=8.8Hz, 1H), 5.37 (d, J=7.0Hz, 1H), 5.15 (s, 2H), 5.10–4.99 (m, 2H), 3.22( s, 3H), 2.72–2.60 (m, 1H), 2.24 (s, 3H), 1.82 (d, J=15.0Hz, 4H), 1.60–1.45 (m, 5H), 1.41 (d, J=7.0Hz, 3H), 1.34 (s, 9H), 0.97 (d, J=6.4Hz, 6H).

[0797] Example 25 Synthesis of Compound 25

[0798] Reference Example 23: Synthesis of Compound 23, wherein diglycolic anhydride was used instead of succinic anhydride to obtain Compound 25 (0.34 g, yield: 61.27%, HPLC: 95.771%).

[0799] MS:1172.4830[M+H + ]

[0800] 1H NMR (400MHz, DMSO) δ (ppm) 12.73 (s, 1H), 10.17 (s, 1H), 8.20 (d, J = 5.4Hz, 1H), 7.95 (dd, J = 19.8, 8.2Hz, 3H), 7.73 (t, J = 7.2Hz, 1H), 7.65 (dd, J = 7.7 , 4.1Hz, 4H), 7.42 (t, J=7.5Hz, 2H), 7.35 (d, J=8.5Hz, 4H), 7.18 (t, J=7.2 Hz, 1H), 5.82 (t, J=8.9Hz, 1H), 5.37 (d, J=6.9Hz, 1H), 5.15 (s, 2H), 5.09– 4.99 (m, 2H), 4.95 (d, J=9.8Hz, 1H), 4.70 (s, 1H), 4.50 (t, J=7.1Hz, 2H), 4 .12 (s, 2H), 4.03 (s, 4H), 3.75 (dd, J=10.1, 6.8Hz, 1H), 3.59 (d, J=6.8Hz, 1H), 3.32(s, 2H), 3.22(s, 3H), 2.67(t, J=14.9Hz, 1H), 2.25(s, 3H), 1.80 (s, 4H), 1.58–1.46 (m, 6H), 1.40 (s, 1H), 1.35 (s, 11H), 1.00–0.95 (m, 6H).

[0801] Example 26 Synthesis of Compound 26

[0802] Reference Example 23: Synthesis of Compound 23, wherein glutaric anhydride was used instead of succinic anhydride to obtain Compound 26 (200 mg, yield: 36%, HPLC purity: 98.17%).

[0803] MS: 1170.5096[M+H + ]

[0804] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 12.02 (s, 1H), 10.07 (s, 1H), 8.14 (d, J = 7.1Hz, 1H), 7.95 (dd, J = 21.3, 8.1Hz, 3H), 7.73 (t, J = 7.3Hz, 1H), 7.64 (dd, J=10.1, 8.3Hz, 4H), 7.42 (t, J=7.6Hz, 2H), 7.39–7.27 (m, 4H), 7.18 (t, J=7.2Hz, 1H), 5.82 (t, J=8.8Hz, 1H), 5.37 (d, J=7.0Hz, 1H), 5.15 (s, 2H ), 5.10–4.92(m, 3H), 4.70(s, 1H), 4.50(s, 1H), 4.40(p, J=7.0Hz, 1H), 4.02(s, 2H), 3.76(dd, J=10.3, 6.7Hz, 1H), 3.59(d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.73–2.61 (m, 1H), 2.26–2.15 (m, 7H), 1.85–1.67 (m, 6H), 1.60–1.44 (m, 5H), 1.39–1.25 (m, 12H), 0.98 (d, J=7.1Hz, 6H).

[0805] Example 27 Synthesis of Compound 27

[0806] 27b:

[0807] At 0-10°C, under nitrogen, DIC (8.05 g, 63.8 mmol) was added dropwise to a solution of Boc-glycine methyl ester hydrochloride (10.10 g, 58.0 mmol) and HOBt (8.62 g, 63.8 mmol) in dichloromethane (100 ml), and the mixture was stirred for 30 minutes. 27a (8.00 g, 63.8 mmol) was added to a solution of dichloromethane (100 ml), and the pH was adjusted to 9-10 with triethylamine at 0-10°C under nitrogen. The mixture was stirred for 5 minutes, filtered, and the filtrate was added dropwise to the Boc-glycine reaction solution. The mixture was stirred at 20-25°C for 60 minutes. The reaction solution was washed with 0.3 mol / L hydrochloric acid (200 ml), 50% sodium bicarbonate solution (200 ml), and saturated sodium chloride (200 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [V PE / V EA =1:1] separation and purification gave 11.80 g of a light yellow oily substance with a yield of 83%.

[0808] 27c:

[0809] Lithium hydroxide monohydrate (3.12 g, 44.7 mmol) was dissolved in water (20 ml) at 0°C and added dropwise to a solution of 27b (5.50 g, 22.3 mmol) in tetrahydrofuran (30 ml). The reaction was stirred at 15-25°C for 1 hour. The reaction solution was cooled to 0-5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2-3. Ethyl acetate (100 ml) was added for extraction. The upper organic phase was collected, washed with saturated brine (60 ml), and dried over anhydrous sodium sulfate. The resulting solid was 4.30 g (yield: 83%).

[0810] 27e:

[0811] At 0-10°C, under nitrogen protection, DIC (8.05 g, 63.8 mmol) was added dropwise to a solution of 27d (10.00 g, 25.8 mmol) and HOBt (3.84 g, 28.4 mmol) in dichloromethane (100 ml), and the mixture was stirred and heated for 30 minutes. Glycine methyl ester hydrochloride (3.56 g, 28.4 mmol) was added to a dichloromethane (40 ml) solution, and the pH value was adjusted to 9-10 with triethylamine under nitrogen protection at 0-10°C. After stirring for 5 minutes, the mixture was filtered and the filtrate was added dropwise to the Fmoc phenylalanine reaction solution. The mixture was stirred at 20-25°C for 60 minutes. The reaction solution was washed with 50% sodium bicarbonate solution (200 ml) and saturated sodium chloride (100 ml×2), dried over anhydrous sodium sulfate, and concentrated. The residue was slurried with petroleum ether (100 ml) and separated and purified to obtain 11.0 g of a light yellow oil with a yield of 93%.

[0812] 27f:

[0813] 27e (11.00 g, 23.99 mmol) was dissolved in N,N-dimethylformamide (50 mL), cooled to 0-10°C, and diethylamine (15 mL) was added dropwise under nitrogen. The mixture was stirred at 0-10°C for 1 hour. 6N hydrochloric acid was added dropwise to adjust the pH to 4-5. Water (100 mL) was added and stirred for 10 minutes. The mixture was filtered and the filtrate was collected and washed with methyl tert-butyl ether (100 mL x 2). The pH was adjusted to 8-9 with solid sodium bicarbonate. The mixture was extracted with dichloromethane (100 mL x 2). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to give 5.67 g of a colorless oil (yield: 100%).

[0814] 27g:

[0815] At 0-10°C, under nitrogen protection, DIC (2.80 g, 22.2 mmol) was added dropwise to a solution of 27d (4.30 g, 18.5 mmol) and HOBt (3.00 g, 22.2 mmol) in dichloromethane (25 ml) / N,N-dimethylformamide (5 mL), and the mixture was stirred at 10-15°C for 30 minutes. 27f (5.11 g, 16.2 mmol) was dissolved in dichloromethane (25 ml) and added dropwise to the reaction mixture of 27-M2, and the mixture was stirred at 10-15°C for 30 minutes. The reaction mixture was washed with 50% sodium bicarbonate solution (30 ml × 2) and saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [V DCM / V MeOH =20:1] separation and purification gave 6.30 g of a white solid with a yield of 75%.

[0816] 27h:

[0817] Lithium hydroxide monohydrate (186 mg, 4.44 mmol) was dissolved in water (5 ml) at 0-10°C and added dropwise to a solution of 27 g (1.00 g, 2.22 mmol) in tetrahydrofuran (10 ml). The mixture was stirred at 15-25°C for 1 hour. The reaction solution was cooled to 0-5°C and the pH was adjusted to 2-3 by dropwise addition of 6N hydrochloric acid. Ethyl acetate (50 ml) was added for extraction. The upper organic phase was collected, washed with saturated brine (30 ml), and dried over anhydrous sodium sulfate. The resulting white foamy solid (500 mg) was concentrated to yield 52%.

[0818] 27i:

[0819] At room temperature, EEDQ (567 mg, 2.29 mmol) and p-aminobenzyl alcohol (148 mg, 1.20 mmol) were added to a solution of 27h (500 mg, 1.15 mmol) in dichloromethane (20 ml) / methanol (2 ml) in sequence, and the mixture was stirred at room temperature for 16 hours. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeOH =12:1] separation and purification gave 540 mg of a white solid with a yield of 87%.

[0820] Synthesis of 27:

[0821] At 0-5°C, under nitrogen protection, 27i (150 mg, 0.28 mmol) was dissolved in dichloromethane (10 ml) / N,N-dimethylformamide (1 mL). Under nitrogen protection, 1j (277 mg, 0.28 mmol) and N,N-dimethylpyridine (37 mg, 0.33 mmol) were added in sequence. The mixture was stirred at 15-25°C for 3 hours. Dichloromethane (50 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (30 ml × 2) and saturated sodium chloride aqueous solution (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =24:1] separation and purification gave 210 mg of a white solid with a yield of 54% and a HPLC purity of 99.720%.

[0822] MS:1403.6128[M+H + ]

[0823] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 9.93 (s, 1H), 8.42 (s, 1H), 8.19 (s, 1H), 7.95 (d, J = 18.3Hz, 4H), 7.69 (d, J = 31.6Hz, 5 H), 7.31 (dd, J=67.3, 25.3Hz, 12H), 6.98 (s, 1H), 5.79 (d, J=26.4Hz, 1H), 5.37 (s, 1H), 5.15 (s, 2H), 5.02 (d, J=41. 7Hz, 3H), 4.70 (s, 1H), 4.50 (s, 2H), 4.15–3.73 (m, 6H), 3.60 (d, J=33.6Hz, 4H), 3.30–3.26 (s, 3H), 3.22 (s, 3H), 3. 08(d, J=10.2Hz, 1H), 2.88–2.76(m, 1H), 2.67(s, 1H), 2.25(s, 3H), 1.80(s, 4H), 1.61–1.13(m, 23H), 0.98(s, 6H).

[0824] Example 28 Synthesis of Compound 28

[0825] 28b:

[0826] Trifluoroacetic acid (6 ml) was added dropwise to a solution of 27 g (1.50 g, 3.33 mmol) in dichloromethane (6 ml) at 0-10°C under nitrogen. The mixture was stirred at 25-30°C for 60 minutes. The mixture was concentrated, and dichloromethane (30 ml x 2) was added to the residue, followed by concentration to afford 1.16 g of a light yellow oil (yield: 100%).

[0827] 28c:

[0828] At 0-10°C, under nitrogen protection, DIC (464 mg, 3.67 mmol) was added dropwise to a solution of pivalic acid (375 mg, 3.67 mmol) and HOBt (496 mg, 3.67 mmol) in dichloromethane (30 ml), and the mixture was stirred and heated for 30 minutes. 28b (1.16 g, 3.34 mmol) was added to a solution of dichloromethane (30 ml), and the pH was adjusted to 9-10 with triethylamine under nitrogen protection at 0-10°C. The mixture was stirred for 5 minutes, filtered, and the filtrate was added dropwise to the pivalic acid reaction solution. The mixture was stirred and reacted for 30 minutes at 20-25°C. The reaction solution was washed with 50% sodium bicarbonate solution (50 ml) and saturated sodium chloride (50 ml × 2), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [V DCM / V MeOH =20:1] separation and purification gave 520 mg of a white solid, yield: 36%.

[0829] 28d:

[0830] Lithium hydroxide monohydrate (100 mg, 2.39 mmol) was dissolved in water (3 ml) at 0-10°C and added dropwise to a solution of 28c (520 mg, 1.20 mmol) in tetrahydrofuran (6 ml). The reaction was stirred at 15-25°C for 1 hour. The reaction solution was cooled to 0-5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2-3. Ethyl acetate (50 ml) was added for extraction. The upper organic phase was collected, washed with saturated brine (30 ml), and dried over anhydrous sodium sulfate. The resultant solution was concentrated to a white foamy solid (420 mg, yield: 83%).

[0831] 28e:

[0832] At room temperature, EEDQ (494 mg, 2.00 mmol) and p-aminobenzyl alcohol (129 mg, 1.05 mmol) were added to a solution of 28d (420 mg, 1.00 mmol) in dichloromethane (15 ml) / methanol (1.5 ml) in sequence and stirred at room temperature for 1 hour. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeOH =15:1] separation and purification gave 330 mg of a white solid, yield: 63%.

[0833] Synthesis of 28

[0834] At 0-5°C, under nitrogen protection, 28-M7 (150 mg, 0.28 mmol) was dissolved in dichloromethane (10 ml) / N, N-dimethylformamide (1 mL). Under nitrogen protection, 1j (285 mg, 0.28 mmol) and N, N-dimethylpyridine (38 mg, 0.31 mmol) were added in sequence. The mixture was stirred at 15-25°C for 3 hours. Dichloromethane (50 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (30 ml × 2) and saturated sodium chloride aqueous solution (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =24:1] separation and purification gave 220 mg of a white solid with a yield of 55% and a HPLC purity of 99.61%.

[0835] HRMS: 1387.6291[M+H + ]

[0836] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 9.92 (s, 1H), 8.38 (t, J = 5.7Hz, 1H), 8.19 (d, J = 8.0Hz , 1H), 8.03–7.85 (m, 4H), 7.79–7.69 (m, 2H), 7.69–7.58 (m, 4H), 7.42 (t, J=7.5Hz, 2 H), 7.35 (d, J=8.1Hz, 4H), 7.26 (d, J=4.3Hz, 4H), 7.23–7.13 (m, 2H), 5.82 (t, J=8.6 Hz, 1H), 5.37 (d, J=6.9Hz, 1H), 5.15 (s, 2H), 5.11–4.99 (m, 2H), 4.95 (d, J=9.7Hz, 1H ), 4.70 (s, 1H), 4.57–4.42 (m, 2H), 4.02 (s, 2H), 3.90 (d, J = 3.6Hz, 2H), 3.82–3.72 ( m, 2H), 3.63 (ddd, J=15.4, 8.6, 3.9Hz, 4H), 3.29 (s, 3H), 3.22 (s, 3H), 3.09 (dd, J=13 .8, 4.3Hz, 1H), 2.90–2.81 (m, 1H), 2.68 (d, J=13.0Hz, 1H), 2.25 (s, 3H), 1.80 (s, 4H ), 1.61–1.44(m, 5H), 1.35(s, 8H), 1.24(s, 1H), 1.11(s, 9H), 0.98(d, J=6.8Hz, 6H).

[0837] Example 29 Synthesis of Compound 29

[0838] Referring to the synthesis of compound 23 in Example 23, N-Fmoc-L-alanine was replaced with N-Fmoc-L-alanine to obtain compound 29 (170 mg, yield: 48%, HPLC purity: 95.80%).

[0839] MS: 1142.4742[M+H + ]

[0840] 1 H NMR (400 MHz, DMSO-d6) 1 H NMR (400MHz, DMSO) δ (ppm) 12.10 (s, 1H), 9.93 (s, 1H), 8.25 (t, J=5.8Hz, 1H), 7.95 (dd, J=21.3, 8.2Hz, 3H), 7.73 (t, J=7.3Hz, 1H), 7.64 (dd, J=13.2, 8.1H z, 4H), 7.42 (t, J=7.6Hz, 2H), 7.39–7.31 (m, 4H), 7.18 (t, J=7.2Hz, 1H), 5.8 2(t, J=8.8Hz, 1H), 5.37(d, J=6.9Hz, 1H), 5.15(s, 2H), 5.10–4.99(m, 2H), 4. 95 (d, J=9.5Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.88 (d, J=5.8H z, 2H), 3.75 (dd, J=10.2, 6.7Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3H), 3.2 2(s, 3H), 2.66 (dd, J=18.1, 11.8Hz, 1H), 2.44 (dd, J=11.1, 5.8Hz, 4H), 2.24 (s, 3H), 1.80 (s, 4H), 1.58–1.46 (m, 5H), 1.35 (s, 9H), 0.98 (d, J=6.9Hz, 6H).

[0841] Example 30 Synthesis of Compound 30

[0842] Referring to the synthesis of compound 23 in Example 23, N-Fmoc-L-phenylalanine was used to replace N-Fmoc-L-alanine to obtain compound 30 (130 mg, yield: 60%, HPLC purity: 96.97%).

[0843] MS:1232.5266[M+H + ]

[0844] 1 H NMR (400 MHz, DMSO-d6)1 H NMR (400MHz, DMSO) δ (ppm) 11.87 (s, 1H), 10.10 (s, 1H), 8.31 (d, J = 8.1Hz, 1H), 7 .95 (dd, J=22.1, 8.2Hz, 3H), 7.73 (t, J=7.2Hz, 1H), 7.64 (dd, J=18.0, 8.0Hz, 4H ), 7.42 (t, J=7.5Hz, 2H), 7.35 (t, J=7.4Hz, 4H), 7.26 (dd, J=7.6, 5.6Hz, 4H), 7. 22–7.13 (m, 2H), 5.82 (t, J=8.7Hz, 1H), 5.37 (d, J=6.9Hz, 1H), 5.15 (s, 2H), 5.11 –4.91(m, 3H), 4.71(s, 1H), 4.65(dd, J=14.0, 8.5Hz, 1H), 4.50(s, 1H), 4.02(s, 2H), 3.81–3.72(m, 1H), 3.59(d, J=6.6Hz, 1H), 3.29(s, 3H), 3.22(s, 3H), 3.05(d d, J=13.7, 5.4Hz, 1H), 2.87 (dd, J=13.7, 9.4Hz, 1H), 2.73–2.61 (m, 1H), 2.42–2 .19(m, 7H), 1.81(s, 4H), 1.58–1.42(m, 5H), 1.35(s, 9H), 0.98(d, J=7.3Hz, 6H).

[0845] Example 31 Synthesis of Compound 31

[0846] Referring to the synthesis of compound 23 in Example 23, N-Fmoc-L-phenylalanine was used to replace N-Fmoc-L-alanine, and oxalyl chloride was used to replace succinic anhydride to obtain compound 31 (60 mg, yield: 56%, HPLC purity: 93.17%).

[0847] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 12.10 (s, 1H), 10.26 (s, 1H), 8.63 (d, J = 8.3Hz, 1H), 7.95 (dd, J = 22.0, 8.2Hz, 3H), 7.73 (t, J = 7.3Hz, 1H), 7.64 (t, J = 7. 5. 15(s, 2H), 5.10–4.98(m, 2H), 4.95(d, J=9.7Hz, 1H), 4.75–4.65(m, 2H), 4.49 (s, 1H), 4.01 (s, 2H), 3.80–3.71 (m, 1H), 3.59 (d, J=6.7Hz, 1H), 3.28 (s, 3H), 3.21 (s, 3H), 3.11 (d, J = 7.8Hz, 2H), 2.73–2.60 (m, 1H), 2.24 (s, 3H), 1.80 (s, 4H), 1.59–1.45 (m, 5H), 1.34 (s, 9H), 0.97 (d, J=6.2Hz, 6H).

[0848] Example 32 Synthesis of Compound 32

[0849] Referring to the synthesis of compound 23 in Example 23, N-Fmoc-L-valine was used to replace N-Fmoc-L-alanine to obtain compound 32 (300 mg, yield: 74%, HPLC purity: 97.53%).

[0850] MS:1184.5182[M+H + ]

[0851] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 12.07 (s, 1H), 10.11 (s, 1H), 8.06 (d, J = 8.6Hz, 1H), 7 .98 (d, J=7.3Hz, 2H), 7.92 (d, J=9.0Hz, 1H), 7.73 (t, J=7.3Hz, 1H), 7.65 (dd, J=7 .6, 5.6Hz, 4H), 7.42 (t, J=7.6Hz, 2H), 7.39–7.26 (m, 4H), 7.18 (t, J=7.2Hz, 1H), 5.82(t, J=8.9Hz, 1H), 5.36(t, J=8.9Hz, 1H), 5.15(s, 2H), 5.10–4.99(m, 2H), 4. 95 (d, J=9.9Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.30 (t, J=8.0Hz, 1H), 4.02 (s, 2 H), 3.75 (dd, J=10.3, 6.7Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H ), 2.72–2.61 (m, 1H), 2.47–2.39 (m, 4H), 2.24 (s, 3H), 2.03 (dd, J=13.6, 6.8Hz, 1 H), 1.82 (d, J=13.5Hz, 4H), 1.58–1.43 (m, 5H), 1.34 (s, 9H), 1.03–0.85 (m, 12H).

[0852] Example 33 Synthesis of Compound 33

[0853] Referring to the synthesis of compound 23 in Example 23, N-Fmoc-L-leucine was used instead of N-Fmoc-L-alanine to obtain compound 33 (320 mg, yield: 79%, HPLC purity: 97.17%).

[0854] MS: 1198.5364[M+H + ]

[0855] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 12.09 (s, 1H), 10.03 (s, 1H), 8.16 (d, J = 7.9Hz, 1H), 7.95 (dd, J = 22.3, 8.2Hz, 3H), 7.77–7.62 (m, 5H), 7.39 (dt, J = 14. 5, 8.0Hz, 6H), 7.18 (t, J=7.1Hz, 1H), 5.82 (t, J=8.9Hz, 1H), 5.38 (d, J=6 .9Hz, 1H), 5.15(s, 2H), 5.12–4.91(m, 3H), 4.71(s, 1H), 4.56–4.39(m, 2 H), 4.02 (s, 2H), 3.76 (dd, J=10.1, 6.8Hz, 1H), 3.59 (d, J=6.8Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (dd, J=17.9, 11.7Hz, 1H), 2.46–2.39 (m, 4H ), 2.25 (s, 3H), 1.82 (d, J = 13.8Hz, 4H), 1.71–1.58 (m, 2H), 1.55–1.45 (m, 6H), 1.35 (s, 9H), 0.98 (d, J = 6.8Hz, 6H), 0.90 (dd, J = 15.3, 6.5Hz, 6H).

[0856] Example 34 Synthesis of Compound 34

[0857] 34b:

[0858] p-Aminobenzyl alcohol (1.21 g, 9.79 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (4.84 g, 19.6 mmol) were added to a solution of 34a (1.00 g, 9.79 mmol) in dichloromethane (20 mL) and stirred at room temperature for 2 h. The reaction solution was concentrated and purified by silica gel column chromatography (V PE :V EA =1:1) separation and purification gave 1.50 g of a light yellow solid with a yield of 74%.

[0859] 34:

[0860] 34b (125 mg, 0.60 mmol) was dissolved in dichloromethane (8 mL). 4-Dimethylaminopyridine (81 mg, 0.66 mmol) and PNP-CBTX (1j) (603 mg, 0.60 mmol) were added at 0-5°C under nitrogen protection. The mixture was stirred at 20-25°C for 1.5 hours. Dichloromethane (20 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (20 ml × 2) and saturated sodium chloride aqueous solution (20 ml), respectively. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed by concentration under reduced pressure. The residue was purified by silica gel column chromatography [V PE / V EA =2:1] separation and purification gave 480 mg of a white solid with a yield of 74% and a HPLC purity of 99.28%.

[0861] HR-MS: 1069.5667[M+H + ]

[0862] 1 H NMR (400 MHz, DMSO-d6) 1 H NMR (400MHz, DMSO) δ (ppm) 9.95 (s, 1H), 8.03–7.87 (m, 3H), 7.73 (t, J = 7.3Hz, 1 H), 7.64 (dd, J=15.9, 8.1Hz, 4H), 7.42 (t, J=7.6Hz, 2H), 7.34 (dd, J=13.4, 8.0 Hz, 4H), 7.18 (t, J=7.3Hz, 1H), 5.82 (t, J=8.7Hz, 1H), 5.37 (d, J=7.0Hz, 1H), 5 .14(s, 2H), 5.10–4.92(m, 3H), 4.70(s, 1H), 4.50(s, 1H), 4.02(s, 2H), 3.75(d d, J=10.4, 6.7Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.71– 2.59(m, 1H), 2.31(t, J=7.4Hz, 2H), 2.24(d, J=7.4Hz, 3H), 1.85–1.72(m, 4H), 1.58 (dd, J=14.9, 7.4Hz, 2H), 1.49 (d, J=17.1Hz, 4H), 1.35 (s, 9H), 1.29 (dd, J =15.3, 6.9Hz, 2H), 1.24 (s, 1H), 0.99 (t, J = 9.4Hz, 6H), 0.90 (t, J = 7.3Hz, 3H).

[0863] Example 35 Synthesis of Compound 35

[0864] Reference Example 34: Synthesis of Compound 34: Using 4-fluorobenzoic acid instead of valeric acid to obtain Compound 35 (410 mg, yield: 82%, HPLC purity: 98.60%).

[0865] MS:1135.5671[M+H + ]

[0866] 1 H NMR (400 MHz, DMSO-d6) 1 H NMR (400MHz, DMSO) δ (ppm) 9.99 (s, 1H), 7.98 (d, J = 7.3Hz, 2H), 7.92 (d, J = 9.0Hz, 1H), 7.73 (t, J = 7.3Hz, 1H), 7.69–7.57 (m, 4H), 7.42 (t, J = 7.6Hz, 2H), 7.39–7.26 (m, 6H), 7.18 (t, J=7.2Hz, 1H), 7.10 (ddd, J=8.9, 5.9, 2.5Hz, 2H) , 5.82 (t, J=8.8Hz, 1H), 5.37 (d, J=7.1Hz, 1H), 5.13 (s, 2H), 5.08 (d, J=8.0H z, 1H), 5.05–4.99 (m, 1H), 4.95 (d, J=9.8Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.76 (dd, J=10.4, 6.7Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3 H), 3.22 (s, 3H), 2.90 (t, J=7.6Hz, 2H), 2.63 (dd, J=17.4, 9.5Hz, 3H), 2.24 ( s, 3H), 1.80 (s, 4H), 1.59–1.44 (m, 5H), 1.35 (s, 9H), 0.98 (d, J=6.5Hz, 6H).

[0867] Example 36 Synthesis of Compound 36

[0868] Reference Example 34: Synthesis of Compound 34: Using trifluoroacetic acid instead of valeric acid to obtain Compound 36 (0.42 g, yield: 85.1%, HPLC purity: 98.621%).

[0869] LC-MS: 1081.4994 [M+H + ]

[0870] 1H NMR (400MHz, DMSOd-6) δ11.33 (s, 1H), 9.72 (s, 1H), 8.10–7.83 (m, 3H), 7.72 (dd, J=13.7, 7.9Hz, 2H), 7.65 (t, J=7.5Hz, 2H), 7.55–7.39 (m, 4H), 7 .33 (dd, J=18.5, 7.6Hz, 3H), 7.18 (t, J=6.9Hz, 1H), 5.81 (s, 1H), 5.37 (d, J=6.8Hz, 1H), 5.20 (s, 1H), 5.11 (d, J=8.7Hz, 1H), 5.06 (dd, J=12.6, 7.3 Hz, 1H), 4.95 (d, J=9.5Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.07–3.96 (m, 2H), 3.83–3.68(m, 1H), 3.59(d, J=6.9Hz, 1H), 3.29(d, J=1.3Hz, 3H), 3. 22(d, J=1.6Hz, 3H), 2.67(s, 1H), 2.24(s, 3H), 1.81(d, J=23.3Hz, 4H), 1 .64–1.44(m, 5H), 1.35(s, 8H), 1.26–1.22(m, 2H), 0.97(d, J=6.4Hz, 6H).

[0871] Example 37 Synthesis of Compound 37

[0872] Reference Example 34: Synthesis of Compound 34: Using acetic anhydride instead of valeric acid to obtain Compound 37 (0.42 g, yield: 75.1%, HPLC purity: 97.678%).

[0873] LC-MS: 1027.5267 [M+H + ]

[0874] 1H NMR (400MHz, DMSOd-6) δ10.01 (s, 1H), 7.95 (dd, J=21.0, 8.2Hz, 3H), 7.73 (t, J=7.1Hz, 1H), 7.69–7.55 (m, 4H), 7.42 (t, J=7.5Hz, 2H), 7 .39–7.27 (m, 4H), 7.18 (t, J=7.0Hz, 1H), 5.82 (t, J=8.5Hz, 1H), 5.37 (d, J=6.9Hz, 1H), 5.14 (s, 2H), 5.10–4.92 (m, 3H), 4.70 (s, 1H), 4.5 0 (s, 1H), 4.02 (s, 1H), 3.75 (dd, J=9.8, 6.8Hz, 1H), 3.59 (d, J=6.7Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.66 (dd, J=19.1, 10.4Hz, 1H), 2.2 4 (s, 3H), 2.05 (s, 3H), 1.81 (d, J = 20.1Hz, 4H), 1.59–1.44 (m, 5H), 1.32 (d, J = 19.3Hz, 8H), 1.25 (d, J = 9.5Hz, 2H), 0.98 (d, J = 6.2Hz, 6H).

[0875] Example 38 Synthesis of Compound 38

[0876] Reference Example 34: Synthesis of Compound 34: Using 4-fluorobenzoic acid instead of valeric acid to obtain Compound 38 (280 mg, yield: 62%, HPLC purity: 98.09%).

[0877] MS:1107.5308[M+H + ]

[0878] 1 H NMR (400 MHz, DMSO-d6) 1 H NMR (400 MHz, DMSO) δ (ppm) 1H NMR (400MHz, DMSO) δ10.34 (s, 1H), 8.04 (dd, J=8.9, 5.5Hz, 2H), 7.99–7.93 (m, 3H), 7.79 (s, 2H), 7.73 (t, J=7.4Hz, 1H), 7.64 (dd, J=1 4.6, 7.4Hz, 2H), 7.46–7.28 (m, 8H), 7.18 (t, J=7.3Hz, 1H), 5.82 (t, J=8.9Hz, 1H), 5.37 (d, J=7.0Hz, 1H), 5.18 (s, 2H), 5.12–4.99 (m, 2H), 4.96 (d, J=9.7Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.76 (dd, J=10.2, 6.7Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.28 (s, 3H) , 3.22 (s, 3H), 2.66 (dd, J=12.9, 6.9Hz, 1H), 2.25 (s, 3H), 1.86–1.71 (m, 4H), 1.59–1.45 (m, 5H), 1.35 (s, 9H), 0.98 (d, J=7.3Hz, 6H).

[0879] Example 39 Synthesis of Compound 39

[0880] Reference Example 34: Synthesis of Compound 34: Using di-tert-butyl dicarbonate instead of valeric acid to obtain Compound 39 (250 mg, yield: 47%, HPLC purity: 97.52%).

[0881] MS:1085.5689[M+H + ]

[0882] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 9.44 (s, 1H), 7.95 (dd, J=20.5, 8.1Hz, 3H), 7.72 (d, J=7.7Hz, 1H), 7.64 (dd, J=14.2, 7.0Hz, 2H), 7.48 (d, J=8.5Hz, 2H), 7. 42(t, J=7.6Hz, 2H), 7.36(t, J=6.0Hz, 2H), 7.30(t, J=7.8Hz, 2H), 7.21–7. 16 (m, 1H), 5.81 (t, J=8.7Hz, 1H), 5.37 (d, J=6.6Hz, 1H), 5.11 (s, 2H), 5.07 (d, J=8.0Hz, 1H), 5.05–4.99 (m, 1H), 4.96 (d, J=9.4Hz, 1H), 4.70 (s, 1H), 4.02 (s, 2H), 3.75 (dd, J=10.4, 6.7Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3H), 3.22(s, 3H), 2.73–2.61(m, 1H), 2.24(s, 3H), 1.78(s, 4H), 1.51(d, J= 4.6Hz, 4H), 1.48 (s, 9H), 1.35 (s, 9H), 1.24 (s, 2H), 0.97 (d, J=6.3Hz, 6H).

[0883] Example 40 Synthesis of Compound 40

[0884] Reference Example 34: Synthesis of Compound 34: Using octanoic acid instead of pentanoic acid to obtain Compound 40 (0.48 g, yield: 86.5%, HPLC: 97.997%).

[0885] MS:1111.6170[M+H + ]

[0886] 1H NMR (400MHz, DMSO-d6) δ (ppm) 9.94 (s, 1H), 7.95 (dd, J = 22.5, 8.1Hz, 3H), 7.73 (t , J=7.3Hz, 1H), 7.66 (d, J=7.7Hz, 2H), 7.62 (d, J=8.6Hz, 2H), 7.41 (d, J=7.4Hz, 2 H), 7.34 (dd, J=13.5, 8.1Hz, 4H), 7.18 (t, J=7.2Hz, 1H), 5.82 (t, J=8.8Hz, 1H), 5 .37 (d, J=7.0Hz, 1H), 5.14 (s, 2H), 5.08 (d, J=8.0Hz, 1H), 5.02 (t, J=8.4Hz, 1H), 4.95 (d, J=9.8Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 1H), 3.75 (dd, J=10.4, 6.7Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.72–2.62 (m, 1H), 2.30(t, J=7.4Hz, 2H), 2.24(s, 3H), 1.79(s, 3H), 1.61–1.56(m, 2H), 1.51(s, 4H) , 1.35 (s, 9H), 1.32–1.20 (m, 11H), 0.98 (d, J = 6.4Hz, 6H), 0.86 (t, J = 6.9Hz, 3H).

[0887] Example 41 Synthesis of Compound 41

[0888] Reference Example 34: Synthesis of Compound 34: Using acetic anhydride instead of valeric acid, and using 2-aminobenzyl alcohol instead of p-aminobenzyl alcohol, Compound 41 (0.22 g, yield: 42.88%, HPLC: 99.114%) was obtained.

[0889] LC-MS: 1027.5243 [M+H + ]

[0890] 1H NMR (400MHz, DMSO) δ9.60 (s, 1H), 7.96 (dd, J=14.9, 8.2Hz, 3H), 7.73 (t, J=7.2Hz, 1H), 7.65 (t, J=7.5Hz, 2H), 7.46–7.41 (m, 3H) , 7.35 (t, J = 7.4Hz, 4H), 7.21 (dt, J = 14.4, 7.3Hz, 2H), 5.84 (t, J = 8.6Hz, 1H), 5.37 (d, J = 6.9Hz, 1H), 5.20 (s, 2H), 5.11–5.02 (m, 2H), 4.95 (d, J=9.4Hz, 1H), 4.70 (s, 1H), 4.49 (s, 1H), 4.02 (s, 2H), 3.75 (dd, J=10.2, 6.8Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s , 3H), 3.22(s, 3H), 2.70–2.61(m, 1H), 2.25(s, 3H), 2.06(s, 3H), 1.80(s, 4H), 1.51(s, 4H), 1.35(s, 9H), 0.98(d, J=7.6Hz, 6H).

[0891] Example 42 Synthesis of Compound 42

[0892] Reference Example 34: Synthesis of Compound 34: Using di-tert-butyl dicarbonate instead of valeric acid, and using 2-aminobenzyl alcohol instead of p-aminobenzyl alcohol, to obtain Compound 42 (320 mg, yield: 69%, HPLC purity: 98.62%).

[0893] HR-MS: 1085.5679[M+H + ]

[0894] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 8.80 (s, 1H), 7.96 (dd, J = 19.4, 8.0Hz, 3H), 7.73 (t, J = 7.3Hz, 1H), 7.65 (t, J = 7.5Hz, 2H), 7.46–7.30 ( m, 7H), 7.19 (dt, J=11.3, 5.5Hz, 2H), 5.85 (t, J=8.7Hz, 1H), 5.38 (d, J=7.0Hz, 1H), 5.23 (q, J=13.0Hz, 2H), 5.12–5.01 (m, 2H), 4. 95 (d, J=9.6Hz, 1H), 4.69 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.75 (dd, J=10.3, 6.7Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3.29 (s, 3H), 3. 21 (s, 3H), 2.66 (dt, J=9.4, 8.0Hz, 1H), 2.25 (s, 3H), 1.80 (s, 4H), 1.51 (s, 5H), 1.46 (s, 9H), 1.35 (s, 9H), 0.98 (d, J=8.6Hz, 6H).

[0895] Example 43 Synthesis of Compound 43

[0896] Reference Example 34: Synthesis of Compound 34: Using di-tert-butyl dicarbonate instead of valeric acid, and using 3-amino-4-methoxybenzyl alcohol instead of p-aminobenzyl alcohol to obtain Compound 43 (390 mg, yield: 73%, HPLC purity: 96.69%).

[0897] MS:1115.5066[M+H + ]

[0898] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 8.02–7.88 (m, 4H), 7.81 (s, 1H), 7.73 (t, J = 7.3Hz, 1H), 7.65 (t, J = 7.5Hz, 2H), 7.42 (t, J = 7.6Hz, 2H), 7.35 (d, J = 7.5Hz, 2H), 7.18 (t, J=7.2Hz, 1H), 7.07 (dd, J=8.3, 1.8Hz, 1H), 7.01 (d, J=8.4Hz, 1H), 5.83 (t, J=8.8Hz, 1H), 5.38 (d, J=7.0Hz, 1H), 5.11 (s , 2H), 5.09–4.99 (m, 2H), 4.95 (d, J=10.0Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.85–3.73 (m, 4H), 3.60 (d, J=7.0Hz, 1H), 3.29 (s , 3H), 3.22(s, 3H), 2.74–2.61(m, 1H), 2.25(s, 3H), 1.87–1.74(m, 4H), 1.62–1.48(m, 5H), 1.46(s, 9H), 1.34(s, 9H), 0.98(d, J=7.2Hz, 6H).

[0899] Example 44 Synthesis of Compound 44

[0900] Reference Example 34: Synthesis of Compound 34: Using di-tert-butyl dicarbonate instead of valeric acid, and using 4-amino-3-methoxybenzyl alcohol instead of 34a, to give Compound 44 (0.36 g, yield: 80.78%, HPLC: 99.479%).

[0901] MS: 1115.4948[M+H + ]

[0902] 1H NMR (400MHz, DMSO) δ7.96 (dd, J=17.4, 7.3Hz, 4H), 7.76–7.70 (m, 2H), 7.65 (t , J=7.5Hz, 2H), 7.43 (t, J=7.5Hz, 2H), 7.36 (d, J=7.4Hz, 2H), 7.18 (t, J=7.2Hz , 1H), 7.04 (s, 1H), 6.94 (d, J=8.2Hz, 1H), 5.82 (t, J=8.8Hz, 1H), 5.37 (d, J=6 .9Hz, 1H), 5.16 (t, J=9.6Hz, 2H), 5.11–5.07 (m, 1H), 5.06–5.00 (m, 1H), 4.95 ( d, J=9.5Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.82 (s, 3H), 3.75 (d d, J=10.2, 6.7Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.66 ( dd, J=17.9, 11.9Hz, 1H), 2.25(s, 3H), 1.99(s, 1H), 1.85–1.75(m, 4H), 1.56(d , J=9.5Hz, 1H), 1.51 (s, 3H), 1.46 (s, 9H), 1.35 (s, 9H), 0.98 (d, J=6.7Hz, 6H).

[0903] Example 45 Synthesis of Compound 45

[0904] Cabazitaxel (0.4 g, 0.48 mmol) was dissolved in dichloromethane (4 ml) and cooled to 5°C under a nitrogen atmosphere. 4-Dimethylaminopyridine (12 mg, 0.1 mmol) and N,N-diisopropylethylamine (0.19 g, 1.44 mmol) were added, and a 1.5 ml dichloromethane solution of benzyl chloroformate (0.16 g, 0.96 mmol) was added dropwise. The mixture was stirred at room temperature for 10 minutes. Dichloromethane (40 ml) was added, and the mixture was washed twice with 5% aqueous citric acid (10 ml), washed with saturated sodium chloride (20 ml), dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 45 as a white solid (0.42 g, yield: 90%, HPLC purity: 96.793%).

[0905] LC-MS: 970.5028 [M+H + ]

[0906] 1H NMR (400MHz, DMSOd-6) δ7.98 (d, J=7.3Hz, 2H), 7.93 (d, J=9.0Hz, 1H), 7.72 (d, J=7.3Hz, 1H), 7.64 (t, J=7.5Hz, 2H), 7.46–7. 34 (m, 9H), 7.19 (t, J = 7.2Hz, 1H), 5.83 (t, J = 8.8Hz, 1H), 5.38 (d, J = 7.1Hz, 1H), 5.22 (s, 2H), 5.12–5.01 (m, 2H), 4.95 (d, J = 9. 6Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.00 (s, 1H), 3.75 (dd, J=10.4, 6.7Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.75–2.61(m, 1H), 2.25(s, 3H), 1.86–1.76(m, 4H), 1.61–1.46(m, 5H), 1.35(s, 8H), 1.24(s, 2H), 0.98(d, J=7.1Hz, 6H).

[0907] Example 46 Synthesis of Compound 46

[0908] 4-Methoxybenzyl alcohol (62 mg, 0.45 mmol) was dissolved in dichloromethane (6 mL). PNP-CBTX (450 mg, 0.45 mmol) and 4-dimethylaminopyridine (61 mg, 0.49 mmol) were added at 0-5°C under nitrogen protection. The mixture was stirred at 20-25°C for 1.5 hours. Dichloromethane (20 ml) was added to the reaction solution, and the mixture was washed with 0.5N hydrochloric acid (15 ml) and saturated sodium chloride aqueous solution (15 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V PE / V EA =2:1] separation and purification gave 300 mg of a white solid with a yield of 66% and a HPLC purity of 96.72%.

[0909] MS:1000.5115[M+H + ]

[0910] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 7.95 (dd, J=25.5, 8.1Hz, 3H), 7.73 (t, J=7.3Hz, 1H), 7.65 (t, J=7.5Hz, 2H), 7.42 (t, J=7.6Hz, 2H), 7.39–7. 31 (m, 4H), 7.18 (t, J = 7.2Hz, 1H), 6.96 (d, J = 8.7Hz, 2H), 5.83 (t, J = 8.7Hz, 1H), 5.38 (d, J = 7.0Hz, 1H), 5.13 (s, 2H), 5.09–4.99 (m, 2H) , 4.96 (d, J = 9.6Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.80–3.71 (m, 4H), 3.59 (d, J = 7.0Hz, 1H), 3.30 (s, 3H), 3.22 (s, 3H), 2 .67 (ddd, J=15.6, 9.5, 6.5Hz, 1H), 2.25 (s, 3H), 1.80 (s, 4H), 1.49 (d, J=16.6Hz, 4H), 1.34 (s, 9H), 1.24 (s, 1H), 0.98 (d, J=6.4Hz, 6H).

[0911] Example 47 Synthesis of Compound 47

[0912] Reference Example 46: Synthesis of Compound 46: Using 2-methoxybenzyl alcohol instead of 4-methoxybenzyl alcohol to obtain Compound 47 (0.32 g, yield: 80%, HPLC purity: 99.013%).

[0913] LC-MS: 1000.4451 [M+H + ]

[0914] 1H NMR (400MHz, DMSOd-6) δ7.96 (dd, J=21.3, 8.2Hz, 3H), 7.73 (t, J=7.3Hz, 1H), 7.64 (t, J=7.5Hz, 2H), 7.46–7.31 (m, 6H), 7.19 (t, J=7.2Hz, 1H), 7.07 (d, J=8.2Hz, 1H), 6.97 (t, J=7.4Hz, 1H), 5.84 (t, J=8.7Hz, 1H), 5.38 (d, J=7.0Hz, 1H), 5.18 (s, 2H), 5.10–4.99 (m, 2H), 4.96 (d, J=9.6Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.02 (s, 1H), 3.81 (s, 3H), 3.76 (dd, J=10.4, 6.7Hz, 1H), 3.60 (d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.75 –2.60 (m, 1H), 2.26 (s, 3H), 1.82 (s, 4H), 1.61–1.53 (m, 1H), 1.51 (s, 3H), 1.32 (d, J = 18.7Hz, 9H), 1.25 (d, J = 9.5Hz, 2H), 0.98 (d, J = 7.9Hz, 6H).

[0915] Example 48 Synthesis of Compound 48

[0916] Reference Example 46: Synthesis of Compound 46: Using 3-methoxybenzyl alcohol instead of 4-methoxybenzyl alcohol to obtain Compound 48 (400 mg, yield: 89%, HPLC purity: 98.22%).

[0917] HR-MS: 1000.4426 [M+H + ]

[0918] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 7.96 (dd, J=16.4, 8.2Hz, 3H), 7.73 (t, J=7.3Hz, 1H), 7.65 (t, J=7.5Hz, 2H), 7.43 (t, J=7.6Hz, 2H), 7. 39–7.29 (m, 3H), 7.19 (t, J=7.2Hz, 1H), 6.95 (dd, J=10.4, 2.5Hz, 3H), 5.83 (t, J=8.8Hz, 1H), 5.38 (d, J=7.0Hz, 1H), 5.24–5.14 (m , 2H), 5.13–5.01 (m, 2H), 4.95 (d, J=9.7Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.77 (s, 4H), 3.59 (d, J=6.8Hz, 1H), 3.2 9(s, 3H), 3.22(s, 3H), 2.72–2.61(m, 1H), 2.25(s, 3H), 1.79(s, 4H), 1.49(m, 5H), 1.30(d, J=48.0Hz, 9H), 0.98(d, J=7.0Hz, 6H).

[0919] Example 49 Synthesis of Compound 49

[0920] Reference Example 46: Synthesis of Compound 46: Using 4-methoxybenzylamine instead of 4-methoxybenzyl alcohol to obtain Compound 49 (400 mg, yield: 88%, HPLC purity: 98.19%).

[0921] MS: 999.4600[M+H + ]

[0922] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 7.97 (d, J = 7.2Hz, 3H), 7.82–7.71 (m, 2H), 7.66 (t, J = 7.4Hz, 2H), 7.41 (t, J = 7.6Hz, 2H), 7.33 (d, J = 7.4Hz, 2H) ), 7.15 (dd, J=18.6, 7.9Hz, 3H), 6.87 (d, J=8.6Hz, 2H), 5.76 (t, J=8.7Hz, 1H), 5.35 (d, J=7.2Hz, 1H), 5.07 (d, J=8.5Hz, 1H), 4.94 (d, J=1 0.1Hz, 2H), 4.68 (s, 1H), 4.42 (s, 1H), 4.12 (d, J=6.1Hz, 2H), 4.01 (s, 2H), 3.77–3.71 (m, 4H), 3.56 (d, J=7.1Hz, 1H), 3.28 (s, 3H), 3.20 ( s, 3H), 2.65 (ddd, J=15.7, 9.5, 6.3Hz, 1H), 2.24 (s, 3H), 1.84–1.70 (m, 4H), 1.47 (m, 5H), 1.30 (d, J=50.0Hz, 9H), 0.96 (d, J=7.3Hz, 6H).

[0923] Example 50 Synthesis of Compound 50

[0924] Reference Example 23: Synthesis of Compound 23: Using 3-aminobenzyl alcohol instead of p-aminobenzyl alcohol to obtain Compound 50 (100 mg, yield: 32%, HPLC purity: 98.46%).

[0925] MS:1156.6531[M+H + ]

[0926] 1H NMR (400MHz, DMSO) δ (ppm) 12.07 (s, 1H), 9.98 (s, 1H), 8.20 (d, J = 7.1Hz, 1H), 7.9 6(dd, J=18.4, 8.2Hz, 3H), 7.78–7.69(m, 2H), 7.65(t, J=7.5Hz, 2H), 7.59(d, J=8 .1Hz, 1H), 7.38 (ddd, J=15.7, 13.9, 7.8Hz, 5H), 7.18 (t, J=7.1Hz, 1H), 7.08 (d, J =7.5Hz, 1H), 5.84 (t, J = 8.8Hz, 1H), 5.38 (d, J = 7.0Hz, 1H), 5.17 (s, 2H), 5.13–5. 00 (m, 2H), 4.96 (d, J = 9.8Hz, 1H), 4.70 (s, 1H), 4.51 (s, 1H), 4.39 (p, J = 7.0Hz, 1H ), 4.03 (d, J=7.8Hz, 2H), 3.75 (dd, J=10.2, 6.7Hz, 1H), 3.59 (d, J=6.9Hz, 1H), 3. 29(s, 3H), 3.22(s, 3H), 2.73–2.60(m, 1H), 2.48–2.36(m, 4H), 2.25(s, 3H), 1.83 (d, J=18.7Hz, 4H), 1.61–1.43 (m, 5H), 1.40–1.24 (m, 12H), 0.98 (d, J=7.9Hz, 6H).

[0927] Example 51 Synthesis of Compound 51

[0928] 51b:

[0929] Referring to the synthesis of 1j in Example 1, docetaxel was used instead of cabazitaxel to obtain 51b (1.00 g, yield: 41%).

[0930] Synthesis of 51

[0931] By using the synthesis of compound 10 in reference example 10, CBTX-PNP was replaced by 51b, and 10e was replaced by 51c (prepared by using diethylamine instead of morpholine in the synthesis of intermediate 10e in reference example 10) to obtain compound 51 (220 mg, yield: 46%, HPLC purity: 96.26%).

[0932] MS: 1207.6[M-2OH - ]

[0933] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.09 (s, 1H), 8.31 (d, J = 6.9Hz, 1H), 8.25 (d, J = 8.6Hz, 1H ), 7.98 (d, J = 7.3Hz, 2H), 7.91 (d, J = 9.1Hz, 1H), 7.73 (t, J = 7.3Hz, 1H), 7.64 (t, J = 7.8Hz , 4H), 7.42 (t, J=7.6Hz, 2H), 7.39–7.24 (m, 4H), 7.17 (t, J=7.2Hz, 1H), 5.79 (d, J=8.8Hz , 1H), 5.40 (m, 1H), 5.23–5.04 (m, 4H), 5.02 (dd, J=11.8, 4.8Hz, 2H), 4.92 (dd, J=11.1, 6 .4Hz, 2H), 4.40 (dd, J=14.4, 7.3Hz, 2H), 4.23 (dd, J=8.5, 6.7Hz, 1H), 4.14–3.92 (m, 3H) , 3.64(d, J=7.0Hz, 1H), 3.21(s, 2H), 3.05(s, 4H), 2.68(s, 2H), 2.34–2.15(m, 4H), 2.00 (dq, J=13.3, 6.7Hz, 1H), 1.82 (dd, J=15.3, 9.3Hz, 1H), 1.75–1.60 (m, 4H), 1.52 (s, 4H), 1.33 (d, J=10.0Hz, 11H), 1.24 (s, 1H), 1.18 (t, J=7.2Hz, 6H), 0.98 (s, 6H), 0.91 (s, 6H).

[0934] Example 52 Synthesis of Compound 52

[0935] Referring to the synthesis of compound 8 in Example 8, 51b was used to replace 1j to obtain compound 52 (160 mg, yield: 19%, HPLC purity: 96.94%).

[0936] MS:1297.6132[M+H + ]

[0937] 1H NMR (400MHz, DMSO-d6) δ10.10 (s, 1H), 7.98 (td, J=32.2, 7.9Hz, 4H), 7.78–7.59 (m, 5H), 7.37 (dd, J=28.1, 7.3Hz, 6H), 7.14 (dd, J=19.0, 7.6Hz, 2H), 5.97 (s, 1H), 5.78 (s, 1H), 5.41 (s, 3H), 5.23–4.85 (m, 8H), 4.48–4.33 (m, 2H), 4.17 (t, J=7.9Hz, 1H ), 4.03 (d, J=8.6Hz, 3H), 3.64 (d, J=6.5Hz, 1H), 3.08–2.91 (m, 2H), 2.24 (s, 4H), 2.05 (dd, J=13.2, 6.4Hz, 1H), 1.81 (d, J=9. 5Hz, 1H), 1.77–1.57 (m, 6H), 1.52 (s, 4H), 1.29 (d, J=41.7Hz, 11H), 1.13 (s, 9H), 0.99 (s, 6H), 0.85 (dd, J=15.2, 6.4Hz, 6H).

[0938] Example 53 Synthesis of Compound 53

[0939] Reference Example 34: Synthesis of Compound 34, using di-tert-butyl dicarbonate instead of valeric acid, and using 51b instead of CBTX-PNP to obtain 53 (0.22 g, yield: 67.5%, HPLC purity: 96.41%).

[0940] MS: 1057.4618[M+H + ]

[0941] 1H NMR (400MHz, DMSO) δ (ppm) 9.44 (s, 1H), 7.99 (d, J = 7.2Hz, 2H), 7.91 (d, J = 8.8Hz, 1H), 7.71 (d, J = 6.9Hz, 1H), 7.64 (t, J = 7.1Hz, 2H) , 7.48 (d, J = 8.1Hz, 2H), 7.44–7.39 (m, 2H), 7.35 (d, J = 7.0Hz, 2H), 7.28 (d, J = 8.1Hz, 2H), 7.17 (t, J = 6.7Hz, 1H), 5.78 (s, 1H), 5.40 ( d, J=6.7Hz, 1H), 5.15–5.07 (m, 4H), 5.05–4.98 (m, 2H), 4.91 (d, J=10.3Hz, 2H), 4.43 (s, 1H), 4.03 (d, J=8.9Hz, 3H), 3.65 (d, J=6.4 Hz, 1H), 2.25 (s, 3H), 1.89–1.79 (m, 1H), 1.73 (s, 3H), 1.64 (d, J=12.5Hz, 2H), 1.52 (s, 4H), 1.48 (s, 9H), 1.34 (s, 9H), 0.99 (s, 6H).

[0942] Example 54 Synthesis of Compound 54

[0943] Reference Example 46: Synthesis of Compound 46, replacing 4-methoxybenzyl alcohol with 2-methoxybenzyl alcohol, and replacing CBTX-PNP with 51b to obtain 54 (0.17 g, yield: 42%, HPLC purity: 95.24%).

[0944] MS: 972.4084[M+H + ]

[0945] 1H NMR (400MHz, DMSO) δ (ppm) 7.99 (d, J = 7.3Hz, 2H), 7.91 (d, J = 9.1Hz, 1H), 7.72 (t, J=7.3Hz, 1H), 7.63 (t, J=7.5Hz, 2H), 7.41 (dt, J=7.3, 6.6Hz, 3H), 7.36 (d, J=7.9Hz, 2H), 7.31 (d, J=7.4Hz, 1H), 7.18 (t, J=7.1Hz, 1H), 7.06 (d, J=8.2Hz, 1H), 6.97 (t, J=7.4Hz, 1H), 5.80 (t, J=8.9Hz, 1H), 5.41 (d, J=7.2Hz, 1H), 5.19 (s, 2H), 5.10 (d, J=7.7Hz, 2H), 5.03 (dd, J=15.9, 8.0Hz, 2H), 4.92 (t, J=8.2H z, 2H), 4.43 (s, 1H), 4.09–3.99 (m, 3H), 3.81 (s, 3H), 3.65 (d, J=7.0Hz, 1H), 2. 33–2.26 (m, 1H), 2.25 (s, 3H), 1.85 (dd, J=15.3, 9.3Hz, 1H), 1.72 (s, 3H), 1.64 (d, J=12.0Hz, 1H), 1.59–1.53(m, 1H), 1.52(s, 3H), 1.34(s, 9H), 0.99(s, 6H).

[0946] Example 55 Synthesis of Compound 55

[0947] The synthesis of 46 in reference example 46 was carried out by replacing CBTX-PNP with 51b to give 55 (100 mg, yield: 22%, HPLC purity: 95.32%).

[0948] MS: 972.3974[M+H] +

[0949] 1 H NMR (400 MHz, DMSO-d6) 1H NMR (400MHz, DMSO) δ (ppm) 7.99 (d, J = 7.3Hz, 2H), 7.90 (d, J = 9.1Hz, 1H), 7.72 (t, J = 7.3Hz, 1H), 7.64 (t, J = 7.5Hz, 2H), 7.41 ( t, J=7.6Hz, 2H), 7.38–7.27 (m, 4H), 7.17 (t, J=7.2Hz, 1H), 6.95 (d, J=8.6Hz, 2H), 5.78 (dd, J=15.2, 6.4Hz, 1H), 5.41 (d, J=7. 1Hz, 1H), 5.19–5.06 (m, 4H), 5.06–4.97 (m, 2H), 4.97–4.87 (m, 2H), 4.43 (s, 1H), 4.11–3.97 (m, 3H), 3.76 (s, 3H), 3.65 (d, J=7 .1Hz, 1H), 2.33–2.20 (m, 4H), 1.84 (dd, J=15.2, 9.5Hz, 1H), 1.76–1.61 (m, 4H), 1.58–1.45 (m, 4H), 1.34 (s, 9H), 0.99 (s, 6H).

[0950] Example 56 Synthesis of Compound 56

[0951] 56b:

[0952] Referring to the synthesis of 1j in Example 1, paclitaxel was used instead of cabazitaxel to obtain 56b (2.22 g, yield: 92%).

[0953] Synthesis of 56

[0954] Referring to the synthesis of compound 8 in Example 8, 56b was used to replace 1j to obtain compound 56 (380 mg, yield: 44%, HPLC purity: 95.75%).

[0955] MS: 1343.5960[M+H] +

[0956] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.00 (d, J = 76.1Hz, 1H), 9.26 (d, J = 8.5Hz, 1H), 8.22 (dd, J=127.8, 7.6Hz, 1H), 8.02–7.95 (m, 2H), 7.87–7.76 (m, 2H), 7.79–7.52 (m, 6H) , 7.52–7.38(m, 6H), 7.31(d, J=8.6Hz, 2H), 7.30–7.08(m, 2H), 6.32(s, 1H), 5.96(d d, J=10.7, 5.5Hz, 1H), 5.84 (t, J=8.9Hz, 1H), 5.54 (t, J=8.6Hz, 1H), 5.47–5.33 (m, 4H), 5.14(s, 2H), 4.97–4.87(m, 2H), 4.65(s, 1H), 4.46–4.33(m, 1H), 4.20–4.13(m , 1H), 4.02 (s, 2H), 3.60 (d, J=7.1Hz, 1H), 3.09–2.89 (m, 2H), 2.39–2.22 (m, 4H), 2. 12(d, J=1.0Hz, 3H), 2.04(dt, J=14.3, 7.1Hz, 1H), 1.90–1.69(m, 5H), 1.71–1.30(m , 9H), 1.12 (d, J=3.9Hz, 9H), 1.03 (d, J=10.9Hz, 6H), 0.86 (dt, J=15.1, 6.7Hz, 6H).

[0957] Example 57 Synthesis of Compound 57

[0958] 57-M1

[0959] 57-M0 (2.00 g, 5.03 mmol) was dissolved in a mixture of methanol (10 mL) and dichloromethane (20 mL). Under nitrogen protection, 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (2.24 g, 9.06 mmol) was added at 0-5°C, followed by a solution of o-aminobenzyl alcohol (0.929 g, 7.55 mmol) in dichloromethane (20 mL) and the mixture was allowed to react at room temperature for 4 h. After the reaction, methyl tert-butyl ether (40 mL) was added dropwise to the reaction mixture, stirred at room temperature for 30 minutes, and filtered under reduced pressure. The filter cake was rinsed with methyl tert-butyl ether (20 mL), collected, and concentrated under reduced pressure. Methanol (20 ml) was added to the crude product at room temperature and stirred for 30 minutes. Dichloromethane (20 ml) was then added dropwise and stirred for 30 minutes. Finally, methyl tert-butyl ether (40 ml) was added dropwise and stirred for 30 minutes. The mixture was filtered under reduced pressure, and the filter cake was rinsed with methyl tert-butyl ether (20 ml). The filter cake was collected and concentrated under reduced pressure to obtain 2.0 g of the product 57-M1 as a white solid in a yield of 79%.

[0960] 57-M2

[0961] At 0-5°C under nitrogen protection, PNP-CBTX (4.43 g, 4.43 mmol) and 4-dimethylaminopyridine (594 mg, 4.87 mmol) were added to a solution of compound 57-M1 (1.2 g, 3.98 mmol) in N,N-dimethylacetamide (40 mL) and stirred at -10°C for 16 hours. After the reaction, the reaction solution was quenched by adding hydrochloric acid (0.15N, 40 ml) dropwise and extracted with ethyl acetate (80 ml × 2). The organic phases were combined, washed with saturated sodium chloride aqueous solution (60 ml × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =20:1] The product 57-M2 was separated and purified as an off-white solid (2.9 g). The yield was 48%.

[0962] 57-M3

[0963] At room temperature, compound 57-M2 (2.9 g, 2.13 mmol) was dissolved in acetonitrile (58 ml) under nitrogen protection. Piperidine (542 mg, 6.38 mmol) was added dropwise at 0-5°C. After the addition was complete, the temperature was raised to 20°C and stirred for 4 hours. After the reaction was completed, hydrochloric acid (0.15 N, 40 ml) was added dropwise to quench the reaction solution, and ethyl acetate (80 ml × 2) was added for extraction. The organic phases were combined, washed with saturated sodium chloride aqueous solution (60 ml × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeoH=3:1] The product 57-M3 was separated and purified as an off-white solid (1.2 g). The yield was 49%.

[0964] 57-M4

[0965] At room temperature, Fmoc-L-valine (392 mg, 1.16 mmol) was dissolved in N, N-dimethylacetamide (8 mL) and protected with nitrogen. At 0°C, N, N-diisopropylethylamine (176 mg, 1.37 mmol) and HATU (442 mg, 1.16 mmol) were added in sequence. Stirred at 0°C for 10 minutes, a solution of compound 57-M3 (1.2 g, 1.05 mmol) in N, N-dimethylacetamide (8 mL) was added dropwise. Stirred at 10°C for 2 hours. After the reaction was completed, hydrochloric acid (0.15 N, 25 ml) was added dropwise to quench the reaction solution, and ethyl acetate (60 ml × 2) was added for extraction. The organic phases were combined, washed with a saturated sodium chloride aqueous solution (40 ml × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DDM / V MeOH =16:1] The product 57-M4 was separated and purified as an off-white solid (1.2 g). The yield was 78%.

[0966] 57-M5

[0967] At room temperature, 57-M4 (1.2 g, 0.82 mmol) was dissolved in acetonitrile (6 ml) / N, N-dimethylacetamide (6 mL) under nitrogen protection. Piperidine (209 mg, 2.46 mmol) was added dropwise at 0-5 ° C. After the addition was complete, the temperature was raised to 10 ° C. and stirred for 4 hours. After the reaction was completed, the reaction solution was quenched by adding hydrochloric acid (0.15N, 20 ml) dropwise, and ethyl acetate (40 ml × 2) was added for extraction. The organic phases were combined, washed with saturated sodium chloride aqueous solution (20 ml × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =2:1] The product 57-M5 was separated and purified to obtain 800 mg of an off-white solid in a yield of 78%.

[0968] Compound 57

[0969] At room temperature, compound 57-M5 (800 mg, 0.64 mmol) was dissolved in dichloromethane (12 ml) under nitrogen protection. Triethylamine (110 mg, 1.1 mmol) and pivalic anhydride (180 mg, 0.97 mmol) were added dropwise at 0-5°C, and the temperature was raised to 10°C with stirring for 3 hours. After the reaction was completed, the reaction solution was quenched by adding hydrochloric acid (0.1 N, 20 ml) dropwise, and dichloromethane (60 ml) was added. The organic phase was separated, washed with saturated sodium chloride aqueous solution (20 ml × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =17:1] The product compound 57 was separated and purified to obtain 600 mg of off-white solid with a yield of 70% and a purity of 97.96%.

[0970] MS (ESI): 1325.6[M+1] +

[0971] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 9.81 (s, 1H), 8.16 (d, J = 7.2Hz, 1H), 8.03-7.98 (m, 3H), 7.75 ( t, J=7.3Hz, 1H), 7.67 (t, J=7.5Hz, 2H), 7.46 (t, J=7.5Hz, 2H), 7.42-7.33 (m, 6H), 7.32-7.24 (m, 1H), 7.24-7.13 (m, 2H), 5.99 (t, J=5.7Hz, 1H), 5.86 (t, J=9.1Hz, 1H), 5.40 (d, J=16.6Hz , 3H), 5.18 (s, 2H), 5.17-5.03 (m, 2H), 4.97 (d, J=9.4Hz, 1H), 4.70 (s, 1H), 4.53 (s, 1H), 4.45 (q, J=7.2Hz, 1H), 4.20 (t, J=8.2Hz, 1H), 4.04 (s, 2H), 3.79-3.73 (m, 1H), 3.60 (d, J=7.0Hz, 1H), 3.30 (s, 3H), 3.04 (h, J=6.9Hz, 2H), 2.72-2.62 (m, 1H), 2.27 (s, 3H), 2.06 (dt, J=13.9, 7 .0Hz, 1H), 1.80 (s, 4H), 1.62 (dd, J=24.6, 9.4Hz, 2H), 1.52 (s, 5H), 1.37 (s, 9H), 1.22 (d, J=6 .3Hz, 1H), 1.13 (s, 9H), 1.00 (d, J=8.5Hz, 6H), 0.88 (d, J=6.7Hz, 3H), 0.84 (d, J=6.6Hz, 3H).

[0972] Example 58 Synthesis of Compound 58

[0973] -5~0 ℃, nitrogen protection, stirring and dissolving, triethylamine (153mg, 1.50mmol) was added to a dichloromethane (6mL) solution of 6f (621mg, 0.50mmol), p-toluenesulfonyl chloride (143mg, 0.75mmol) in dichloromethane (2mL) was added dropwise, and the mixture was stirred at -5 ℃ for 2h. Dichloromethane (25ml) was added to dilute the reaction solution, and water (30ml) was added to quench the reaction. The liquid was separated, and the lower organic phase was taken. The organic phase was washed with saturated sodium bicarbonate aqueous solution (30ml) and saturated sodium chloride (30mlx2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =50:1] separation and purification gave 300 mg of a white solid with a yield of 43% and a HPLC purity of 99.03%.

[0974] MS (ESI): 1395.5934[M+1] +

[0975] 1H-NMR (400MHz, DMSO-d6) δ (ppm) 10.04 (s, 1H), 8.11 (d, J = 7.4Hz, 1H), 7.98 (d, J = 7.6Hz, 2 H), 7.92 (d, J=8.9Hz, 1H), 7.73 (t, J=7.3Hz, 1H), 7.68-7.59 (m, 7H), 7.42 (t, J=7.6Hz, 2H ), 7.37-7.29 (m, 6H), 7.18 (t, J = 7.3Hz, 1H), 5.97 (t, J = 5.9Hz, 1H), 5.82 (t, J = 9.3Hz, 1H) , 5.44 (s, 2H), 5.37 (d, J = 7.0Hz, 1H), 5.14 (s, 2H), 5.08-4.99 (m, 2H), 4.95 (d, J = 9.6Hz, 1 H), 4.70 (s, 1H), 4.50 (s, 1H), 4.11 (q, J=7.4Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J=10.4, 6.6H z, 1H), 3.59 (d, J=6.7Hz, 2H), 3.28 (s, 3H), 3.22 (s, 3H), 2.93 (dp, J=26.9, 6.6Hz, 2H), 2. 66 (s, 1H), 2.34 (s, 3H), 2.24 (s, 3H), 1.82 (d, J = 11.8Hz, 5H), 1.52 (d, J = 8.6Hz, 7H), 1.34 (s, 9H), 1.24 (s, 2H), 0.97 (d, J = 6.5Hz, 6H), 0.82 (d, J = 6.7Hz, 3H), 0.79 (d, J = 6.7Hz, 3H).

[0976] Example 59 Synthesis of Compound 59

[0977] 59-M1:

[0978] At room temperature, 59-M0 (5g, 29.56mmol) was dissolved in tetrahydrofuran (100ml) under nitrogen protection. Lithium aluminum hydride (2.24g, 59.12mmol) was added in batches at 0°C. After the addition was complete, the temperature was raised to 50°C and stirred for 5 hours. After the reaction was completed, the reaction mixture was cooled to 0°C and ice water was slowly added dropwise until no obvious bubbles were generated in the reaction solution. The reaction solution was filtered and the filter cake was washed with ethyl acetate (100ml). The filtrate was diluted with ethyl acetate (100ml), and the organic phase was washed with saturated sodium chloride aqueous solution (100ml×2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography [V PE / V EA =1:1] The product 59-M1 was separated and purified as a light brown solid (2.5 g). The yield was 59%.

[0979] Compound 59:

[0980] Reference Example 57: Synthesis of Compound 57, using 59-M1 to replace o-aminobenzyl alcohol to obtain the product Compound 59 (off-white solid 900 mg, yield: 84%; purity: 98.70%).

[0981] MS (ESI): 1343.9[M+1] +

[0982] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 10.36 (s, 1H), 8.15 (d, J = 7.2Hz, 1H), 8.01–7.98 (m, 2H), 7.95 (d, J = 9.1 Hz, 1H), 7.75 (t, J=7.4Hz, 1H), 7.69–7.64 (m, 3H), 7.44 (t, J=7.8Hz, 4H), 7.37 (d, J=7.1Hz, 3H), 7.19 ( t, J=7.4Hz, 1H), 7.13 (d, J=8.7Hz, 1H), 6.00 (t, J=5.8Hz, 1H), 5.84 (t, J=9.1Hz, 1H), 5.45 (s, 2H), 5.3 9 (d, J=7.0Hz, 1H), 5.20 (s, 2H), 5.09 (d, J=7.9Hz, 1H), 5.03 (t, J=8.4Hz, 1H), 4.97 (d, J=9.6Hz, 1H), 4 .72(s, 1H), 4.53(s, 1H), 4.39(q, J=7.1Hz, 1H), 4.18(t, J=8.1Hz, 1H), 4.03(d, J=2.1Hz, 2H), 3.81–3. 73 (m, 1H), 3.60 (d, J=7.0Hz, 1H), 3.31 (s, 3H), 3.02 (dh, J=26.8, 6.7Hz, 2H), 2.68 (s, 1H), 2.26 (s, 3H) , 2.07(dt, J=13.8, 6.8Hz, 1H), 1.83(s, 4H), 1.74–1.56(m, 3H), 1.52(s, 3H), 1.48–1.39(m, 2H), 1.35( s, 9H), 1.22 (s, 1H), 1.14 (s, 9H), 0.99 (d, J = 7.2Hz, 6H), 0.89 (d, J = 6.7Hz, 3H), 0.85 (d, J = 6.6Hz, 3H).

[0983] Example 60 Synthesis of Compound 60

[0984] 60d:

[0985] Reference Example 1 Synthesis of Compound 1d using D-guanidine Replacing la gives compound 60d.

[0986] Referring to the synthesis of compound 8 in Example 8, 60d was substituted for 1d to give compound 60 (white solid 1.7 g, yield: 88%).

[0987] MS (ESI): 1326.6 [M+2H] +

[0988] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 9.91 (s, 1H), 8.41 (d, J = 8.0Hz, 1H), 8.04–7.91 (m, 3H), 7.73 ( dd, J=7.8, 5.1Hz, 3H), 7.65 (t, J=7.5Hz, 2H), 7.43 (t, J=7.6Hz, 2H), 7.34 (dt, J=7.9, 5.6Hz, 5H), 7.18 (t, J=7.3Hz, 1H), 5.97 (t, J=5.8Hz, 1H), 5.82 (t, J=9.2Hz, 1H), 5.42 (s, 2H), 5.37 (d, J=7.0Hz, 1H), 5.15 (d, J=2.8Hz, 2H), 5.07 (d, J=7.9Hz, 1H), 5.02 (t, J=8.4Hz, 1H), 4.95 ( d, J=9.7Hz, 1H), 4.70 (s, 1H), 4.51 (s, 1H), 4.38 (s, 1H), 4.07 (t, J=8.0Hz, 1H), 4.02 (s, 2H) , 3.75 (t, J=8.6Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.98 (dp, J=19.8, 6 .7Hz, 2H), 2.72–2.62(m, 1H), 2.25(s, 3H), 2.03(td, J=13.1, 12.2, 6.1Hz, 1H), 1.80(s, 5H) , 1.51 (s, 8H), 1.35 (s, 9H), 1.12 (s, 9H), 0.97 (d, J = 6.7Hz, 6H), 0.87 (dd, J = 8.2, 6.7Hz, 6H).

[0989] Example 61 Synthesis of Compound 61

[0990] 61d:

[0991] Reference Example 1 Synthesis of Compound 1d using D-guanidine Substitution of 1a for Boc-L-valine with Boc-D-valine gave 61d.

[0992] Compound 61:

[0993] Referring to the synthesis of compound 8 in Example 8, 61d was substituted for 1d to give compound 61 (white solid 580 mg, yield: 91%).

[0994] MS (ESI): 1325.7[M+1] +

[0995] 1 H NMR (400MHz, DMSO-d6) δ (ppm) 10.12 (s, 1H), 8.08 (d, J = 7.3Hz, 1H), 8.01–7.89 (m, 3H), 7.73 ( t, J=7.3Hz, 1H), 7.69–7.59 (m, 4H), 7.43 (t, J=7.6Hz, 2H), 7.35 (dd, J=8.0, 4.1Hz, 4H), 7.16 (dd, J=20.1, 8.0Hz, 2H), 5.98 (t, J=5.9Hz, 1H), 5.82 (t, J=9.2Hz, 1H), 5.43 (s, 2H), 5.37 (d, J=7.1Hz, 1H), 5.15 (s, 2H), 5.10–4.92 (m, 3H), 4.71 (s, 1H), 4.52 (s, 1H), 4.40 (q, J=7.5, 7.0H z, 1H), 4.17 (t, J=8.1Hz, 1H), 4.02 (s, 2H), 3.75 (t, J=8.7Hz, 1H), 3.59 (d, J=7.0Hz, 1H), 3.2 9(s, 3H), 3.22(s, 3H), 2.99(dp, J=27.2, 6.6Hz, 2H), 2.72–2.62(m, 1H), 2.25(s, 3H), 2.05(h, J=6.7Hz, 1H), 1.81 (s, 4H), 1.68 (q, J=6.8, 5.9Hz, 1H), 1.65–1.54 (m, 2H), 1.51 (s, 4H), 1.47 –1.38(m, 2H), 1.35(s, 9H), 1.12(s, 9H), 0.98(d, J=6.8Hz, 6H), 0.85(dd, J=15.3, 6.7Hz, 6H).

[0996] Example 62 Synthesis of Compound 62

[0997] 62b

[0998] Fmoc-L-phenylalanine (5.00 g, 12.91 mmol) was dissolved in methanol (10 ml) and dichloromethane (100 ml), p-aminobenzyl alcohol (2.07 g, 16.78 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (6.38 g, 25.81 mmol) were added, and the mixture was stirred at room temperature for 2.0 hours. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography [V DCM / V MeOH =60:1] to separate 62b as a white solid (4.50 g, yield: 71%).

[0999] 62c

[1000] 62b (1.00 g, 2.03 mmol) was dissolved in acetonitrile (12 ml) by stirring, cooled to 5°C, and piperidine (519 mg, 6.09 mmol) in acetonitrile (3 ml) was added dropwise. The mixture was stirred and reacted for 5 hours. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography [V DCM / V MeOH =12:1] to isolate colorless oil 62c (500 mg, yield: 91%).

[1001] 62d

[1002] 62c (500 mg, 1.85 mmol) was dissolved in dichloromethane (5 ml) by stirring, triethylamine (562 mg, 5.55 mmol) was added, the temperature was lowered to 0°C, a solution of p-toluenesulfonyl chloride (335 mg, 1.76 mmol) in dichloromethane (3 ml) was added dropwise, and the mixture was stirred and reacted for 1 hour. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography [V DCM / V MeOH =60:1] to isolate 62d as a white solid (320 mg, yield: 41%).

[1003] Compound 62

[1004] At -10-0°C under nitrogen protection, 62d (212 mg, 0.50 mmol) and 51b (591 mg, 0.60 mmol) were added to N,N-dimethylacetamide (6.0 mL) and stirred to dissolve. The temperature was lowered to -10°C and 4-dimethylaminopyridine (122.02 mg, 1.0 mmol) was added. The reaction was stirred at -10°C for 20 h. Ethyl acetate (25 ml) and water (30 ml) were added to the reaction solution to quench the reaction. The organic phase was washed twice with saturated sodium chloride solution (30 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH=50:1] was separated and purified to obtain compound 62 (white solid 120 mg, yield: 19%, HPLC purity: 98.89%).

[1005] MS (ESI): 1258.4711[M+1] +

[1006] 1 H-NMR (400 MHz, DMSO-d6) 1 H NMR (400MHz, DMSO) δ (ppm) 10.03 (s, 1H), 8.26 (s, 1H), 8.08–8.01 (m, 2H), 7.97 ( d, J=9.1Hz, 1H), 7.78 (t, J=7.3Hz, 1H), 7.70 (t, J=7.6Hz, 2H), 7.58–7.52 (m, 2H) , 7.48 (t, J=7.5Hz, 2H), 7.44–7.36 (m, 4H), 7.34 (d, J=8.5Hz, 2H), 7.25 (tdd, J= 15.0, 6.6, 4.6Hz, 7H), 7.18 (s, 1H), 5.85 (t, J=9.1Hz, 1H), 5.47 (d, J=7.2Hz, 1H) , 5.25–5.12 (m, 4H), 5.08 (t, J=8.6Hz, 2H), 5.02–4.93 (m, 2H), 4.49 (s, 1H), 4.1 5 (dd, J=19.5, 7.3Hz, 2H), 4.08 (d, J=2.3Hz, 1H), 3.71 (d, J=7.1Hz, 1H), 2.97 (dd , J=13.6, 6.1Hz, 1H), 2.81 (dd, J=13.6, 8.8Hz, 1H), 2.35 (d, J=7.6Hz, 1H), 2.31 (s, 3H), 2.27 (s, 3H), 1.97–1.64 (m, 6H), 1.58 (s, 4H), 1.40 (s, 9H), 1.05 (s, 6H).

[1007] Example 63 Synthesis of Compound 63

[1008] 63-M2

[1009] Boc-L-valine (1.00 g, 4.60 mmol) was dissolved in methanol (2 ml) and dichloromethane (20 ml), p-aminobenzyl alcohol (737 mg, 5.98 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (2.28 g, 9.21 mmol) were added, and the mixture was stirred at room temperature for 1.5 hours. The mixture was concentrated under reduced pressure and purified by column chromatography [V DCM / V MeOH=60:1] separation and purification gave a light yellow solid 63-M2 (800 mg, yield: 54%)

[1010] Compound 63

[1011] At -10°C under nitrogen, 56b (600 mg, 0.59 mmol, 1.1 eq) and 4-dimethylaminopyridine (79 mg, 0.65 mmol, 1.2 eq) were added sequentially to a solution of 63-M2 (170 mg, 0.53 mmol, 1.0 eq) in N,N-dimethylacetamide (8 mL). The mixture was stirred at -10°C for 16 hours. After the reaction, the reaction solution was quenched by dropwise addition of hydrochloric acid (0.1 N, 20 mL) and extracted with ethyl acetate (40 mL × 2). The organic phases were combined, washed with saturated sodium chloride aqueous solution (30 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =40:1] was separated and purified to obtain compound 63 (white solid 130 mg, yield: 18%, HPLC purity: 98.9%).

[1012] MS (ESI): 1202.4972[M+1] +

[1013] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.05 (s, 1H), 9.26 (d, J = 8.5Hz, 1H), 8.03–7.96 (m, 2H), 7. 85–7.79(m, 2H), 7.77–7.68(m, 1H), 7.68–7.59(m, 4H), 7.58–7.52(m, 1H), 7.51–7.46(m, 2H), 7.45(d, J=5.1Hz, 4H), 7.35–7.28(m, 2H), 7.20(ddd, J=8.8, 5.5, 3.3Hz, 1H), 6.88(d , J=8.5Hz, 1H), 6.32 (s, 1H), 5.84 (t, J=9.1Hz, 1H), 5.54 (t, J=8.6Hz, 1H), 5.43 (d, J=7.2 Hz, 1H), 5.37 (d, J=8.8Hz, 1H), 5.15 (s, 2H), 4.96–4.88 (m, 2H), 4.65 (s, 1H), 4.13 (dt, J= 10.5, 6.8Hz, 1H), 4.02 (q, J=8.3Hz, 2H), 3.93 (t, J=8.1Hz, 1H), 3.61 (d, J=7.2Hz, 1H), 2. 39–2.30 (m, 1H), 2.27 (s, 3H), 2.12 (s, 3H), 1.99 (h, J=7.0Hz, 1H), 1.90–1.79 (m, 4H), 1.7 0–1.55 (m, 2H), 1.51 (s, 3H), 1.39 (s, 9H), 1.03 (d, J = 11.3Hz, 6H), 0.90 (d, J = 6.7Hz, 6H).

[1014] Example 64 Synthesis of Compound 64

[1015] 64-M1:

[1016] At 0-5°C under nitrogen, piperidine (2.87 g, 33.74 mmol) was dissolved in acetonitrile (15 mL) and added dropwise to a solution of compound 64-M0 (5.00 g, 11.25 mmol) in acetonitrile (60 mL) and N,N'-dimethylacetamide (60 mL). The mixture was stirred at 0-5°C for 2 h. The solvent was then concentrated under reduced pressure to remove the remaining solution of compound 64-M1 in N,N'-dimethylacetamide, which was directly used in the next step with a 100% yield.

[1017] 64-M2:

[1018] At 0-5°C under nitrogen protection, pivalic anhydride (12.57 g, mmol) was added dropwise to a solution of compound 64-M1 in N,N'-dimethylacetamide, and the mixture was stirred at 0°C for 30 minutes. Dichloromethane (100 ml) was added to the reaction solution for extraction. The organic phase was washed with 0.05N hydrochloric acid (50 ml × 3) and a saturated sodium chloride aqueous solution (50 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =40:1] separation and purification gave 3.1 g of a yellow viscous substance with a yield of 83%.

[1019] Compound 64

[1020] At -5 to 0°C under nitrogen protection, a solution of 4-dimethylaminopyridine (160 mg, 1.31 mmol) and 51b (762 mg, 0.78 mmol) in dichloromethane (3 mL) was added dropwise to a solution of compound 64-M2 (200 mg, 0.65 mmol) in dichloromethane (5 mL), and the mixture was stirred at -5°C for 20 hours. Dichloromethane (20 ml) was added to the reaction solution, and the mixture was washed with 0.05N hydrochloric acid (15 ml) and saturated sodium chloride aqueous solution (15 ml), respectively, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [V DCM / V MeOH =30:1] separation and purification gave 600 mg of a white solid, which was then purified using an acetonitrile-water system to give 300 mg of a white solid (yield: 40.3%), HPLC purity: 99.56%.

[1021] MS (ESI): 1140.5180 [M+1] +

[1022] 1H NMR (400MHz, DMSO-d6) δ (ppm) 10.16 (s, 1H), 8.02–7.95 (m, 2H), 7.90 (d, J=9. 2Hz, 1H), 7.77–7.68 (m, 1H), 7.68–7.60 (m, 4H), 7.41 (t, J=7.6Hz, 2H), 7.35 ( dd, J=7.7, 4.6Hz, 4H), 7.27 (d, J=8.6Hz, 1H), 7.17 (t, J=7.3Hz, 1H), 5.79 (t, J=9.0Hz, 1H), 5.41(d, J=7.1Hz, 1H), ...

Claims

1. A compound as shown in formula I or a pharmaceutically acceptable salt thereof, T is Formula A, Formula B or Formula C: Z is O or NH; m is 0, 1, 2, 3, 4 or 5; o is 0, 1, 2, 3, 4, or 5; n is 0, 1, 2, 3, 4 or 5; Each R 1 are independently hydrogen, deuterium, halogen or C1-C4 alkyl; Each R is independently deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, -OR a 、-SR a 、-NR a R a , nitro, cyano, -C(=O)R a 、-C(=O)OR a 、-C(=O)NR a R a 、-S(=O)2NR a R a 、-S(=O)R a 、-S(=O)2OR a , nitro, cyano, optionally substituted by one or more R a Substituted C1-C 20 Alkyl, optionally replaced by one or more R a Substituted C1-C 20 The alkoxy group, optionally with one or more R a Substituted C2-C 20 The alkenyl group, optionally substituted by one or more R a Substituted C2-C 20 Alkynyl, optionally substituted by one or more R a substituted 3-10 membered heteroalkenyl, optionally substituted by one or more R a substituted 3-10 membered heteroalkynyl or unsubstituted, optionally substituted with multiple R a substituted 3-20 membered heteroalkyl; each R a are independently hydrogen, deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, nitro, cyano, C1-C 20 Alkyl or 3-20 membered heteroalkyl; the -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, C1-C 20 The alkyl and 3-20 membered heteroalkyl groups are optionally substituted with any substituent; Each R c -NR e -XY; Each R e are independently hydrogen, deuterium or C1-C4 alkyl; Each X is X1, X2-X3 or X4-X5-X6-X7; The X1 is The X2 is The X3 is The X4 is The X5 is The X6 is The X7 is Each Y is -C(=O)R b or -S(=O)2R b ; Each R b are independently -OH, -NHR b-1 、-NR b-1 R b-1 、-C(=O)R b-1 、S(=O)2R b-1 、-S(=O)R b-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1 replace; Each R b-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1 、-NR b- 1-1 R b-1-1 、-C(=O)R b-1-1 、S(=O)2R b-1-1 、-S(=O)R b-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1 replace; Each R b-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1-1 、-NR b- 1-1-1 R b-1-1-1 、-C(=O)R b-1-1-1 、S(=O)2R b-1-1-1 、-S(=O)R b-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1-1 replace; Each R b-1-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR b-1-1-1-1 、-NR b-1-1-1-1 R b-1-1-1-1 、-C(=O)R b-1-1-1-1 、S(=O)2R b-1-1-1-1 、-S(=O)R b-1-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 an aromatic hydrocarbon group, a 5-10 membered heteroaromatic hydrocarbon group or a 5-10 membered heteroaromatic hydrocarbon group; said R b-1-1-1-1 Substituted C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R b-1-1-1-1 replace; Each R b-1-1-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkylNH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylNH-, (3-8 membered heteroalkyl)(3-8 membered heteroalkyl)N-, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkylNH-, (3-8 membered heterocycloalkyl)(3-8 membered heterocycloalkyl)N-, C3-C8 cycloalkyloxy, 3-8 membered heterocycloalkyloxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 aryloxy, 5-10 membered heteroaryl or 5-10 membered heteroaryloxy; Each R d are independently -NR d-0 Y d-1 OR d- 2; Each R d-0 are independently hydrogen, deuterium or C1-C4 alkyl; Each Y d-1 -C(=O)R d-1 or -S(=O)2R d-1 ; Each R d-1 As above R b defined; Each R d-2 C1-C6 alkyl, 3-8 membered heteroalkyl, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C6-C 10 The aromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl group, 3-8 membered heteroalkyl group, C3-C8 cycloalkyl group, 3-8 membered heterocycloalkyl group, C6-C 10 The aromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally replaced by one or more R d-2-1 replace; Each R d-2-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR d-2-1-1 、-NR d-2- 1-1 R d-2-1-1 、-C(=O)R d-2-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R d-2-1-1 replace; Each R d-2-1-1 are independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHR d-2-1-1-1 、-NR d-2-1-1-1 R d-2-1-1-1 、-C(=O)R d-2-1-1-1 , C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, 5-10 membered heteroaromatic hydrocarbon group or 5-10 membered heteroaromatic hydrocarbon group; the C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, 3-8 membered heteroalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 The aromatic hydrocarbon group, the 5-10 membered heteroaromatic hydrocarbon group and the 5-10 membered heteroaromatic hydrocarbon group are optionally substituted by one or more R d-2-1-1-1 replace; Each R d-2-1-1-1 and independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3-8 membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkylNH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3-8 membered heteroalkoxy, 3-8 membered heteroalkylNH-, (3-8 membered heteroalkyl)(3-8 membered heteroalkyl)N-, C3-C8 cycloalkyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkylNH-, (3-8 membered heterocycloalkyl)(3-8 membered heterocycloalkyl)N-, C3-C8 cycloalkyloxy, C3-C8 cycloalkylNH-, (C3-C8 cycloalkyl)(C3-C8 cycloalkyl)N-, 3-8 membered heterocycloalkoxy, C6-C 10 Aromatic hydrocarbon groups, C6-C 10 Aromatic oxy, C6-C 10 5-10 membered heteroaryl, 5-10 membered heteroaryloxy or 5-10 membered heteroarylNH-; The heteroatoms are independently selected from one, two or three of O, S and N; and the number of the heteroatoms is independently one, two or three.

2. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein: The compound represented by formula I is a compound represented by IA to a compound represented by IP: Alternatively, the compound represented by formula I is a compound represented by formula I-1 to I-12: Alternatively, the compound represented by formula I is a compound represented by formula I-13 to I-24: Alternatively, the compound represented by formula I is a compound represented by formula II-1, II-2 or II-3, Alternatively, the compound represented by formula I is a compound represented by formula II-4, II-5 or II-6, Alternatively, the compound represented by formula I is a compound represented by formula II-7, II-8, II-9, II-10, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-19, II-20 or II-21, Alternatively, the compound represented by Formula I is a compound represented by Formula Ia, Ib or Ic:

3. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein: Y is -C(=O)R b ; The R b is a C1-C6 alkyl, a C1-C6 alkoxy, -OR b-1 、C6-C 10 aromatic hydrocarbon group, -C(=O)OH or 3-8 membered heteroalkyl group; the C1-C6 alkyl group, C1-C6 alkoxy group, C6-C 10 The aromatic hydrocarbon group and the 3-8 membered heteroalkyl group are optionally replaced by one or more R b-1 Substitute; each R b-1 are independently C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, halogens, -NR f R f , 3-8 membered heterocycloalkyl or -C(=O)OH; the C1-C6 alkyl, C6-C 10 The aromatic hydrocarbon group and the 3-8 membered heterocycloalkyl group are optionally replaced by one or more R b-1-1 Substitute; each R f are independently C1-C6 alkyl; each of the R b-1-1 are independently halogen; or, The R b N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C 10 Alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3-8 membered heterocycloalkyl C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon groups, C(=O)OH C0-C6 alkyl groups, C1-C 10 Alkoxy, C6-C 10 Aromatic C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group: C1-C6 alkyl or C(=O)OH 3-8 membered heteroalkyl.

4. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein: Y d-1 -C(=O)R d-1 ; The R d-1 C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon group, C1-C6 alkoxy group or -OR d-1-1 The C1-C6 alkyl, C6-C 10 The aromatic hydrocarbon group and the C1-C6 alkoxy group are optionally replaced by one or more R d-1-1 Substitute; each R d-1-1 are independently C1-C6 alkyl, C6-C 10 Aromatic hydrocarbon group or halogen; the C1-C6 alkyl and C6-C 10 The aromatic hydrocarbon group is optionally replaced by one or more R d-1-1-1 Substitute; each R d-1-1-1 are independently halogen; or, The R d-1 C1-C 10 Alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group C1-C6 alkyl, 1-3 halogen-substituted C1-C6 alkyl, 1-3 halogen-substituted C6-C 10 Aromatic hydrocarbon group or C1-C 10 of alkoxy.

5. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein: R d-2 It is a C1-C6 alkyl group.

6. The compound of formula I according to claim 1 is any one of the following compounds:

7. A pharmaceutical composition comprising the compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

8. Use of a compound in the preparation of a medicament, wherein the compound is a compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 7, wherein the medicament is used to treat and / or prevent cancer; the cancer may be selected from solid tumors or hematological tumors; the solid tumor may be selected from breast cancer or prostate cancer.

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