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

[0001] The present 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 contents of the above Chinese patent applications are incorporated herein by reference in their entirety. TECHNICAL FIELD

[0002] The present disclosure relates to a taxane conjugate drug and a preparation method and use thereof. BACKGROUND

[0003] Chemotherapy is a major treatment modality for various cancers, employing drugs to inhibit or kill rapidly proliferating cancer cells, but it also presents certain problems and side effects. Traditional cytotoxic chemotherapy drugs often affect normal cells, resulting in a series of side effects such as nausea, vomiting, fatigue, hair loss, digestive problems, and impairment of the immune system. These side effects may affect patients' quality of life and treatment compliance. Some tumor cells may develop resistance to chemotherapy, leading to weakened or ineffective therapeutic effects. This may require changing or adjusting the drug combination or adopting other treatment methods. The effect of chemotherapy drugs on normal cells is an important issue during the treatment process. In order to mitigate this impact, the medical community has adopted several strategies and technical approaches to improve the safety and efficacy of chemotherapy, and has attempted methods such as using prodrugs, and conjugating peptides or antibodies targeting specific receptors or antigens. For example, enzyme-activated prodrug strategies, which design drugs in an inactive form that are only activated under specific conditions. This can be achieved through the action of enzymes in vivo, which are usually highly expressed in tumor tissues. This approach can reduce the impact of drugs on normal cells, because the drug is only activated near cancer cells.

[0004] Patent US20050187147A1 describes a novel conjugate, which includes a drug component and a protein kinase or lipid kinase substrate (the substrate is usually a polypeptide with an amino acid sequence of 7 residues or more). In the process of preparing this conjugate, the document discloses a compound PA-1 in which the hydrogen of the hydroxyl group at the 2' position of the C-13 side chain of paclitaxel is substituted with a benzyloxycarbonyl group (see Table 1).

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

[0006] CN101374856A reveals a class of novel peptide-conjugated drug molecules, which target the tumor-specific protease Legumain in the tumor microenvironment. Legumain is a cysteine protease specifically expressed in tumor cells and tumor-associated macrophages, and it can recognize peptide bonds containing asparagine (Asn) and cleave peptides containing asparagine (Asn).

[0007] CN109420179A discloses a docetaxel-like polypeptide-conjugated targeted prodrug, which is covalently conjugated with a polypeptide through a degradable bridging group, wherein the polypeptide is a substrate of matrix metalloproteinase MMP-7, cysteine protease B, and fibroblast activation protein a, and the polypeptide is an octapeptide containing asparagine.

[0008] CN109422799A also reveals a polypeptide-based docetaxel-like targeted prodrug, wherein the docetaxel-like drug is covalently bound to a polypeptide via a degradable bridging group. Here, the polypeptide is an octapeptide containing asparagine, serving as a recognition substrate for matrix metalloproteinases MMP-2 and MMP-9.

[0009] CN102413842A reveals a paclitaxel conjugate of an albumin-binding carrier cleaved by prostate-specific antigen. Among these, the two amino acids adjacent to the active moiety are sequentially leucine (Leu)-serine (Ser), and compounds PA-3 and PA-4 are disclosed (see Table 1).

[0010] Patent WO2017093719A1 discloses a membrane-type matrix metalloproteinase (MT-MMP)-sensitive paclitaxel polypeptide-conjugated prodrug, wherein one of the amino acid sequences of the peptide is -Arg-Ser-Cit (citrulline)-Gly-Hof (homophenylalanine)-Tyr-Leu-, with the two amino acids adjacent to the active moiety being sequentially leucine (Leu)-tyrosine (Tyr). Compound PA-5 is disclosed (see Table 1).

[0011] CN106715457A reveals a polypeptide-conjugated compound with targeted activation and improved solubility properties. This asparagine-containing polypeptide is conjugated with a cleavable linker, which can be selectively recognized and cleaved by asparagine endopeptidase in the tumor microenvironment, thereby releasing a drug with novel targeting, activation, and metabolic characteristics.

[0012] Patent CN107847607A reveals a nucleic acid aptamer-conjugated paclitaxel conjugate and involves the preparation of such conjugates using compound PA-6 (see Table 1).

[0013] CN101935336A reveals a class of polyethylene glycol-modified polypeptide-conjugated drugs with high water solubility, which can be recognized by cathepsin B to release the active ingredient. This study disclosed the tolerability and efficacy of the prodrug PTX in MCF-7 and Hela cell lines as well as animal experiments, but did not disclose the stability of the prodrug in human or mouse serum and plasma. It also disclosed two compounds, PA-7 and PA-8 (see Table 1).

[0014] WO2015136545A1 discloses a polymer, the preparation of which involves compound PA-9 (see Table 1).

[0015] The literature "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 glucuronate prodrug, aiming to achieve tumor-specific activation through the tumor-activated prodrug (TAP) strategy. It discloses compound PA-10 (see Table 1).

[0016] The literature "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." introduces a novel fluoro-glucuronate prodrug. Introducing fluorine into drug compounds can modulate their properties, thereby influencing pharmacodynamics and pharmacokinetics. The disclosed compounds include PA-11 and PA-12 (see Table 1).

[0017] CN103641925A discloses a class of covalent polymers of water-soluble polysaccharides and taxane compounds, with one of the compounds involved in the polymer preparation being PA-13 (see Table 1).

[0018] The literature "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 photoactivatable paclitaxel prodrug, wherein one compound involved is PA-14 (see Table 1). Related content is also disclosed in EP2565188A1. Studies have shown that derivatization substitution at C1 has a minor impact on the activity of paclitaxel, while esterification at C7 or C2' leads to the loss of in vitro microtubule assembly activity but does not affect cytotoxicity.

[0019] The literature "Damen E W P, Nevalainen T J, van den Bergh T J M, et al. Synthesis of novel paclitaxel prodrugs designed for bioreductive activation in hypoxic tumour tissue [J]. Bioorganic & medicinal chemistry, 2002, 10(1): 71-77." discloses a method of esterification at C2' to reduce the toxicity of paclitaxel, using the reduction of aromatic nitro compounds as a trigger. Researchers developed low-toxicity paclitaxel prodrugs that are selectively activated in hypoxic tissues. The disclosed compound includes PA-15 (see Table 1).

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

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

[0022] Evidence suggests that polyethylene glycol (PEG) can trigger immunogenic reactions, particularly when combined with other materials such as proteins and nanocarriers. Certain PEG-modified compounds can induce additional anti-polyethylene glycol antibodies, which may adversely affect drug efficacy and safety. Accelerated blood clearance (known as the "ABC phenomenon") is an unexpected immunogenic reaction observed in PEG conjugates, leading to the rapid clearance of PEGylated nanocarriers. The ABC phenomenon has been widely observed upon repeated administration, which reduces the effectiveness of PEG conjugates and nanocarriers. Another unexpected immune reaction is a hypersensitivity reaction known as CARPA, which significantly reduces the safety of PEGylated nanocarriers and is associated with reduced efficacy of PEGylated therapies in clinical trials. The CARPA phenomenon has been classified as a nonIgE-mediated pseudoallergic reaction caused by complement system activation. (Chen B M, Cheng T L, 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 literature 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 disclosed a class of polypeptide conjugates specifically hydrolyzed by asparagine endopeptidase Legubicin, investigating the efficacy of three compounds (LEG-2 / 3 / 4) in tumor-bearing mice, which described that "the compound LEG-4 is not cleaved by Legubicin and does not have antitumor activity, whereas LEG-2 and LEG-3 converted by Legubicin demonstrate in vivo antitumor effects". It can be observed that the three compounds have similar structures, with LEG-4 lacking one amino acid compared to LEG-2 / 3, indicating that due to enzyme specificity, compounds with structural differences exhibit poor predictability.

[0024] As mentioned above, multiple prodrug design strategies for taxane drugs have been disclosed, including: (1) targeting peptides; (2) polymers; (3) specific enzyme recognition; (4) dedicated transporters; (5) photoactivation methods; (6) hypoxia-activated strategies; (7) bioorthogonal prodrugs; (8) or combinations of multiple strategies. To date, the strategy of specific enzyme recognition for activating drug release faces challenges 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 dosage and / or cellular permeability and / or efficacy against specific tumor cells and / or highly active prodrugs and / or stability in systemic circulation and / or targeting capability and / or good stability in plasma and serum remains an area lacking clear guidance. Therefore, there is an urgent need for comprehensive research and development to create novel prodrugs of cytotoxic agents.

[0025] Table 1: Similar compounds disclosed in the prior art aa I fl=A AA oA h3c        oh =. NH / \X \AZ O^0'PPP) 6 0 HO 1 o'Tk >° °Y°I 0       1 CT^ HO op h3c        oh NH pp / Vj v\p°11' v^App o X0 HO 1 O'An >0 oyo?Lo 0       1 0^^ P Ao o A h3c 1,0 0H / =\ -NH / \aVP P / Vp''' VpPpp o o ho i opp >0 vl 0       [ O'^ -p nh2 AA o P Ao °0 HA A-A. oh P / Pp'' O' 0 HO E o'Vl >0 oV°lUo o       1 0^^ 6 h2n PA-1 PA-2 PA-3 PA-4 P Ao O / HA A~A. OH z=\ nh PPP pH^01 "a^ppp o o HO i c / V\ >° °Y°I 0       1 O'^ pNH —( nh2 P A0 Op H:iC\_PP^ OH —~ NH / A / VJ pppp311 ■ ppp) d b HO i 0Pi >° vX 0         O /      V—NH —hnA h2n o A NH >0 h2n 0 Q-cAfl / Tr-Jd 0 NH O'’V / A'° AvAA °h 6 \ A o / fl O Q Anh 1 hnA--x n Ap    yNH2 OyNH        0 pA PEG ,          HO 0 OH a HsCPPh °Ah o-flyx) aaA„AA °vo °yNH / hnA^ h Ay, yA     0 ?A> PEG PA-5 PA-6 PA-7 PA-8 A A»° ™ oPpPP 0 NH 0‘PpPo AVP. oh b \ L Ji 0       0 o 0 A£ >°Pa ' P n P^nh r 0 0 ° °AA A fX / " u-V va \ O'. / \A / 0H Xo° H°P\P 9 °YoA HO- / 0  0 V hA “Po^ H0 bH O j pP HAf0 AA \ o-' / \00 / °H °? o rOpp Ao H0 i V- / 0 °yAA 0 0 000 HO ' P A A\ ."h "' / A AA \ 0'0 00 / 0H o PPPh) py P CP 0 \    HN H° A PA-9 PA-10 PA-11 PA-12 ,          HO 0 OH "Jo H3CyV|A A / h O-'U / X)) Arvv< L IJ ; O 0= / %A >2 A / / / • HO _        1 WH 0      6 o ° °= / / A CL NH H3CaX° Vy \ O'. / \2f / OH o tA / 'h) )=0 H0 ; W o   voo-n o2n \      , /  0 $ H3C0 och3 O 0 / A -NH nVJLo \L_ / \ 0" / \A\ / ,0H °x o 7\—Ah \ Ao  H0 ; \A o   Vo? □ 0,N   \       A J   o d d o2n O j VVkAo VA \ Ou. / Vd\ / 0H °y 0 / vP-h) d=0    P*®     \ - / ? V°JV d o' o2n PA-13 PA-14 PA-15 PA-16 d3 ° 0= / / A A\Ah HAr 0 A / \ o.A / / / / °H / o W-4h) Ao HO ; V- / o VAU o2n \        / /  0 & d i_i              o     0 V ho3s h =-v    o 0 \ nA    o V “ PA-17 SUMMARY

[0026] The present disclosure provides a class of taxane conjugate drugs having antitumor activity, as well as preparation methods and uses thereof. A first aspect of the present disclosure provides a compound represented by Formula I or a pharmaceutically acceptable salt thereof, n I

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

[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 R1 is independently hydrogen, deuterium, halogen, nitro, cyano, -OR1-1, -SR1-1, - NR1-1R1-1, -C(=O)R1-1, -S(=O)2R1-1, -S(=O)R1-1, -P(=O)R1-1R1-1, C1-C20 alkyl, C2-C20 alkenyl, C2- C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20-membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20-membered heteroalkynyl, 3- to 20membered heterocycloalkyl, 3- to 20-membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, or 5- to 20-membered heteroaryl; the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20-membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20-membered heteroalkynyl, 3- to 20membered heterocycloalkyl, 3- to 20-membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, and 5- to 20-membered heteroaryl are optionally substituted with one or more R1-1;

[0033] each R1-1 is independently hydrogen, deuterium, halogen, nitro, cyano, -OR1-1-1, -SR1-1-1, -NR1-1-1R1-1-1, -C(=O)R1-1-1, -S(=O)2R1-1-1, -S(=O)R1-1-1, -P(=O)R1-1-1R1-1-1, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20-membered heteroalkynyl, 3- to 20-membered heterocycloalkyl, 3- to 20-membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, or 5- to 20-membered heteroaryl; the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20-membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20-membered heteroalkynyl, 3- to 20membered heterocycloalkyl, 3- to 20-membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, and 5- to 20-membered heteroaryl are optionally substituted with one or more R1-1-1;

[0034] each R1-1-1 is independently hydrogen, deuterium, halogen, nitro, cyano, -OR1-1-1-1, -SR1-1-1-1, -NR1-1-1-1R1-1-1-1, -C(=O)R1-1-1-1, -S(=O)2R1-1-1-1, -S(=O)R1-1-1-1, -P(=O)R1-1-1-1R1-1-1-1, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20-membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20-membered heteroalkynyl, 3- to 20-membered heterocycloalkyl, 3- to 20-membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, or 5- to 20-membered heteroaryl; the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20-membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20-membered heteroalkynyl, 3- to 20-membered heterocycloalkyl, 3- to 20-membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, and 5- to 20-membered heteroaryl are optionally substituted with one or more R1-1-1-1;

[0035] each R1-1-1-1 is independently hydrogen, deuterium, halogen, nitro, cyano, -OR1-1-1-1-1 1-1-1-1-1 -NR1-1-1-1-1R1-1-1-1-1, -C(=O)R1-1-1-1-1, -S(=O)2R1-1-1-1-1, -S(=O)R1-1-1-1-1, -P(=O)R1-1-1-1- 1R1-1-1-1-1, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20-membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20membered heteroalkynyl, 3- to 20-membered heterocycloalkyl, 3- to 20-membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, or 5- to 20-membered heteroaryl; the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20-membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20-membered heteroalkynyl, 3- to 20-membered heterocycloalkyl, 3- to 20membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, and 5- to 20membered heteroaryl are optionally substituted with one or more R1-1-1-1-1;

[0036] each R1-1-1-1-1 is 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-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C3-C20 cycloalkynyl, 3- to 20-membered heteroalkyl, 4- to 20-membered heteroalkenyl, 4- to 20-membered heteroalkynyl, 3- to 20-membered heterocycloalkyl, 3- to 20-membered heterocycloalkenyl, 3- to 20-membered heterocycloalkynyl, C6-C20 aryl, or 5- to 20-membered heteroaryl;

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

[0038] R is defined as R1 above;

[0039] Rc is -NRe-X-Y;

[0040] Re is defined as R1 above;

[0041] X is 1 amino acid residue or a peptide chain formed by 2-10 amino acids;

[0042] Y is -C(=O)Rb, -S(=O)2Rb, -S(=O)Rb, or -P(=O)RbRb;

[0043] Rb is defined as R1 above;

[0044] Rd is independently -NRd-0Yd-1 or -ORd-2;

[0045] Rd-0 is defined as R1 above;

[0046] Rd-2 is defined as R1 above;

[0047] Yd-1 is -C(=O)Rd-1, -S(=O)2Rd-1, -S(=O)Rd-1, or -P(=O)Rd-1Rd-1;

[0048] Rd-1 is defined as R1 above.

[0049] In some embodiments, in the compound represented by Formula I or the pharmaceutically acceptable salt thereof, certain groups have the following definitions, and the definitions of groups not mentioned are as described in any one of the embodiments of the present disclosure (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 R1 is independently hydrogen, deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, -OR1-1, -SR1-1, -NR1-1R1-1, nitro, cyano, -C(=O)R1-1, -C(=O)OR1-1, -C(=O)NR1-1R1-1, -S(=O)2NR1-1R1-1, -S(=O)OR1-1, -S(=O)2OR1-1, C1-C20 alkyl optionally substituted with more than one R1-1, C2-C20 alkenyl optionally substituted with one or more R1-1, C2-C20 alkynyl optionally substituted with one or more R1-1, 3- to 10-membered heteroalkenyl optionally substituted with one or more R1-1, 3- to 10-membered heteroalkynyl optionally substituted with one or more R1-1, or 3- to 20-membered heteroalkyl optionally substituted with more than one R1-1;

[0055] each R1-1 is 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-C20 alkyl, or 3- to 20membered heteroalkyl; the -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, C1-C20 alkyl, and 3- to 20-membered heteroalkyl 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, -ORa, -SRa, -NRaRa, nitro, cyano, -C(=O)Ra, -C(=O)ORa, -C(=O)NRaRa, -S(=O)2NRaRa, -S(=O)Ra, -S(=O)2ORa, nitro, cyano, C1-C20 alkyl optionally substituted with one or more Ra, C1-C20 alkoxy optionally substituted with one or more Ra, C2-C20 alkenyl optionally substituted with one or more Ra, C2-C20 alkynyl optionally substituted with one or more Ra, 3- to 10-membered heteroalkenyl optionally substituted with one or more Ra, 3- to 10membered heteroalkynyl optionally substituted with one or more Ra, or 3- to 20-membered heteroalkyl unsubstituted or optionally substituted with more than one Ra; each Ra is 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-C20 alkyl, or 3- to 20-membered heteroalkyl; the -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, C1-C20 alkyl, and 3- to 20-membered heteroalkyl are optionally substituted with any substituent;

[0057] each Rd is defined as R above;

[0058] Rc is -NH-X-Y;

[0059] X is 1 amino acid residue or a peptide chain formed by 2-4 amino acids;

[0060] Y is -C(=O)ORb, -C(=O)Rb, -C(=O)NRbRb, -S(=O)2NRbRb, -S(=O)2ORb, -S(=O)2Rb, -S(=O)Rb, -S(=O)NRbRb, -S(=O)ORb, -P(=O)(ORb)2, -P(=O)NRbRb(ORb), -P(=O)(NRbRb)2, -PH(=O)ORb, -PH(=O)NRbRb, or -PH(=O)Rb; Rb is independently hydrogen, -C(=O)OH, C1-C20 alkyl, C1-C20 alkoxy, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 20membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10-membered heterocycloalkyl, or 5- to 12-membered heteroaryl; the C1-C20 alkyl, C1-C20 alkoxy, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 20-membered heteroalkyl, 3-to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10-membered heterocycloalkyl, and 5- to 12-membered heteroaryl are optionally substituted with any substituent;

[0061] the heteroatom is independently selected from 1, 2, 3, or 4 types of O, P, S, and N; the number of heteroatoms is independently 1, 2, 3, or 4.

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

[0063] In some embodiments, the heteroatom is independently selected from 1, 2, 3, or 4 types of O, P, S, and N; the number of heteroatoms is independently 1, 2, 3, or 4.

[0064] In some embodiments, two heteroatoms heteroatom is oxo-substituted.

[0065] In some embodiments, the compound represented by Formula I-A: O^T I R1 1 OxL-R Re m LA .

[0066] In some embodiments, the compound represented by Formula I-B: are not connected by a single bond unless one represented by Formula I is a compound represented by Formula I is a compound

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

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

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

[0070] In some embodiments, the compound represented by Formula I is a represented by Formula I-F: compound 1-F

[0071] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-G: l-G

[0072] In some embodiments, the compound represented by Formula I-G is a compound represented by Formula I-G-A: I-G-A

[0073] In some embodiments, the compound represented by Formula I-G is a compound represented by Formula I-G-B:

[0074] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-H: I Re I-H .

[0075] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-I: I-I

[0076] In some embodiments, the represented by Formula I-J: O^T |Ra)„ I-J .

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

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

[0079] In some embodiments, the represented by Formula I-M: compound represented by Formula I is a compound

[0080] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-N: O^ / T NHYd'1 I-N .

[0081] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-O: CK / T 1-0 .

[0082] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-P: / T NHY' I-P .

[0083] In some embodiments, R1 is independently hydrogen, deuterium, halogen, or C1-C4 alkyl.

[0084] In some embodiments, R1 is 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, Re is independently hydrogen, deuterium, or C1-C4 alkyl.

[0095] In some embodiments, Re is independently hydrogen.

[0096] In some embodiments, Rd-0 is independently hydrogen, deuterium, or C1-C4 alkyl.

[0097] In some embodiments, Rd-0 is independently hydrogen.

[0098] In some embodiments, n is 0.

[0099] In some embodiments, Y is -C(=O)Rb, -S(=O)2Rb, or -S(=O)Rb, and Rb is -OH, -NH2, -NHRb-1, -NRb-1Rb-1, -C(=O)Rb-1, -S(=O)2Rb-1, -S(=O)Rb-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3-to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; and the number of heteroatoms is 1, 2, or 3.

[0100] In some embodiments, each Rb-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1, -NRb-1-1Rb-1-1, -C(=O)Rb-1-1, -S(=O)2Rb-1-1, -S(=O)Rb-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; and the number of heteroatoms is independently 1, 2, or 3.

[0101] In some embodiments, each Rb-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1-1, -NRb-1-1-1Rb-1-1-1, -C(=O)Rb-1-1-1, -S(=O)2Rb-1-1-1, -S(=O)Rb-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10- membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; and the number of heteroatoms is independently 1, 2, or 3.

[0102] In some embodiments, each Rb-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1-1-1, -NRb-1-1-1-1Rb-1-1-1-1, -C(=O)Rb-1-1-1-1, -S(=O)2Rb-1-1-1-1, -S(=O)Rb-1-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the Rb-1-1-1-1-substituted C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; and the number of heteroatoms is independently 1, 2, or 3.

[0103] In some embodiments, each Rb-1-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkyl-NH-, (3- to 8-membered heteroalkyl)(3- to 8-membered heteroalkyl)N-, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, 3- to 8-membered heterocycloalkyl-NH-, (3- to 8-membered heterocycloalkyl)(3- to 8-membered heterocycloalkyl)N-, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10membered heteroaryloxy; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; and the number of heteroatoms is independently 1, 2, or 3.

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

[0105] In some embodiments, Y is -C(=O)Rb, -S(=O)2Rb, or -S(=O)Rb, wherein Rb is 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- to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3-to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, or C5-C10 heteroaryl-3- to 8-membered heteroalkylamino; wherein 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, N(C1-C6 alkyl)(C0-C6 alkyl)3-to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3- to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8-membered heteroalkylamino, C6-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, and C5-C10 heteroaryl-3- to 8-membered heteroalkylamino are optionally substituted with one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, or -C(=O)OH; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0106] In some embodiments, Y is -C(=O)Rb, -S(=O)2Rb, or -S(=O)Rb, wherein Rb is 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-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkoxy substituted with 1-3 halogens, C1-C6 alkylamino substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, C6-C10 aryl substituted with 1-3 halogens, C6-C10 aryloxy substituted with 1-3 halogens, C6-C10 arylamino substituted with 13 halogens, C(=O)OH-C0-C6 alkyl, C(=O)OH-C0-C6 alkoxy, C(=O)OH-C0-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkoxy substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkylamino substituted with 1-3 halogens, C(=O)OH-3- to 8-membered heteroalkyl, C(=O)OH-3- to 8-membered heteroalkoxy, or C(=O)OH-3- to 8-membered heteroalkylamino; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0107] In some embodiments, Y is -C(=O)Rb, -S(=O)2Rb, or -S(=O)Rb, wherein Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or C(=O)OH-3- to 8-membered heteroalkyl; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

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

[0109] In some embodiments, Rb is 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- to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl- C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3- to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8-membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, or C5-C10 heteroaryl-3- to 8-membered heteroalkylamino; wherein 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, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3-to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, and C5-C10 heteroaryl-3- to 8-membered heteroalkylamino are optionally substituted with one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, or -C(=O)OH; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0110] In some embodiments, Rb is 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-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkoxy substituted with 1-3 halogens, C1-C6 alkylamino substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, C6-C10 aryl substituted with 1-3 halogens, C6-C10 aryloxy substituted with 1-3 halogens, C6-C10 arylamino substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C(=O)OH-C0-C6 alkoxy, C(=O)OH-C0-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl-C1- C6 alkoxy substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkylamino substituted with 1-3 halogens, C(=O)OH-3- to 8-membered heteroalkyl, C(=O)OH-3- to 8-membered heteroalkoxy, or C(=O)OH-3- to 8-membered heteroalkylamino; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0111] In some embodiments, Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or C(=O)OH-3- to 8-membered heteroalkyl.

[0112] In some embodiments, Yd-1 is -C(=O)Rd-1, -S(=O)2Rd-1, or -S(=O)Rd-1, wherein Rd-1 is -OH, -NHRd-1-1, -NRd-1-1Rd-1-1, -C(=O)Rd-1-1, S(=O)2Rd-1-1, -S(=O)Rd-1-1, C1-C6 alkyl, 3- to 8membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10membered heteroaryloxy are optionally substituted with one or more Rd-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0113] In some embodiments, each Rd-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRd-1-1-1, -NRd-1-1-1Rd-1-1-1, -C(=O)Rd-1-1-1, S(=O)2Rd-1-1-1, -S(=O)Rd-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rd-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0114] In some embodiments, each Rd-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRd-1-1-1-1, -NRd-1-1-1-1Rd-1-1-1-1, -C(=O)Rd-1-1-1-1, S(=O)2Rd-1-1-1-1, -S(=O)Rd-1-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rd-1-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0115] In some embodiments, each Rd-1-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRd-1-1-1-1-1, -NRd-1-1-1-1-1Rd-1-1-1-1-1, -C(=O)Rd-1-1-1-1-1, S(=O)2Rd-1-1-1-1-1, -S(=O)Rd-1-1-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the Rd-1-1-1-1-1-substituted C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rd-1-1-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0116] In some embodiments, each Rd-1-1-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkyl-NH-, (3- to 8-membered heteroalkyl)(3- to 8-membered heteroalkyl)N-, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkyl-NH-, (3- to 8membered heterocycloalkyl)(3- to 8-membered heterocycloalkyl)N-, C3-C8 cycloalkoxy, 3- to 8membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; and the number of heteroatoms is independently 1, 2, or 3.

[0117] In some embodiments, Yd-1 is -C(=O)Rd-1, -S(=O)2Rd-1, or -S(=O)Rd-1, wherein Rd-1 is 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- to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8membered heterocycloalkyl-3- to 8-membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3-to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3- to 8-membered heteroalkyl, C6-C10 aryl-3- to 8membered heteroalkoxy, C6-C10 aryl-3- to 8-membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, or C5-C10 heteroaryl-3- to 8-membered heteroalkylamino; wherein 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, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8membered heterocycloalkyl-3- to 8-membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3- to 8membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8-membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, and C5-C10 heteroaryl-3- to 8-membered heteroalkylamino are optionally substituted with one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, or -C(=O)OH; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0118] In some embodiments, Yd-1 is -C(=O)Rd-1, -S(=O)2Rd-1, or -S(=O)Rd-1, wherein Rd-1 is 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-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkoxy substituted with 1-3 halogens, C1-C6 alkylamino substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, C6-C10 aryl substituted with 1-3 halogens, C6-C10 aryloxy substituted with 1-3 halogens, C6-C10 arylamino substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C(=O)OH-C0-C6 alkoxy, C(=O)OH-C0-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkoxy substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkylamino substituted with 1-3 halogens, C(=O)OH-3- to 8membered heteroalkyl, C(=O)OH-3- to 8-membered heteroalkoxy, or C(=O)OH-3- to 8membered heteroalkylamino; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0119] In some embodiments, Yd-1 is -C(=O)Rd-1, -S(=O)2Rd-1, or -S(=O)Rd-1, wherein Rd-1 is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or C(=O)OH-3- to 8-membered heteroalkyl; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0120] In some embodiments, Yd-1 is -C(=O)Rd-1.

[0121] In some embodiments, Rd-1 is 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- to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl- C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3- to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8-membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, or C5-C10 heteroaryl-3- to 8-membered heteroalkylamino; wherein 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, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3-to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, and C5-C10 heteroaryl-3- to 8-membered heteroalkylamino are optionally substituted with one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, or -C(=O)OH; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0122] In some embodiments, Rd-1 is 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-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkoxy substituted with 1-3 halogens, C1-C6 alkylamino substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, C6-C10 aryl substituted with 1-3 halogens, C6-C10 aryloxy substituted with 1-3 halogens, C6-C10 arylamino substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C(=O)OH-C0-C6 alkoxy, C(=O)OH-C0-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl-C1- C6 alkoxy substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkylamino substituted with 1-3 halogens, C(=O)OH-3- to 8-membered heteroalkyl, C(=O)OH-3- to 8-membered heteroalkoxy, or C(=O)OH-3- to 8-membered heteroalkylamino; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0123] In some embodiments, Rd-1 is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or C(=O)OH-3- to 8-membered heteroalkyl.

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

[0125] In some embodiments, Rd-2 is C1-C6 alkyl, 3- to 8-membered heteroalkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more Rd-2-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0126] In some embodiments, each Rd-2-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRd-2-1-1, -NRd-2-1-1Rd-2-1-1, -C(=O)Rd-2-1-1, C1-C6 alkyl, 3- to 8membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10membered heteroaryloxy are optionally substituted with one or more Rd-2-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0127] In some embodiments, each Rd-2-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRd-2-1-1-1, -NRd-2-1-1-1Rd-2-1-1-1, -C(=O)Rd-2-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10membered heteroaryloxy are optionally substituted with one or more Rd-2-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0128] In some embodiments, each Rd-2-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkyl-NH-, (3- to 8-membered heteroalkyl)(3- to 8-membered heteroalkyl)N-, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, 3- to 8-membered heterocycloalkyl-NH-, (3- to 8-membered heterocycloalkyl)(3- to 8-membered heterocycloalkyl)N-, C3-C8 cycloalkoxy, C3-C8 cycloalkyl-NH-, (C3-C8 cycloalkyl)(C3-C8 cycloalkyl)N-, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-NH-, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy, or 5- to 10-membered heteroaryl-NH-; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0129] In some embodiments, Rd-2 is C1-C6 alkyl.

[0130] In some embodiments, Rd-2 is methyl.

[0131] In some embodiments, R is deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRa, -NRaRa, -C(=O)Ra, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Ra; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0132] In some embodiments, each Ra is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRa-1, -NRa-1Ra-1, -C(=O)Ra-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3-to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Ra-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0133] In some embodiments, each Ra-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRa-1-1, -NRa-1-1Ra-1-1, -C(=O)Ra-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3-to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Ra-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0134] In some embodiments, each Ra-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRa-1-1-1, -NRa-1-1-1Ra-1-1-1, -C(=O)Ra-1-1-1, C1-C6 alkyl, 3- to 8membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10membered heteroaryloxy are optionally substituted with one or more Ra-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0135] In some embodiments, each Ra-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRa-1-1-1-1, -NRa-1-1-1-1Ra-1-1-1-1, -C(=O)Ra-1-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10- membered heteroaryloxy are optionally substituted with one or more Ra-1-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0136] In some embodiments, each Ra-1-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkyl-NH-, (3- to 8-membered heteroalkyl)(3- to 8-membered heteroalkyl)N-, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, 3- to 8-membered heterocycloalkyl-NH-, (3- to 8-membered heterocycloalkyl)(3- to 8-membered heterocycloalkyl)N-, C3-C8 cycloalkoxy, C3-C8 cycloalkyl-NH-, (C3-C8 cycloalkyl)(C3-C8 cycloalkyl)N-, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-NH-, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy, or 5- to 10-membered heteroaryl-NH-; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of 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- to 8membered heteroalkyl, N(C0-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C0-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3- to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8-membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, or C5-C10 heteroaryl-3- to 8-membered heteroalkylamino; wherein 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, N(C0-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkyl, N(C0-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C0-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3-to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, and C5-C10 heteroaryl-3- to 8-membered heteroalkylamino are optionally substituted with deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, or -C(=O)OH; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of 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-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkoxy substituted with 1-3 halogens, C1-C6 alkylamino substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, C6-C10 aryl substituted with 1-3 halogens, C6-C10 aryloxy substituted with 1-3 halogens, C6-C10 arylamino substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C(=O)OH-C0-C6 alkoxy, C(=O)OH-C0-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C56C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkoxy substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkylamino substituted with 1-3 halogens, C(=O)OH-3- to 8-membered heteroalkyl, C(=O)OH-3- to 8-membered heteroalkoxy, or C(=O)OH-3- to 8-membered heteroalkylamino; the heteroatom is independently selected from 1, 2, or 3 types 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- to 8-membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkyl-NH-, (3- to 8-membered heteroalkyl)(3- to 8-membered heteroalkyl)N-, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, 3- to 8-membered heterocycloalkyl-NH-, (3- to 8-membered heterocycloalkyl)(3- to 8-membered heterocycloalkyl)N-, C3-C8 cycloalkoxy, C3-C8 cycloalkyl-NH-, (C3-C8 cycloalkyl)(C3-C8 cycloalkyl)N-, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, C6-C10 aryl-NH-, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy, or 5- to 10-membered heteroaryl-NH-; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of 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-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, -C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or -C(=O)OH-3- to 8-membered heteroalkyl; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0141] In some embodiments, each R is independently deuterium, halogen, nitro, cyano, -OH, - SH, -NH2, -C(=O)OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, 3- to 6-membered heteroalkyl, 3- to 6-membered heteroalkoxy, or 3- to 6-membered heteroalkylamino; the heteroatom is independently selected from 1, 2, or 3 types 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 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of        0 and , X may be the same or different; preferably 1, 2, 3, or 4, more preferably 2.

[0145] In some embodiments, X is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of        ° HN , and HN '2 , X may be the same or different; preferably 1, 2, 3, or 4, more preferably 2.

[0146] In some embodiments, X is X1, X2-X3, or X4-X5-X6-X7;

[0147] X1 is ; X3 is or ; X4 is ; X5 is O , or

[0148] In some embodiments, X1 is or

[0149]

[0150]

[0151]

[0152]

[0153]

[0154]

[0155]

[0156]

[0157] HN In some embodiments, X2 is        0 In some embodiments, X2 is In some embodiments, X3 is In some embodiments, X3 is In In or 0    , or some some In some embodiments, X6 is In some embodiments, X7 is O In some embodiments, X is

[0158] In some embodiments, X is

[0159] In some embodiments, Y is -C(=O)ORb, -C(=O)Rb, -C(=O)NRbRb, -S(=O)2NRbRb, -S(=O)2ORb, -S(=O)2Rb, -S(=O)Rb, -S(=O)NRbRb, -S(=O)ORb, -P(=O)(ORb)2, -P(=O)NRbRb(ORb), -P(=O)(NRbRb)2, -PH(=O)ORb, -PH(=O)NRbRb, or -PH(=O)Rb; Rb is independently hydrogen, - C(=O)OH, C1-C20 alkyl, C1-C20 alkoxy, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10-membered heterocycloalkyl, or 5- to 12-membered heteroaryl; the C1-C20 alkyl, C1-C20 alkoxy, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10-membered heterocycloalkyl, and 5- to 12-membered heteroaryl are optionally substituted with one or more Rb-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0160] In some embodiments, each Rb-1 is independently deuterium, halogen, hydroxyl, -NRfRf, C1-C20 alkoxy, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3-to 10-membered heterocycloalkyl, 5- to 12-membered heteroaryl, -C(=O)ORf, -C(=O)Rf, -C(=O)NRfRf, -S(=O)2NRfRf, -S(=O)2ORf, -S(=O)2Rf, -S(=O)Rf, -P(=O)RfRf, or -PH(=O)Rf; the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10- membered heterocycloalkyl, and 5- to 12-membered heteroaryl are optionally substituted with one or more Rb-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0161] In some embodiments, each Rb-1-1 is independently deuterium, halogen, hydroxyl, amino, C1-C20 alkoxy, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3-to 10-membered heterocycloalkyl, 5- to 12-membered heteroaryl, -C(=O)OH, -C(=O)H, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, -S(=O)2H, -S(=O)Rf, or -P(=O)2(OH)2; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0162] In some embodiments, Rf is independently hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10-membered heterocycloalkyl, or 5- to 12membered heteroaryl; the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10-membered heterocycloalkyl, and 5- to 12-membered heteroaryl are optionally substituted with one or more Rf-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0163] In some embodiments, each Rf-1 is independently deuterium, halogen, hydroxyl, amino, C1-C20 alkoxy, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3-to 10-membered heterocycloalkyl, or 5- to 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 heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0164] In some embodiments, Y is -C(=O)ORb or -C(=O)Rb; Rb is independently C1-C20 alkyl or C6-C10 aryl-C(=O)ORf; the C1-C20 alkyl and C6-C10 aryl are optionally substituted with one or more Rb-1.

[0165] In some embodiments, each Rb-1 is independently halogen, -NRfRf, C1-C20 alkyl, C1-C20 alkoxy, C6-C10 aryl, 3- to 10-membered heterocycloalkyl, or -C(=O)ORf; the C1-C20 alkyl, C6-C10 aryl, and 3- to 10-membered heterocycloalkyl are optionally substituted with one or more Rb-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0166] In some embodiments, each Rb-1-1 is independently halogen or -C(=O)OH.

[0167] In some embodiments, Rf is independently hydrogen or C1-C20 alkyl.

[0168] In some embodiments, Y is -C(=O)Rb; Rb is independently C1-C20 alkyl, C1-C20 alkoxy, 3- to 8-membered heteroalkyl, -COOH, or C6-C10 aryl; the C1-C20 alkyl, C1-C20 alkoxy, 3- to 8membered heteroalkyl, and C6-C10 aryl are optionally substituted with one or more Rb-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0169] In some embodiments, each Rb-1 is independently halogen, -NRfRf, 3- to 10-membered heterocycloalkyl, C6-C10 aryl, or -C(=O)OH; the C6-C10 aryl is optionally substituted with one or more Rb-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0170] In some embodiments, each Rb-1-1 is independently halogen.

[0171] In some embodiments, Rf is independently C1-C20 alkyl.

[0172] In some embodiments, a halogen is not connected to a heteroatom.

[0173] In some embodiments, Y is

[0174] 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, -ORa, -SRa, -NRaRa, nitro, cyano, -C(=O)Ra, -C(=O)ORa, -C(=O)NRaRa, -S(=O)2NRaRa, -S(=O)2Ra, -S(=O)2ORa, nitro, cyano, C1-C20 alkyl optionally substituted with one or more Ra, C1-C20 alkoxy optionally substituted with one or more Ra, C2-C20 alkenyl optionally substituted with one or more Ra, C2-C20 alkynyl optionally substituted with one or more Ra, 3- to 8-membered heteroalkyl optionally substituted with one or more Ra, 3- to 10-membered heteroalkenyl optionally substituted with one or more Ra, or 3- to 10- membered heteroalkynyl optionally substituted with one or more Ra; each Ra is 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-C20 alkyl, or 3- to 20-membered heteroalkyl; the -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, C1-C20 alkyl, and 3- to 20-membered heteroalkyl are optionally substituted with one or more Ra-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0175] In some embodiments, each Ra-1 is independently C1-C20 alkyl, C1-C20 alkoxy, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10-membered heterocycloalkyl, or 5- to 12-membered heteroaryl; the C1-C20 alkyl, C1-C20 alkoxy, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3- to 8-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl, 3- to 10-membered heterocycloalkyl, and 5- to 12-membered heteroaryl are optionally substituted with one or more Ra-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0176] In some embodiments, each Ra-1-1 is independently deuterium, halogen, -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, nitro, cyano, C1-C20 alkyl, C6-C10 aryl, or 3- to 20-membered heteroalkyl; the C6-C10 aryl, C1-C20 alkyl, and 3- to 20-membered heteroalkyl are optionally substituted with one or more Ra-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0177] In some embodiments, each Ra-1-1-1 is independently halogen.

[0178] In some embodiments, each Rd is independently -NHYd-1 or C1-C20 alkoxy.

[0179] In some embodiments, each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl, C1-C20 alkoxy, or C6-C10 aryl; the C1-C20 alkyl, C1-C20 alkoxy, and C6-C10 aryl are optionally substituted with one or more Rd-1-1.

[0180] In some embodiments, each Rd-1-1 is independently halogen, C6-C10 aryl, or C1-C20 alkyl; the C6-C10 aryl and C1-C20 alkyl are optionally substituted with one or more Rd-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0181] In some embodiments, each Rd-1-1-1 is independently halogen.

[0182] In some embodiments, Rd is -NHYd-1.

[0183] In some embodiments, Yd-1 is -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl, C1-C20 alkoxy, or C6-C10 aryl; the C1-C20 alkyl, C1-C20 alkoxy, and C6-C10 aryl are optionally substituted with one or more Rd-1-1.

[0184] In some embodiments, each Rd-1-1 is independently halogen, C6-C10 aryl, or C1-C20 alkyl; the C6-C10 aryl and C1-C20 alkyl are optionally substituted with one or more Rd-1-1-1; the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

[0185] In some embodiments, each Rd-1-1-1 is independently halogen.

[0186] In some embodiments, Rd is C1-C20 alkoxy. In some embodiments, each Yd-1 is independently

[0187]

[0188] In some embodiments, Rd-0 is H.

[0189] In some embodiments, Rd-2 is methyl.

[0190] In some embodiments, the compound represented by Formula I is a compound represented by Formulas I-1 to I-12: 1-4 1-5 1-6 or

[0191] In some embodiments, the compound represented by Formula I is a compound represented by Formulas I-13 to I-24:

[0192] In some embodiments, the compound represented by Formula I is a compound represented by Formula I-a, I-b, or I-c:

[0193] In some embodiments, the compound represented by Formula I-a is a compound represented by Formula I-a-1, I-a-2, I-a-3, I-a-4, or I-a-5, or

[0194] In some embodiments, in the compound represented by Formula I-a-1, Rc is -NH-X-Y; X is X1, X2-X3, or X4-X5-X6-X7; X1 is , , or

[0195] or

[0196] X3 is

[0197] X4 is o ; X5 is O ; X7 is        0

[0198] Y is -C(=O)ORb or -C(=O)Rb; Rb is independently C1-C20 alkyl, C6-C10 aryl, or C(=O)ORf; the C1-C20 alkyl and C6-C10 aryl are optionally substituted with one or more Rb-1; each Rb-1 is independently halogen, -NRfRf, C1-C20 alkoxy, C1-C20 alkyl, C6-C10 aryl, 3- to 10-membered heterocycloalkyl, or -C(=O)ORf; the C1-C20 alkoxy, C1-C20 alkyl, C6-C10 aryl, and 3- to 10membered heterocycloalkyl are optionally substituted with one or more Rb-1-1; each Rb-1-1 is independently halogen or -C(=O)OH; Rf is independently hydrogen or C1-C20 alkyl; the heteroatom of the heterocycloalkyl is N and / or O, and the number of heteroatoms is 1 or 2.

[0199] In some embodiments, Y is -C(=O)Rb, wherein Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or C(=O)OH-3- to 8membered heteroalkyl.

[0200] In some embodiments, in the compound represented by Formula I-a-2, Rd is -NHYd-1 or C1-C20 alkoxy, and the C1-C20 alkoxy is optionally substituted with one or more Rd-1; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl, C1-C20 alkoxy, or C6-C10 aryl; the C1-C20 alkyl, C1-C20 alkoxy, and C6-C10 aryl are optionally substituted with one or more Rd-11; each Rd-1-1 is independently halogen, C6-C10 aryl, or C1-C20 alkyl; the C6-C10 aryl and C1-C20 alkyl are optionally substituted with one or more Rd-1-1-1; each Rd-1-1-1 is independently halogen.

[0201] In some embodiments, Rd is -NHYd-1, wherein Yd-1 is -C(=O)Rd-1, and Rd-1 is C1-C10 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl substituted with 1-3 halogens, or C1-C10 alkoxy.

[0202] In some embodiments, in the compound represented by Formula I-a-3, Rd is -NHYd-1 or C1-C20 alkoxy, and the C1-C20 alkoxy is optionally substituted with one or more Rd-1; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl or C1-C20 alkoxy.

[0203] In some embodiments, in the compound represented by Formula I-a-4, each Rd is independently -NHYd-1 or C1-C20 alkoxy, and the C1-C20 alkoxy is optionally substituted with one or more Rd-1; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl or C1-C20 alkoxy.

[0204] In some embodiments, in the compound represented by Formula I-a-5, Rc is -NH-X-Y; X o HN^f is Xi; Xi is            ; Y is -C(=O)Rb; Rb is independently C1-C20 alkyl; the C1-C20 alkyl is optionally substituted with one or more Rb-1; each Rb-1 is independently -C(=O)ORd; Rd is independently hydrogen.

[0205] In some embodiments, the compound represented by Formula I-b is a compound represented by Formula I-b-i, I-b-2, or I-b-3, O        HO

[0206] In some embodiments, in the compound represented by Formula I-b-1, Rc is -NH-X-Y; X is X2-X3;

[0207] X2 is or

[0208] X3 is

[0209] Y is -C(=O)Rb; Rb is C1-C20 alkyl or -NRfRf; Rf is independently hydrogen or C1-C20 alkyl.

[0210] In some embodiments, Y is -C(=O)Rb, wherein Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, or C1-C10 alkoxy.

[0211] In some embodiments, in the compound represented by Formula I-b-2, Rd is -NHYd-1; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkoxy.

[0212] In some embodiments, in the compound represented by Formula I-b-3, Rd is C1-C6 alkoxy.

[0213] In some embodiments, the compound represented by Formula I-c is a compound Rc represented by Formula I-c-1

[0214] In some embodiments, in the compound represented by Formula I-c-1, Rc is -NH-X-Y; X is X2-X3; X2 is or 0    ; X3 is ; Y is -C(=O)Rb; Rb is C1-C20 alkyl, preferably C1-C8 alkyl.

[0215] In some embodiments, X is X1 or X2-X3;

[0216] X1 is 0    ; X2 is or       0    ; X3 is

[0217] Y is -C(=O)ORb or -C(=O)Rb; Rb is independently C1-C20 alkyl or C6-C10 aryl; the C1-C20 alkyl and C6-C10 aryl are optionally substituted with one or more Rb-1; each Rb-1 is independently halogen, -NRfRf, 3- to 10-membered heterocycloalkyl, or -C(=O)ORf; Rf is independently hydrogen or C1-C20 alkyl (e.g., Y is 0     ).

[0218] In some embodiments, Y is -C(=O)Rb; Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1- C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C2-C6 alkyl, or C1-C10 alkoxy.

[0219] In some embodiments, Y is -C(=O)Rb; Rb is not an electron-withdrawing group, such as -C(=O)OH.

[0220] In some embodiments, each Rd is independently -NHYd-1 or C1-C20 alkoxy; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl or C1-C20 alkoxy (e.g., each Rd

[0221] In some embodiments, X is X1 or X2-X3; , or methoxy; each Yd-1 is

[0222] X1 is 0    ; X2 is or 0    ; X3 is

[0223] Y is -C(=O)ORb or -C(=O)Rb; Rb is independently C1-C20 alkyl; the C1-C20 alkyl is optionally substituted with one or more Rb-1; each Rb-1 is independently halogen or -NRfRf; Rf is independently hydrogen or C1-C20 alkyl (e.g., Y is

[0224] In some embodiments, Y is -C(=O)Rb; Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, or C1-C10 alkoxy.

[0225] In some embodiments, each Rd is independently -NHYd-1 or C1-C20 alkoxy; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl or C1-C20 alkoxy (e.g., each Rd is independently       °         or methoxy, each Yd-1 is independently       °    ).

[0226] In some embodiments, X is X2-X3; o    ; X3 is        / HN          HN V-NH2

[0227] X2 is        O       or

[0228] Y is -C(=O)ORb or -C(=O)Rb; Rb is independently C1-C20 alkyl or C6-C10 aryl; the C1-C20 alkyl and C6-C10 aryl are optionally substituted with one or more Rb-1; each Rb-1 is independently halogen, -NRfRf, 3- to 10-membered heterocycloalkyl, or -C(=O)ORf; Rf is independently hydrogen or C1-C20 alkyl (e.g., Y is or         0    ).

[0229] In some embodiments, Y is -C(=O)Rb; Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1- C10 alkyl, or C1-C10 alkoxy.

[0230] In some embodiments, each Rd is independently -NH-Yd-1 or C1-C20 alkoxy optionally substituted with one or more Rd-1; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is "y     NH—| independently C1-C20 alkyl or C1-C20 alkoxy (e.g., each Rd is independently       °         or methoxy, each Yd-1 is independently       0    ).

[0231] In some embodiments,

[0232] X is X1 or X2-X3;

[0233] X1 is 0    ; X2 is or 0    ; X3 is

[0234] Y is -C(=O)Rb; Rb is independently C1-C20 alkyl or C6-C10 aryl; the C1-C20 alkyl and C6-C10 aryl are optionally substituted with one or more Rb-1; each Rb-1 is independently halogen, -NRfRf, 3- to 10-membered heterocycloalkyl, or -C(=O)ORf; Rf is independently hydrogen or C1- C20 alkyl (e.g., Y is or         °    ).

[0235] In some embodiments, Y is -C(=O)Rb; Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1- C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C2-C6 alkyl, or C1-C10 alkoxy.

[0236] In some embodiments, each Rd is independently -NHYd-1 or C1-C20 alkoxy optionally substituted with one or more Rd-1; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl or C1-C20 alkoxy (e.g., each Rd is independently , or methoxy; each Yd-1 is independently or        0    ).

[0237] In some embodiments,

[0238] X is X2-X3;

[0239] X2 is 0    ; X3 is

[0240] Y is -C(=O)ORb or -C(=O)Rb; Rb is independently C1-C20 alkyl or C6-C10 aryl; the C1-C20 alkyl and C6-C10 aryl are optionally substituted with one or more Rb-1; each Rb-1 is independently -NRfRf or 3- to 10-membered heterocycloalkyl; Rf is independently hydrogen or C1-C20 alkyl (e.g., Y is ).

[0241] In some embodiments, Y is -C(=O)Rb; Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl or 3- to 8-membered heterocycloalkyl-C1-C6 alkyl.

[0242] In some embodiments, each Rd is independently -NHYd-1; each Yd-1 is independently - X 0 C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl (e.g., each Rd is independently           or ; each Yd-1 is independently 0            \ I or         0    ).

[0243] In some embodiments,

[0244] X is X2-X3;

[0245] X2 is         O        or      O ; X3 is        /    ;

[0246] Y is -C(=O)Rb; Rb is independently C1-C20 alkyl; the C1-C20 alkyl is optionally substituted with one or more Rb-1; each Rb-1 is independently -NRfRf; Rf is independently hydrogen or C1-C20 alkyl (e.g., Y is or ).

[0247] In some embodiments, Y is -C(=O)Rb; Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl or C1-C10 alkyl.

[0248] In some embodiments,

[0249] each Rd is independently -NHYd-1; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl or C1-C20 alkoxy (e.g., each R is independently ; each Yd-1 is independently o ).

[0250] In some embodiments,

[0251] X is X2-X3;

[0252] HN X2 is        0 or 0    ; X3 is

[0253] Y is -C(=O)Rb; Rb is independently C1-C20 alkyl; the C1-C20 alkyl is optionally substituted with one or more Rb-1; each Rb-1 is independently -NRfRf or -C(=O)ORf; Rf is independently hydrogen or C1-C20 alkyl (e.g., Y is

[0254] In some embodiments, Y is -C(=O)Rb; Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1- C10 alkyl, or C(=O)OH-C2-C6 alkyl.

[0255] In some embodiments, each Rd is independently -NHYd-1; each Yd-1 is independently -C(=O)Rd-1; each Rd-1 is independently C1-C20 alkyl or C1-C20 alkoxy (e.g., each R is independently 2V-o s                     \-o  1 -y  y-NH—]                 -y yy 0        ; each Yd-1 is independently        O ).

[0256] In some embodiments, Y is -C(=O)Rb; Rb is independently C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C10 aryl, or C6-C10 aryloxy; the C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C10 aryl, and C6-C10 aryloxy are optionally substituted with Rb-1; the Rb-1 is -C(=O)OH, halogen, C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C10 aryl, or C6-C10 aryloxy.

[0257] In some embodiments, Yd-1 is -C(=O)Rd-1; Rd-1 is independently C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C10 aryl, or C6-C10 aryloxy; the C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C10 aryl, and C6-C10 aryloxy are optionally substituted with Rd-1; the Rd-1 is -C(=O)OH, halogen, C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C10 aryl, or C6-C10 aryloxy.

[0258] In some embodiments, Rd-2 is C1-C8 alkyl, C3-C8 cycloalkyl, or C6-C10 aryl; the C1-C8 alkyl, C3-C8 cycloalkyl, and C6-C10 aryl are optionally substituted with Rd-2-1; the Rd-2-1 is -C(=O)OH, halogen, C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy, C6-C10 aryl, or C6-C10 aryloxy.

[0259] In some embodiments, the compound represented by Formula I excludes any one of compounds PA-1 to PA-16, or an optical isomer of any one thereof.

[0260] In some embodiments, Rd-1 or Rb excludes a polyethylene glycol moiety (         n1, n- 1 is an integer >2), hydroxyl-substituted 6-membered oxacycloalkoxy, or (C=O)OHC1-C6 alkylOC1-C6 alkyl.

[0261] In some embodiments, all chiral amino acid residues are L-amino acid residues.

[0262] In some embodiments, the amino terminus of X is connected to Y, and the carbonyl terminus of X is connected to -NRe-.

[0263] In some embodiments, X is formed by two or more amino acids, each connected via an amide bond.

[0264] In some embodiments, R excludes nitro (-NO2) or amino (-NH2).

[0265] In some embodiments, Rd-2 excludes R'NHC(=O)C1-C6 alkyl, wherein R' is any substituent.

[0266] In some embodiments, Y is -C(=O)C2-C4 linear alkyl Rb, -S(=O)2C2-C4 linear alkyl Rb, -S(=O)C2-C4 linear alkyl Rb, or -P(=O)(C2-C4 linear alkyl Rb)Rb.

[0267] In some embodiments, Yd-1 is -C(=O)C2-C4 linear alkyl Rd-1, -S(=O)2C2-C4 linear alkyl Rd-1, -S(=O)C2-C4 linear alkyl Rd-1, or -P(=O)(C2-C4 linear alkyl Rd-1)Rd-1.

[0268] In some embodiments, Rd-1 in Yd-1 is an electron-donating group.

[0269] In some embodiments, Yd-1 excludes -C(=O)CF3.

[0270] In some embodiments, -ORd-2 is at the para position of benzyloxycarbonyl, and Rd-2 is an electron-donating group.

[0271] In some embodiments, Rc is at the para position of benzyloxycarbonyl.

[0272] In some embodiments, the compound represented by Formula I is a compound represented by Formula II-1, II-2, or II-3,

[0273] X2 or X3 are each independently selected from alanine residue, citrulline residue, valine residue, glycine residue, phenylalanine residue, leucine residue, cysteine residue, aspartic acid residue, glutamic acid residue, histidine residue, isoleucine residue, lysine residue, methionine residue, asparagine residue, proline residue, glutamine residue, arginine residue, serine residue, threonine residue, tryptophan residue, and tyrosine residue.

[0274] In some embodiments, Y is -C(=O)Rb, S(=O)2Rb, or -S(=O)Rb.

[0275] In some embodiments, Rb is -NHRb-1, -NRb-1Rb-1, -C(=O)Rb-1, -ORb-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10membered heteroaryloxy are optionally substituted with one or more Rb-1.

[0276] In some embodiments, each Rb-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1, -NRb-1-1Rb-1-1, -ORb-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3-to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1-1.

[0277] In some embodiments, each Rb-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1-1, -NRb-1-1-1Rb-1-1-1, -ORb-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1-1-1.

[0278] In some embodiments, each Rb-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1-1-1, -NRb-1-1-1-1Rb-1-1-1-1, -ORb-1-1-1-1, C1-C6 alkyl, 3- to 8membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the Rb-1-1-1-1-substituted C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5-to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1-1-1-1.

[0279] In some embodiments, each Rb-1-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkyl-NH-, (3- to 8-membered heteroalkyl)(3- to 8-membered heteroalkyl)N-, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, 3- to 8-membered heterocycloalkyl-NH-, (3- to 8-membered heterocycloalkyl)(3- to 8-membered heterocycloalkyl)N-, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10membered heteroaryloxy.

[0280] In some embodiments, two heteroatoms are not connected by a single bond unless one heteroatom is oxo-substituted; the heteroatom is O, S, or N.

[0281] In some embodiments, Rb excludes a polyethylene glycol moiety (            , n-1 is an integer >2), hydroxyl-substituted 6-membered oxacycloalkoxy, or (C=O)OHC1-C6 alkylOCi-C6 alkyl.

[0282] In some embodiments, X2 is an L-citrulline residue or an L-alanine residue, and X3 is an O N vNH h L-valine residue; X2-X3 is preferably '                             or          u           .

[0283] In some embodiments, Y is -C(=O)Rb, -S(=O)2Rb, or -S(=O)Rb, wherein Rb is 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- to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3-to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, or C5-C10 heteroaryl-3- to 8-membered heteroalkylamino; wherein 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, N(C1-C6 alkyl)(C0-C6 alkyl)3-to 8-membered heteroalkyl, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkoxy, N(C1-C6 alkyl)(C0-C6 alkyl)3- to 8-membered heteroalkylamino, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, 3- to 8-membered heteroalkyl, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkylamino, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkoxy, 3- to 8-membered heterocycloalkylamino, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkyl, 3- to 8-membered heterocycloalkyl-3- to 8-membered heteroalkoxy, 3- to 8-membered heterocycloalkyl-3- to 8membered heteroalkylamino, -C(=O)OH, C6-C10 aryl, C6-C10 aryloxy, C6-C10 arylamino, C5-C10 heteroaryl, C5-C10 heteroaryloxy, C5-C10 heteroarylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-3- to 8-membered heteroalkyl, C6-C10 aryl-3- to 8-membered heteroalkoxy, C6-C10 aryl-3- to 8-membered heteroalkylamino, C5-C10 heteroaryl-C1-C6 alkyl, C5-C10 heteroaryl-C1-C6 alkoxy, C5-C10 heteroaryl-C1-C6 alkylamino, C5-C10 heteroaryl-3- to 8-membered heteroalkyl, C5-C10 heteroaryl-3- to 8-membered heteroalkoxy, and C5-C10 heteroaryl-3- to 8-membered heteroalkylamino are optionally substituted with one or more deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, or -C(=O)OH.

[0284] In some embodiments, Y is -C(=O)Rb, -S(=O)2Rb, or -S(=O)Rb, wherein Rb is 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-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkoxy substituted with 1-3 halogens, C1-C6 alkylamino substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkoxy, 3- to 8-membered heterocycloalkyl-C1-C6 alkylamino, C6-C10 aryl substituted with 1-3 halogens, C6-C10 aryloxy substituted with 1-3 halogens, C6-C10 arylamino substituted with 13 halogens, C(=O)OH-C0-C6 alkyl, C(=O)OH-C0-C6 alkoxy, C(=O)OH-C0-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkoxy, C6-C10 aryl-C1-C6 alkylamino, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkoxy substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkylamino substituted with 1-3 halogens, C(=O)OH-3- to 8-membered heteroalkyl, C(=O)OH-3- to 8-membered heteroalkoxy, or C(=O)OH-3- to 8-membered heteroalkylamino.

[0285] In some embodiments, Y is -C(=O)Rb, -S(=O)2Rb, or -S(=O)Rb, wherein Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or C(=O)OH-3- to 8-membered heteroalkyl.

[0286] In some embodiments, Y is -C(=O)Rb.

[0287] In some embodiments, Rb is C1-C6 alkyl, C1-C6 alkoxy, -ORb-1, C6-C10 aryl, -C(=O)OH, or 3- to 8-membered heteroalkyl; the C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, and 3- to 8-membered heteroalkyl are optionally substituted with one or more Rb-1.

[0288] In some embodiments, each Rb-1 is independently C1-C6 alkyl, C6-C10 aryl, halogen, -NRfRf, 3- to 8-membered heterocycloalkyl, or -C(=O)OH; the C1-C6 alkyl, C6-C10 aryl, and 3- to 8-membered heterocycloalkyl are optionally substituted with one or more Rb-1-1.

[0289] In some embodiments, each Rf is independently C1-C6 alkyl.

[0290] In some embodiments, each Rb-1-1 is independently halogen.

[0291] In some embodiments, Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or C(=O)OH-3- to 8-membered heteroalkyl.

[0292] In some embodiments, the compound represented by Formula II-1 is a compound represented by Formula II-1-1, II-1-2, II-1-3, or II-1-4:

[0293] In some embodiments, Rb is as defined in the moiety of the compound represented by Formula II-1, II-2, or II-3.

[0294] In some embodiments, Rb is C1-C6 alkyl, C1-C6 alkoxy, -ORb-1, or C6-C10 aryl; the C1-C6 alkyl, C1-C6 alkoxy, and C6-C10 aryl are optionally substituted with one or more Rb-1.

[0295] In some embodiments, each Rb-1 is independently -NRfRf, halogen, 3- to 8-membered heterocycloalkyl, -C(=O)OH, or C1-C6 alkyl.

[0296] In some embodiments, each Rf is independently C1-C6 alkyl.

[0297] In some embodiments, Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C8 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, or C1-C8 alkoxy.

[0298] In some embodiments, each Rb-1 is independently -NRfRf, halogen, 3- to 8-membered heterocycloalkyl, -C(=O)OH, C6-C10 aryl, or C1-C6 alkyl; the C6-C10 aryl is optionally substituted with one or more Rb-1-1.

[0299] In some embodiments, each Rb-1-1 is independently halogen.

[0300] In some embodiments, Rb is C1-C10 alkyl, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, 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-C10 alkoxy.

[0301] In some embodiments, the compound represented by Formula II-2 is a compound represented by Formula II-2-1, II-2-2, II-2-3, or II-2-4:

[0302] In some embodiments, Rb is as defined in the moiety of the compound represented by Formula II-1-1, II-1-2, II-1-3, or II-1-4.

[0303] In some embodiments, Rb is C1-C6 alkyl; the C1-C6 alkyl is optionally substituted with one or more Rb-1.

[0304] In some embodiments, each Rb-1 is independently -NRfRf.

[0305] In some embodiments, each Rf is independently C1-C6 alkyl.

[0306] In some embodiments, Rb is C1-C6 alkyl.

[0307] In some embodiments, Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl.

[0308] In some embodiments, the compound represented by Formula II-3 is a compound represented by Formula II-3-1, II-3-2, II-3-3, or II-3-4:

[0309] In some embodiments, Rb is as defined in the moiety of the compound represented by Formula II-2-1, II-2-2, II-2-3, or II-2-4.

[0310] In some embodiments, Rb is C1-C8 alkyl.

[0311] In some embodiments, the compound represented by Formula I is a compound represented by Formula II-4, II-5, or II-6,

[0312] Xi is an amino acid residue, preferably an a-amino acid residue, preferably an alanine residue, citruline residue, valine residue, glycine residue, phenylalanine residue, leucine residue, cysteine residue, aspartic acid residue, glutamic acid residue, histidine residue, isoleucine residue, lysine residue, methionine residue, asparagine residue, proline residue, glutamine residue, arginine residue, serine residue, threonine residue, tryptophan residue, tyrosine residue, more preferably an L-alanine residue, L-citruline residue, L-valine residue, glycine residue, L-phenylalanine residue, L-leucine residue, L-cysteine residue, L-aspartic acid residue, L-glutamic acid residue, L-histidine residue, L-isoleucine residue, L-lysine residue, L-methionine residue, L-asparagine residue, L-proline residue, L-glutamine residue, L-arginine residue, L-serine residue, L-threonine residue, L-tryptophan residue, or L-tyrosine residue;

[0313] Y is -C(=O)Rb, S(=O)2Rb, or -S(=O)Rb. In some embodiments, Y is -C(=O)Rb.

[0314] In some embodiments, Rb is as defined in the moiety of the compound represented by Formula II-3-i, II-3-2, II-3-3, or II-3-4.

[0315] In some embodiments, Rb is Ci-C6 alkyl, -C(=O)OH, or 3- to 8-membered heteroalkyl; the C1-C6 alkyl and 3- to 8-membered heteroalkyl are optionally substituted with one or more Rb-1

[0316] In some embodiments, each Rb-1 is independently -C(=O)OH.

[0317] In some embodiments, Rb is C(=O)OH-C0-C6 alkyl or C(=O)OH-3- to 8-membered heteroalkyl.

[0318] In some embodiments, the compound represented by Formula II-4 is a compound represented by Formula II-4-1, II-4-2, II-4-3, II-4-4, II-4-5, II-4-6, II-4-7, II-4-8, II-4-9, II-4-10, II-4-11, or II-4-12:

[0319] In some embodiments, Rb is as defined in the moiety of the compound represented by Formula II-4, II-5, or II-6.

[0320] In some embodiments, Rb is C1-C6 alkyl; the C1-C6 alkyl is optionally substituted with one or more Rb-1.

[0321] In some embodiments, Rb is C1-C6 alkyl or -C(=O)OH; the C1-C6 alkyl is optionally substituted with one or more Rb-1.

[0322] In some embodiments, each Rb-1 is independently -C(=O)OH.

[0323] In some embodiments, Rb is C(=O)OH-C1-C6 alkyl.

[0324] In some embodiments, Rb is C(=O)OH-C0-C6 alkyl.

[0325] In some embodiments, the compound represented by Formula II-5 is a compound represented by Formula II-5-1, II-5-2, II-5-3, II-5-4, II-5-5, II-5-6, II-5-7, II-5-8, II-5-9, II-5-10, II-5-11, or II-5-12:

[0326] In some embodiments, Rb is as defined in the moiety of the compound represented by Formula II-4-1, II-4-2, II-4-3, II-4-4, II-4-5, II-4-6, II-4-7, II-4-8, II-4-9, II-4-10, II-4-11, or II-4-12.

[0327] In some embodiments, the compound represented by Formula II-6 is a compound represented by Formula II-6-1, II-6-2, II-6-3, II-6-4, II-6-5, II-6-6, II-6-7, II-6-8, II-6-9, II-6-10, II-6-11, or II-6-12:

[0328] In some embodiments, Rb is as defined in the moiety of the compound represented by Formula II-4-1, II-4-2, II-4-3, II-4-4, II-4-5, II-4-6, II-4-7, II-4-8, II-4-9, II-4-10, II-4-11, or II-4- 12.

[0329] 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,

[0330] In some embodiments, Yd-1 is -C(=O)Rd-1, S(=O)2Rd-1 or -S(=O)Rd-1.

[0331] In some embodiments, Yd-1 is -C(=O)Rd-1.

[0332] In some embodiments, Rd-1 is as defined in the moiety Rb of the compound represented by Formula II-4-1, II-4-2, II-4-3, II-4-4, II-4-5, II-4-6, II-4-7, II-4-8, II-4-9, II-4-10, II-4-11, or II-4-12.

[0333] In some embodiments, Rd-1 is C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or -ORd-1-1; the C1-C6 alkyl, C6-C10 aryl, and C1-C6 alkoxy are optionally substituted with one or more Rd-1-1.

[0334] In some embodiments, each Rd-1-1 is independently C1-C6 alkyl, C6-C10 aryl, or halogen; the C1-C6 alkyl and C6-C10 aryl are optionally substituted with one or more Rd-1-1-1.

[0335] In some embodiments, each Rd-1-1-1 is independently halogen.

[0336] In some embodiments, Rd-2 is C1-C6 alkyl.

[0337] In some embodiments, Rd-2 is C1-C3 alkyl.

[0338] In some embodiments, Rd-2 is methyl.

[0339] In some embodiments, Rd-1 is C1-C6 alkyl or C1-C6 alkoxy; Rd-2 is C1-C6 alkyl.

[0340] In some embodiments, Rd-1 is C1-C10 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl substituted with 1-3 halogens, or C1-C10 alkoxy.

[0341] In some embodiments, Rd-1 is C1-C10 alkyl or C1-C10 alkoxy; Rd-2 is C1-C6 alkyl.

[0342] In some embodiments, the compound represented by Formula II-7 is a compound represented by Formula II-7-1 or II-7-2:

[0343] In some embodiments, Rd-1 is as defined in the moiety of 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.

[0344] In some embodiments, the compound represented by Formula II-8 is a compound represented by Formula II-8-1 or II-8-2:

[0345] In some embodiments, Rd-1 is as defined in the moiety of the compound represented by Formula II-7-1 or II-7-2.

[0346] In some embodiments, Rd-1 is C1-C6 alkyl, C1-C6 alkoxy, or -ORd-1-1.

[0347] In some embodiments, each Rd-1-1 is independently C1-C6 alkyl.

[0348] In some embodiments, Rd-1 is C1-C6 alkyl or C1-C6 alkoxy.

[0349] In some embodiments, the compound represented by Formula II-9 is a compound represented by Formula II-9-1 or II-9-2:

[0350] In some embodiments, Rd-1 is as defined in the moiety of the compound represented by Formula II-8-1 or II-8-2.

[0351] In some embodiments, Rd-1 is C1-C6 alkoxy; Rd-2 is C1-C6 alkyl.

[0352] In some embodiments, the compound represented by Formula II-10 is a compound represented by Formula II-10-1 or II-10-2:

[0353] In some embodiments, Rd-1 and Rd-2 are as defined in the moiety of the compound represented by Formula II-9-1 or II-9-2.

[0354] In some embodiments, Rd-1 is C1-C6 alkoxy; Rd-2 is C1-C6 alkyl.

[0355] In some embodiments, the compound represented by Formula II-12 is a compound represented by Formula II-12-1 or II-12-2:

[0356] In some embodiments, Rd-1 is as defined in the moiety of the compound represented by Formula II-8-1 or II-8-2.

[0357] In some embodiments, Rd-1 is C1-C6 alkoxy or -ORd-1-1.

[0358] In some embodiments, each Rd-1-1 is independently C1-C6 alkyl.

[0359] In some embodiments, Rd-1 is C1-C6 alkoxy.

[0360] Another aspect of the present disclosure provides a compound or a pharmaceutically acceptable salt thereof, wherein the compound is any one of the following compounds: Compound 1 h3co 0-( H3VX°, och3 .=-, NH / "x / V^Z V / v^5 ''' VjAZh) 0 o HO i o'Tn . 5 3A Vnh 0 J / N\L^ v-nh / ' _e HN—( r-N        \       ' / ? ( HN y-NH2 0 Compound 2 'X h3co oX H3e         och3 o' o HO ioXX >0 °V°AX o X Vnh 0 o ' )—NH -HN—C NH )=° h2n Compound 3 h3co 0=(               OCH3 NH / X / V-Z (XX) °>o° 0° ojtt 0       1 ex' HN / X —( HN—( 0 )—( '—\ NH 0    ^NH f^(          XH2 F F              d Compound 4 'X h3co 0=(  H3C\_^-VX 0CH3 / =A NH     / V#v^°'' V^v) 6 X0 HO i O'V- >° vl 0          1 O'""^ HN V HN-f0 °x\ / ^  '-\ )VNH 0    —NH ^NH2 0 Compound 5 ^o     H3CO o=( H3C\2<^VX och3 —NH AX / VZ (X''XXQ o° 6jy° F           0     To^ o (  ' -\ HN—( ^MH pNH2 0 Compound 6 ■^0      h3co °X H3C\X^X OCHs nh r\x O<x01' yo° oVjv’ x o ym o, p H2N       \      NH NH °x_ )—NH ir OH Compound 7 X o       h3co 0=(               OCH3 -=, NH XX / VZ O^0,,'VSm V \X0 0         [ 0^'" HN o      Vo \ VnH HN—( Vh z —\ o    —NH >0 h2n Compound 8 X o      h3co 0=(               OCH3 / =. NH / ^X / 'XpZ °>O° OyX° O          1 C)''' x HXo VnH HN—_ 0 JA. —\ O    —NH >0 h2n Compound 9 h3co 0=(               och3 NH         V-Z OXy-vSK) bY ApA X J Qty V \    VNH 0 Compound 10 ^b     h3co 0=( H3C          och3 ,=3   nh CJA0"AAj (°A           °>°° °v6Jk 0 ^N           O    Jo^^ / / ° A   O hnV A x    Xnh 0 Compound 11 h3co O=( H3C\XAO» OCH3 NH b\ / \4Z JAAk'''AAA 0'   0 HO i o'Tn >0 °v°x 0 ,,o / VNH P A A A hnV x    A NH 0 Compound 12 h3co °A H3C\LAA och3 =. NH / k / Vj 3                     b X0 HO iOxTn \                     ovo9 Lo \---v                         0 / ? A kJ X^-XV x Anh 0 Compound 13 ^0     h3co oX             0CH3 nh r\x V- / A^A1 AAA) F                   <5   0 HO 1 0' In b   A ^kNxH ,? / =( A ~\ HNA = x Xnh 0 Compound 14 h3co oA H3c\_A^k'° och3 O^0,''Vaa) ,—.               b 0 ho i o' A AA          >0 ov°jA \=(             0      1? / ? / =(    kJ x    Anh 0 Compound 15 h3co 0=( nA^A-sX OCH3 ,=3 NH AA / WZ f       VM° ’ ’ J ,                  0 0 HO E ocTk O      >° vlL \=(              0 A\H ,° A kJ °-X< 9 \    ^NH 0 Compound 16 h3co 0=( H3c\ / M3. OCHg / =\ ,nh / \ / V-Z JAb-k'1 AAA (5 O HO 1 o'Xb >° Yx b 0 xhP 0 Compound 17 ■X h3co oA            och3 nh r\x\L^ OAaAXA) V a°a° F            0     Ah'" Ff7Xnho A 0 "-X b X   ^NH 0 Compound 18 A    H3C0 oX H3C\_bbX 0CH3 NH / ““V / Vx jAb-p AAA ci 0 HO =o'An >0 °AA —\             0 ^bN.H 9 / =\ kJ ’-99 b x Anh 0 Compound 19 H3CO o9 H3°\_J99 OCH3 =, ,NH / / / ' / -I ,                   6' o HO = o'Yn A        >° °Y°X m           °\    Jo ^Ah / / °   / =\   o A hn7 J \    ^NH 0 Compound 20 h3co O=( H3C\®®Jb OCH3 / =\ -NH / d 0 ho 1 o'V- OH           >0 Op'°X O^           0     J\ )=NH ,°     / =<     kJ °_(i< 9 \ yNH 0 Compound 21 h3co O=( H3C\L^ / i OCH3 NH f\ / VZ 6 O HO £ o'Vn >0 °v°x \             0      Jo Ayo J o °9 p V \    ^NH 0 Compound 22 h3co 0=( HsC          och3 / =\ -NH bx / V-Z C. / \ 6  0 ho 1 o'\X O        >° °Y°1 °\ Anh p P P °~A9 9 \    Anh 0 Compound 23 h3co 0=(  9 99, OCH3 =, NH / =9 / \9( AAA'pbAj 0   0 HO )=° °v°X 0           1 0' A 0 0 9 z 9 ANH 0 Compound 24 / °          0CH3 H3C     I z0 / =^ NH (=9--9, OCH3 4 P \ / °"\ X / \ }—z pyp'H / P 0 H0 9'A >0  0=,0( L-o O>      9-Z HO P / =(       L. l] O HN—( )^NH 0 Compound 25 h3co 0=(               OCH3 =^ nh r\^- \AZ CHA aS® °(=o° • ,s HN—(   / -7 Fnh 0 Compound 26 H3C0 o9 H3C\ 9.0 och3 =, NH 9=9 / \LJ 0 0 HO =0'VJ >0 °v°X 0       1 0"^ , Anh hnA / — / ° HQ A 0 Compound 27 \®    ”^0     H3CO 0      o=( H39_9~9° och3 90 z=\ ~NH 99 / 9- / HN / / -( P"'\ 9 / 9) > Py-J 0=(           0   0 HO - 0' V n NH      >0 °v°l A a AA HN9 pp     Anh 0 Compound 28 9 » Pr-AP 14°     0 " 1 0 op X -    0 / —01 1 \f I JP-9 °7xJ\ 0 \= / o O'"' ( / \ 9° a9P o-P-A <? Compound 29 h3co oX             °ch3 _== nh r\x \LJ. CxAA'AOxx o' O HO = 0X )=° °A o           1 A 6 °    v NH 0 Compound 30 ~X> h3co 0=( nA^-X^AX OCH3 NH A / \W OAaaAx °>o° 0       10^^ x 6 X ? v 0      Anh HN Compound 31 h3co o=^ H3C\_aAX OCH3 NH Ax / \AZ Caa^aaa °>o° O° o       1 (y^ A 6 HO O 0 M ° hn ' AA Compound 32 A h3co O=( H3C\ Jx° OCH3 NH AX / V-Z CaaaAx °>0° 0      10^^ = Anh hnA °\\ A^ A / — /   0 7 HO Compound 33 h3co o=( H3A_x^A\ och3 ==. nh r\y V-Z {AQn axx 0' O HO = oXl >0 CX 0       1 oz^ Anh HNX    / oaH  \ / —7   0     x HO Compound 34 ”^o     H3CO oX hx JX °cH3 -=, NH / ^X / V-Z \_f O'X / X / X V / a MZx 6 0 HO = oxl >0 oALo 0       1 ox' X 6 XNH 0 Compound 35 ~X> h3co oX H3C, XX OCHg -=, NH XX / vA Ax) 0' 0 HO i XX >° 0 XX 0          1 , Anh A / F Compound 36 ~”^b      h3co °X HaCAAA °ch3 =, NH XX / \Z-Z \_O'X X, / X x ? a Axx? 6' O HO =oXX A A°X 0     10^ z4 6 XX XNH 0 Compound 37 h3co 0=( ^=,00 och3 -== NH b \__f O‘"(    / \ 0 / \__^ 0007 o 0 HO OO >0 0°1 0       1 0^' 0 6 0NH 0 Compound 38 "^b      H3C0 0=( H3C........... / P OCH3 nh r^KxXLJ \_0" /   / \ 0 O HO i( / n (=0 °v°X A 6 0 F Compound 39 h3co oA H3CA och3 / =\ .NH r\x\Ll 0^071 00° °70^ / y NH 0 Compound 40 h3co O A H3C\        OCH3 -=X NH   r\x \£-( 5=o° 0     Ax"' \         ) Qj O A NH o Compound 41 ”^b      h3co o0 H3C\000 och3 ,_= NH b=\ / \JJ \__O'A / A. 000-0 6 O HO ;oM 0o °v°lj O    o       1 0^"" ’ b  b Compound 42 H3CO O=( H3C\         och3 === NH Ax / XZ-Z \O"(   / \ o' O HO i 000 0-° °x      1° 6 Compound 43 h3co 0=( HsC          och3 r=x NH AX^V-Z W00 ’' 0700) o>° AA jrk 0 HN—C 7 0 \ Compound 44 ”^0     h3co O0 H3°\ =0=0 och3 oYo,''Q07 o' O HO iO'0 00 A V™ 0 Compound 45 h3co 0=(               och3 z=\ NH /     XX 0 0 HO X / k / 0 ov°I; 0       1 0^^ d i Compound 46 ~^b      h3co o=( hscy och3 nh / =\ / XZ-Z \__f O"'(   / \ 0' 0 HO ioXX >0 °Ya 0          1 d * —0 Compound 47 ox / wm oy y).....y ° / =\ °" ¥r° T 1J 10 — (J : £ X° 0 i J u ~ 'x°v'C'° ° / 3 1 0 / X     0 u 1 Compound 48 H3CO 0=^ Hd. Y / 0CH3 NH XX / XA / \__<'   O"'(    / \ vyxyy 0'  0 HO i oXX >0 oV°X 0         1 ox'~ Compound 49 h3co o=( h3c IY och3 NH Xd / \fj V-d O'"( / / / \ yyyy yy / 6' O HO iAd >0 o^yy° HN        1 OX~ 0 i 0 \ Compound 50 I 0 1^° i'lo Q chy0^0'- / ^^0^ a f1 ° cA<? I -    0 ,—.    01 1 \f I yyx oy / \ “° \= / ox 0.....< A / 0 drfX °==o Compound 51 HO X / d / OH / ^=\ NH / ^VxVy v / v{1'' «                    0   0 HO £ 0' lo 0     >° vy °\ A? '—a 0 Y 0 Ydv X    ^NH 0 Compound 52 HO 0=(              oh NH    / \X GX’-'VY® ^0° o^6?J-o 0Z      1 0^" /     y—nh —< HN^( / —NH 0       NH r\ 7 x                h2n Compound 53 ^O     HO 0=( H3CT OH NH >=\ / \fj / \__^  0"'(    / \ V / T-t 6 o HO Ain >o oV°X o       1 OX T 6 TVP 0 Compound 54 ”~^b        HO oA H3A___T^T OH .-=, NH A\ AJJ \__C o-( o' 0 HO i o'T n >° °v°X -y 6 Compound 55 ^O     HO oA H3C A / , oh ,-, NH A\ / \fJ /  \__x'   O"(    / \ /  \ V / A-t A^aa o' 0 HO =0'Y\ >o ovT o        1 0Z~" 0 / 0 \ Compound 56 O I )= / °=<              OH G^°"'VaT O>o0 Ov^L^° o          1 .. /      y—nh —< hnA V ANH 0      NH T\ ' x                  h2n

[0361] Another aspect of the present disclosure provides a compound or a pharmaceutically acceptable salt thereof, wherein the compound is any one of the following compounds: Compound 59 h3co o=(  H3C\_<x^x^ NH / \zV< O"v<° "Qx( °)=o° 0              [ o'" A F X VX \ /      HN H H )=° ^N  N—< 0 XX ■' \ H ).0 h2n Compound 60 "^b      h3co °H             Pch3 C>X''XXX °)=O° 0(0X0 V 6 \ /        HN — pH  H )=° N—< 0 )X X H ---<    0          N >0 h2n Compound 61 ~^b      h3co o=(               och3 NH   / ^X / VX OXxPxA 0 0 ho £ ox 1 >=° vx 0            1 0 0 \ / HN -A H H )=° N N—( °  )-¼    \ H --< O        N \          >=0 h2n Compound 62 HO 0=( nX—XX 0H —NH XX / V- / / -x     ( / / \ / ° \ / x(() 9» / X>- vx XXX X X?'NH Compound 63 y X 0=( h3c          oh / _=x NH   A\X YX UX'PS® xv„ ■ v vP oX / Xly0  X y      0 Compound 64 0X1 xV 0 r 1        1 x L JX / °^°''X'"z=cd 11            1 0 0^0 1 rvp o“xAx X / o 0.....( A / ° Vq V(a / XX- X 0 o^xX'g Compound 65 ^0     HO o=(              oh / =\ -NH / v V-Z O'xrxSv? d O HO E OCA * H^yo   >0 VX /      ^0        ’oz V 6 L II H HN'X-NH N j « & ^0 ° Compound 66 p A o=\ H!C\Xa0. oh NH Ax / XX"VX( 0    0 HO = o-' V I >=° ovPX : = « JXO 0 Compound 67 o=( h3c == nh o o HC )=o k II H HN"\^NH ^X^N.   / H H         o o II o^^ P^pP OH PPP / rX f) Compound 68 ck / y-o /        J o=< yy °5 o y V ).....° ° / =y i ro n \ / / yj TO — £ °V° o r ii i          H UX" / "o o 10 .x J1   >< O Compound 69 HO O=(   H30x         OH == NH         \xZ Xx hv   °)=o° °°rdjy° \ '  - \ „ H HN-X-NH /      A " ' « 0 0       u Compound 70 ~^o       HO °=< HaC\         oh O^V4''PPSpP 6 o ho = O'-r \ )=°  0  0 1^0 . / 5 1 / 0 Compound 71 ^O     HO o=( h3c JL =^ NH Xx / CXyx o O HO i >° o o 0            I o M * o H o OH P"H / oPo Compound 72 n A o=( H= PP OH == NH           \Z-Z OU'QSx o O HO £ o''U * >° °vPk O            1 o —o Compound 73 p i 0=( Hy l =, nh yX —<' O A X VX X o 0 HO = >0 C oy a 0 II o X / 0H X"H / Compound 74 \°p ’ i kk 9? x O^O-X "z^ O^ 11 I 1 °cA> z i y ,O x / it FVy °‘9PV t \= / o o.....< A / ° Vq yU /     - r* o Compound 75 o o=( NH        H2 o P H3°\          OH rvM htV< ;   O"<   ><  / u\ O      \__ / 'P'-H / Boc^       O o     HO 6 JVo <y 04° <r Compound 76 p I O=( H3c NH r\^ €HyQ o o HO £ >=O o^c 0            1 0 0 i' 0 JI ,0 y? oh 0 / "H / p"O Compound 77 04 V ).....°x vy T 11 T" ° " V V                   -r” 1 «lxo O :                                                      1 £ °v° O            A° o p ° 1 ''Vzi " o--,K o Compound 78 ~Xd h3co °=(  H3C\_-^^4\ Pch3 NH / ^\x VX °>°° o°o o             1 0 rf6 \ / HN “A H H >° XN NO 0                 H —< O \          )=0 h2n Compound 79 w q zzx                  ° ° -0,¾ o O I ---   O I yB>”

[0362] In some embodiments, an amino group of an amino acid in X is linked to Y.

[0363] In some embodiments, the halogen may be fluorine, chlorine, bromine, or iodine, such as fluorine or chlorine.

[0364] In some embodiments, the C1-C20 alkyl may be C1-C10 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n-hexyl.

[0365] In some embodiments, the C2-C20 alkenyl may be C2-C10 alkenyl, and the C2-C20 alkenyl may contain 1, 2, or 3 carbon-carbon double bonds; for example, vinyl, 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.

[0366] In some embodiments, the C2-C20 alkynyl may be C2-C10 alkynyl, and the C2-C20 alkynyl 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.

[0367] In some embodiments, the C3-C20 cycloalkyl may be C3-C10 cycloalkyl, and may further be C3-C8 cycloalkyl; the C3-C20 cycloalkyl may be monocyclic or polycyclic; for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0368] In some embodiments, the C3-C20 cycloalkenyl may be C3-C10 cycloalkenyl; the C3-C20 cycloalkenyl may be monocyclic or polycyclic; the C3-C20 cycloalkenyl may contain 1, 2, or 3 carbon-carbon double bonds; for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, or cyclohexenyl.

[0369] In some embodiments, the C3-C20 cycloalkynyl may be C3-C10 cycloalkynyl; the C3-C20 cycloalkynyl may be monocyclic or polycyclic; the C3-C20 cycloalkynyl may contain 1, 2, or 3 carbon-carbon triple bonds; for example, cyclopropynyl, cyclobutynyl, cyclopentynyl, or cyclohexynyl.

[0370] In some embodiments, the 3- to 20-membered heteroalkyl may be 3- to 10-membered heteroalkyl, and may further be 3- to 8-membered heteroalkyl; the heteroatom of the 3- to 20membered heteroalkyl may be selected from 1, 2, 3, or 4 types 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).

[0371] In some embodiments, the 4- to 20-membered heteroalkenyl may be 4- to 10-membered heteroalkenyl; the heteroatom of the 4- to 20-membered heteroalkenyl may be selected from 1, 2, 3, or 4 types 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- to 20-membered heteroalkenyl may contain 1, 2, or 3 carboncarbon double bonds.

[0372] In some embodiments, the 4- to 20-membered heteroalkynyl may be 4- to 10-membered heteroalkynyl; the heteroatom of the 4- to 20-membered heteroalkynyl may be selected from 1, 2, 3, or 4 types 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- to 20-membered heteroalkynyl may contain 1, 2, or 3 carboncarbon triple bonds.

[0373] In some embodiments, the 3- to 20-membered heterocycloalkyl may be 3- to 10membered heterocycloalkyl; the heteroatom of the 3- to 20-membered heterocycloalkyl may be selected from 1, 2, 3, or 4 types of N, O, P, and S (preferably N and / or O), and the number of 77 heteroatoms may be 1, 2, 3, or 4 (preferably 1 or 2); for example, oxiranyl, oxetanyl, oxolanyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, or homopiperazinyl.

[0374] In some embodiments, the 3- to 20-membered heterocycloalkenyl may be 3- to 10membered heterocycloalkenyl; the heteroatom of the 3- to 20-membered heterocycloalkenyl may be selected from 1, 2, 3, or 4 types 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- to 20-membered heterocycloalkenyl may contain 1, 2, or 3 carbon-carbon double bonds.

[0375] In some embodiments, the 3- to 20-membered heterocycloalkynyl may be 3- to 10membered heterocycloalkynyl; the heteroatom of the 3- to 20-membered heterocycloalkynyl may be selected from 1, 2, 3, or 4 types 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- to 20-membered heterocycloalkynyl may contain 1, 2, or 3 carbon-carbon double bonds.

[0376] In some embodiments, the C6-C20 aryl may be C6-C10 aryl; for example, phenyl or naphthyl.

[0377] In some embodiments, the 5- to 20-membered heteroaryl may be 5- to 10-membered heteroaryl; the heteroatom of the 5- to 20-membered heteroaryl may be selected from 1, 2, 3, or 4 types of N, O, P, and S (preferably selected from 1, 2, or 3 types 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.

[0378] In some embodiments, the C1-C6 alkoxy may be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, or n-hexoxy.

[0379] In some embodiments, the 3- to 8-membered heteroalkoxy is a 3- to 8-membered heteroalkyl connected through oxygen, and the definition of the 3- to 8-membered heteroalkyl is the same as that of the 3- to 8-membered heteroalkyl.

[0380] In some embodiments, the C3-C8 cycloalkoxy may be cyclopropoxy, cyclobutoxy, cyclopentoxy, or cyclohexoxy.

[0381] In some embodiments, the 3- to 8-membered heterocycloalkoxy is a 3- to 8-membered heterocycloalkyl connected through oxygen, and the definition of the 3- to 8-membered heterocycloalkyl is the same as that of the 3- to 8-membered heterocycloalkyl.

[0382] In some embodiments, the C6-C10 aryloxy may be -O-phenyl or -O-naphthyl.

[0383] In some embodiments, the 5- to 10-membered heteroaryloxy is a 5- to 10-membered heteroaryl connected through oxygen, and the definition of the 5- to 10-membered heteroaryl is the same as that of the 5- to 10-membered heteroaryl.

[0384] In some embodiments, the C6-C10 arylamino may be -NH-phenyl or -NH-naphthyl.

[0385] In some embodiments, the 3- to 8-membered heteroalkylamino is a 3- to 8-membered heteroalkyl connected through amino, and the definition of the 3- to 8-membered heteroalkyl is the same as that of the 3- to 8-membered heteroalkyl.

[0386] In some embodiments, the C5-C10 heteroarylamino is a 5- to 10-membered heteroaryl connected through amino, and the definition of the 5- to 10-membered heteroaryl is the same as that of the 5- to 10-membered heteroaryl.

[0387] In some embodiments, in Rb, the C1-C20 alkyl may be C1-C10 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n-hexyl.

[0388] In some embodiments, in Rb, the C6-C10 aryl may be phenyl or naphthyl, such as phenyl.

[0389] In some embodiments, in Rb-1, the halogen may be fluorine, chlorine, bromine, or iodine, such as fluorine or chlorine.

[0390] In some embodiments, in Rb-1, the C1-C20 alkyl may be C1-C10 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n-hexyl.

[0391] In some embodiments, in Rb-1, the C6-C10 aryl may be phenyl or naphthyl, such as phenyl.

[0392] In some embodiments, in Rb-1, the heteroatom of the 3- to 10-membered heterocycloalkyl may be selected from 1, 2, 3, or 4 types 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- to 10-membered heterocycloalkyl is / — preferably 3- to 6-membered heterocycloalkyl, such as pyrrolidinyl ().

[0393] In some embodiments, in Rb-1-1, the halogen may be fluorine, chlorine, bromine, or iodine, such as fluorine or chlorine.

[0394] In some embodiments, in Rf, the C1-C20 alkyl may be C1-C10 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n-hexyl.

[0395] In some embodiments, in R, the halogen may be fluorine, chlorine, bromine, or iodine, such as fluorine or chlorine.

[0396] In some embodiments, in R, the C1-C20 alkyl may be C1-C10 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n- hexyl.

[0397] In some embodiments, in R, the C1-C20 alkoxy may be C1-C10 alkoxy, preferably C1-C6 alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tertbutoxy, n-pentoxy, isopentoxy, neopentoxy, or n-hexoxy.

[0398] In some embodiments, in R, the C2-C20 alkenyl may be C2-C10 alkenyl, and the C2-C20 alkenyl may contain 1, 2, or 3 carbon-carbon double bonds; for example, vinyl, 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.

[0399] In some embodiments, in R, the C2-C20 alkynyl may be C2-C10 alkynyl, and the C2-C20 alkynyl 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.

[0400] In some embodiments, in R, the heteroatom of the 3- to 8-membered heteroalkyl may be selected from 1, 2, 3, or 4 types 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 heteroatom of the 3- to 8-membered heteroalkyl is not at both ends of the substituent.

[0401] In some embodiments, in R, the heteroatom of the 3- to 10-membered heteroalkenyl may be selected from 1, 2, 3, or 4 types 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- to 10-membered heteroalkenyl may contain 1, 2, or 3 carbon-carbon double bonds; the 3- to 10-membered heteroalkenyl may be 3- to 6-membered heteroalkenyl.

[0402] In some embodiments, in R, the heteroatom of the 3- to 10-membered heteroalkynyl may be selected from 1, 2, 3, or 4 types 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- to 10-membered heteroalkynyl may contain 1, 2, or 3 carbon-carbon triple bonds; the 3- to 10-membered heteroalkenyl may be 3- to 6-membered heteroalkynyl.

[0403] In some embodiments, in Ra, the halogen may be fluorine, chlorine, bromine, or iodine, such as fluorine or chlorine.

[0404] In some embodiments, in Ra, the heteroatom of the 3- to 20-membered heteroalkyl may be selected from 1, 2, 3, or 4 types 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- to 20-membered heteroalkyl may be 2-to 6-membered heteroalkyl.

[0405] In some embodiments, in Ra-1, the C1-C20 alkyl may be C1-C10 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n-hexyl.

[0406] In some embodiments, in Ra-1, the C1-C20 alkoxy may be C1-C10 alkoxy, preferably C1-C6 alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tertbutoxy, n-pentoxy, isopentoxy, neopentoxy, or n-hexoxy.

[0407] In some embodiments, in Ra-1, the C2-C20 alkenyl may be C2-C10 alkenyl, and the C2-C20 alkenyl may contain 1, 2, or 3 carbon-carbon double bonds; for example, vinyl, 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.

[0408] In some embodiments, in Ra-1, the C2-C20 alkynyl may be C2-C10 alkynyl, and the C2-C20 alkynyl 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.

[0409] In some embodiments, in Ra-1, the C3-C10 cycloalkyl may be C3-C8 cycloalkyl; the C3-C10 cycloalkyl may be monocyclic or polycyclic; for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0410] In some embodiments, in Ra-1, the C6-C10 aryl may be phenyl or naphthyl, such as phenyl.

[0411] In some embodiments, in Ra-1, the heteroatom of the 3- to 8-membered heteroalkyl may be selected from 1, 2, 3, or 4 types 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).

[0412] In some embodiments, in Ra-1, the heteroatom of the 3- to 10-membered heteroalkenyl may be selected from 1, 2, 3, or 4 types 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- to 10-membered heteroalkenyl may contain 1, 2, or 3 carbon-carbon double bonds; the 3- to 10-membered heteroalkenyl may be 3- to 6-membered heteroalkenyl.

[0413] In some embodiments, in Ra-1, the heteroatom of the 3- to 10-membered heteroalkynyl may be selected from 1, 2, 3, or 4 types 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- to 10-membered heteroalkynyl may contain 1, 2, or 3 carbon-carbon triple bonds.

[0414] In some embodiments, in Ra-1, the heteroatom of the 3- to 10-membered heterocycloalkyl may be selected from 1, 2, 3, or 4 types 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- to 10-membered heterocycloalkyl is / — N preferably 3- to 6-membered heterocycloalkyl, such as pyrrolidinyl ().

[0415] In some embodiments, in Ra-1, the heteroatom of the 5- to 12-membered heteroaryl may be selected from 1, 2, 3, or 4 types 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- to 12-membered heteroaryl may be 5-to 6-membered heteroaryl, such as thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, or indolyl.

[0416] In some embodiments, in Ra-1-1, the halogen may be fluorine, chlorine, bromine, or iodine, such as fluorine or chlorine.

[0417] In some embodiments, in Ra-1-1, the C1-C20 alkyl may be C1-C10 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n-hexyl.

[0418] In some embodiments, in Ra-1-1, the C6-C10 aryl may be phenyl or naphthyl, such as phenyl.

[0419] In some embodiments, in Ra-1-1, the heteroatom of the 3- to 20-membered heteroalkyl may be selected from 1, 2, 3, or 4 types 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- to 20-membered heteroalkyl may be 2-to 6-membered heteroalkyl.

[0420] In some embodiments, in Ra-1-1-1, the halogen may be fluorine, chlorine, bromine, or iodine, such as fluorine or chlorine.

[0421] In some embodiments, in Rd, the C1-C20 alkoxy may be C1-C10 alkoxy, preferably C1-C6 alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tertbutoxy, n-pentoxy, isopentoxy, neopentoxy, or n-hexoxy.

[0422] In some embodiments, in Rd-1, the C1-C20 alkyl may be C1-C10 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n-hexyl.

[0423] In some embodiments, in Rd-1, the C1-C20 alkoxy may be C1-C10 alkoxy, preferably C1-C6 alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tertbutoxy, n-pentoxy, isopentoxy, neopentoxy, or n-hexoxy.

[0424] In some embodiments, in Rd-1, the C6-C10 aryl may be phenyl or naphthyl, such as phenyl.

[0425] Another aspect of the present disclosure provides a pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof as described herein, and a pharmaceutically acceptable carrier.

[0426] Another aspect of the present disclosure provides a use of a compound in the manufacture of a medicament, wherein the compound is the compound or the pharmaceutically acceptable salt thereof as described herein, and the medicament is for treating and / or preventing cancer.

[0427] Another aspect of the present disclosure provides a use of a composition in the manufacture of a medicament, wherein the composition is the pharmaceutical composition as described herein, and the medicament is for treating and / or preventing cancer.

[0428] Another aspect of the present disclosure provides a compound for use as a medicament, wherein the compound is the compound or the pharmaceutically acceptable salt thereof as described herein.

[0429] Another aspect of the present disclosure provides a composition for use as a medicament, wherein the composition is the pharmaceutical composition as described herein.

[0430] Another aspect of the present disclosure provides a compound for use in treating and / or preventing cancer, wherein the compound is the compound or the pharmaceutically acceptable salt thereof as described herein, or the pharmaceutical composition as described herein.

[0431] Another aspect of the present disclosure provides a composition for use in treating and / or preventing cancer, wherein the composition is the pharmaceutical composition as described herein.

[0432] Another aspect of the present disclosure provides a method of treating and / or preventing cancer, comprising administering to a subject an effective amount of the compound or the pharmaceutically acceptable salt thereof as described herein.

[0433] Another aspect of the present disclosure provides a method of treating and / or preventing cancer, comprising administering to a subject an effective amount of the pharmaceutical composition as described herein.

[0434] In some embodiments, the cancer is selected from a solid tumor and a hematologic malignancy. In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is a hematologic malignancy.

[0435] Another aspect of the present disclosure provides a preparation method for the compound as described herein, wherein the preparation method is Method 1, Method 2, Method 3, or Method 4;

[0436] Method 1,

[0437] the Method 1 comprises the following step: in a solvent, in the presence of a catalyst, reacting a compound represented by Formula a with a compound represented by Formula a' to undergo an exchange reaction as shown in the following formula to obtain the compound represented by Formula I; a’

[0438] each substituent is as defined in the first aspect.

[0439] In some embodiments, Z is O.

[0440] In some embodiments, a' is

[0441] In some embodiments, the solvent is an organic solvent, such as a mixed solvent of N,N-dimethylformamide and dichloromethane, dichloromethane, N,N-dimethylformamide, or a mixed solvent of tetrahydrofuran and dichloromethane.

[0442] In some embodiments, the catalyst is 4-dimethylaminopyridine.

[0443] In some embodiments, the exchange reaction is carried out under the protection of an inert gas, such as nitrogen or argon.

[0444] In some embodiments, the exchange reaction is carried out at room temperature.

[0445] In some embodiments, the temperature when mixing the compound represented by Formula a and the compound represented by Formula a' is 0-5°C.

[0446] Method 2,

[0447] the Method 2 comprises the following step: in a solvent, in the presence of a base, reacting a compound represented by Formula b with a compound represented by Formula b' to undergo a condensation reaction as shown below to obtain the compound represented by Formula I;

[0448] wherein b' is an acid anhydride, W-C(=O)Rb, W-C(=O)Rb, W-C(=O)NRbRb, W-S(=O)2NRbRb, W-S(=O)2ORb, W-S(=O)2Rb, W-S(=O)Rb, W-S(=O)NRbRb, W-S(=O)ORb, W-P(=O)(ORb)2, W-P(=O)NRbRb(ORb), W-P(=O)(NRbRb)2, W-PH(=O)ORb, W-PH(=O)NRbRb, or W-PH(=O)Rb; W is halogen or hydroxyl; each substituent is as defined in the first aspect.

[0449] In some embodiments, b' is succinic anhydride, oxalyl chloride,

[0450] In some embodiments, b is

[0451] In some embodiments, Z is O.

[0452] In some embodiments, the mixing of the compound represented by Formula b and the compound represented by Formula b' is performed at 0-5°C.

[0453] In some embodiments, the solvent is an organic solvent, such as dichloromethane or tetrahydrofuran.

[0454] In some embodiments, the base is an organic base, such as pyridine or triethylamine.

[0455] In some embodiments, the condensation reaction is carried out at room temperature.

[0456] In some embodiments, the condensation reaction is carried out under the protection of an inert gas, such as nitrogen or argon.

[0457] Method 3,

[0458] the Method 3 comprises the following step: in a solvent, in the presence of a catalyst, reacting a compound represented by Formula c with a compound represented by Formula c' to undergo an exchange reaction as shown in the following formula to obtain the compound represented by Formula I; c

[0459] each substituent is as defined in the first aspect.

[0460] In some embodiments, Z is O.

[0461] In some embodiments, the compound represented by Formula c is

[0462] In some embodiments, the solvent is an organic solvent, such as dichloromethane.

[0463] In some embodiments, the exchange reaction is carried out at room temperature.

[0464] In some embodiments, the exchange reaction is carried out under the protection of an inert gas, preferably nitrogen or argon.

[0465] In some embodiments, the mixing of the compound represented by Formula I-c and the compound represented by Formula I-c' is performed at 0-5°C.

[0466] In some embodiments, the catalyst is 4-dimethylaminopyridine.

[0467] 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.

[0468] Method 4,

[0469] the Method 4 comprises the following step: in a solvent, in the presence of a catalyst, reacting a compound represented by Formula d with a compound represented by Formula c' to undergo an exchange reaction as shown in the following formula to obtain the compound represented by Formula I; d

[0470] each substituent is as defined in the first aspect, and Hal is chlorine, bromine, or iodine.

[0471] In some embodiments, Z is O. o   / —

[0472] In some embodiments, the compound represented by Formula d is ci         .

[0473] In some embodiments, the solvent is an organic solvent, such as dichloromethane.

[0474] In some embodiments, the exchange reaction is carried out at room temperature.

[0475] In some embodiments, the exchange reaction is carried out under the protection of an inert gas, preferably nitrogen or argon.

[0476] In some embodiments, the mixing of the compound represented by Formula d and the compound represented by Formula c' is performed at 0-5°C.

[0477] In some embodiments, the catalyst is 4-dimethylaminopyridine.

[0478] 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.

[0479] Unless otherwise specified in the present disclosure, the relevant terms are defined as follows.

[0480] In the present disclosure, the term "pharmaceutically acceptable carrier" refers to excipients and additives used in pharmaceutical production and prescription formulation, which are substances other than the active ingredient that have been reasonably evaluated for safety and are included in pharmaceutical preparations. In addition to serving as excipients, carriers, and improving stability, pharmaceutical excipients also have important functions such as solubilization, co-solubilization, and sustained / controlled release, and are critical components that may affect the quality, safety, and efficacy of pharmaceutical products. Based on their origin, they can be classified into natural, semi-synthetic, and fully synthetic substances. Based on their functions and uses, they can be categorized as: solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, aromatics, anti-adherents, antioxidants, chelating agents, penetration enhancers, pH adjusters, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, release retardants, etc.; based on their routes of administration, they can be classified as oral, injectable, mucosal, transdermal or topical, nasal or oral inhalation, and ocular administration, etc. The same pharmaceutical excipient can be used in drug preparations for different routes of administration and has different functions and purposes.

[0481] In the present disclosure, the term "pharmaceutical composition" refers to a formulation that can be prepared into various suitable dosage forms according to the route of administration. For example, tablets, capsules, granules, oral solutions, oral suspensions, oral emulsions, powders, tinctures, syrups, injections, suppositories, ointments, creams, pastes, ophthalmic preparations, pills, implants, aerosols, powder sprays, and sprays.

[0482] In the present disclosure, the term "pharmaceutically acceptable salt" or "medicinal salt" generally refers to a salt of the compound of the present disclosure, or a salt of the compound described in the present disclosure, which can be safe and / or effective when used in mammals and may possess the desired biological activity. The compounds of the present disclosure can 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.

[0483] The compounds of the present disclosure may exist as solvates (e.g., hydrates), wherein the compounds incorporate polar solvents, particularly such as water, methanol, or ethanol, as structural elements of their crystal lattice. The amount of polar solvent, particularly water, may be present in stoichiometric or non-stoichiometric ratios.

[0484] The term "subject" refers to any animal including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates, most preferably humans.

[0485] In the present disclosure, the term "alkyl" refers to a saturated linear or branched hydrocarbon group. As used herein, the term "C1-20 alkyl" refers to a saturated linear or branched hydrocarbon group having 1-20 carbon atoms (e.g., 1, 2, 3, 4, 5, or 6 carbon atoms). "C1-6 alkyl" is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or n-hexyl.

[0486] In the present disclosure, the term "heteroalkyl" refers to an alkyl group containing at least one heteroatom selected from N, O, P, and S. Preferably, the number of heteroatoms is 1, 2, 0 .A,                   HO A 3, or 4. Both ends are non-heteroatoms, such as            whereas     ' or          is not considered heteroalkyl. The definition of "alkyl" is as described above.

[0487] In the present disclosure, the term "alkoxy" refers to an alkyl group connected to another group via oxygen. The definition of "alkyl" is as described above.

[0488] In the present disclosure, the term "alkenyl" refers to a linear or branched aliphatic hydrocarbon group having one or more carbon-carbon double bonds. For example, the term "C2-20 alkenyl" as used herein refers to an alkenyl group having 2-20 carbon atoms and one, two, or three (preferably one) carbon-carbon double bonds (e.g., vinyl, 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, and 4-methyl-3-pentenyl).

[0489] In the present disclosure, the term "heteroalkenyl" refers to an alkyl group containing at least one heteroatom selected from N, O, P, and S. Preferably, the number of heteroatoms is 1, 2, 3, or 4. The definition of "alkenyl" is as described above.

[0490] In the present disclosure, the term "alkynyl" refers to a linear or branched aliphatic hydrocarbon group having one or more carbon-carbon triple bonds. For example, the term "C2-20 alkynyl" as used herein refers to an alkynyl group having 2-20 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, and 5-hexynyl).

[0491] In the present disclosure, the term "heteroalkynyl" refers to an alkyl group containing at least one heteroatom selected from N, O, P, and S. Preferably, the number of heteroatoms is 1, 2, 3, or 4. The definition of "alkynyl" is as described above.

[0492] The term "heterocycloalkyl" refers to a saturated or partially saturated non-aromatic cyclic group containing at least one ring member selected from the heteroatoms N, O, P, and S, preferably, the number of heteroatoms is 1, 2, 3, or 4. For example, 3- to 20-membered, 3- to 12membered, 3- to 8-membered, or 3- to 6-membered heterocycloalkyl. Specific examples include, but are not limited to, oxiranyl, oxetanyl, oxolanyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, homopiperazinyl, etc.

[0493] The term "heterocycloalkenyl" refers to a heterocycloalkyl containing one or more double bonds, and the meaning of "heterocycloalkyl" is as described above.

[0494] The term "heterocycloalkynyl" refers to a heterocycloalkyl containing one or more triple bonds, and the meaning of "heterocycloalkyl" is as described above.

[0495] In the present disclosure, the terms "aryl", "aromatic group", or "aromatic ring" refer to monocyclic and polycyclic systems containing one or more conjugated n-electron systems. For example, C6-C20 aryl, preferably C6-C10 aryl, such as phenyl or naphthyl.

[0496] In the present disclosure, the terms "heteroaryl", "heteroaromatic group", or "heteroaromatic ring" refer to monocyclic and fused heterocyclic systems containing one or more conjugated n-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. The heteroaryl or heteroaromatic ring may be characterized by the number of ring atoms. For example, 5- to 12-membered heteroaryl may contain 5-12 (e.g., 5, 6, 7, 8, 9, 10, 11, or 12) ring atoms, particularly containing 5, 6, 9, or 10 ring atoms. Examples of heteroaryl include thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, indolyl, etc.

[0497] In the present disclosure, the term "cycloalkyl" refers to a saturated or partially saturated, monocyclic or polycyclic (e.g., bicyclic) non-aromatic hydrocarbon group. For example, "C3-12 cycloalkyl" or "3- to 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, cyclobutenyl, cyclopentenyl, and cyclohexenyl; or bicyclic cycloalkyl groups, including fused, bridged, or spiro rings, such as bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, bicyclo[3.2.1]octyl, bicyclo[5.2.0]nonyl, and decahydronaphthyl.

[0498] The term "heteroalkoxy" refers to a heteroalkyl group connected to another group via oxygen. The definition of "heteroalkyl" is as described above.

[0499] The term "cycloalkoxy" refers to a cycloalkyl group connected to another group via oxygen. The definition of "cycloalkyl" is as described above.

[0500] The term "heterocycloalkoxy" refers to a heterocycloalkyl group connected to another group via oxygen. The definition of "heterocycloalkyl" is as described above.

[0501] The term "aryloxy" refers to an aryl group connected to another group via oxygen. The definition of "aryl" is as described above.

[0502] The term "heteroaryloxy" refers to a heteroaryl group connected to another group via oxygen. The definition of "heteroaryl" is as described above.

[0503] The term "heteroalkylamino" refers to a heteroalkyl group connected to another group via -NH-. The definition of "heteroalkyl" is as described above.

[0504] The term "cycloalkylamino" refers to a cycloalkyl group connected to another group via -NH-. The definition of "cycloalkyl" is as described above.

[0505] The term "heterocycloalkyloxy" refers to a heterocycloalkyl group connected to another group via -NH-. The definition of "heterocycloalkyl" is as described above.

[0506] The term "aryloxy" refers to an aryl group connected to another group via -NH-. The definition of "aryl" is as described above.

[0507] The term "heteroaryloxy" refers to a heteroaryl group connected to another group via -NH-. The definition of "heteroaryl" is as described above.

[0508] The term "N(w)(C0-C6 alkyl)q" refers to N being connected to "w", "q", and "C0-C6 alkyl" respectively; wherein 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.

[0509] The term "amino acid residue" refers to a natural or unnatural amino acid residue, such as an a-amino acid residue, preferably an alanine residue, citruline residue, valine residue, glycine residue, phenylalanine residue, leucine residue, cysteine residue, aspartic acid residue, glutamic acid residue, histidine residue, isoleucine residue, lysine residue, methionine residue, asparagine residue, proline residue, glutamine residue, arginine residue, serine residue, threonine residue, tryptophan residue, or tyrosine residue, more preferably an L-alanine residue, L-citruline residue, L-valine residue, glycine residue, L-phenylalanine residue, L-leucine residue, L-cysteine residue, L-aspartic acid residue, L-glutamic acid residue, L-histidine residue, L-isoleucine residue, L-lysine residue, L-methionine residue, L-asparagine residue, L-proline residue, L-glutamine residue, L-arginine residue, L-serine residue, L-threonine residue, L-tryptophan residue, or L-tyrosine residue, wherein the residue means one less H on the amino group and one less OH on the carboxyl group.

[0510] The term "electron-donating group" refers to a group that, when substituted for a hydrogen on a benzene ring, increases the electron density on the benzene ring.

[0511] The term "cycloalkenyl" refers to a cycloalkyl group containing one or more double bonds, and the meaning of "cycloalkyl" is as described above.

[0512] The term "cycloalkynyl" refers to a cycloalkyl containing one or more triple bonds, wherein the meaning of "cycloalkyl" is as described above.

[0513] In the present disclosure, the term "halogen" generally refers to fluorine, chlorine, bromine, or iodine, for example, it may be fluorine or chlorine, or it may be fluorine.

[0514] In the present disclosure, "C(=O)OH-f" generally means that C(=O)OH is indirectly attached to f, wherein f is connected to another group in the molecule. If f is absent, such as C0, then C(=O)OH is directly connected to another group in the molecule.

[0515] In the present disclosure, the term "each independently" means that at least two groups (or moieties) with the same or similar ranges of values in the structure may have the same or different meanings in specific contexts. 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 can be either hydrogen or halogen, hydroxyl, cyano, alkyl, or aryl; similarly, when substituent Y is hydrogen, substituent X can be either hydrogen or halogen, hydroxyl, cyano, alkyl, or aryl.

[0516] In the present disclosure, the term "optional" or "optionally" generally means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs and instances where it does not. For example, "a heterocyclic group optionally substituted with alkyl" means that the alkyl group may but does not necessarily exist, 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.

[0517] In the present disclosure, the term "substituted" generally means that one or more hydrogen atoms in a group, for example, up to 5, such as 1 to 3 hydrogen atoms, are each independently substituted with a corresponding number of substituents. Substituents are only present at their possible chemical positions, and those skilled in the art can determine (through experimentation or theory) possible or impossible substitutions without undue effort. For example, an amino or hydroxyl group with a free hydrogen may be unstable when bonded to a carbon atom with an unsaturated (e.g., olefinic) bond.

[0518] In the present disclosure, one or more hydrogen atoms in a group, for example, up to 5, such as 1 to 3 hydrogen atoms, are each independently substituted with a corresponding number of substituents. Substituents are only present at their possible chemical positions, and those skilled in the art can determine (through experimentation or theory) possible or impossible substitutions without undue effort. For example, an amino or hydroxyl group with a free hydrogen may be unstable when bonded to a carbon atom with an unsaturated (e.g., olefinic) bond.

[0519] As used herein, either alone or in combination with other groups, the term "oxo" refers to =O.

[0520] In the present disclosure, the term "comprising" generally means including the explicitly specified features, but not excluding other elements. The terms "or more" and "or less" generally include the stated number itself.

[0521] In the present disclosure, the meaning of any substituent is being substituted with 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-C20 alkyl, C1-C20 alkoxy, C2-C20 alkenyl, C2-C20 alkynyl, 3- to 20-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkynyl or unsubstituted, 3- to 10-membered heterocycloalkyl, C6-C10 aryl, or 5- to 12membered heteroaryl.

[0522] Unless otherwise specified, the structures described in the present disclosure may also include compounds that differ only in the presence or absence of one or more isotopically enriched atoms. For example, compounds where hydrogen atoms are replaced by deuterium or tritium, or carbon atoms are replaced by carbon-13 or carbon-14, while the remaining parts are consistent with the structures of the present disclosure, are within the scope of the present disclosure.

[0523] The terms "active ingredient", "therapeutic agent", "active substance", or "active agent" refer to a chemical entity that can effectively treat one or more symptoms of a target disorder or condition.

[0524] As used herein, the term "effective amount" (e.g., "therapeutically effective amount" or "prophylactically effective amount") refers to the amount of an active ingredient that, when administered, achieves the intended effect to some extent, such as alleviating one or more symptoms of the treated disorder or preventing the occurrence of the disorder or its symptoms.

[0525] Unless otherwise specified, as used herein, the term "treating" means reversing, alleviating, inhibiting the progression of the disorder or condition to which such term applies or one or more symptoms thereof, or preventing such disorder or condition or one or more symptoms thereof.

[0526] All substituent descriptions may select 1 to N-1 kinds, wherein N is the number of substituent types. For example, if the substituents are A, B, C, 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, B; in some embodiments, the substituents are A, C; in some embodiments, the substituents are A, D; in some embodiments, the substituents are B, C; in some embodiments, the substituents are B, D; in some embodiments, the substituents are C, D; in some embodiments, the substituents are A, B, C; in some embodiments, the substituents are A, B, D; in some embodiments, the substituents are A, C, D; in some embodiments, the substituents are B, C, D; although these contents are not explicitly written, they are also included herein.

[0527] Unless otherwise specified, the expression of numerical ranges "in some embodiments, the range includes any range between integers". For example, in some embodiments, it is a 3- to 6-membered cycloalkyl, which also means: in some embodiments, it is a 3- to 4-membered cycloalkyl; in some embodiments, it is a 3- to 5-membered cycloalkyl; in some embodiments, it is a 4- to 5-membered cycloalkyl; in some embodiments, it is a 4- to 6-membered cycloalkyl; in some embodiments, it is a 5- to 6-membered cycloalkyl. Although these are not explicitly written, they are also included herein.

[0528] The principle for substituent matching follows the minimum substitution layer rule and the maximum matching atoms on the chain rule. When the nearest layer substitution cannot match, the next outer layer substitution is matched, and so on for subsequent layers.

[0529] The general formula of the present disclosure excludes any compounds disclosed in the prior art.

[0530] Unless otherwise specified, the connection mode of amino acid residues or peptide chains is that the carbonyl terminus is connected to the amino group, and the amino terminus is connected to the substituent Y.

[0531] The structural formula of CBTX-PNP or PNP-CBTX is as follows:

[0532] Without departing from the common knowledge in the art, the above preferred conditions can be arbitrarily combined to obtain various preferred examples of the present disclosure.

[0533] The reagents and raw materials used in the present disclosure are all commercially available.

[0534] The positive and progressive effects of the present disclosure are as follows:

[0535] The compounds of the present disclosure exhibit the following effects: high in vitro antitumor bioactivity, with a half-maximal inhibitory concentration (IC50) below 1 uML, more preferably 500 nM / L or less, even more preferably 200 nM / L or less, further preferably 100 nM / L or less, still more preferably 50 nM / L or less, 20 nM / L or less, 10 nM / L or less, and 5 nM / L or less. BRIEF DESCRIPTION OF THE DRAWINGS

[0536] FIG. 1 shows the body weight change curve of experimental animals after the start of treatment.

[0537] FIG. 2 shows the growth curve of the DU145 subcutaneous xenograft model after the start of treatment.

[0538] FIG. 3 shows the body weight change curve of experimental animals after the start of treatment.

[0539] FIG. 4 shows the growth curve of the human prostate cancer PC-3 subcutaneous xenograft model after the start of treatment.

[0540] FIG. 5 shows the body weight change curve of experimental animals after the start of treatment.

[0541] FIG. 6 shows the growth curve of the human breast cancer MDA-MB-231 subcutaneous xenograft model after the start of treatment.

[0542] FIG. 7 shows the body weight change curve of experimental animals after the start of treatment.

[0543] FIG. 8 shows the growth curve of the human pancreatic cancer Capan-1 subcutaneous xenograft model after the start of treatment.

[0544] mpk is mg / kg; QW is once weekly; wks indicates weeks; BIW indicates twice weekly. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0545] The present disclosure is further illustrated by the following examples, which are not intended to limit the scope of the present disclosure to the described embodiments. Experimental methods without specified conditions in the following examples are selected according to conventional methods and conditions, or according to the manufacturer's instructions.

[0546] The compounds of the present disclosure represented by Formula I may be prepared with reference to the following general procedures:

[0547] (1) Some of the compounds are prepared via Route a-1-A or Route a-1-B:

[0548] A1 and A2 are benzyl, methyl, hydrogen, isobutyl, butyl, or ; R2 is C1-C4 alkyl, preferably methyl; other substituents are as defined in the first aspect.

[0549] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0550] (2) Some compounds are prepared using Route a-2-A or a-2-B: a-2-5

[0551] A1 and A2 are benzyl, methyl, hydrogen, isobutyl, butyl, or ; R2 is C1-C4 alkyl, preferably methyl; R4 is as defined in Rb of the first aspect; other substituents are as defined in the first aspect.

[0552] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0553] (3) Some of the compounds are prepared via Route a-3:

[0554] A1 and A2 are benzyl, methyl, hydrogen, isobutyl, butyl, or ; R2 is C1-C4 alkyl, preferably methyl; p is 1, 2, 3, 4, 5, or 6; Seti is selected from          and       q ; R3            ( R>y Set2 is selected from   3   ' and       q ; each R3 is independently hydrogen, deuterium, or C1-C4 alkyl; Y is O, S, N, or C; q and R are each independently 0, 1, 2, or 3; Hal is chlorine, bromine, or iodine; other substituents are as defined in the first aspect.

[0555] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0556] (4) Some of the compounds are prepared via Route a-4-A or a-4-B:

[0557] A1 and A2 are benzyl, methyl, hydrogen, isobutyl, butyl, or ; R2 is r3 r / NH Yw C1-C4 alkyl, preferably methyl; s is 1, 2, 3, 4, 5, or 6; Seti is selected from Rs      and       q ; R3            ( R>y Set2 is selected from 3 ' and       q ; other substituents are as defined in the first aspect.

[0558] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0559] (5) Some of the compounds are prepared via Route a-5:

[0560] A1, A2, A3, or A4 is benzyl, methyl, hydrogen, isobutyl, butyl, or R2 is C1-C4 alkyl, preferably methyl; other substituents are as defined in the first aspect.

[0561] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0562] (6) Some of the compounds are prepared via Route a-6: a-6-3 a-6-4 I-a-6

[0563] A1, A2, A3, or A4 is benzyl, methyl, hydrogen, isobutyl, butyl, or R2 is C1-C4 alkyl, preferably methyl; R4 is as defined in Rb of the first aspect; other substituents are as defined in the first aspect.

[0564] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0565] (7) Some of the compounds are prepared via Route b-1, b-2-A, or b-2-B: 0 h2n^n / ^^ /

[0566] A1, A2, A3, or A4 is benzyl, methyl, hydrogen, isobutyl, butyl, or        H          ; R2 is C1-C4 alkyl, preferably methyl; Set3 is C(=O)OHRd-1, or when the terminal of Rd-1 is - C(=O)OH, it is HalC(=O)Rd-1(C=O)Hal, or when the terminal of Rd-1 is -C(=O)OH, it forms a X>° lactone structure R       with the C(=O)OH connected to the other end; Set4 is as defined in Y of the first aspect, wherein Y is -C(=O)Rb; other substituents are as defined in the first aspect.

[0567] In some embodiments,

[0568] Set3 is selected from and      0   0    ; Set4 is selected from H0^0^ HO^ 0        0 and 0   0   ; Hal is selected from Cl, Br, and I; s is 1, 2, 3, 4, or 5; each t is independently 1, 2, 3, 4, or 5; u is 0, 1, 2, 3, 4, 5, or 6.

[0569] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0570] (8) Some of the compounds are prepared via Route c-1:

[0571] Set5 is Rd-1(=O)O(=O)Rd-1 or Rd-1(=O)OH; Set6 is Rd-1; Rd is -ORd-2; other substituents are as defined in the first aspect.

[0572] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0573] (9) Some of the compounds are prepared via Route c-2: c-2-1                               c-2

[0574] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples.

[0575] Rd is -ORd-2; other substituents are as defined in the first aspect.

[0576] (10) Some of the compounds are prepared via Route c-3: c-3-1                                  c-3

[0577] Rd is -ORd-2; Hal is selected from Cl, Br, and I; other substituents are as defined in the first aspect.

[0578] Unless otherwise specified, the reactions involved in the above routes can be prepared under conditions similar to those of prior art reactions, and specific reaction conditions can be found in the relevant examples. Abbreviation Structural Formula or Name Abbreviation Structural Formula or Name HOBt 1-Hydroxybenzotriazole EDC 1-Ethyl-(3- dimethylaminopropyl)carbodiimide hydrochloride Boc- O     I PE Petroleum ether DIC N,N'- Diisopropylcarbodiimide EA Ethyl acetate EEDQ 2-Ethoxy-1- ethoxycarbonyl-1,2-dihydroquinoline DCM Dichloromethane Fmoc- 0 0¾ MEOH Methanol

[0579] HATU     refers     to     2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0580] The amino acids used in the examples, if containing chiral carbons, are all L-amino acids.

[0581] Among them, Example 60 employs D-citrulline, Example 61 employs D-citrulline and D-valine, and Example 78 employs D-valine.

[0582] Example 1: Synthesis of Compound 1

[0583]  1b:

[0584] At 0 to 10oC, 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). After completion of the dropwise addition, the mixture was stirred for 10 minutes, heated to 60°C and stirred for 3 hours, then cooled to room temperature. Dichloromethane (100 mL) was added, and the mixture was concentrated under reduced pressure. A pale yellow oil 7b (15.9 g, yield: 100%) was obtained.

[0585] 1c:

[0586] 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 mixture was filtered. The filtrate was set aside for later use. Boc-L-valine (12.89 g, 59.33 mmol) was dissolved in dichloromethane (150 mL). Under nitrogen protection, the solution was cooled to 5oC, and 1-hydroxybenzotriazole (8.82 g, 65.27 mmol) was added. N,N'-Diisopropylcarbodiimide (10.11 mL, 65.27 mmol) was added dropwise. The mixture was warmed to room temperature and stirred for 20 minutes. The prepared 7-M1 was then added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 0.5 hours.

[0587] The mixture 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. The residue was subjected to column chromatography to obtain 7c (25 g, yield: 92%) as a white solid.

[0588] 1d:

[0589] 1c (8.0 g, 20.59 mmol) was dissolved in dichloromethane (15 mL), and trifluoroacetic acid (15 mL) was added dropwise at 5oC. The mixture was warmed to room temperature and stirred for 1.0 hour. Dichloromethane (30 mL) was added, and the mixture was concentrated under reduced pressure. The residue was subjected to column chromatography to obtain 8-M1 (6.20 g, yield: 74%) as a pale yellow oil.

[0590] 1e:

[0591] At 0 to 10°C under nitrogen protection, DIC (1.92 g, 15.2 mmol) was added dropwise to a solution of 3-chloropropionic acid (1.50 g, 13.8 mmol) and HOBt (2.05 g, 15.2 mmol) in dichloromethane (60 mL). The reaction mixture was stirred at the same temperature for 30 minutes. 1d (5.01 g, 12.4 mmol) was added to dichloromethane (40 mL) solution, and under nitrogen protection at 0 to 10°C, the pH was adjusted to 9-10 with triethylamine. After stirring for 5 minutes, the solution was added to the 3-chloropropionic acid reaction mixture and stirred at 20 to 25°C for 30 minutes. The solvent was removed by concentration, and the residue was purified by silica gel column chromatography [VDCM / VMeOH = 8:1] to obtain a white solid (3.00 g, yield: 57%).

[0592]  1f:

[0593] At 0 to 10°C, lithium hydroxide monohydrate (664 mg, 15.8 mmol) was dissolved in water (8 mL) and added dropwise to a solution of 1b (3.00 g, 7.92 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at 15 to 25°C for 0.5 hours. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 3 to 4. The solvent and water were removed by concentration, and the residue was further dried by coevaporation with tetrahydrofuran (30 mL x 2) to obtain a white foamy solid (2.89 g, yield: 100%).

[0594]  1g:

[0595] At room temperature, EEDQ (3.39 g, 13.7 mmol) and p-aminobenzyl alcohol (844 mg, 6.85 mmol) were sequentially added to a solution of 1c (2.50 g, 6.85 mmol) in dichloromethane (60 mL) / methanol (10 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 [VDCM / VMeOH = 15:1] to obtain a white solid (630 mg, yield: 20%).

[0596] 1h:

[0597] At room temperature, diethylamine (467 mg, 6.38 mmol) and potassium iodide (424 mg, 2.55 mmol) were added to a solution of 1d (600 mg, 1.28 mmol) in 95% ethanol (20 mL). 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 [VDCM / VMeOH = 5:1] to obtain an off-white solid (300 mg, yield: 46%).

[0598] 1j:

[0599] 1i (0.50 g, 5.98 mmol) was dissolved in dichloromethane (8 mL), followed by the sequential addition of 4-dimethylaminopyridine (15 mg, 0.12 mmol) and diisopropylethylamine (0.23 g, 1.79 mmol). Under nitrogen protection, the mixture was cooled to -5oC, and a solution of p-nitrophenyl chloroformate (0.24 g, 1.20 mmol) in dichloromethane (3 mL) was added dropwise. The mixture was warmed to room temperature and stirred for 0.5 hours. Dichloromethane (80 mL) was added, and the mixture was washed twice with 0.3N hydrochloric acid (20 mL), followed by sequential washes with saturated sodium bicarbonate (20 mL) and saturated sodium chloride (20 mL). The organic phase was dried over anhydrous sodium sulfate, concentrated to dryness, and subjected to column chromatography to obtain 1j (CBTX-PNP) (0.55 g, yield: 92%) as a white solid.

[0600] 1H NMR (400 MHz, DMSO-d6) 6(ppm) 8.40 - 8.30 (m, 2H), 8.00 (dd, J = 18.2, 8.2 Hz, 3H), 7.72 (t, J = 7.3 Hz, 1H), 7.64 (t, J = 7.5 Hz, 2H), 7.55 (d, J = 9.1 Hz, 2H), 7.45 (dt, J = 14.8, 7.6 Hz, 4H), 7.23 (t, J = 7.0 Hz, 1H), 5.88 (t, J = 8.8 Hz, 1H), 5.38 (d, J = 7.0 Hz, 1H), 5.24 (d, J = 7.6 Hz, 1H), 5.14 (t, J = 8.3 Hz, 1H), 4.94 (d, J = 9.6 Hz, 1H), 4.68 (s, 1H), 4.54 (s, 1H), 4.02 (d, J = 8.8 Hz, 2H), 3.72 (dd, J = 10.3, 6.7 Hz, 1H), 3.58 (d, J = 7.0 Hz, 1H), 3.27 (s, 3H), 3.18 (s, 3H), 2.70 - 2.58 (m, 1H), 2.25 (s, 3H), 1.85 (dd, J = 15.3, 9.3 Hz, 1H), 1.78 (s, 3H), 1.63 (dd, J = 15.2, 9.1 Hz, 1H), 1.47 (d, J = 21.2 Hz, 4H), 1.39 (s, 8H), 1.25 (d, J = 10.3 Hz, 1H), 1.03 - 0.95 (m, 6H).

[0601] Synthesis of 1:

[0602] At 0 to 5°C under nitrogen protection, 1h (200 mg, 0.39 mmol) was dissolved in dichloromethane (12 mL) / N,N-dimethylformamide (2 mL). 1j (395 mg, 0.39 mmol) and N,N-dimethylpyridine (48 mg, 0.39 mmol) were added sequentially. The reaction mixture was stirred at 15 to 25°C for 2 hours. Dichloromethane (50 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (30 mL x 2) and saturated sodium chloride aqueous solution (30 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 6:1] to obtain a white solid (220 mg, yield: 46%, HPLC purity: 96.26%).

[0603] LC-MS: 1368.6941 [M+H+].

[0604] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 10.15 (s, 1H), 8.34 - 8.18 (m, 2H), 7.95 (dd, J = 20.3, 8.2 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.7 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.39 - 7.28 (m, 4H), 7.18 (t, J = 7.2 Hz, 1H), 6.10 (s, 1H), 5.82 (t, J = 8.7 Hz, 1H), 5.45 (s, 2H), 5.37 (d, J = 7.1 Hz, 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, 8.2 Hz, 1H), 4.24 (dd, J = 8.4, 6.7 Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.2, 6.8 Hz, 1H), 3.69 -3.61 (m, 1H), 3.59 (d, J = 6.5 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.99 (ddd, J = 24.1, 13.1, 6.4 Hz, 6H), 2.71 - 2.62 (m, 2H), 2.24 (s, 3H), 2.01 (td, J = 13.5, 6.9 Hz, 1H), 1.79 (d, J = 12.8 Hz, 4H), 1.75 - 1.67 (m, 1H), 1.66 - 1.59 (m, 1H), 1.57 - 1.43 (m, 6H), 1.29 (d, J = 43.8 Hz, 12H), 1.15 (s, 6H), 0.98 (d, J = 7.5 Hz, 6H), 0.87 (dd, J = 11.9, 6.8 Hz, 6H).

[0605] Example 2: Synthesis of Compound 2 NH          2 2d                                    H2N— 0

[0606] 2b:

[0607] Acetic acid (1.0 g, 16.65 mmol) was dissolved in dichloromethane (20 mL). Under nitrogen protection, the mixture was cooled to 5oC, and 1-hydroxybenzotriazole (2.48 g, 18.32 mmol) was added. N,N'-Diisopropylcarbodiimide (2.31 g, 18.32 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 30 minutes. 1d (4.80 g, 11.93 mmol) was dissolved in dichloromethane (30 mL), and the pH was adjusted to 9 with N,N-diisopropylethylamine. This solution was added dropwise to the reaction mixture, and the resulting mixture was stirred at room temperature for 30 minutes. The mixture was concentrated directly to dryness. The residue was subjected to column chromatography to obtain 2-M1 (3.58 g, yield: 65%) as a white solid.

[0608] 2c:

[0609] 2b (3.58 g, 10.84 mmol) was dissolved in tetrahydrofuran (40 mL), followed by the addition of lithium hydroxide monohydrate aqueous solution (0.91 g, 21.67 mmol). The mixture was stirred at room temperature for 30 minutes. Tetrahydrofuran (40 mL) was added, and at -5oC, the pH was adjusted to 5 with 6N hydrochloric acid. The mixture was concentrated to dryness to obtain 2-M2 (3.4 g, yield: 99%) as a pale yellow oil.

[0610]  2d:

[0611] 2c (3.4 g, 10.75 mmol) was dissolved in methanol (10 mL) and dichloromethane (100 mL). p-Aminobenzyl alcohol (1.32 g, 10.75 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (5.32 g, 21.49 mmol) were added, and the mixture was stirred at room temperature for 1.5 hours. The mixture was concentrated under reduced pressure and subjected to column chromatography to obtain 2-M3 (1.25 g, yield: 28%) as a pale yellow solid.

[0612] 1H NMR (400 MHz, DMSO- d6) 5 9.93 (ppm) (s, 1H), 8.12 (d, J = 7.7 Hz, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.56 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 6.06 (dd, J = 18.9, 13.4 Hz, 1H), 5.43 (s, 2H), 5.11 (s, 1H), 4.53 - 4.32 (m, 3H), 2.98 (ddt, J = 19.3, 13.1, 6.5 Hz, 2H), 1.97 (dt, J = 13.4, 6.7 Hz, 1H), 1.90 (d, J = 8.5 Hz, 3H), 1.70 (dd, J = 13.9, 6.5 Hz, 1H), 1.60 (ddd, J = 18.4, 9.1, 4.7 Hz, 1H), 1.50 - 1.33 (m, 2H), 0.87 (d, J = 6.8 Hz, 3H), 0.84 (d, J = 6.8 Hz, 3H).

[0613] Synthesis of 2:

[0614] 2d (0.15 g, 0.36 mmol) and 1j (0.36 g, 0.36 mmol) were dissolved in tetrahydrofuran (4 mL). 4-Dimethylaminopyridine (48 mg, 0.39 mmol) was added, and 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 combined organic phases were washed twice with 0.6N hydrochloric acid (30 mL), followed by sequential washes with saturated sodium bicarbonate (20 mL) and saturated sodium chloride (20 mL). The organic phase was dried over anhydrous sodium sulfate, concentrated to dryness, and subjected to column chromatography to obtain 2 (0.16 g, yield: 35%, HPLC purity: 95.935%) as a white solid.

[0615] LC-MS: 1283.6118 [M+H+].

[0616] 1H NMR (400 MHz, DMSOd-6) 5 (ppm) 10.02 (s, 1H), 8.13 (d, J = 7.5 Hz, 1H), 8.02 - 7.83 (m, 4H), 7.77 - 7.57 (m, 5H), 7.38 (dt, J = 13.4, 8.0 Hz, 6H), 7.18 (t, J = 7.1 Hz, 1H), 5.97 (t, J = 5.9 Hz, 1H), 5.82 (t, J = 8.6 Hz, 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 = 9.9 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.39 (dd, J = 13.2, 8.2 Hz, 1H), 4.19 (dd, J = 8.4, 6.8 Hz, 1H), 4.03 - 4.00 (m, 2H), 3.75 (dd, J = 10.2, 6.8 Hz, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 3.07 - 2.90 (m, 2H), 2.69 (d, J = 15.4 Hz, 1H), 2.24 (s, 3H), 2.08 - 1.92 (m, 3H), 1.82 (d, J = 12.4 Hz, 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 = 7.4 Hz, 6H), 0.86 (dd, J = 11.0, 6.8 Hz, 6H).

[0617] Example 3: Synthesis of Compound 3

[0618] 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%).

[0619] LC-MS: 1337.5764 [M+H+].

[0620] 1H NMR (400 MHz, DMSOd-6) 5 (ppm) 10.14 (s, 1H), 9.41 (d, J = 8.4 Hz, 1H), 8.42 (d, J = 7.3 Hz, 1H), 7.95 (dd, J = 23.3, 8.1 Hz, 3H), 7.73 (t, J = 7.2 Hz, 1H), 7.64 (dd, J = 12.2, 8.1 Hz, 4H), 7.38 (dt, J = 12.5, 8.1 Hz, 6H), 7.18 (t, J = 7.3 Hz, 1H), 5.98 (t, J = 5.7 Hz, 1H), 5.82 (t, J = 8.4 Hz, 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, 7.6 Hz, 1H), 4.23 (t, J = 8.4 Hz, 1H), 4.03 - 4.00 (m, 2H), 3.75 (dd, J = 10.1, 6.9 Hz, 1H), 3.59 (d, J = 6.9 Hz, 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, 6.9 Hz, 1H), 1.81 (s, 3H), 1.77 - 1.55 (m, 3H), 1.48 (d, J = 18.3 Hz, 5H), 1.42 - 1.29 (m, 9H), 1.24 (s, 2H), 1.05 - 0.78 (m, 12H).

[0621] Example 4: Synthesis of Compound 4

[0622] Referring to the synthetic route of Compound 1 in Example 1, pyrrolidine was used instead of diethylamine to obtain Compound 4 (165 mg, yield: 24%, HPLC purity: 94.76%).

[0623] LC-MS: 1319.5 [M-OH-OMe].

[0624] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 10.17 (s, 1H), 8.24 (t, J = 7.7 Hz, 2H), 7.95 (dd, J = 19.9, 8.2 Hz, 3H), 7.77 - 7.59 (m, 5H), 7.43 (t, J = 7.6 Hz, 2H), 7.38 - 7.26 (m, 4H), 7.18 (t, J = 7.2 Hz, 1H), 6.12 (t, J = 5.5 Hz, 1H), 5.82 (t, J = 8.7 Hz, 1H), 5.46 (s, 2H), 5.37 (d, J = 6.9 Hz, 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, 8.3 Hz, 1H), 4.24 (dd, J = 8.3, 6.9 Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.1, 6.8 Hz, 1H), 3.59 (d, J = 6.8 Hz, 1H), 3.30 - 3.24 (m, 6H), 3.22 (s, 3H), 3.06 - 2.92 (m, 3H), 2.77 - 2.62 (m, 3H), 2.24 (s, 3H), 2.05 - 1.86 (m, 5H), 1.79 (d, J = 12.1 Hz, 4H), 1.75 - 1.53 (m, 3H), 1.55 - 1.40 (m, 6H), 1.40 - 1.19 (m, 11H), 0.98 (d, J = 7.5 Hz, 6H), 0.87 (dd, J = 11.1, 6.8 Hz, 6H).

[0625] Example 5: Synthesis of Compound 5

[0626] Referring to the synthesis of Compound 2 in Example 2, p-fluorobenzoic acid was used instead of acetic acid to obtain Compound 5 (350 mg, yield: 51%, HPLC purity: 99.03%).

[0627] LC-MS: 1363.6000 [M+H+].

[0628] 1H NMR (400 MHz, DMSO-d6) S(ppm) 10.07 (s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 7.5 Hz, 1H), 7.95 (ddd, J = 16.4, 11.0, 7.4 Hz, 5H), 7.73 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 8.3 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.38 - 7.27 (m, 6H), 7.18 (t, J = 7.2 Hz, 1H), 5.98 (t, J = 5.8 Hz, 1H), 5.82 (t, J = 8.6 Hz, 1H), 5.45 - 5.34 (m, 3H), 5.15 (s, 2H), 5.10 - 4.99 (m, 2H), 4.95 (d, J = 10.1 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.42 (dd, J = 13.4, 7.9 Hz, 1H), 4.35 (t, J = 8.1 Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.3, 6.8 Hz, 1H), 3.59 (d, J = 7.0 Hz, 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, 6.8 Hz, 1H), 1.86 - 1.75 (m, 4H), 1.75 - 1.68 (m, 1H), 1.63 (dd, J = 9.1, 4.6 Hz, 1H), 1.49 (d, J = 17.7 Hz, 5H), 1.44 - 1.21 (m, 11H), 1.03 - 0.89 (m, 12H).

[0629] Example 6: Synthesis of Compound 6 h2n h2n

[0630]  6b:

[0631] 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 mixed solution of N-Fmoc-L-citrulline (10.00 g, 25.2 mmol) in dichloromethane (100 mL) / methanol (60 mL), and 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 collected filter cake was dried to obtain a white solid (7.20 g, yield: 57%).

[0632] 6c:

[0633] At 0 to 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 a solution of 6b (1.00 g, 1.99 mmol) in tetrahydrofuran (30 mL). The reaction mixture was stirred at 40°C for 3 hours. Ethyl acetate (60 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (20 mL x 2) and saturated sodium chloride aqueous solution (30 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 25:1] to obtain a white solid (2.56 g, yield: 94%).

[0634] 6d:

[0635] At 0 to 5°C under nitrogen protection, piperidine (820 mg, 9.75 mmol) was added dropwise to a solution of 6c (1.33 g, 0.97 mmol) in acetonitrile (100 mL). The reaction mixture was stirred at 5 to 10°C for 3 hours. Ethyl acetate (100 mL) was added to the reaction mixture, followed by washing with 5% citric acid aqueous solution (60 mL) and saturated sodium chloride aqueous solution (60 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 10:1] to obtain a white solid (0.95 g, yield: 85%).

[0636]  6e:

[0637] At 10 to 15°C under nitrogen protection, 6d (700 mg, 0.61 mmol), (7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (280 mg, 0.73 mmol), and diisopropylethylamine (159 mg, 1.23 mmol) were sequentially added to a solution of N-Fmoc-L-valine (250 mg, 25.2 mmol) in N,N-dimethylacetamide (10 mL). The mixture was stirred at room temperature for 0.5 hours. At 10 to 15°C, water (20 mL) was added dropwise, and the solid precipitated. After stirring for 30 minutes, the mixture was subjected to suction filtration, and the filter cake was collected. The filter cake was purified by silica gel column chromatography [VDCM / VMeOH = 30:1] to obtain a white solid (650 mg, yield: 72%).

[0638]  6f:

[0639] At 0 to 5°C under nitrogen protection, piperidine (189 mg, 2.22 mmol) was diluted with acetonitrile (4 mL) and added dropwise to a solution of 6e (650 mg, 0.44 mmol) in acetonitrile (20 mL). The reaction mixture was stirred at 5 to 10°C for 2.5 hours. Ethyl acetate (50 mL) was added to the reaction mixture, followed by washing with 5% citric acid aqueous solution (60 mL) and saturated sodium chloride aqueous solution (60 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 5:1] to obtain a white solid (240 mg, yield: 43%).

[0640] 6:

[0641] At 0 to 5°C under nitrogen protection, succinic anhydride (39 mg, 0.39 mmol) and pyridine (46 mg, 0.58 mmol) were sequentially added to a solution of 6e (240 mg, 0.19 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 1 hour. Dichloromethane (20 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (15 mL x 2) and saturated sodium chloride aqueous solution (20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 10:1] to obtain a white solid (130 mg, yield: 50%, HPLC purity: 98.73%).

[0642] LC-MS: 1341.6045 [M+H+].

[0643] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 8 (ppm) 12.15 (s, 1H), 9.95 (s, 1H), 8.10 (d, J = 7.4 Hz, 1H), 7.95 (dd, J = 20.5, 7.8 Hz, 4H), 7.80 - 7.53 (m, 5H), 7.38 (dt, J = 13.6, 7.9 Hz, 6H), 7.18 (t, J = 7.1 Hz, 1H), 6.04 (s, 1H), 5.82 (t, J = 8.9 Hz, 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, 8.0 Hz, 1H), 4.24 - 4.15 (m, 1H), 4.02 (s, 2H), 3.82 - 3.70 (m, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 3.00 (dtd, J = 19.6, 13.2, 6.5 Hz, 2H), 2.74 - 2.60 (m, 1H), 2.44 (s, 3H), 2.41 (s, 1H), 2.24 (s, 3H), 2.00 (dq, J = 13.1, 6.7 Hz, 1H), 1.91 - 1.53 (m, 7H), 1.56 - 1.39 (m, 6H), 1.35 (s, 9H), 0.98 (d, J = 7.4 Hz, 6H), 0.86 (dd, J = 11.1, 6.8 Hz, 6H).

[0644] Example 7: Synthesis of Compound 7

[0645]  7b:

[0646] 1c (3.0 g, 7.72 mmol) was dissolved in tetrahydrofuran (20 mL), followed by the addition of a solution of lithium hydroxide monohydrate (0.65 g, 15.45 mmol) in water (8 mL). The mixture was stirred at room temperature for 1 hour. At -5oC, the pH was adjusted to 5 with 1N hydrochloric acid. Ethyl acetate (80 mL) was added for extraction (twice). The combined organic phases were dried over anhydrous sodium sulfate and concentrated to dryness to obtain 7d (2.7 g, yield: 93%) as a white solid.

[0647] 7c:

[0648] 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. The mixture was stirred at room temperature for 2 hours. The mixture was concentrated under reduced pressure and subjected to column chromatography to obtain BH259e (3.0 g, yield: 88%) as a white solid.

[0649] 1H NMR (400 MHz, DMSOd-6) 6(ppm) 9.97 (s, 1H), 7.97 (d, J = 7.7 Hz, 1H), 7.54 (d, J = 8.5 Hz, 2H), 7.24 (d, J = 8.5 Hz, 2H), 6.75 (d, J = 8.9 Hz, 1H), 5.97 (t, J = 5.7 Hz, 1H), 5.40 (s, 2H), 5.09 (t, J = 5.7 Hz, 1H), 4.45 (t, J = 8.2 Hz, 3H), 3.95 - 3.73 (m, 1H), 3.12 - 2.87 (m, 2H), 2.51 (dt, J = 3.5, 1.7 Hz, 2H), 1.96 (dt, J = 13.4, 6.7 Hz, 1H), 1.66 (ddd, J = 18.3, 12.7, 6.9 Hz, 2H), 1.39 (s, 9H), 0.85 (dd, J = 15.8, 6.7 Hz, 6H).

[0650]  7:

[0651] 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 under reflux for 2 hours. Dichloromethane (40 mL) and water (20 mL) were added, and the phases were separated. The aqueous phase was extracted with dichloromethane (40 mL). The combined organic phases were washed twice with 0.3N hydrochloric acid (20 mL), followed by sequential washes with saturated sodium bicarbonate (20 mL) and saturated sodium chloride (20 mL). The organic phase was dried over anhydrous sodium sulfate, concentrated to dryness, and subjected to column chromatography to obtain 7 (0.17 g, yield: 43.4%, HPLC purity: 99.536%) as a white solid.

[0652] LC-MS: 1341.6259 [M+H+].

[0653] 1H NMR (400 MHz, DMSOd-6) 5 (ppm) 10.17 (s, 1H), 8.13 - 7.91 (m, 4H), 7.83 - 7.64 (m, 5H), 7.44 (dt, J = 13.3, 8.0 Hz, 6H), 7.24 (t, J = 7.2 Hz, 1H), 6.80 (d, J = 8.8 Hz, 1H), 6.02 (t, J = 5.8 Hz, 1H), 5.88 (t, J = 8.6 Hz, 1H), 5.52 - 5.36 (m, 3H), 5.20 (s, 2H), 5.15 - 5.04 (m, 2H), 5.01 (d, J = 10.0 Hz, 1H), 4.76 (s, 1H), 4.58 - 4.44 (m, 2H), 4.07 (s, 2H), 3.99 - 3.65 (m, 3H), 3.65 - 3.56 (m, 1H), 3.35 (s, 3H), 3.31 - 3.26 (m, 3H), 3.05 (ddt, J = 31.4, 13.2, 6.6 Hz, 2H), 2.30 (s, 3H), 2.02 (dd, J = 13.6, 7.0 Hz, 1H), 1.88 (d, J = 12.5 Hz, 4H), 1.80 - 1.70 (m, 1H), 1.66 (dd, J = 9.2, 4.7 Hz, 1H), 1.54 (d, J = 18.5 Hz, 5H), 1.48 - 1.37 (m, 18H), 1.29 (s, 2H), 1.03 (d, J = 7.3 Hz, 6H), 0.90 (dd, J = 16.0, 6.7 Hz, 6H).

[0654] Example 8: Synthesis of Compound 8

[0655] 8b:

[0656] 1d (4.4 g, 15.40 mmol) was added to dichloromethane (30 mL), and the pH was adjusted to 9 with diisopropylethylamine, then set aside.

[0657] Pivalic acid (1.57 g, 15.40 mmol) was dissolved in dichloromethane (50 mL). Under nitrogen protection, the solution was cooled to 5oC, and 1-hydroxybenzotriazole (2.29 g, 16.94 mmol) was added. N,N'-Diisopropylcarbodiimide (2.14 g, 16.94 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 20 minutes. The prepared 1d solution was then added dropwise to the reaction mixture, and the resulting mixture was stirred at room temperature for 0.5 hours. The mixture was washed with 0.3N hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and saturated sodium chloride (20 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was subjected to column chromatography to obtain 8c (1.40 g, yield: 24.4%) as a white solid.

[0658] 8c:

[0659] 8b (1.4 g, 3.76 mmol) was dissolved in tetrahydrofuran (20 mL), followed by the addition of a solution of lithium hydroxide monohydrate (0.32 g, 7.52 mmol) in water (4 mL). The mixture was stirred at room temperature for 30 minutes. At -5oC, the pH was adjusted to 5 with 1N hydrochloric acid. Ethyl acetate (80 mL) was added for extraction (twice). The combined organic phases were dried over anhydrous sodium sulfate and concentrated to dryness to obtain 8d (0.75 g, yield: 55%) as a white solid.

[0660] 8d:

[0661] 8c (0.75 g, 2.08 mmol) was dissolved in dichloromethane (10 mL), followed by the addition of p-aminobenzyl alcohol (0.26 g, 2.08 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (1.03 g, 4.16 mmol). The mixture was stirred at room temperature for 2 hours. The mixture was concentrated under reduced pressure and subjected to column chromatography to obtain 8e (0.45 g, yield: 47%) as a white solid.

[0662] 1H NMR (400 MHz, DMSO-d6) 5(ppm) 9.94 (s, 1H), 8.01 (d, J = 7.5 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.7 Hz, 1H), 5.96 (t, J = 5.7 Hz, 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, 6.8 Hz, 1H), 1.76 - 1.64 (m, 1H), 1.58 (ddd, J = 18.3, 8.9, 4.6 Hz, 1H), 1.51 - 1.29 (m, 2H), 1.12 (s, 9H), 0.85 (dd, J = 14.6, 6.7 Hz, 6H).

[0663] Synthesis of 8

[0664] 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). 4-Dimethylaminopyridine (49 mg, 0.40 mmol) was added, and the mixture was stirred at room temperature for 2 hours. Dichloromethane (40 mL) and water (20 mL) were added, and the phases were separated. The aqueous phase was extracted with dichloromethane (40 mL). The combined organic phases were washed twice with 0.3N hydrochloric acid (20 mL), followed by sequential washes with saturated sodium bicarbonate (20 mL) and saturated sodium chloride (20 mL). The organic phase was dried over anhydrous sodium sulfate, concentrated to dryness, and subjected to column chromatography to obtain 8 (0.29 g, yield: 59.7%, HPLC purity: 98.95%) as a white solid.

[0665] LC-MS: 1325.6407 [M+H+].

[0666] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 10.10 (s, 1H), 8.09 - 7.86 (m, 4H), 7.78 - 7.57 (m, 5H), 7.38 (dt, J = 13.5, 8.0 Hz, 6H), 7.24 - 7.09 (m, 2H), 5.97 (t, J = 5.7 Hz, 1H), 5.82 (t, J = 8.9 Hz, 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, 7.8 Hz, 1H), 4.17 (t, J = 8.1 Hz, 1H), 4.02 (s, 1H), 3.75 (dd, J = 10.1, 6.8 Hz, 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, 6.9 Hz, 1H), 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 = 7.5 Hz, 6H), 0.85 (dd, J = 15.1, 6.7 Hz, 6H).

[0667] Example 9: Synthesis of Compound 9

[0668] 9b:

[0669] Compound 9a (25.00 g, 280.6 mmol) was dissolved in methanol (150 mL). Under nitrogen protection, the solution was cooled to 0 to 10°C, and thionyl chloride (50 mL, 701.5 mmol) was added dropwise while controlling the addition rate to maintain the internal temperature below 25°C. After completion of the dropwise addition, the temperature was gradually increased to 60°C (10°C / 5 min), and the mixture was stirred for 3 hours. The solvent was removed by concentration, and dichloromethane (75 mL / time) was added to the residue, followed by concentration. This operation was repeated twice to obtain a white solid (39.17 g, yield: 100%).

[0670]  9c:

[0671] At 0 to 10°C under nitrogen protection, DIC (38.96 g, 308.69 mmol) was added dropwise to a solution of Boc-L-valine (60.97 mg, 280.6 mmol) and HOBt (41.71 g, 308.7 mmol) in dichloromethane (250 mL). The reaction mixture was stirred at the same temperature for 30 minutes. Compound 9b (39.17 g, 280.6 mmol) was dissolved in dichloromethane (250 mL). Under nitrogen protection at 0 to 10°C, the pH was adjusted to 9-10 with diisopropylethylamine, and the mixture was stirred for 5 minutes. The mixture was subjected to suction filtration, and the filtrate was added dropwise to the Boc-L-valine reaction mixture. The resulting mixture was stirred at 10 to 15°C for 30 minutes. The reaction mixture was washed with 0.3 mol / L hydrochloric acid (300 mL), 50% sodium bicarbonate solution (300 mL), and saturated sodium chloride (300 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was triturated with [VPE / VEA = 4:1, 250 mL], then dried to obtain a white solid (47.65 g, yield: 56%).

[0672] 1H NMR (400 MHz, DMSO-d6) 8 (ppm) 9.91 (s, 1H), 8.04 (d, J = 7.1 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.24 (d, J = 8.5 Hz, 2H), 6.72 (d, J = 8.8 Hz, 1H), 5.08 (t, J = 5.7 Hz, 1H), 4.43 (t, J = 5.3 Hz, 3H), 3.91 - 3.74 (m, 1H), 1.96 (dq, J = 13.3, 6.8 Hz, 1H), 1.38 (s, 9H), 1.30 (d, J = 7.1 Hz, 3H), 0.87 (d, J = 6.8 Hz, 3H), 0.82 (d, J = 6.7 Hz, 3H).

[0673]  9d:

[0674] Compound 9c (25.00 g, 82.68 mmol) was dissolved in dichloromethane (20 mL), cooled to 0 to 10°C, and trifluoroacetic acid (45 mL) was added dropwise under nitrogen protection. The mixture was warmed to 30oC and stirred for 3 hours. The solvent and part of the trifluoroacetic acid were removed by concentration. The residue was added with dichloromethane (125 mL / time) and concentrated, and the operation was repeated twice. The residue was purified by silica gel column chromatography [VPE / VEA= 1:1] to obtain a white solid (12.20 g, yield: 47%).

[0675] 9e:

[0676] At 0 to 10°C under nitrogen protection, DIC (1.95 g, 15.4 mmol) was added dropwise to a solution of pivalic acid (1.50 g, 14.7 mmol) and HOBt (2.08 g, 15.4 mmol) in dichloromethane (25 mL). The reaction mixture was stirred at 10 to 15°C for 20 minutes. Compound 9d (5.11 g, 16.2 mmol) was dissolved in dichloromethane (25 mL). Under nitrogen protection at 0 to 10°C, the pH was adjusted to 9-10 with diisopropylethylamine, and the solution was added dropwise to the Boc-L-valine reaction mixture.  The resulting mixture was stirred at 10 to 15°C for 30 minutes. The reaction mixture was washed with 50% sodium bicarbonate solution (30 mL x 2) and saturated sodium chloride (30 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [VPE / VEA = 1:1] to obtain a white solid (2.50 g, yield: 59%).

[0677]  9f:

[0678] At 0°C, lithium hydroxide monohydrate (916 mg, 21.8 mmol) was dissolved in water (6 mL) and added dropwise to a solution of compound 9e (2.50 g, 8.72 mmol) in tetrahydrofuran (16 mL). The reaction mixture was stirred at 15 to 25°C for 1 hour. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2 to 3. Ethyl acetate (80 mL) was added for extraction. The upper organic phase was collected, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to obtain a white foamy solid (2.10 g, yield: 88%).

[0679] 9g:

[0680] At room temperature, EEDQ (3.81 g, 15.4 mmol) and p-aminobenzyl alcohol (950 mg, 7.71 mmol) were sequentially added to a solution of compound 9f (2.10 g, 7.71 mmol) in dichloromethane (40 mL). The mixture was 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 [VDCM / VMeOH = 70:1] to obtain a white solid (1.56 g, yield: 54%).

[0681] 9h:

[0682] At 0 to 5°C under nitrogen protection, 4-nitrophenyl chloroformate (662 mg, 15.4 mmol) was dissolved in dichloromethane (6 mL) and added dropwise to a solution of compound 9g (950 mg, 7.71 mmol), diisopropylethylamine (2.10 g, 7.71 mmol), and N,N-dimethylpyridine (2.10 g, 7.71 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at room temperature for 30 minutes. Dichloromethane (30 mL) and water (30 mL) were added to the reaction mixture. The mixture was shaken well, and the phases were separated. The lower organic phase was collected, 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 [VDCM / VMeOH = 60:1] to obtain a white solid (850 mg, yield: 95%).

[0683] Synthesis of 9

[0684] At 0 to 5°C under nitrogen protection, compound 9h (200 mg, 0.37 mmol) was dissolved in dichloromethane (20 mL). 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 sequentially. The reaction mixture was stirred at 15 to 25°C for 16 hours. Dichloromethane (30 mL) and water (30 mL) were added to the reaction mixture. The mixture was shaken well, and the phases were separated. The lower organic phase was collected, washed with 0.5 N 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 [VPE / VEA = 1:1] to obtain a white solid (230 mg, yield: 95%, HPLC purity: 99.725%).

[0685] 1H NMR (400 MHz, DMSO-d6) 8 (ppm)10.05 (s, 1H), 8.15 (d, J = 6.7 Hz, 1H), 7.98 (d, J = 7.4 Hz, 2H), 7.93 (d, J = 9.0 Hz, 1H), 7.74 (t, J = 7.2 Hz, 1H), 7.64 (dd, J = 14.8, 8.0 Hz, 4H), 7.43 (t, J = 7.5 Hz, 2H), 7.39 - 7.28 (m, 4H), 7.19 (t, J = 7.2 Hz, 1H), 7.09 (d, J = 8.6 Hz, 1H), 5.83 (t, J = 8.8 Hz, 1H), 5.38 (d, J = 6.9 Hz, 1H), 5.15 (s, 2H), 5.11 - 4.99 (m, 2H), 4.96 (d, J = 9.7 Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.40 (p, J = 6.7 Hz, 1H), 4.17 (t, J = 8.0 Hz, 1H), 4.03 (s, 2H), 3.76 (dd, J = 10.0, 6.9 Hz, 1H), 3.60 (d, J = 6.8 Hz, 1H), 3.30 (s, 3H), 3.23 (s, 3H), 2.68 (t, J = 10.3 Hz, 1H), 2.25 (s, 3H), 2.05 (dt, J = 13.8, 6.7 Hz, 1H), 1.81 (s, 4H), 1.59 - 1.45 (m, 5H), 1.38 - 1.29 (m, 11H), 1.25 (d, J = 9.1 Hz, 2H), 1.13 (s, 9H), 0.98 (d, J = 7.1 Hz, 6H), 0.89 (d, J = 6.7 Hz, 3H), 0.84 (d, J = 6.7 Hz, 3H).

[0686] Example 10: Synthesis of Compound 10

[0687]  10b:

[0688] At 0 to 10°C under nitrogen protection, 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 mixture. After completion of the dropwise addition, the mixture was stirred at room temperature for 30 minutes. The system was cooled to 0°C, and 0.1N hydrochloric acid (30 mL) was added to quench the reaction. The phases were separated, and the lower organic phase was collected, washed with 50% sodium bicarbonate solution (30 mL * 2) and saturated sodium chloride (30 mL), dried over anhydrous sodium sulfate, and concentrated to obtain a white solid (4.50 g, yield: 81%).

[0689]  10c:

[0690] 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 reaction mixture was stirred at 15 to 25°C for 0.5 hours. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2 to 3. Ethyl acetate (50 mL) was added, and the upper organic phase was collected, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to obtain a pale yellow solid (4.00 g, yield: 93%).

[0691] 10d:

[0692] At room temperature, EEDQ (7.10 g, 28.7 mmol) and p-aminobenzyl alcohol (1.77 g, 14.4 mmol) were sequentially added to a mixed solution of 10c (4.00 g, 14.4 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. The residue was triturated with [VPE / VEA = 5:1] for 1 hour, followed by suction filtration and drying to obtain a white solid (2.60 g, yield: 41%).

[0693] 10e:

[0694] 10d (1.0 g, 2.61 mmol) and morpholine (0.91 g, 10.45 mmol) were dissolved in ethanol (15 mL), followed by the addition of potassium iodide (0.865 g, 5.21 mmol). The mixture was stirred for 5 minutes, then heated to 50°C and stirred for 1.0 hour. The reaction mixture was concentrated to dryness, and dichloromethane (30 mL) was added. The mixture was washed with saturated sodium bicarbonate aqueous solution (30 mL x 2) and saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated to dryness, and subjected to column chromatography [VDCM / VMEOH = 20:1] to obtain a pale yellow foamy solid (0.76 g, yield: 67.14%).

[0695] 10:

[0696] 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 an ice bath. After completion of the addition, the reaction was carried out at 30°C for 2.5 hours. The reaction mixture 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 [VDCM / VMEOH = 20:1] to obtain an off-white solid (0.12 g, yield: 35.6%, HPLC: 99.56%).

[0697] HR-MS: 1296.6019 [M+H+].

[0698] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 10.06 (s, 1H), 8.27 (dd, J = 10.1, 8.0 Hz, 2H), 8.01 (dd, J = 23.8, 8.1 Hz, 3H), 7.79 (t, J = 7.4 Hz, 1H), 7.70 (dd, J = 10.2, 8.2 Hz, 4H), 7.48 (t, J = 7.6 Hz, 2H), 7.43 - 7.37 (m, 4H), 7.24 (t, J = 7.1 Hz, 1H), 5.88 (t, J = 8.9 Hz, 1H), 5.43 (d, J = 6.9 Hz, 1H), 5.21 (s, 2H), 5.15 - 5.06 (m, 2H), 5.01 (d, J = 9.9 Hz, 1H), 4.76 (s, 1H), 4.56 (s, 1H), 4.47 (p, J = 7.0 Hz, 1H), 4.30 (dd, J = 8.6, 6.4 Hz, 1H), 4.08 (s, 2H), 3.81 (dd, J = 10.2, 6.8 Hz, 1H), 3.62 (dd, J = 9.8, 4.8 Hz, 5H), 3.35 (s, 3H), 3.28 (s, 3H), 2.77 - 2.71 (m, 1H), 2.62 (dd, J = 12.3, 7.0 Hz, 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 = 5.4 Hz, 6H), 0.95 (d, J = 6.8 Hz, 3H), 0.91 (d, J = 6.8 Hz, 3H).

[0699] Example 11: Synthesis of Compound 11

[0700] 11b:

[0701] At 0 to 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). The reaction mixture was stirred at the same temperature for 30 minutes. 9d (7.58 g, 24.0 mmol) was added to dichloromethane (40 mL). Under nitrogen protection at 0 to 10°C, the pH was adjusted to 8-9 with triethylamine, and the mixture was stirred for 5 minutes. The mixture was subjected to suction filtration, and the filtrate was added dropwise to the acetic acid reaction mixture. The resulting mixture was stirred at 20 to 25°C for 30 minutes. The reaction mixture was washed with 50% sodium bicarbonate solution (50 mL) and saturated sodium chloride (50 mL x 2), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 30:1] to obtain a white solid (2.30 g, yield: 36%).

[0702] 11c:

[0703] At 0 to 10°C, lithium hydroxide monohydrate (790 mg, 18.8 mmol) was dissolved in water (10 mL) and added dropwise to a solution of 11b (2.30 g, 1.17 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at 15 to 25°C for 1 hour. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2-3. The majority of the solvent was removed by concentration, and the residue was treated with tetrahydrofuran (20 mL x 2) followed by concentration to obtain a yellow oil (2.17 g, yield: 100%).

[0704] 11d:

[0705] At room temperature, EEDQ (4.66 g, 18.8 mmol) and p-aminobenzyl alcohol (1.22 g, 9.90 mmol) were sequentially added 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 [VDCM / VMeOH = 12:1] to obtain a white solid (800 mg, yield: 25%).

[0706] 11:

[0707] At 0 to 5°C under nitrogen protection, 11d (150 mg, 0.45 mmol) was dissolved in dichloromethane (10 mL) / N,N-dimethylformamide (1 mL). Under nitrogen atmosphere, 1j (448 mg, 0.45 mmol) and N,N-dimethylpyridine (60 mg, 0.49 mmol) were added sequentially. The reaction mixture was stirred at 20 to 25°C for 3 hours. Dichloromethane (50 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (30 mL x 2) and saturated sodium chloride aqueous solution (30 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 24:1] to obtain a white solid (150 mg, yield: 28%, HPLC purity: 98.03%).

[0708] HR-MS: 1197.5599 [M+H+].

[0709] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 9.96 (s, 1H), 8.20 (d, J = 7.0 Hz, 1H), 8.02 - 7.84 (m, 4H), 7.73 (t, J = 7.4 Hz, 1H), 7.69 - 7.54 (m, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.38 - 7.25 (m, 4H), 7.18 (t, J = 7.3 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.14 (s, 2H), 5.10 - 4.90 (m, 3H), 4.70 (s, 1H), 4.50 (s, 1H), 4.39 (p, J = 7.1 Hz, 1H), 4.17 (dd, J = 8.4, 6.9 Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.3, 6.7 Hz, 1H), 3.59 (d, J = 6.8 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (ddd, J = 15.3, 9.8, 6.9 Hz, 1H), 2.24 (s, 3H), 1.97 (dt, J = 13.6, 6.8 Hz, 1H), 1.88 (s, 3H), 1.86 - 1.72 (m, 4H), 1.60 - 1.43 (m, 5H), 1.30 (dd, J = 25.5, 18.4 Hz, 12H), 0.98 (d, J = 7.2 Hz, 6H), 0.86 (dd, J = 14.0, 6.8 Hz, 6H).

[0710] Example 12: Synthesis of Compound 12

[0711] Referring to the synthesis of Compound 9 in Example 9, n-octanoic acid was used instead of pivalic acid to obtain Compound 12 (130 mg, yield: 24%, HPLC purity: 96.23%).

[0712] ESI-MS: 1281.6244 [M+H+].

[0713] 1H NMR (400 MHz, DMSO-d6) 6 (ppm) 10.04 (s, 1H), 8.20 (d, J = 7.0 Hz, 1H), 8.04 (d, J = 7.4 Hz, 2H), 7.98 (d, J = 9.0 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.79 (t, J = 7.2 Hz, 1H), 7.76 -7.66 (m, 4H), 7.48 (t, J = 7.6 Hz, 2H), 7.44 - 7.34 (m, 4H), 7.24 (t, J = 7.1 Hz, 1H), 5.88 (t, J = 8.7 Hz, 1H), 5.43 (d, J = 7.0 Hz, 1H), 5.20 (s, 2H), 5.15 - 5.04 (m, 2H), 5.01 (d, J = 9.6 Hz, 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, 6.8 Hz, 1H), 3.65 (d, J = 6.8 Hz, 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). Example 13: Synthesis of Compound 13

[0714] Example 13: Synthesis of Compound 13

[0715] 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%).

[0716] HR-MS: 1277.5629 [M+H+].

[0717] 1H NMR (400 MHz, DMSO-d6) 6 (ppm) 10.01 (s, 1H), 8.31 (t, J = 7.6 Hz, 2H), 7.97 (dd, J = 8.6, 5.6 Hz, 5H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (dd, J = 11.4, 8.2 Hz, 4H), 7.42 (t, J = 7.5 Hz, 2H), 7.33 (dt, J = 17.8, 6.7 Hz, 6H), 7.17 (dd, J = 16.8, 8.1 Hz, 1H), 5.82 (t, J = 8.7 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.14 (s, 2H), 5.10 - 4.99 (m, 2H), 4.95 (d, J = 9.8 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.43 (t, J = 7.0 Hz, 1H), 4.34 (t, J = 8.1 Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.2, 6.8 Hz, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (s, 1H), 2.23 (d, J = 6.7 Hz, 3H), 2.14 (td, J = 13.6, 6.8 Hz, 1H), 1.80 (s, 4H), 1.58 - 1.46 (m, 5H), 1.35 - 1.23 (m, 12H), 1.02 -0.90 (m, 12H).

[0718] Example 14: Synthesis of Compound 14

[0719] 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%).

[0720] HR-MS: 1287.5961 [M+H+].

[0721] 1H NMR (400 MHz, DMSO-d6) 6 (ppm) 9.98 (s, 1H), 8.19 (d, J = 6.9 Hz, 1H), 7.98 (d, J = 7.4 Hz, 2H), 7.90 (dd, J = 17.6, 8.8 Hz, 2H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (t, J = 8.4 Hz, 4H), 7.42 (t, J = 7.5 Hz, 2H), 7.37 - 7.32 (m, 4H), 7.26 - 7.16 (m, 6H), 5.82 (t, J = 8.6 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.14 (s, 2H), 5.05 (dd, J = 17.6, 8.3 Hz, 2H), 4.95 (d, J = 9.8 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.38 (dd, J = 13.9, 6.9 Hz, 1H), 4.21 - 4.16 (m, 1H), 4.02 (s, 2H), 3.79 - 3.71 (m, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.82 (t, J = 7.5 Hz, 2H), 2.67 (s, 1H), 2.58 - 2.52 (m, 1H), 2.44 (dd, J = 14.6, 7.9 Hz, 1H), 2.24 (s, 3H), 1.94 (dd, J = 13.4, 6.7 Hz, 1H), 1.80 (s, 4H), 1.51 (s, 5H), 1.37 - 1.30 (m, 12H), 0.98 (d, J = 6.6 Hz, 6H), 0.84 (d, J = 6.7 Hz, 3H), 0.80 (d, J = 6.7 Hz, 3H).

[0722] Example 15: Synthesis of Compound 15

[0723] 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: 99.587%).

[0724] HR-MS: 1305.5900 [M+H+].

[0725] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 9.99 (s, 1H), 8.19 (d, J = 6.8 Hz, 1H), 8.02 -7.79 (m, 4H), 7.72 (d, J = 6.9 Hz, 1H), 7.70 - 7.55 (m, 4H), 7.50 - 7.27 (m, 6H), 7.29 - 7.21 (m, 2H), 7.18 (t, J = 7.1 Hz, 1H), 7.07 (t, J = 8.8 Hz, 2H), 5.82 (t, J = 8.9 Hz, 1H), 5.37 (d, J = 6.6 Hz, 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 = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.80 (t, J = 7.6 Hz, 2H), 2.66 (dd, J = 19.2, 11.1 Hz, 1H), 2.48 - 2.37 (m, 2H), 2.24 (s, 3H), 1.94 (dt, J = 13.2, 6.5 Hz, 1H), 1.82 (d, J = 14.3 Hz, 4H), 1.62 - 1.42 (m, 5H), 1.41 - 1.15 (m, 12H), 0.97 (d, J = 6.6 Hz, 6H), 0.80 (dd, J = 17.3, 6.7 Hz, 6H).

[0726] Example 16: Synthesis of Compound 16

[0727] 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%).

[0728] HR-MS: 1253.6158 [M+H+].

[0729] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 9.99 (s, 1H), 8.13 (d, J = 6.9 Hz, 1H), 8.02 - 7.87 (m, 3H), 7.78 - 7.68 (m, 2H), 7.64 (t, J = 8.7 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.39 - 7.26 (m, 4H), 7.18 (t, J = 7.3 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.14 (s, 2H), 5.10 - 4.98 (m, 2H), 4.95 (d, J = 9.9 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.39 (p, J = 7.0 Hz, 1H), 4.17 (dd, J = 8.3, 7.0 Hz, 1H), 4.02 (d, J = 1.4 Hz, 2H), 3.75 (dd, J = 10.3, 6.7 Hz, 1H), 3.59 (d, J = 6.9 Hz, 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, 9.7 Hz, 4H), 1.87 - 1.70 (m, 4H), 1.61 - 1.41 (m, 5H), 1.38 - 1.28 (m, 11H), 0.97 (d, J = 9.6 Hz, 15H), 0.87 (dd, J = 12.3, 6.8 Hz, 6H).

[0730] Example 17: Synthesis of Compound 17

[0731] 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%).

[0732] HR-MS: 1255.6322 [M+H+].

[0733] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 9.99 (s, 1H), 8.27 (d, J = 6.6 Hz, 1H), 8.17 (d, J = 8.7 Hz, 1H), 7.95 (dd, J = 22.4, 8.1 Hz, 3H), 7.72 (d, J = 6.9 Hz, 1H), 7.64 (dd, J = 12.6, 7.9 Hz, 4H), 7.38 (dd, J = 29.2, 7.4 Hz, 6H), 7.19 (d, J = 6.6 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 6.5 Hz, 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 = 10.7 Hz, 3H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (t, J = 15.2 Hz, 1H), 2.24 (s, 3H), 1.98 (td, J = 13.0, 6.5 Hz, 1H), 1.82 (d, J = 13.4 Hz, 4H), 1.61 - 1.43 (m, 5H), 1.33 (d, J = 13.4 Hz, 12H), 1.11 - 0.73 (m, 12H).

[0734] Example 18: Synthesis of Compound 18

[0735] Referring to the synthesis of Compound 9 in Example 9, n-octanoic acid was used instead of pivalic acid to obtain Compound 18 (130 mg, yield: 24%, HPLC purity: 96.23%).

[0736] LC-MS: 1239.5839 [M+H+].

[0737] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 9.98 (s, 1H), 8.15 (d, J = 6.9 Hz, 1H), 7.95 (dd, J = 23.1, 8.2 Hz, 3H), 7.81 (d, J = 8.6 Hz, 1H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (t, J = 8.7 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.37 - 7.27 (m, 4H), 7.18 (t, J = 7.2 Hz, 1H), 5.82 (t, J = 8.9 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.14 (s, 2H), 5.10 - 4.99 (m, 2H), 4.95 (d, J = 10.0 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.39 (p, J = 7.0 Hz, 1H), 4.17 (dd, J = 8.4, 7.0 Hz, 1H), 4.00 (s, 1H), 3.75 (dd, J = 10.2, 6.8 Hz, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.66 (dd, J = 17.6, 12.1 Hz, 1H), 2.51 (s, 1H), 2.23 (d, J = 8.0 Hz, 3H), 2.21 - 2.10 (m, 2H), 1.96 (d, J = 6.8 Hz, 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 = 7.1 Hz, 6H), 0.91 - 0.82 (m, 9H).

[0738] Example 19: Synthesis of Compound 19 CF3COOH 19b

[0739]  19b

[0740] At 0 to 10°C under nitrogen protection, the pH of a solution of 9d (9.22 g, 29.1 mmol) in 123 dichloromethane (50 mL) was adjusted to 9-10 with diisopropylethylamine. Acrylic acid (2.00 g, 27.7 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.98 g, 41.6 mmol), and N,N-dimethylpyridine (0.34 g, 2.78 mmol) were added sequentially. The reaction mixture was stirred at 20 to 25°C for 1 hour. Dichloromethane (100 mL) was added to the reaction mixture, which was then washed with 50% ammonium chloride aqueous solution (50 mL), saturated sodium bicarbonate aqueous solution (50 mL), and saturated sodium chloride aqueous solution (50 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VPE / VEA = 2:1] to obtain an off-white solid (2.20 g, yield: 62%).

[0741]  19c

[0742] At 0 to 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). The mixture was heated to 60 to 65°C and stirred for 16 hours. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography [VDCM / VMeOH = 19:1] to obtain a pale yellow solid (2.05 g, yield: 80%).

[0743] 19d

[0744] At 0°C, lithium hydroxide monohydrate (637 mg, 15.2 mmol) was dissolved in water (6 mL) and added dropwise to a solution of 19c (2.00 g, 6.07 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at 15 to 25°C for 0.5 hours. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2 to 3. 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 obtain a yellow solid (1.91 g, yield: 100%).

[0745]  19e

[0746] At room temperature, EEDQ (2.99 g, 12.1 mmol) and p-aminobenzyl alcohol (0.746 g, 6.05 mmol) were sequentially added to a solution of 19d (1.91 g, 6.05 mmol) in a mixture of tetrahydrofuran (30 mL) and methanol (4 mL). 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 [VDCM / VMeOH = 20:1] to obtain a white solid (350 mg, yield: 14%).

[0747] 19f

[0748] At 0 to 5°C under nitrogen protection, 4-nitrophenyl chloroformate (396 mg, 1.95 mmol) was dissolved in dichloromethane (5 mL) and added dropwise to a solution of 19e (330 mg, 0.78 mmol), diisopropylethylamine (304 mg, 2.35 mmol), and N,N-dimethylpyridine (29 mg, 0.23 mmol) in dichloromethane (15 mL). The reaction mixture was stirred at room temperature for 40 minutes. Dichloromethane (50 mL) was added to the reaction mixture, followed by washing with 0.1 N hydrochloric acid (40 mL) and saturated sodium chloride aqueous solution (30 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 35:1] to obtain a white solid (135 mg, yield: 29%).

[0749] 19

[0750] At 0 to 5°C under nitrogen protection, 19f (130 mg, 0.22 mmol) was dissolved in dichloromethane (15 mL). Cabazitaxel (195 mg, 0.23 mmol) and N,N-dimethylpyridine (30 mg, 0.24 mmol) were added sequentially. The reaction mixture was stirred at 20 to 25°C for 16 hours. Dichloromethane (30 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (25 mL x 2) and saturated sodium chloride aqueous solution (60 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 40:1] to obtain an off-white solid (72 mg, yield: 24%, HPLC purity: 99.62%).

[0751] 1H NMR (400 MHz, DMSO-d6) 5(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), 4.45 - 4.35 (m, 1H), 4.26 - 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).

[0752] Example 20: Synthesis of Compound 20

[0753]  20b:

[0754] At 0 to 10°C under nitrogen protection, N,N’-dicyclohexylcarbodiimide (5.84 g, 28.3 mmol) was dissolved in tetrahydrofuran (15 mL) and added 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). The mixture was stirred at 20 to 25°C for 40 minutes, then subjected to suction filtration, and the filtrate was collected. The filtrate was added 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). The mixture was stirred at 20 to 25°C for 2.5 hours. The solvent tetrahydrofuran was removed by concentration, and dichloromethane (80 mL) was added for extraction. The organic phase was washed with 0.6 N hydrochloric acid (30 mL) and saturated sodium chloride aqueous solution (40 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was triturated with petroleum ether (40 mL) to obtain a white solid (5.00 g, yield: 54%).

[0755]  20c:

[0756] At room temperature, EEDQ (6.00 g, 24.4 mmol) and p-aminobenzyl alcohol (1.70 g, 13.40 mmol) were sequentially added to a mixed solution of 20b (5.00 g, 12.2 mmol) in dichloromethane (35 mL) and methanol (3.5 mL). The reaction mixture was stirred at room temperature for 16 hours. Dichloromethane (50 mL) was added to the reaction mixture, which was then washed with 0.6 N hydrochloric acid (40 mL) and saturated sodium chloride aqueous solution (50 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was triturated with petroleum ether (20 mL) to obtain a white solid (1.50 g, yield: 24%).

[0757] 20d:

[0758] At 10 to 15°C under nitrogen protection, PNP-CBTX (780 mg, 0.78 mmol) and 4-dimethylaminopyridine (105 mg, 0.85 mmol) were added to a solution of 20c (400 mg, 0.78 mmol) in tetrahydrofuran (8 mL). The reaction mixture was stirred at 30°C for 5 hours. Dichloromethane (30 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (20 mL) and saturated sodium chloride aqueous solution (20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 80:1] to obtain a white solid (650 mg, yield: 61%).

[0759] 20e:

[0760] At 0 to 5°C under nitrogen protection, piperidine (377 mg, 4.43 mmol) was dissolved in dichloromethane (2 mL) and added dropwise to a solution of 20d (610 mg, 0.44 mmol) in dichloromethane (4 mL). The reaction mixture was stirred at 10 to 15°C for 1 hour. Dichloromethane (40 mL) was added to the reaction mixture, which was then washed with 0.1 N hydrochloric acid (20 mL), saturated sodium bicarbonate solution (20 mL), and saturated sodium chloride aqueous solution (20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 50:1] to obtain a white solid (270 mg, yield: 53%).

[0761] Synthesis of 20

[0762] At 0 to 5°C under nitrogen protection, succinic anhydride (35 mg, 0.35 mmol) and pyridine (37 mg, 0.47 mmol) were sequentially added to a solution of 20e (270 mg, 0.23 mmol) in dichloromethane (12 mL). The reaction mixture was stirred at room temperature for 0.5 hours. Dichloromethane (30 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (20 mL x 2) and saturated sodium chloride aqueous solution (20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 30:1] to obtain a white solid (170 mg, yield: 58%, HPLC purity: 97.34%).

[0763] LC-MS: 1255.5622 [M+H+].

[0764] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 12.09 (s, 1H), 9.91 (s, 1H), 8.14 (d, J = 6.9 Hz, 1H), 7.95 (dd, J = 21.8, 8.0 Hz, 4H), 7.73 (t, J = 7.1 Hz, 1H), 7.64 (d, J = 8.2 Hz, 4H), 7.39 (dt, J = 13.0, 7.8 Hz, 6H), 7.18 (t, J = 7.0 Hz, 1H), 5.82 (t, J = 8.5 Hz, 1H), 5.37 (d, J = 6.7 Hz, 1H), 5.15 (s, 2H), 5.11 - 4.99 (m, 2H), 4.95 (d, J = 9.6 Hz, 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 = 6.7 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (dt, J = 15.7, 7.9 Hz, 1H), 2.43 (d, J = 8.0 Hz, 5H), 2.24 (s, 3H), 1.99 (dq, J = 13.7, 6.9 Hz, 1H), 1.82 (d, J = 13.2 Hz, 4H), 1.61 - 1.42 (m, 5H), 1.41 - 1.26 (m, 11H), 0.98 (d, J = 6.9 Hz, 6H), 0.87 (dd, J = 14.0, 6.7 Hz, 6H).

[0765] Example 21: Synthesis of Compound 21

[0766]  21b:

[0767] At 0°C, lithium hydroxide monohydrate (1.35 g, 33.1 mmol) was dissolved in water (10 mL) and added dropwise to a solution of 21a (5.00 g, 16.5 mmol) in tetrahydrofuran (40 mL). The reaction mixture was stirred at 15 to 25°C for 0.5 hours. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2 to 3. Ethyl acetate (100 mL x 2) was added for extraction. The combined organic phases were washed with saturated sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, and concentrated to obtain a white solid (4.40 g, yield: 92%).

[0768]  21c:

[0769] At room temperature, EEDQ (7.50 g, 30.6 mmol) and p-aminobenzyl alcohol (2.26 g, 18.3 mmol) were sequentially added to a mixed 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 triturated with ethyl acetate / petroleum ether (V / V = 1:3, 400 mL) for 1 hour. The mixture was subjected to suction filtration, and the filter cake was washed with petroleum ether (30 mL). The collected filter cake was dried at 30°C to obtain a white solid (3.8 g, yield: 63%).

[0770]  21d:

[0771] At 0 to 5°C under nitrogen protection, 4-nitrophenyl chloroformate (645 mg, 3.20 mmol) was dissolved in dichloromethane (6 mL) and added dropwise to a solution of 21c (630 mg, 1.60 mmol), diisopropylethylamine (621 mg, 4.80 mmol), and N,N-dimethylpyridine (39 mg, 0.32 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at room temperature for 30 minutes. Dichloromethane (50 mL) was added to the reaction mixture, followed by washing with 0.1 N hydrochloric acid (40 mL) and saturated sodium chloride aqueous solution (30 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VPE / VEA = 1:1] to obtain a white solid (820 mg, yield: 91%).

[0772] Synthesis of 21:

[0773] At 0 to 5°C under nitrogen protection, 21d (220 mg, 0.39 mmol) was dissolved in dichloromethane (15 mL). Cabazitaxel (330 mg, 0.39 mmol) and N,N-dimethylpyridine (53 mg, 0.43 mmol) were added sequentially. The reaction mixture was stirred at 20 to 25°C for 16 hours. Dichloromethane (40 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (25 mL x 2) and saturated sodium chloride aqueous solution (30 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VPE / VEA = 1:1] to obtain an off-white solid (270 mg, yield: 55%, HPLC purity: 97.99%).

[0774] ESI-MS: 1255.5779 [M+H+].

[0775] 1H NMR (400 MHz, DMSO-d6) S (ppm) 10.06 (s, 1H), 8.07 (d, J = 6.9 Hz, 1H), 7.95 (dd, J = 23.2, 8.1 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (dd, J = 14.5, 8.0 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.38 - 7.28 (m, 4H), 7.18 (t, J = 7.2 Hz, 1H), 6.71 (d, J = 8.7 Hz, 1H), 5.82 (t, J = 8.6 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.14 (s, 2H), 5.10 - 4.98 (m, 2H), 4.95 (d, J = 9.9 Hz, 1H), 4.70 (s, 1H), 4.45 (dd, J = 19.7, 12.9 Hz, 2H), 4.02 (s, 2H), 3.82 (dd, J = 20.5, 13.3 Hz, 1H), 3.75 (dd, J = 10.4, 6.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 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, 11.6 Hz, 21H), 0.98 (d, J = 7.0 Hz, 6H), 0.87 (d, J = 6.7 Hz, 3H), 0.82 (d, J = 6.7 Hz, 3H).

[0776] Example 22: Synthesis of Compound 22

[0777] Referring to the synthesis of Compound 10 in Example 10, pyrrolidine was used instead of morpholine to obtain Compound 22 (0.18 g, yield: 50%, HPLC: 99.91%).

[0778] MS: 1280.6056 [M+H+].

[0779] 1H NMR (400 MHz, DMSO-d6) S (ppm) 10.07 (s, 1H), 8.26 (d, J = 7.8 Hz, 2H), 7.96 (dd, J = 20.7, 8.4 Hz, 3H), 7.74 (t, J = 7.5 Hz, 1H), 7.65 (t, J = 7.4 Hz, 4H), 7.43 (t, J = 7.5 Hz, 2H), 7.35 (t, J = 6.4 Hz, 4H), 7.18 (t, J = 7.5 Hz, 1H), 5.82 (t, J = 9.2 Hz, 1H), 5.38 (d, J = 7.1 Hz, 1H), 5.15 (s, 2H), 5.10 - 5.00 (m, 2H), 4.96 (d, J = 9.4 Hz, 1H), 4.71 (s, 1H), 4.51 (s, 1H), 4.42 (t, J = 7.1 Hz, 1H), 4.23 (t, J = 7.5 Hz, 1H), 4.02 (s, 2H), 3.80 - 3.72 (m, 1H), 3.59 (d, J = 7.1 Hz, 1H), 3.12 (s, 2H), 3.06 - 2.94 (m, 3H), 2.63 (q, J = 10.4, 7.2 Hz, 3H), 2.25 (s, 3H), 2.01 (q, J = 6.7 Hz, 1H), 1.85 (s, 4H), 1.80 (s, 3H), 1.51 (s, 3H), 1.33 (d, J = 14.0 Hz, 12H), 1.28 - 1.17 (m, 3H), 0.98 (d, J = 7.6 Hz, 6H), 0.90 (d, J = 6.8 Hz, 3H), 0.86 (d, J = 6.8 Hz, 3H).

[0780] Example 23: Synthesis of Compound 23

[0781]  23b:

[0782] 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-Fmoc-L-alanine (3.00 g, 9.64 mmol) in dichloromethane (40 mL) / methanol (5 mL). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with sodium bicarbonate aqueous solution (30 mL), 0.3 N hydrochloric acid (20 mL), and saturated brine (20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was triturated with petroleum ether / ethyl acetate (V / V = 4:1, 25 mL), subjected to suction filtration, and the filter cake was collected and dried to obtain a white solid (2.90 g, yield: 72%).

[0783] 23c:

[0784] At 0 to 5°C under nitrogen protection, PNP-CBTX (800 mg, 0.80 mmol) and 4-dimethylaminopyridine (108 mg, 0.88 mmol) were added to a solution of 23b (330 mg, 0.79 mmol) in tetrahydrofuran (5 mL). The reaction mixture was stirred at 25 to 30°C for 2 hours. Dichloromethane (30 mL x 2) was added to the reaction mixture for extraction. The combined organic phases were washed with 0.5 N hydrochloric acid (20 mL x 2) and saturated sodium chloride aqoeous 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 [VDCM / VMeOH = 85:1] to obtain a white solid (640 mg, yield: 63%).

[0785] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 10.08 (s, 1H), 7.98 (d, J = 7.3 Hz, 2H), 7.91 (s, 1H), 7.89 (s, 1H), 7.75 (d, J = 7.3 Hz, 2H), 7.71 (s, 1H), 7.70 - 7.66 (m, 2H), 7.65 (s, 2H), 7.63 (s, 1H), 7.43 (d, J = 7.6 Hz, 3H), 7.40 (s, 1H), 7.38 - 7.31 (m, 7H), 7.18 (t, J = 7.2 Hz, 1H), 5.83 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.15 (s, 2H), 5.04 (dd, J = 17.0, 8.3 Hz, 2H), 4.95 (d, J = 10.2 Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.29 (d, J = 6.1 Hz, 2H), 4.22 (dd, J = 14.5, 7.2 Hz, 2H), 4.02 (s, 2H), 3.76 (dd, J = 10.4, 6.8 Hz, 1H), 3.59 (d, J = 7.0 Hz, 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 = 9.2 Hz, 1H), 1.49 (d, J = 17.2 Hz, 5H), 1.35 - 1.31 (m, 12H), 0.98 (d, J = 6.3 Hz, 6H).

[0786] 23d:

[0787] 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). The reaction mixture was stirred at -1 to 3°C for 2 hours. Dichloromethane (40 mL) was added to the reaction mixture, which was then washed with saturated sodium bicarbonate aqoeous solution (20 mL x 2), water (20 mL x 2), and saturated sodium chloride aqoeous solution (20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 30:1] to obtain a white solid (300 mg, yield: 58%).

[0788] Synthesis of 23

[0789] At 0 to 5°C under nitrogen protection, succinic anhydride (46 mg, 0.46 mmol) and pyridine (54 mg, 0.68 mmol) were sequentially added to a solution of 23d (250 mg, 0.23 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 1 hour. Dichloromethane (30 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (15 mL x 2) and saturated sodium chloride aqueous solution (20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 20:1] to obtain a white solid (210 mg, yield: 77%, HPLC purity: 99.39%).

[0790] MS: 642.2583 [M / 2+H+].

[0791] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 12.10 (s, 1H), 9.96 (s, 1H), 8.22 (d, J = 7.2 Hz, 1H), 7.95 (dd, J = 20.7, 8.2 Hz, 3H), 7.77 - 7.56 (m, 5H), 7.39 (dt, J = 13.4, 8.0 Hz, 6H), 7.18 (t, J = 7.2 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.15 (s, 2H), 5.10 - 4.99 (m, 2H), 4.95 (d, J = 9.8 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.40 (p, J = 7.1 Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.2, 6.8 Hz, 1H), 3.59 (d, J = 6.9 Hz, 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 = 14.6 Hz, 4H), 1.61 - 1.43 (m, 5H), 1.40 - 1.24 (m, 12H), 0.98 (d, J = 7.1 Hz, 6H).

[0792] Example 24: Synthesis of Compound 24

[0793] Referring to the synthesis of Compound 23 in Example 23, oxalyl chloride was used instead of succinic anhydride to obtain Compound 24 (100 mg, yield: 37%, HPLC purity: 94.03%).

[0794] MS:

[0795] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 12.10 (s, 1H),10.18 (s, 1H), 8.72 (d, J = 7.5 Hz, 1H), 7.95 (dd, J = 20.3, 8.2 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (dd, J = 11.3, 8.2 Hz, 4H), 7.46 - 7.32 (m, 6H), 7.18 (t, J = 7.3 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.15 (s, 2H), 5.10 - 4.99 (m, 2H), 4.95 (d, J = 9.7 Hz, 1H), 4.70 (s, 1H), 4.55 - 4.45 (m, 2H), 4.01 (s, 2H), 3.75 (dd, J = 10.0, 6.9 Hz, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.72 - 2.60 (m, 1H), 2.24 (s, 3H), 1.82 (d, J = 15.0 Hz, 4H), 1.60 - 1.45 (m, 5H), 1.41 (d, J = 7.0 Hz, 3H), 1.34 (s, 9H), 0.97 (d, J = 6.4 Hz, 6H).

[0796] Example 25: Synthesis of Compound 25

[0797] Referring to the synthesis of Compound 23 in Example 23, diglycolic anhydride was used instead of succinic anhydride to obtain Compound 25 (0.34 g, yield: 61.27%, HPLC: 95.771%).

[0798] MS: 1172.4830 [M+H+].

[0799] 1H NMR (400 MHz, DMSO) 5 (ppm) 12.73 (s, 1H), 10.17 (s, 1H), 8.20 (d, J = 5.4 Hz, 1H), 7.95 (dd, J = 19.8, 8.2 Hz, 3H), 7.73 (t, J = 7.2 Hz, 1H), 7.65 (dd, J = 7.7, 4.1 Hz, 4H), 7.42 (t, J = 7.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 4H), 7.18 (t, J = 7.2 Hz, 1H), 5.82 (t, J = 8.9 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.15 (s, 2H), 5.09 - 4.99 (m, 2H), 4.95 (d, J = 9.8 Hz, 1H), 4.70 (s, 1H), 4.50 (t, J = 7.1 Hz, 2H), 4.12 (s, 2H), 4.03 (s, 4H), 3.75 (dd, J = 10.1, 6.8 Hz, 1H), 3.59 (d, J = 6.8 Hz, 1H), 3.32 (s, 2H), 3.22 (s, 3H), 2.67 (t, J = 14.9 Hz, 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).

[0800] Example 26: Synthesis of Compound 26

[0801] Referring to the synthesis of Compound 23 in Example 23, glutaric anhydride was used instead of succinic anhydride to obtain Compound 26 (200 mg, yield: 36%, HPLC purity: 98.17%).

[0802] MS: 1170.5096 [M+H+].

[0803] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 12.02 (s, 1H), 10.07 (s, 1H), 8.14 (d, J = 7.1 Hz, 1H), 7.95 (dd, J = 21.3, 8.1 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (dd, J = 10.1, 8.3 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.39 - 7.27 (m, 4H), 7.18 (t, J = 7.2 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.15 (s, 2H), 5.10 - 4.92 (m, 3H), 4.70 (s, 1H), 4.50 (s, 1H), 4.40 (p, J = 7.0 Hz, 1H), 4.02 (s, 2H), 3.76 (dd, J = 10.3, 6.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 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 = 7.1 Hz, 6H).

[0804] Example 27: Synthesis of Compound 27 0 BocHN. A OH 27a 27e 27f

[0805]  27b:

[0806] At 0 to 10°C under nitrogen protection, 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). The reaction mixture was stirred at the same temperature for 30 minutes. 27a (8.00 g, 63.8 mmol) was added to dichloromethane (100 mL). Under nitrogen protection at 0 to 10°C, the pH was adjusted to 9-10 with triethylamine, and the mixture was stirred for 5 minutes. The mixture was subjected to suction filtration, and the filtrate was added dropwise to the Boc-glycine reaction mixture. The resulting mixture was stirred at 20 to 25°C for 60 minutes. The reaction mixture was washed with 0.3 mol / L hydrochloric acid (200 mL), 50% sodium bicarbonate solution (200 mL), and saturated sodium chloride (200 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography [VPE / VEA = 1:1] to obtain a pale yellow oil (11.80 g, yield: 83%).

[0807]  27c:

[0808] At 0°C, lithium hydroxide monohydrate (3.12 g, 44.7 mmol) was dissolved in water (20 mL) and added dropwise to a solution of 27b (5.50 g, 22.3 mmol) in tetrahydrofuran (30 mL). The reaction mixture was stirred at 15 to 25°C for 1 hour. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2 to 3. Ethyl acetate (100 mL) was added for extraction. The upper organic phase was collected, washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, and concentrated to obtain a white solid (4.30 g, yield: 83%).

[0809] 27e:

[0810] At 0 to 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). The reaction mixture was stirred at the same temperature for 30 minutes. Glycine methyl ester hydrochloride (3.56 g, 28.4 mmol) was added to dichloromethane (40 mL). Under nitrogen protection at 0 to 10°C, the pH was adjusted to 9-10 with triethylamine, and the mixture was stirred for 5 minutes. The mixture was subjected to suction filtration, and the filtrate was added dropwise to the Fmoc-phenylalanine reaction mixture. The resulting mixture was stirred at 20 to 25°C for 60 minutes. The reaction mixture was washed with 50% sodium bicarbonate solution (200 mL) and saturated sodium chloride (100 mL x 2), dried over anhydrous sodium sulfate, and concentrated. The residue was triturated with petroleum ether (100 mL) and purified to obtain a pale yellow oil (11.0 g, yield: 93%).

[0811] 27f:

[0812] 27e (11.00 g, 23.99 mmol) was dissolved in N,N-dimethylformamide (50 mL). The solution was cooled to 0 to 10°C, and diethylamine (15 mL) was added dropwise under nitrogen protection. The mixture was stirred at 0 to 10°C for 1 hour. 6N hydrochloric acid was added dropwise to adjust the pH to 4-5, followed by the addition of water (100 mL) and stirring for 10 minutes. The mixture was filtered, and the filtrate was collected. The filtrate was washed with methyl tert-butyl ether (100 mL x 2), and the pH was adjusted to 8-9 with solid sodium bicarbonate. The mixture was extracted with dichloromethane (100 mL x 2), and the combined organic phases were dried over anhydrous sodium sulfate and concentrated to obtain a colorless oil (5.67 g, yield: 100%).

[0813] 27g:

[0814] At 0 to 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). The reaction mixture was stirred at 10 to 15°C for 30 minutes. A solution of 27f (5.11 g, 16.2 mmol) in dichloromethane (25 mL) was added dropwise to the 27-M2 reaction mixture, and the resulting mixture was stirred at 10 to 15°C for 30 minutes. The reaction mixture was washed with 50% sodium bicarbonate solution (30 mL x 2) and saturated sodium chloride (30 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 20:1] to obtain a white solid (6.30 g, yield: 75%).

[0815] 27h:

[0816] At 0 to 10°C, lithium hydroxide monohydrate (186 mg, 4.44 mmol) was dissolved in water (5 mL) and added dropwise to a solution of 27g (1.00 g, 2.22 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at 15 to 25°C for 1 hour. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2 to 3. Ethyl acetate (50 mL) was added for extraction. The upper organic phase was collected, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and concentrated to obtain a white foamy solid (500 mg, yield: 52%).

[0817] 27i:

[0818] At room temperature, EEDQ (567 mg, 2.29 mmol) and p-aminobenzyl alcohol (148 mg, 1.20 mmol) were sequentially added to a solution of 27h (500 mg, 1.15 mmol) in dichloromethane (20 mL) / methanol (2 mL). The reaction 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 [VDCM / VMeOH = 12:1] to obtain a white solid (540 mg, yield: 87%).

[0819] Synthesis of 27:

[0820] At 0 to 5°C under nitrogen protection, 27i (150 mg, 0.28 mmol) was dissolved in dichloromethane (10 mL) / N,N-dimethylformamide (1 mL). Under nitrogen atmosphere, 1j (277 mg, 0.28 mmol) and N,N-dimethylpyridine (37 mg, 0.33 mmol) were added sequentially. The reaction mixture was stirred at 15 to 25°C for 3 hours. Dichloromethane (50 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (30 mL x 2) and saturated sodium chloride aqueous solution (30 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 24:1] to obtain a white solid (210 mg, yield: 54%, HPLC purity: 99.720%).

[0821] MS: 1403.6128 [M+H+].

[0822] 1H NMR (400 MHz, DMSO-d6) 6 (ppm) 9.93 (s, 1H), 8.42 (s, 1H), 8.19 (s, 1H), 7.95 (d, J = 18.3 Hz, 4H), 7.69 (d, J = 31.6 Hz, 5H), 7.31 (dd, J = 67.3, 25.3 Hz, 12H), 6.98 (s, 1H), 5.79 (d, J = 26.4 Hz, 1H), 5.37 (s, 1H), 5.15 (s, 2H), 5.02 (d, J = 41.7 Hz, 3H), 4.70 (s, 1H), 4.50 (s, 2H), 4.15 - 3.73 (m, 6H), 3.60 (d, J = 33.6 Hz, 4H), 3.30 - 3.26 (s, 3H), 3.22 (s, 3H), 3.08 (d, J= 10.2 Hz, 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).

[0823] Example 28: Synthesis of Compound 28

[0824] 28b:

[0825] At 0 to 10°C under nitrogen protection, trifluoroacetic acid (6 mL) was added dropwise to a solution of 27g (1.50 g, 3.33 mmol) in dichloromethane (6 mL). The mixture was stirred at 25 to 30°C for 60 minutes. The mixture was concentrated, and dichloromethane (30 mL x 2) was added to the residue. After concentration, a pale yellow oil (1.16 g, yield: 100%) was obtained.

[0826]  28c:

[0827] At 0 to 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). The reaction mixture was stirred at the same temperature for 30 minutes. 28b (1.16 g, 3.34 mmol) was added to dichloromethane (30 mL). Under nitrogen protection at 0 to 10°C, the pH was adjusted to 9-10 with triethylamine, and the mixture was stirred for 5 minutes. The mixture was subjected to suction filtration, and the filtrate was added dropwise to the pivalic acid reaction mixture. The resulting mixture was stirred at 20 to 25°C for 30 minutes. The reaction mixture was washed with 50% sodium bicarbonate solution (50 mL) and saturated sodium chloride (50 mL x 2), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 20:1] to obtain a white solid (520 mg, yield: 36%).

[0828] 28d:

[0829] At 0 to 10°C, lithium hydroxide monohydrate (100 mg, 2.39 mmol) was dissolved in water (3 mL) and added dropwise to a solution of 28c (520 mg, 1.20 mmol) in tetrahydrofuran (6 mL). The reaction mixture was stirred at 15 to 25°C for 1 hour. The reaction mixture was cooled to 0 to 5°C, and 6N hydrochloric acid was added dropwise to adjust the pH to 2 to 3. Ethyl acetate (50 mL) was added for extraction. The upper organic phase was collected, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and concentrated to obtain a white foamy solid (420 mg, yield: 83%).

[0830] 28e:

[0831] At room temperature, EEDQ (494 mg, 2.00 mmol) and p-aminobenzyl alcohol (129 mg, 1.05 mmol) were sequentially added to a solution of 28d (420 mg, 1.00 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 [VDCM / VMeOH = 15:1] to obtain a white solid (330 mg, yield: 63%).

[0832] Synthesis of 28

[0833] At 0 to 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 atmosphere, 1j (285 mg, 0.28 mmol) and N,N-dimethylpyridine (38 mg, 0.31 mmol) were added sequentially. The reaction mixture was stirred at 15 to 25°C for 3 hours. Dichloromethane (50 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (30 mL x 2) and saturated sodium chloride aqueous solution (30 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 24:1] to obtain a white solid (220 mg, yield: 55%, HPLC purity: 99.61%).

[0834] HRMS: 1387.6291 [M+H+].

[0835] 1H NMR (400 MHz, DMSO-d6) 8 (ppm) 9.92 (s, 1H), 8.38 (t, J = 5.7 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.03 - 7.85 (m, 4H), 7.79 - 7.69 (m, 2H), 7.69 - 7.58 (m, 4H), 7.42 (t, J = 7.5 Hz, 2H), 7.35 (d, J = 8.1 Hz, 4H), 7.26 (d, J = 4.3 Hz, 4H), 7.23 - 7.13 (m, 2H), 5.82 (t, J = 8.6 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.15 (s, 2H), 5.11 - 4.99 (m, 2H), 4.95 (d, J = 9.7 Hz, 1H), 4.70 (s, 1H), 4.57 - 4.42 (m, 2H), 4.02 (s, 2H), 3.90 (d, J = 3.6 Hz, 2H), 3.82 - 3.72 (m, 2H), 3.63 (ddd, J = 15.4, 8.6, 3.9 Hz, 4H), 3.29 (s, 3H), 3.22 (s, 3H), 3.09 (dd, J = 13.8, 4.3 Hz, 1H), 2.90 - 2.81 (m, 1H), 2.68 (d, J = 13.0 Hz, 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 = 6.8 Hz, 6H).

[0836] Example 29: Synthesis of Compound 29

[0837] Referring to the synthesis of Compound 23 in Example 23, N-Fmoc-glycine was used instead of N-Fmoc-L-alanine to obtain Compound 29 (170 mg, yield: 48%, HPLC purity: 95.80%).

[0838] MS: 1142.4742 [M+H+].

[0839] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 12.10 (s, 1H), 9.93 (s, 1H), 8.25 (t, J = 5.8 Hz, 1H), 7.95 (dd, J = 21.3, 8.2 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (dd, J = 13.2, 8.1 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.39 - 7.31 (m, 4H), 7.18 (t, J = 7.2 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.15 (s, 2H), 5.10 - 4.99 (m, 2H), 4.95 (d, J = 9.5 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.88 (d, J = 5.8 Hz, 2H), 3.75 (dd, J = 10.2, 6.7 Hz, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.66 (dd, J = 18.1, 11.8 Hz, 1H), 2.44 (dd, J = 11.1, 5.8 Hz, 4H), 2.24 (s, 3H), 1.80 (s, 4H), 1.58 - 1.46 (m, 5H), 1.35 (s, 9H), 0.98 (d, J = 6.9 Hz, 6H).

[0840] Example 30: Synthesis of Compound 30

[0841] Referring to the synthesis of Compound 23 in Example 23, N-Fmoc-L-phenylalanine was used instead of N-Fmoc-L-alanine to obtain Compound 30 (130 mg, yield: 60%, HPLC purity: 96.97%).

[0842] MS: 1232.5266 [M+H+].

[0843] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 11.87 (s, 1H), 10.10 (s, 1H), 8.31 (d, J = 8.1 Hz, 1H), 7.95 (dd, J = 22.1, 8.2 Hz, 3H), 7.73 (t, J = 7.2 Hz, 1H), 7.64 (dd, J = 18.0, 8.0 Hz, 4H), 7.42 (t, J = 7.5 Hz, 2H), 7.35 (t, J = 7.4 Hz, 4H), 7.26 (dd, J = 7.6, 5.6 Hz, 4H), 7.22 - 7.13 (m, 2H), 5.82 (t, J = 8.7 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.15 (s, 2H), 5.11 - 4.91 (m, 3H), 4.71 (s, 1H), 4.65 (dd, J = 14.0, 8.5 Hz, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.81 - 3.72 (m, 1H), 3.59 (d, J = 6.6 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 3.05 (dd, J = 13.7, 5.4 Hz, 1H), 2.87 (dd, J = 13.7, 9.4 Hz, 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 = 7.3 Hz, 6H).

[0844] Example 31: Synthesis of Compound 31

[0845] Referring to the synthesis of Compound 23 in Example 23, N-Fmoc-L-phenylalanine was used instead of N-Fmoc-L-alanine, and oxalyl chloride was used instead of succinic anhydride to obtain Compound 31 (60 mg, yield: 56%, HPLC purity: 93.17%).

[0846] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 8 (ppm) 12.10 (s, 1H), 10.26 (s, 1H), 8.63 (d, J = 8.3 Hz, 1H), 7.95 (dd, J = 22.0, 8.2 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (t, J = 7.5 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.42 (t, J = 7.5 Hz, 2H), 7.35 (d, J = 8.2 Hz, 4H), 7.28 - 7.15 (m, 6H), 5.82 (t, J = 8.6 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.15 (s, 2H), 5.10 - 4.98 (m, 2H), 4.95 (d, J = 9.7 Hz, 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 = 6.7 Hz, 1H), 3.28 (s, 3H), 3.21 (s, 3H), 3.11 (d, J = 7.8 Hz, 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 = 6.2 Hz, 6H).

[0847] Example 32: Synthesis of Compound 32

[0848] Referring to the synthesis of Compound 23 in Example 23, N-Fmoc-L-valine was used instead of N-Fmoc-L-alanine to obtain Compound 32 (300 mg, yield: 74%, HPLC purity: 97.53%).

[0849] MS: 1184.5182 [M+H+].

[0850] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 8 (ppm) 12.07 (s, 1H), 10.11 (s, 1H), 8.06 (d, J = 8.6 Hz, 1H), 7.98 (d, J = 7.3 Hz, 2H), 7.92 (d, J = 9.0 Hz, 1H), 7.73 (t, J = 7.3 Hz, 1H), 7.65 (dd, J = 7.6, 5.6 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.39 - 7.26 (m, 4H), 7.18 (t, J = 7.2 Hz, 1H), 5.82 (t, J = 8.9 Hz, 1H), 5.36 (t, J = 8.9 Hz, 1H), 5.15 (s, 2H), 5.10 - 4.99 (m, 2H), 4.95 (d, J = 9.9 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.30 (t, J = 8.0 Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.3, 6.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 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, 6.8 Hz, 1H), 1.82 (d, J = 13.5 Hz, 4H), 1.58 - 1.43 (m, 5H), 1.34 (s, 9H), 1.03 - 0.85 (m, 12H).

[0851] Example 33: Synthesis of Compound 33

[0852] 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%).

[0853] MS: 1198.5364 [M+H+].

[0854] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 8 (ppm) 12.09 (s, 1H), 10.03 (s, 1H), 8.16 (d, J = 7.9 Hz, 1H), 7.95 (dd, J = 22.3, 8.2 Hz, 3H), 7.77 - 7.62 (m, 5H), 7.39 (dt, J = 14.5, 8.0 Hz, 6H), 7.18 (t, J = 7.1 Hz, 1H), 5.82 (t, J = 8.9 Hz, 1H), 5.38 (d, J = 6.9 Hz, 1H), 5.15 (s, 2H), 5.12 - 4.91 (m, 3H), 4.71 (s, 1H), 4.56 - 4.39 (m, 2H), 4.02 (s, 2H), 3.76 (dd, J = 10.1, 6.8 Hz, 1H), 3.59 (d, J = 6.8 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.67 (dd, J = 17.9, 11.7 Hz, 1H), 2.46 - 2.39 (m, 4H), 2.25 (s, 3H), 1.82 (d, J = 13.8 Hz, 4H), 1.71 - 1.58 (m, 2H), 1.55 -1.45 (m, 6H), 1.35 (s, 9H), 0.98 (d, J = 6.8 Hz, 6H), 0.90 (dd, J = 15.3, 6.5 Hz, 6H).

[0855] Example 34: Synthesis of Compound 34

[0856] 34b:

[0857] 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). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by silica gel column chromatography (VPE: VEA = 1:1) to obtain a pale yellow solid (1.50 g, yield: 74%).

[0858] 34:

[0859] 34b (125 mg, 0.60 mmol) was dissolved in dichloromethane (8 mL). At 0 to 5°C under nitrogen protection, 4-dimethylaminopyridine (81 mg, 0.66 mmol) and PNP-CBTX (1j) (603 mg, 0.60 mmol) were added. The reaction mixture was stirred at 20 to 25°C for 1.5 hours. Dichloromethane (20 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (20 mL x 2) and saturated sodium chloride aqueous solution (20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VPE / VEA = 2:1] to obtain a white solid (480 mg, yield: 74%, HPLC purity: 99.28%).

[0860] HR-MS: 1069.5667 [M+H+].

[0861] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 9.95 (s, 1H), 8.03 - 7.87 (m, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (dd, J = 15.9, 8.1 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.34 (dd, J = 13.4, 8.0 Hz, 4H), 7.18 (t, J = 7.3 Hz, 1H), 5.82 (t, J = 8.7 Hz, 1H), 5.37 (d, J = 7.0 Hz, 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 (dd, J = 10.4, 6.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.71 - 2.59 (m, 1H), 2.31 (t, J = 7.4 Hz, 2H), 2.24 (d, J = 7.4 Hz, 3H), 1.85 - 1.72 (m, 4H), 1.58 (dd, J = 14.9, 7.4 Hz, 2H), 1.49 (d, J = 17.1 Hz, 4H), 1.35 (s, 9H), 1.29 (dd, J = 15.3, 6.9 Hz, 2H), 1.24 (s, 1H), 0.99 (t, J = 9.4 Hz, 6H), 0.90 (t, J = 7.3 Hz, 3H).

[0862] Example 35: Synthesis of Compound 35

[0863] Referring to the synthesis of Compound 34 in Example 34, 4-fluorobenzoic acid was used instead of valeric acid to obtain Compound 35 (410 mg, yield: 82%, HPLC purity: 98.60%).

[0864] MS: 1135.5671 [M+H+].

[0865] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 9.99 (s, 1H), 7.98 (d, J = 7.3 Hz, 2H), 7.92 (d, J = 9.0 Hz, 1H), 7.73 (t, J = 7.3 Hz, 1H), 7.69 - 7.57 (m, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.39 - 7.26 (m, 6H), 7.18 (t, J = 7.2 Hz, 1H), 7.10 (ddd, J = 8.9, 5.9, 2.5 Hz, 2H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 7.1 Hz, 1H), 5.13 (s, 2H), 5.08 (d, J = 8.0 Hz, 1H), 5.05 -4.99 (m, 1H), 4.95 (d, J = 9.8 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.76 (dd, J = 10.4, 6.7 Hz, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.90 (t, J = 7.6 Hz, 2H), 2.63 (dd, J = 17.4, 9.5 Hz, 3H), 2.24 (s, 3H), 1.80 (s, 4H), 1.59 - 1.44 (m, 5H), 1.35 (s, 9H), 0.98 (d, J = 6.5 Hz, 6H).

[0866] Example 36: Synthesis of Compound 36

[0867] Referring to the synthesis of Compound 34 in Example 34, trifluoroacetic acid was used instead of valeric acid to obtain Compound 36 (0.42 g, yield: 85.1%, HPLC purity: 98.621%).

[0868] LC-MS: 1081.4994 [M+H+].

[0869] 1H NMR (400 MHz, DMSOd-6) 5 11.33 (s, 1H), 9.72 (s, 1H), 8.10 - 7.83 (m, 3H), 7.72 (dd, J = 13.7, 7.9 Hz, 2H), 7.65 (t, J = 7.5 Hz, 2H), 7.55 - 7.39 (m, 4H), 7.33 (dd, J = 18.5, 7.6 Hz, 3H), 7.18 (t, J = 6.9 Hz, 1H), 5.81 (s, 1H), 5.37 (d, J = 6.8 Hz, 1H), 5.20 (s, 1H), 5.11 (d, J = 8.7 Hz, 1H), 5.06 (dd, J = 12.6, 7.3 Hz, 1H), 4.95 (d, J = 9.5 Hz, 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 = 6.9 Hz, 1H), 3.29 (d, J = 1.3 Hz, 3H), 3.22 (d, J = 1.6 Hz, 3H), 2.67 (s, 1H), 2.24 (s, 3H), 1.81 (d, J = 23.3 Hz, 4H), 1.64 - 1.44 (m, 5H), 1.35 (s, 8H), 1.26 - 1.22 (m, 2H), 0.97 (d, J = 6.4 Hz, 6H).

[0870] Example 37: Synthesis of Compound 37

[0871] Referring to the synthesis of Compound 34 in Example 34, acetic anhydride was used instead of valeric acid to obtain Compound 37 (0.42 g, yield: 75.1%, HPLC purity: 97.678%).

[0872] LC-MS: 1027.5267 [M+H+].

[0873] 1H NMR (400 MHz, DMSOd-6) 5 10.01 (s, 1H), 7.95 (dd, J = 21.0, 8.2 Hz, 3H), 7.73 (t, J = 7.1 Hz, 1H), 7.69 - 7.55 (m, 4H), 7.42 (t, J = 7.5 Hz, 2H), 7.39 - 7.27 (m, 4H), 7.18 (t, J = 7.0 Hz, 1H), 5.82 (t, J = 8.5 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.14 (s, 2H), 5.10 - 4.92 (m, 3H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 1H), 3.75 (dd, J = 9.8, 6.8 Hz, 1H), 3.59 (d, J = 6.7 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.66 (dd, J = 19.1, 10.4 Hz, 1H), 2.24 (s, 3H), 2.05 (s, 3H), 1.81 (d, J = 20.1 Hz, 4H), 1.59 - 1.44 (m, 5H), 1.32 (d, J = 19.3 Hz, 8H), 1.25 (d, J = 9.5 Hz, 2H), 0.98 (d, J = 6.2 Hz, 6H).

[0874] Example 38: Synthesis of Compound 38

[0875] Referring to the synthesis of Compound 34 in Example 34, 4-fluorobenzoic acid was used instead of valeric acid to obtain Compound 38 (280 mg, yield: 62%, HPLC purity: 98.09%).

[0876] MS: 1107.5308 [M+H+].

[0877] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 1H NMR (400 MHz, DMSO) 5 10.34 (s, 1H), 8.04 (dd, J = 8.9, 5.5 Hz, 2H), 7.99 - 7.93 (m, 3H), 7.79 (s, 2H), 7.73 (t, J = 7.4 Hz, 1H), 7.64 (dd, J = 14.6, 7.4 Hz, 2H), 7.46 - 7.28 (m, 8H), 7.18 (t, J = 7.3 Hz, 1H), 5.82 (t, J = 8.9 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.18 (s, 2H), 5.12 - 4.99 (m, 2H), 4.96 (d, J = 9.7 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.76 (dd, J = 10.2, 6.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 1H), 3.28 (s, 3H), 3.22 (s, 3H), 2.66 (dd, J = 12.9, 6.9 Hz, 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 = 7.3 Hz, 6H).

[0878] Example 39: Synthesis of Compound 39

[0879] Referring to the synthesis of Compound 34 in Example 34, di-tert-butyl dicarbonate was used instead of valeric acid to obtain Compound 39 (250 mg, yield: 47%, HPLC purity: 97.52%).

[0880] MS: 1085.5689 [M+H+].

[0881] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 9.44 (s, 1H), 7.95 (dd, J = 20.5, 8.1 Hz, 3H), 7.72 (d, J = 7.7 Hz, 1H), 7.64 (dd, J = 14.2, 7.0 Hz, 2H), 7.48 (d, J = 8.5 Hz, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 6.0 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H), 7.21 - 7.16 (m, 1H), 5.81 (t, J = 8.7 Hz, 1H), 5.37 (d, J = 6.6 Hz, 1H), 5.11 (s, 2H), 5.07 (d, J = 8.0 Hz, 1H), 5.05 - 4.99 (m, 1H), 4.96 (d, J = 9.4 Hz, 1H), 4.70 (s, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.4, 6.7 Hz, 1H), 3.59 (d, J = 6.9 Hz, 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 = 4.6 Hz, 4H), 1.48 (s, 9H), 1.35 (s, 9H), 1.24 (s, 2H), 0.97 (d, J = 6.3 Hz, 6H).

[0882] Example 40: Synthesis of Compound 40

[0883] Referring to the synthesis of Compound 34 in Example 34, octanoic acid was used instead of valeric acid to obtain Compound 40 (0.48 g, yield: 86.5%, HPLC: 97.997%).

[0884] MS: 1111.6170 [M+H+].

[0885] 1H NMR (400 MHz, DMSO-d6) 5(ppm) 9.94 (s, 1H), 7.95 (dd, J = 22.5, 8.1 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.66 (d, J = 7.7 Hz, 2H), 7.62 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 7.4 Hz, 2H), 7.34 (dd, J = 13.5, 8.1 Hz, 4H), 7.18 (t, J = 7.2 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 7.0 Hz, 1H), 5.14 (s, 2H), 5.08 (d, J = 8.0 Hz, 1H), 5.02 (t, J = 8.4 Hz, 1H), 4.95 (d, J = 9.8 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 1H), 3.75 (dd, J = 10.4, 6.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.72 - 2.62 (m, 1H), 2.30 (t, J = 7.4 Hz, 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 = 6.4 Hz, 6H), 0.86 (t, J = 6.9 Hz, 3H).

[0886] Example 41: Synthesis of Compound 41

[0887] Referring to the synthesis of Compound 34 in Example 34, acetic anhydride was used instead of valeric acid, and 2-aminobenzyl alcohol was used instead of p-aminobenzyl alcohol to obtain Compound 41 (0.22 g, yield: 42.88%, HPLC: 99.114%).

[0888] LC-MS: 1027.5243 [M+H+].

[0889] 1H NMR (400 MHz, DMSO) 8 9.60 (s, 1H), 7.96 (dd, J = 14.9, 8.2 Hz, 3H), 7.73 (t, J = 7.2 Hz, 1H), 7.65 (t, J = 7.5 Hz, 2H), 7.46 - 7.41 (m, 3H), 7.35 (t, J = 7.4 Hz, 4H), 7.21 (dt, J = 14.4, 7.3 Hz, 2H), 5.84 (t, J = 8.6 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.20 (s, 2H), 5.11 - 5.02 (m, 2H), 4.95 (d, J = 9.4 Hz, 1H), 4.70 (s, 1H), 4.49 (s, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.2, 6.8 Hz, 1H), 3.59 (d, J = 6.9 Hz, 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 = 7.6 Hz, 6H).

[0890] Example 42: Synthesis of Compound 42

[0891] Referring to the synthesis of Compound 34 in Example 34, di-tert-butyl dicarbonate was used instead of valeric acid, and 2-aminobenzyl alcohol was used instead of p-aminobenzyl alcohol to obtain Compound 42 (320 mg, yield: 69%, HPLC purity: 98.62%).

[0892] HR-MS: 1085.5679 [M+H+].

[0893] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 8 (ppm) 8.80 (s, 1H), 7.96 (dd, J = 19.4, 8.0 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.5 Hz, 2H), 7.46 - 7.30 (m, 7H), 7.19 (dt, J = 11.3, 5.5 Hz, 2H), 5.85 (t, J = 8.7 Hz, 1H), 5.38 (d, J = 7.0 Hz, 1H), 5.23 (q, J = 13.0 Hz, 2H), 5.12 - 5.01 (m, 2H), 4.95 (d, J = 9.6 Hz, 1H), 4.69 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.3, 6.7 Hz, 1H), 3.59 (d, J = 6.9 Hz, 1H), 3.29 (s, 3H), 3.21 (s, 3H), 2.66 (dt, J = 9.4, 8.0 Hz, 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 = 8.6 Hz, 6H).

[0894] Example 43: Synthesis of Compound 43

[0895] Referring to the synthesis of Compound 34 in Example 34, di-tert-butyl dicarbonate was used instead of valeric acid, and 3-amino-4-methoxybenzyl alcohol was used instead of p-aminobenzyl alcohol to obtain Compound 43 (390 mg, yield: 73%, HPLC purity: 96.69%).

[0896] MS: 1115.5066 [M+H+].

[0897] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 8 (ppm) 8.02 - 7.88 (m, 4H), 7.81 (s, 1H), 7.73 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.5 Hz, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.35 (d, J = 7.5 Hz, 2H), 7.18 (t, J = 7.2 Hz, 1H), 7.07 (dd, J = 8.3, 1.8 Hz, 1H), 7.01 (d, J = 8.4 Hz, 1H), 5.83 (t, J = 8.8 Hz, 1H), 5.38 (d, J = 7.0 Hz, 1H), 5.11 (s, 2H), 5.09 - 4.99 (m, 2H), 4.95 (d, J = 10.0 Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.85 - 3.73 (m, 4H), 3.60 (d, J = 7.0 Hz, 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 = 7.2 Hz, 6H).

[0898] Example 44: Synthesis of Compound 44

[0899] Referring to the synthesis of Compound 34 in Example 34, di-tert-butyl dicarbonate was used instead of valeric acid, and 4-amino-3-methoxybenzyl alcohol was used instead of 34a to obtain Compound 44 (0.36 g, yield: 80.78%, HPLC: 99.479%).

[0900] MS: 1115.4948 [M+H+].

[0901] 1H NMR (400 MHz, DMSO) 5 7.96 (dd, J = 17.4, 7.3 Hz, 4H), 7.76 - 7.70 (m, 2H), 7.65 (t, J = 7.5 Hz, 2H), 7.43 (t, J = 7.5 Hz, 2H), 7.36 (d, J = 7.4 Hz, 2H), 7.18 (t, J = 7.2 Hz, 1H), 7.04 (s, 1H), 6.94 (d, J = 8.2 Hz, 1H), 5.82 (t, J = 8.8 Hz, 1H), 5.37 (d, J = 6.9 Hz, 1H), 5.16 (t, J = 9.6 Hz, 2H), 5.11 - 5.07 (m, 1H), 5.06 - 5.00 (m, 1H), 4.95 (d, J = 9.5 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.82 (s, 3H), 3.75 (dd, J = 10.2, 6.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.66 (dd, J = 17.9, 11.9 Hz, 1H), 2.25 (s, 3H), 1.99 (s, 1H), 1.85 - 1.75 (m, 4H), 1.56 (d, J = 9.5 Hz, 1H), 1.51 (s, 3H), 1.46 (s, 9H), 1.35 (s, 9H), 0.98 (d, J = 6.7 Hz, 6H).

[0902] Example 45: Synthesis of Compound 45

[0903] Cabazitaxel (0.4 g, 0.48 mmol) was dissolved in dichloromethane (4 mL). Under a nitrogen atmosphere, the temperature was lowered to 5°C, followed by the addition of 4-dimethylaminopyridine (12 mg, 0.1 mmol), N,N-diisopropylethylamine (0.19 g, 1.44 mmol), and benzyl chloroformate (0.16 g, 0.96 mmol) in 1.5 mL of dichloromethane. The mixture was stirred at room temperature for 10 minutes. Dichloromethane (40 mL) was added, and the mixture was washed twice with 5% citric acid aqueous solution (10 mL), followed by washing with saturated sodium chloride (20 mL). The organic phase was dried over anhydrous sodium sulfate, concentrated to dryness, and subjected to column chromatography to obtain 45 (0.42 g, yield: 90%, HPLC purity: 96.793%) as a white solid.

[0904] LC-MS: 970.5028 [M+H+].

[0905] 1H NMR (400 MHz, DMSOd-6) 5 7.98 (d, J = 7.3 Hz, 2H), 7.93 (d, J = 9.0 Hz, 1H), 7.72 (d, J = 7.3 Hz, 1H), 7.64 (t, J = 7.5 Hz, 2H), 7.46 - 7.34 (m, 9H), 7.19 (t, J = 7.2 Hz, 1H), 5.83 (t, J = 8.8 Hz, 1H), 5.38 (d, J = 7.1 Hz, 1H), 5.22 (s, 2H), 5.12 - 5.01 (m, 2H), 4.95 (d, J = 9.6 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.00 (s, 1H), 3.75 (dd, J = 10.4, 6.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 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 = 7.1 Hz, 6H).

[0906] Example 46: Synthesis of Compound 46

[0907] 4-Methoxybenzyl alcohol (62 mg, 0.45 mmol) was dissolved in dichloromethane (6 mL). Under nitrogen protection at 0 to 5°C, PNP-CBTX (450 mg, 0.45 mmol) and 4-dimethylaminopyridine (61 mg, 0.49 mmol) were added, and the reaction mixture was stirred at 20 to 25°C for 1.5 hours. Dichloromethane (20 mL) was added to the reaction mixture, followed by washing with 0.5 N hydrochloric acid (15 mL) and saturated sodium chloride aqueous solution (15 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VPE / VEA = 2:1] to obtain a white solid (300 mg, yield: 66%, HPLC purity: 96.72%).

[0908] MS: 1000.5115 [M+H+].

[0909] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 7.95 (dd, J = 25.5, 8.1 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.5 Hz, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.39 - 7.31 (m, 4H), 7.18 (t, J = 7.2 Hz, 1H), 6.96 (d, J = 8.7 Hz, 2H), 5.83 (t, J = 8.7 Hz, 1H), 5.38 (d, J = 7.0 Hz, 1H), 5.13 (s, 2H), 5.09 - 4.99 (m, 2H), 4.96 (d, J = 9.6 Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.80 - 3.71 (m, 4H), 3.59 (d, J = 7.0 Hz, 1H), 3.30 (s, 3H), 3.22 (s, 3H), 2.67 (ddd, J = 15.6, 9.5, 6.5 Hz, 1H), 2.25 (s, 3H), 1.80 (s, 4H), 1.49 (d, J = 16.6 Hz, 4H), 1.34 (s, 9H), 1.24 (s, 1H), 0.98 (d, J = 6.4 Hz, 6H).

[0910] Example 47: Synthesis of Compound 47

[0911] Referring to the synthesis of Compound 46 in Example 46, 2-methoxybenzyl alcohol was used instead of 4-methoxybenzyl alcohol to obtain Compound 47 (0.32 g, yield: 80%, HPLC purity: 99.013%).

[0912] LC-MS: 1000.4451 [M+H+].

[0913] 1H NMR (400 MHz, DMSOd-6) 5 7.96 (dd, J = 21.3, 8.2 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (t, J = 7.5 Hz, 2H), 7.46 - 7.31 (m, 6H), 7.19 (t, J = 7.2 Hz, 1H), 7.07 (d, J = 8.2 Hz, 1H), 6.97 (t, J = 7.4 Hz, 1H), 5.84 (t, J = 8.7 Hz, 1H), 5.38 (d, J = 7.0 Hz, 1H), 5.18 (s, 2H), 5.10 - 4.99 (m, 2H), 4.96 (d, J = 9.6 Hz, 1H), 4.71 (s, 1H), 4.50 (s, 1H), 4.02 (s, 1H), 3.81 (s, 3H), 3.76 (dd, J = 10.4, 6.7 Hz, 1H), 3.60 (d, J = 7.0 Hz, 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 = 18.7 Hz, 9H), 1.25 (d, J = 9.5 Hz, 2H), 0.98 (d, J = 7.9 Hz, 6H).

[0914] Example 48: Synthesis of Compound 48

[0915] Referring to the synthesis of Compound 46 in Example 46, 3-methoxybenzyl alcohol was used instead of 4-methoxybenzyl alcohol to obtain Compound 48 (400 mg, yield: 89%, HPLC purity: 98.22%).

[0916] HR-MS: 1000.4426 [M+H+].

[0917] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 7.96 (dd, J = 16.4, 8.2 Hz, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.5 Hz, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.39 - 7.29 (m, 3H), 7.19 (t, J = 7.2 Hz, 1H), 6.95 (dd, J = 10.4, 2.5 Hz, 3H), 5.83 (t, J = 8.8 Hz, 1H), 5.38 (d, J = 7.0 Hz, 1H), 5.24 - 5.14 (m, 2H), 5.13 - 5.01 (m, 2H), 4.95 (d, J = 9.7 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.02 (s, 2H), 3.77 (s, 4H), 3.59 (d, J = 6.8 Hz, 1H), 3.29 (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 = 48.0 Hz, 9H), 0.98 (d, J = 7.0 Hz, 6H).

[0918] Example 49: Synthesis of Compound 49

[0919] Referring to the synthesis of Compound 46 in Example 46, 4-methoxybenzylamine was used instead of 4-methoxybenzyl alcohol to obtain Compound 49 (400 mg, yield: 88%, HPLC purity: 98.19%).

[0920] MS: 999.4600 [M+H+].

[0921] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 5 (ppm) 7.97 (d, J = 7.2 Hz, 3H), 7.82 - 7.71 (m, 2H), 7.66 (t, J = 7.4 Hz, 2H), 7.41 (t, J = 7.6 Hz, 2H), 7.33 (d, J = 7.4 Hz, 2H), 7.15 (dd, J = 18.6, 7.9 Hz, 3H), 6.87 (d, J = 8.6 Hz, 2H), 5.76 (t, J = 8.7 Hz, 1H), 5.35 (d, J = 7.2 Hz, 1H), 5.07 (d, J = 8.5 Hz, 1H), 4.94 (d, J = 10.1 Hz, 2H), 4.68 (s, 1H), 4.42 (s, 1H), 4.12 (d, J = 6.1 Hz, 2H), 4.01 (s, 2H), 3.77 - 3.71 (m, 4H), 3.56 (d, J = 7.1 Hz, 1H), 3.28 (s, 3H), 3.20 (s, 3H), 2.65 (ddd, J = 15.7, 9.5, 6.3 Hz, 1H), 2.24 (s, 3H), 1.84 - 1.70 (m, 4H), 1.47 (m, 5H), 1.30 (d, J = 50.0 Hz, 9H), 0.96 (d, J = 7.3 Hz, 6H).

[0922] Example 50: Synthesis of Compound 50

[0923] Referring to the synthesis of Compound 23 in Example 23, 3-aminobenzyl alcohol was used instead of p-aminobenzyl alcohol to obtain Compound 50 (100 mg, yield: 32%, HPLC purity: 98.46%).

[0924] MS: 1156.6531 [M+H+].

[0925] 1H NMR (400 MHz, DMSO) 5 (ppm) 12.07 (s, 1H), 9.98 (s, 1H), 8.20 (d, J = 7.1 Hz, 1H), 7.96 (dd, J = 18.4, 8.2 Hz, 3H), 7.78 - 7.69 (m, 2H), 7.65 (t, J = 7.5 Hz, 2H), 7.59 (d, J = 8.1 Hz, 1H), 7.38 (ddd, J = 15.7, 13.9, 7.8 Hz, 5H), 7.18 (t, J = 7.1 Hz, 1H), 7.08 (d, J = 7.5 Hz, 1H), 5.84 (t, J = 8.8 Hz, 1H), 5.38 (d, J = 7.0 Hz, 1H), 5.17 (s, 2H), 5.13 - 5.00 (m, 2H), 4.96 (d, J = 9.8 Hz, 1H), 4.70 (s, 1H), 4.51 (s, 1H), 4.39 (p, J = 7.0 Hz, 1H), 4.03 (d, J = 7.8 Hz, 2H), 3.75 (dd, J = 10.2, 6.7 Hz, 1H), 3.59 (d, J = 6.9 Hz, 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 = 18.7 Hz, 4H), 1.61 - 1.43 (m, 5H), 1.40 - 1.24 (m, 12H), 0.98 (d, J = 7.9 Hz, 6H).

[0926] Example 51: Synthesis of Compound 51

[0927]  51b:

[0928] Referring to the synthesis of 1j in Example 1, docetaxel was used instead of cabazitaxel to obtain 51b (1.00 g, yield: 41%).

[0929] Synthesis of 51

[0930] Referring to the synthesis of Compound 10 in Example 10, 51b was used instead of CBTX-PNP, and 51c (prepared by replacing morpholine with diethylamine in the synthesis of intermediate 10e in Example 10) was used instead of 10e to obtain Compound 51 (220 mg, yield: 46%, HPLC purity: 96.26%).

[0931] MS: 1207.6 [M-2OH-].

[0932] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 10.09 (s, 1H), 8.31 (d, J = 6.9 Hz, 1H), 8.25 (d, J = 8.6 Hz, 1H), 7.98 (d, J = 7.3 Hz, 2H), 7.91 (d, J = 9.1 Hz, 1H), 7.73 (t, J = 7.3 Hz, 1H), 7.64 (t, J = 7.8 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.39 - 7.24 (m, 4H), 7.17 (t, J = 7.2 Hz, 1H), 5.79 (d, J = 8.8 Hz, 1H), 5.40 (m, 1H), 5.23 - 5.04 (m, 4H), 5.02 (dd, J = 11.8, 4.8 Hz, 2H), 4.92 (dd, J = 11.1, 6.4 Hz, 2H), 4.40 (dd, J = 14.4, 7.3 Hz, 2H), 4.23 (dd, J = 8.5, 6.7 Hz, 1H), 4.14 - 3.92 (m, 3H), 3.64 (d, J = 7.0 Hz, 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, 6.7 Hz, 1H), 1.82 (dd, J = 15.3, 9.3 Hz, 1H), 1.75 - 1.60 (m, 4H), 1.52 (s, 4H), 1.33 (d, J = 10.0 Hz, 11H), 1.24 (s, 1H), 1.18 (t, J = 7.2 Hz, 6H), 0.98 (s, 6H), 0.91 (s, 6H).

[0933] Example 52: Synthesis of Compound 52

[0934] Referring to the synthesis of Compound 8 in Example 8, 51b was used instead of 1j to obtain Compound 52 (160 mg, yield: 19%, HPLC purity: 96.94%).

[0935] MS: 1297.6132 [M+H+].

[0936] 1H NMR (400 MHz, DMSO-d6) 5 10.10 (s, 1H), 7.98 (td, J = 32.2, 7.9 Hz, 4H), 7.78 - 7.59 (m, 5H), 7.37 (dd, J = 28.1, 7.3 Hz, 6H), 7.14 (dd, J = 19.0, 7.6 Hz, 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 = 7.9 Hz, 1H), 4.03 (d, J = 8.6 Hz, 3H), 3.64 (d, J = 6.5 Hz, 1H), 3.08 - 2.91 (m, 2H), 2.24 (s, 4H), 2.05 (dd, J = 13.2, 6.4 Hz, 1H), 1.81 (d, J = 9.5 Hz, 1H), 1.77 - 1.57 (m, 6H), 1.52 (s, 4H), 1.29 (d, J = 41.7 Hz, 11H), 1.13 (s, 9H), 0.99 (s, 6H), 0.85 (dd, J = 15.2, 6.4 Hz, 6H).

[0937] Example 53: Synthesis of Compound 53

[0938] Referring to the synthesis of Compound 34 in Example 34, di-tert-butyl dicarbonate was used instead of valeric acid, and 51b was used instead of CBTX-PNP to obtain 53 (0.22 g, yield: 67.5%, HPLC purity: 96.41%).

[0939] MS: 1057.4618 [M+H+].

[0940] 1H NMR (400 MHz, DMSO) 5 (ppm) 9.44 (s, 1H), 7.99 (d, J = 7.2 Hz, 2H), 7.91 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 6.9 Hz, 1H), 7.64 (t, J = 7.1 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H), 7.44 - 7.39 (m, 2H), 7.35 (d, J = 7.0 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 7.17 (t, J = 6.7 Hz, 1H), 5.78 (s, 1H), 5.40 (d, J = 6.7 Hz, 1H), 5.15 - 5.07 (m, 4H), 5.05 - 4.98 (m, 2H), 4.91 (d, J = 10.3 Hz, 2H), 4.43 (s, 1H), 4.03 (d, J = 8.9 Hz, 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 = 12.5 Hz, 2H), 1.52 (s, 4H), 1.48 (s, 9H), 1.34 (s, 9H), 0.99 (s, 6H).

[0941] Example 54: Synthesis of Compound 54

[0942] Referring to the synthesis of Compound 46 in Example 46, 2-methoxybenzyl alcohol was used instead of 4-methoxybenzyl alcohol, and 51b was used instead of CBTX-PNP to obtain 54 (0.17 g, yield: 42%, HPLC purity: 95.24%).

[0943] MS: 972.4084 [M+H+].

[0944] 1H NMR (400 MHz, DMSO) 5 (ppm) 7.99 (d, J = 7.3 Hz, 2H), 7.91 (d, J = 9.1 Hz, 1H), 7.72 (t, J = 7.3 Hz, 1H), 7.63 (t, J = 7.5 Hz, 2H), 7.41 (dt, J = 7.3, 6.6 Hz, 3H), 7.36 (d, J = 7.9 Hz, 2H), 7.31 (d, J = 7.4 Hz, 1H), 7.18 (t, J = 7.1 Hz, 1H), 7.06 (d, J = 8.2 Hz, 1H), 6.97 (t, J = 7.4 Hz, 1H), 5.80 (t, J = 8.9 Hz, 1H), 5.41 (d, J = 7.2 Hz, 1H), 5.19 (s, 2H), 5.10 (d, J = 7.7 Hz, 2H), 5.03 (dd, J = 15.9, 8.0 Hz, 2H), 4.92 (t, J = 8.2 Hz, 2H), 4.43 (s, 1H), 4.09 - 3.99 (m, 3H), 3.81 (s, 3H), 3.65 (d, J = 7.0 Hz, 1H), 2.33 - 2.26 (m, 1H), 2.25 (s, 3H), 1.85 (dd, J = 15.3, 9.3 Hz, 1H), 1.72 (s, 3H), 1.64 (d, J = 12.0 Hz, 1H), 1.59 - 1.53 (m, 1H), 1.52 (s, 3H), 1.34 (s, 9H), 0.99 (s, 6H).

[0945] Example 55: Synthesis of Compound 55

[0946] Referring to the synthesis of 46 in Example 46, 51b was used instead of CBTX-PNP to obtain 55 (100 mg, yield: 22%, HPLC purity: 95.32%).

[0947] MS: 972.3974 [M+H]+.

[0948] 1H NMR (400 MHz, DMSO-d6) 1H NMR (400 MHz, DMSO) 8 (ppm) 7.99 (d, J = 7.3 Hz, 2H), 7.90 (d, J = 9.1 Hz, 1H), 7.72 (t, J = 7.3 Hz, 1H), 7.64 (t, J = 7.5 Hz, 2H), 7.41 (t, J = 7.6 Hz, 2H), 7.38 - 7.27 (m, 4H), 7.17 (t, J = 7.2 Hz, 1H), 6.95 (d, J = 8.6 Hz, 2H), 5.78 (dd, J = 15.2, 6.4 Hz, 1H), 5.41 (d, J = 7.1 Hz, 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 = 7.1 Hz, 1H), 2.33 - 2.20 (m, 4H), 1.84 (dd, J = 15.2, 9.5 Hz, 1H), 1.76 - 1.61 (m, 4H), 1.58 - 1.45 (m, 4H), 1.34 (s, 9H), 0.99 (s, 6H).

[0949] Example 56: Synthesis of Compound 56

[0950]  56b:

[0951] Referring to the synthesis of 1j in Example 1, paclitaxel was used instead of cabazitaxel to obtain 56b (2.22 g, yield: 92%).

[0952] Synthesis of 56

[0953] Referring to the synthesis of Compound 8 in Example 8, 56b was used instead of 1j to obtain Compound 56 (380 mg, yield: 44%, HPLC purity: 95.75%).

[0954] MS: 1343.5960 [M+H]+.

[0955] 1H NMR (400 MHz, DMSO-d6) 8 (ppm) 10.00 (d, J = 76.1 Hz, 1H), 9.26 (d, J = 8.5 Hz, 1H), 8.22 (dd, J = 127.8, 7.6 Hz, 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 = 8.6 Hz, 2H), 7.30 - 7.08 (m, 2H), 6.32 (s, 1H), 5.96 (dd, J = 10.7, 5.5 Hz, 1H), 5.84 (t, J = 8.9 Hz, 1H), 5.54 (t, J = 8.6 Hz, 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 = 7.1 Hz, 1H), 3.09 - 2.89 (m, 2H), 2.39 - 2.22 (m, 4H), 2.12 (d, J = 1.0 Hz, 3H), 2.04 (dt, J = 14.3, 7.1 Hz, 1H), 1.90 - 1.69 (m, 5H), 1.71 - 1.30 (m, 9H), 1.12 (d, J = 3.9 Hz, 9H), 1.03 (d, J = 10.9 Hz, 6H), 0.86 (dt, J = 15.1, 6.7 Hz, 6H).

[0956] Example 57: Synthesis of Compound 57

[0957]  57-M1

[0958] 57-M0 (2.00 g, 5.03 mmol) was dissolved in a mixed solution of methanol (10 mL) / dichloromethane (20 mL). Under nitrogen protection, 2-ethoxy-1-ethoxycarbonyl-1,2- dihydroquinoline (2.24 g, 9.06 mmol) was added at 0 to 5 °C, followed by the dropwise addition of a solution of o-aminobenzyl alcohol (0.929 g, 7.55 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at room temperature for 4 h. After completion of the reaction, methyl tert-butyl ether (40 mL) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 30 minutes. The mixture was subjected to suction filtration under reduced pressure, and the filter cake was washed with methyl tert-butyl ether (20 mL). The filter cake was collected and concentrated under reduced pressure. At room temperature, the crude product was added to methanol (20 mL) and stirred for 30 minutes, followed by the dropwise addition of dichloromethane (20 mL) and stirring for 30 minutes. Finally, methyl tert-butyl ether (40 mL) was added dropwise, and the mixture was stirred for 30 minutes. The mixture was subjected to suction filtration under reduced pressure, and the filter cake was washed with methyl tert-butyl ether (20 mL). The filter cake was collected and concentrated under reduced pressure. The product 57-M1 was obtained as a white solid (2.0 g, yield: 79%).

[0959]  57-M2

[0960] At 0 to 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). The reaction mixture was stirred at -10°C for 16 hours. After completion of the reaction, the reaction mixture was quenched by dropwise addition of hydrochloric acid (0.15 N, 40 mL) and extracted with ethyl acetate (80 mL x 2). The combined organic phases were washed with saturated sodium chloride aqueous solution (60 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 20:1] to obtain the product 57-M2 (2.9 g, yield: 48%) as an off-white solid.

[0961] 57-M3

[0962] At room temperature, Compound 57-M2 (2.9 g, 2.13 mmol) was dissolved in acetonitrile (58 mL) under nitrogen protection. At 0 to 5°C, piperidine (542 mg, 6.38 mmol) was added dropwise. After completion of the dropwise addition, the reaction mixture was warmed to 20°C and stirred for 4 hours. After completion of the reaction, the reaction mixture was quenched by dropwise addition of hydrochloric acid (0.15 N, 40 mL), followed by extraction with ethyl acetate (80 mL x 2). The combined organic phases were washed with saturated sodium chloride aqueous solution (60 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 3:1] to obtain the product 57-M3 (1.2 g, yield: 49%) as an off-white solid.

[0963] 57-M4

[0964] At room temperature, Fmoc-L-valine (392 mg, 1.16 mmol) was dissolved in N,N-dimethylacetamide (8 mL) under nitrogen protection. At 0°C, N,N-diisopropylethylamine (176 mg, 1.37 mmol) and HATU (442 mg, 1.16 mmol) were added sequentially. After stirring 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. The reaction mixture was stirred at 10°C for 2 hours. After completion of the reaction, the reaction mixture was quenched by dropwise addition of hydrochloric acid (0.15 N, 25 mL), followed by extraction with ethyl acetate (60 mL x 2). The combined organic phases were washed with saturated sodium chloride aqueous solution (40 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 16:1] to obtain the product 57-M4 (1.2 g, yield: 78%) as an off-white solid.

[0965] 57-M5

[0966] 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. At 0 to 5°C, piperidine (209 mg, 2.46 mmol) was added dropwise. After completion of the dropwise addition, the reaction mixture was warmed to 10°C and stirred for 4 hours. After completion of the reaction, the reaction mixture was quenched by dropwise addition of hydrochloric acid (0.15 N, 20 mL), followed by extraction with ethyl acetate (40 mL x 2). The combined organic phases were washed with saturated sodium chloride aqueous solution (20 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 2:1] to obtain the product 57-M5 (800 mg, yield: 78%) as an off-white solid.

[0967] Compound 57

[0968] At room temperature, Compound 57-M5 (800 mg, 0.64 mmol) was dissolved in dichloromethane (12 mL) under nitrogen protection. At 0 to 5°C, triethylamine (110 mg, 1.1 mmol) and pivalic anhydride (180 mg, 0.97 mmol) were added dropwise sequentially. After completion of the dropwise addition, the reaction mixture was warmed to 10°C and stirred for 3 hours. After completion of the reaction, the reaction mixture was quenched by dropwise addition of hydrochloric acid (0.1 N, 20 mL), followed by the addition of dichloromethane (60 mL). The organic phase was separated and washed with saturated sodium chloride aqueous solution (20 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 17:1] to obtain the product Compound 57 (600 mg, yield: 70%; purity: 97.96%) as an off-white solid.

[0969] MS (ESI): 1325.6 [M+1]+.

[0970] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 9.81 (s, 1H), 8.16 (d, J = 7.2 Hz, 1H), 8.03 - 7.98 (m, 3H), 7.75 (t, J = 7.3 Hz, 1H), 7.67 (t, J = 7.5 Hz, 2H), 7.46 (t, J = 7.5 Hz, 2H), 7.42 -7.33 (m, 6H), 7.32 - 7.24 (m, 1H), 7.24 - 7.13 (m, 2H), 5.99 (t, J = 5.7 Hz, 1H), 5.86 (t, J = 9.1 Hz, 1H), 5.40 (d, J = 16.6 Hz, 3H), 5.18 (s, 2H), 5.17 - 5.03 (m, 2H), 4.97 (d, J = 9.4 Hz, 1H), 4.70 (s, 1H), 4.53 (s, 1H), 4.45 (q, J = 7.2 Hz, 1H), 4.20 (t, J = 8.2 Hz, 1H), 4.04 (s, 2H), 3.79 - 3.73 (m, 1H), 3.60 (d, J = 7.0 Hz, 1H), 3.30 (s, 3H), 3.04 (h, J = 6.9 Hz, 2H), 2.72 - 2.62 (m, 1H), 2.27 (s, 3H), 2.06 (dt, J = 13.9, 7.0 Hz, 1H), 1.80 (s, 4H), 1.62 (dd, J = 24.6, 9.4 Hz, 2H), 1.52 (s, 5H), 1.37 (s, 9H), 1.22 (d, J = 6.3 Hz, 1H), 1.13 (s, 9H), 1.00 (d, J = 8.5 Hz, 6H), 0.88 (d, J = 6.7 Hz, 3H), 0.84 (d, J = 6.6 Hz, 3H).

[0971] Example 58: Synthesis of Compound 58

[0972] At -5 to 0°C under nitrogen protection, triethylamine (153 mg, 1.50 mmol) was added to a solution of 6f (621 mg, 0.50 mmol) in dichloromethane (6 mL). A solution of p-toluenesulfonyl chloride (143 mg, 0.75 mmol) in dichloromethane (2 mL) was added dropwise, and the reaction mixture was stirred at -5°C for 2 h. The reaction mixture was diluted with dichloromethane (25 mL), quenched with water (30 mL), and the phases were separated. The lower organic phase was collected, washed with saturated sodium bicarbonate aqueous solution (30 mL) and saturated sodium chloride (30 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography [VDCM / VMeOH = 50:1] to obtain a white solid (300 mg, yield: 43%, HPLC purity: 99.03%).

[0973] MS (ESI): 1395.5934 [M+1]+.

[0974] 1H-NMR (400 MHz, DMSO-d6) 5 (ppm) 10.04 (s, 1H), 8.11 (d, J = 7.4 Hz, 1H), 7.98 (d, J = 7.6 Hz, 2H), 7.92 (d, J = 8.9 Hz, 1H), 7.73 (t, J = 7.3 Hz, 1H), 7.68 - 7.59 (m, 7H), 7.42 (t, J = 7.6 Hz, 2H), 7.37 - 7.29 (m, 6H), 7.18 (t, J = 7.3 Hz, 1H), 5.97 (t, J = 5.9 Hz, 1H), 5.82 (t, J = 9.3 Hz, 1H), 5.44 (s, 2H), 5.37 (d, J = 7.0 Hz, 1H), 5.14 (s, 2H), 5.08 - 4.99 (m, 2H), 4.95 (d, J = 9.6 Hz, 1H), 4.70 (s, 1H), 4.50 (s, 1H), 4.11 (q, J = 7.4 Hz, 1H), 4.02 (s, 2H), 3.75 (dd, J = 10.4, 6.6 Hz, 1H), 3.59 (d, J = 6.7 Hz, 2H), 3.28 (s, 3H), 3.22 (s, 3H), 2.93 (dp, J = 26.9, 6.6 Hz, 2H), 2.66 (s, 1H), 2.34 (s, 3H), 2.24 (s, 3H), 1.82 (d, J = 11.8 Hz, 5H), 1.52 (d, J = 8.6 Hz, 7H), 1.34 (s, 9H), 1.24 (s, 2H), 0.97 (d, J = 6.5 Hz, 6H), 0.82 (d, J = 6.7 Hz, 3H), 0.79 (d, J = 6.7 Hz, 3H).

[0975] Example 59: Synthesis of Compound 59 o 59-MO

[0976]  59-M1:

[0977] At room temperature, 59-M0 (5 g, 29.56 mmol) was dissolved in tetrahydrofuran (100 mL) under nitrogen protection. At 0°C, lithium aluminum hydride (2.24 g, 59.12 mmol) was added in portions. After completion of the addition, the mixture was heated to 50°C and stirred for 5 hours. After completion of the reaction, the mixture was cooled to 0°C, and ice water was slowly added dropwise until no obvious gas evolution was observed. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (100 mL). The filtrate was diluted with ethyl acetate (100 mL). The organic phase was washed with saturated sodium chloride aqueous solution (100 mL x 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 [VPE / VEA = 1:1] to obtain the product 59-M1 (2.5 g, yield: 59%) as a pale brown solid.

[0978] Compound 59:

[0979] Referring to the synthesis of Compound 57 in Example 57, 59-M1 was used instead of o-aminobenzyl alcohol to obtain the product Compound 59 (off-white solid, 900 mg, yield: 84%; purity: 98.70%).

[0980] MS (ESI): 1343.9 [M+1]+.

[0981] 1H NMR (400 MHz, DMSO-d6) 8 (ppm) 10.36 (s, 1H), 8.15 (d, J = 7.2 Hz, 1H), 8.01 - 7.98 (m, 2H), 7.95 (d, J = 9.1 Hz, 1H), 7.75 (t, J = 7.4 Hz, 1H), 7.69 - 7.64 (m, 3H), 7.44 (t, J = 7.8 Hz, 4H), 7.37 (d, J = 7.1 Hz, 3H), 7.19 (t, J = 7.4 Hz, 1H), 7.13 (d, J = 8.7 Hz, 1H), 6.00 (t, J = 5.8 Hz, 1H), 5.84 (t, J = 9.1 Hz, 1H), 5.45 (s, 2H), 5.39 (d, J = 7.0 Hz, 1H), 5.20 (s, 2H), 5.09 (d, J = 7.9 Hz, 1H), 5.03 (t, J = 8.4 Hz, 1H), 4.97 (d, J = 9.6 Hz, 1H), 4.72 (s, 1H), 4.53 (s, 1H), 4.39 (q, J = 7.1 Hz, 1H), 4.18 (t, J = 8.1 Hz, 1H), 4.03 (d, J = 2.1 Hz, 2H), 3.81 - 3.73 (m, 1H), 3.60 (d, J = 7.0 Hz, 1H), 3.31 (s, 3H), 3.02 (dh, J = 26.8, 6.7 Hz, 2H), 2.68 (s, 1H), 2.26 (s, 3H), 2.07 (dt, J = 13.8, 6.8 Hz, 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 = 7.2 Hz, 6H), 0.89 (d, J = 6.7 Hz, 3H), 0.85 (d, J = 6.6 Hz, 3H).

[0982] Example 60: Synthesis of Compound 60 —0 cf3cooh h2n 60d

[0983]  60d: HO ,;;P 1         H „

[0984] Referring to the synthesis of Compound 1d in Example 1, D-citrulline 2         NH= was used instead of 1a to obtain Compound 60d.

[0985] Referring to the synthesis of Compound 8 in Example 8, 60d was used instead of 1d to obtain Compound 60 (white solid, 1.7 g, yield: 88%).

[0986] MS(ESI): 1326.6 [M+2H]+.

[0987] 1H NMR (400 MHz, DMSO-d6) 5 (ppm) 9.91 (s, 1H), 8.41 (d, J = 8.0 Hz, 1H), 8.04 - 7.91 (m, 3H), 7.73 (dd, J = 7.8, 5.1 Hz, 3H), 7.65 (t, J = 7.5 Hz, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.34 (dt, J = 7.9, 5.6 Hz, 5H), 7.18 (t, J = 7.3 Hz, 1H), 5.97 (t, J = 5.8 Hz, 1H), 5.82 (t, J = 9.2 Hz, 1H), 5.42 (s, 2H), 5.37 (d, J = 7.0 Hz, 1H), 5.15 (d, J = 2.8 Hz, 2H), 5.07 (d, J = 7.9 Hz, 1H), 5.02 (t, J = 8.4 Hz, 1H), 4.95 (d, J = 9.7 Hz, 1H), 4.70 (s, 1H), 4.51 (s, 1H), 4.38 (s, 1H), 4.07 (t, J = 8.0 Hz, 1H), 4.02 (s, 2H), 3.75 (t, J = 8.6 Hz, 1H), 3.59 (d, J = 7.0 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.98 (dp, J = 19.8, 6.7 Hz, 2H), 2.72 - 2.62 (m, 1H), 2.25 (s, 3H), 2.03 (td, J = 13.1, 12.2, 6.1 Hz, 1H), 1.80 (s, 5H), 1.51 (s, 8H), 1.35 (s, 9H), 1.12 (s, 9H), 0.97 (d, J = 6.7 Hz, 6H), 0.87 (dd, J = 8.2, 6.7 Hz, 6H).

[0988] Example 61: Synthesis of Compound 61

[0989] 61d:

[0990] Referring to the synthesis of Compound 1d in Example 1, D-citrulline was used instead of 1a, and Boc-D-valine was used instead of Boc-L-valine to obtain 61d.

[0991] Compound 61:

[0992] Referring to the synthesis of Compound 8 in Example 8, 61d was used instead of 1d to obtain Compound 61 (white solid, 580 mg, yield: 91%).

[0993] MS (ESI): 1325.7 [M+1]+.

[0994] 1H NMR (400 MHz, DMSO-d6) 6 (ppm) 10.12 (s, 1H), 8.08 (d, J = 7.3 Hz, 1H), 8.01 - 7.89 (m, 3H), 7.73 (t, J = 7.3 Hz, 1H), 7.69 - 7.59 (m, 4H), 7.43 (t, J = 7.6 Hz, 2H), 7.35 (dd, J = 8.0, 4.1 Hz, 4H), 7.16 (dd, J = 20.1, 8.0 Hz, 2H), 5.98 (t, J = 5.9 Hz, 1H), 5.82 (t, J = 9.2 Hz, 1H), 5.43 (s, 2H), 5.37 (d, J = 7.1 Hz, 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, 7.0 Hz, 1H), 4.17 (t, J = 8.1 Hz, 1H), 4.02 (s, 2H), 3.75 (t, J = 8.7 Hz, 1H), 3.59 (d, J = 7.0 Hz, 1H), 3.29 (s, 3H), 3.22 (s, 3H), 2.99 (dp, J = 27.2, 6.6 Hz, 2H), 2.72 - 2.62 (m, 1H), 2.25 (s, 3H), 2.05 (h, J = 6.7 Hz, 1H), 1.81 (s, 4H), 1.68 (q, J = 6.8, 5.9 Hz, 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 = 6.8 Hz, 6H), 0.85 (dd, J = 15.3, 6.7 Hz, 6H).

[0995] Example 62: Synthesis of Compound 62

[0996]  62b

[0997] 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 [VDCM / VMeOH = 60:1] to obtain 62b (4.50 g, yield: 71%) as a white solid.

[0998] 62c

[0999] 62b (1.00 g, 2.03 mmol) was dissolved in acetonitrile (12 mL) with stirring, cooled to 5°C, and then a diluted solution of piperidine (519 mg, 6.09 mmol) in acetonitrile (3 mL) was added dropwise. The reaction mixture was stirred at the same temperature for 5 hours. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography [VDCM / VMeOH = 12:1] to obtain 62c (500 mg, yield: 91%) as a colorless oil.

[1000]  62d

[1001] 62c (500 mg, 1.85 mmol) was dissolved in dichloromethane (5 mL) with stirring, followed by the addition of triethylamine (562 mg, 5.55 mmol). The mixture was cooled to 0°C, and a solution of p-toluenesulfonyl chloride (335 mg, 1.76 mmol) in dichloromethane (3 mL) was added dropwise. The reaction mixture was stirred at this temperature for 1 hour. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography [VDCM / VMeOH = 60:1] to obtain 62d (320 mg, yield: 41%) as a white solid.

[1002] Compound 62

[1003] At -10 to 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. After cooling to -10°C, 4-dimethylaminopyridine (122.02 mg, 1.0 mmol) was added, and the reaction mixture was stirred at -10°C for 20 hours. Ethyl acetate (25 mL) and water (30 mL) were added to the reaction mixture to quench the reaction. The organic phase was washed twice with 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 [VDCM / VMeOH = 50:1] to obtain Compound 62 (white solid, 120 mg, yield: 19%, HPLC purity: 98.89%).

[1004] MS ...

Claims

1. A compound represented by 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 R1 is 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, -ORa, -SRa, -NRaRa, nitro, cyano, -C(=O)Ra, -C(=O)ORa, -C(=O)NRaRa, -S(=O)2NRaRa, -S(=O)Ra, -S(=O)2ORa, nitro, cyano, C1-C20 alkyl optionally substituted with one or more Ra, C1-C20 alkoxy optionally substituted with one or more Ra, C2-C20 alkenyl optionally substituted with one or more Ra, C2-C20 alkynyl optionally substituted with one or more Ra, 3- to 10-membered heteroalkenyl optionally substituted with one or more Ra, 3- to 10-membered heteroalkynyl optionally substituted with one or more Ra, or 3- to 20-membered heteroalkyl unsubstituted or optionally substituted with more than one Ra; each Ra is 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-C20 alkyl, or 3- to 20-membered heteroalkyl; the -OH, -SH, -NH2, -C(=O)H, -C(=O)OH, -C(=O)NH2, -S(=O)2NH2, -S(=O)2OH, C1-C20 alkyl, and 3- to 20-membered heteroalkyl are optionally substituted with any substituent;each Rc is -NRe-X-Y;each Re is independently hydrogen, deuterium, or C1-C4 alkyl;each X is X1, X2-X3, or X4-X5-X6-X7;or         '   ; X2 isX1 is; X3 isor; X4 is; X5 is0    , orO ; X7 is        Oeach Y is -C(=O)Rb or -S(=O)2Rb;each Rb is independently -OH, -NHRb-1, -NRb-1Rb-1, -C(=O)Rb-1, S(=O)2Rb-1, -S(=O)Rb-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1;each Rb-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1, -NRb-1-1Rb-1-1, -C(=O)Rb-1-1, S(=O)2Rb-1-1, -S(=O)Rb-1-1, C1-C6 alkyl, 3- to 8-memberedheteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3-to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1-1;each Rb-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1-1, -NRb-1-1-1Rb-1-1-1, -C(=O)Rb-1-1-1, S(=O)2Rb-1-1-1, -S(=O)Rb-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10membered heteroaryloxy are optionally substituted with one or more Rb-1-1-1;each Rb-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRb-1-1-1-1, -NRb-1-1-1-1Rb-1-1-1-1, -C(=O)Rb-1-1-1-1, -S(=O)2Rb-1-1-1-1, -S(=O)Rb-1-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3-to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryloxy; the Rb-1-1-1-1-substituted C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5-to 10-membered heteroaryloxy are optionally substituted with one or more Rb-1-1-1-1;each Rb-1-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkyl-NH-, (3- to 8-membered heteroalkyl)(3- to 8-membered heteroalkyl)N-, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkyl-NH-,   (3- to 8-memberedheterocycloalkyl)(3- to 8-membered heterocycloalkyl)N-, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, or 5- to 10membered heteroaryloxy;each Rd is independently -NRd-0Yd-1 or -ORd-2;each Rd-0 is independently hydrogen, deuterium, or C1-C4 alkyl;each Yd-1 is -C(=O)Rd-1 or -S(=O)2Rd-1;each Rd-1 is as defined as Rb above;each Rd-2 is C1-C6 alkyl, 3- to 8-membered heteroalkyl, C3-C8 cycloalkyl, 3- to 8-memberedheterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10membered heteroaryl are optionally substituted with one or more Rd-2-1;each Rd-2-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRd-2-1-1, -NRd-2-1-1Rd-2-1-1, -C(=O)Rd-2-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rd-2-1-1;each Rd-2-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, -NHRd-2-1-1-1, -NRd-2-1-1-1Rd-2-1-1-1, -C(=O)Rd-2-1-1-1, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10membered heteroaryl, or 5- to 10-membered heteroaryloxy; the C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, 3- to 8-membered heteroalkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-C8 cycloalkoxy, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl, C6-C10 aryloxy, 5- to 10-membered heteroaryl, and 5- to 10-membered heteroaryloxy are optionally substituted with one or more Rd-2-1-1-1;each Rd-2-1-1-1 is independently deuterium, halogen, nitro, cyano, -OH, -SH, -NH2, -C(=O)OH, C1-C6 alkyl, 3- to 8-membered heteroalkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)(C1-C6 alkyl)N-, 3- to 8-membered heteroalkoxy, 3- to 8-membered heteroalkyl-NH-, (3- to 8-membered heteroalkyl)(3- to 8-membered heteroalkyl)N-, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkyl-NH-, (3- to 8-membered heterocycloalkyl)(3- to 8-membered heterocycloalkyl)N-, C3-C8 cycloalkoxy, C3-C8 cycloalkyl-NH-, (C3-C8 cycloalkyl)(C3-C8 cycloalkyl)N-, 3- to 8-membered heterocycloalkoxy, C6-C10 aryl,C6-C10 aryloxy, C6-C10 aryl-NH-, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy,or 5- to 10-membered heteroaryl-NH-;the heteroatom is independently selected from 1, 2, or 3 types of O, S, and N; the number of heteroatoms is independently 1, 2, or 3.

2. The compound represented by Formula I or the pharmaceutically acceptable salt thereof according to claim 1, wherein the compound represented by Formula I is a compound represented by I-A to I-P:or, the compound represented by Formula I is a compound represented by Formula I-1 to I-12:1-11-12or, the compound represented by Formula I is a compound represented by Formula I-13 to I-24:or, the compound represented by Formula I is a compound represented by Formula II-1, II-2,or II-3,or, the compound represented by Formula I is a compound represented by Formula II-4, II-5,or II-6,or, 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,-X h3co 0=^ H3\ dd 0CH3 =3 NH 7=3 / 3 / 7 \_f o-( / \ / \ V#dd \_j434^) 0' 0 HO i0'Y^ S 0 HN.           II-7 Yd’! X h3co o=^ H3C\d     0CH3 == NH / =3 / \JJ /        O—(   / \ / \ d / dd d^dd 0' O HO i odk >0 odd ^O     1 O^ da' 0 d__U    yd-1 II-8 X h3co 0=(  ^'V-d'd °CH3 ,= NH / =^ / \fj \__0"'(   / \ Vj / J^d 6' O HO io'Yn >0 ovo? u 0Z HN-Yd1         II-9 Rd'2 X h3co 0=( H3c\d 0CH3 == nh r\ / Odds® 0' 0 HO din >0 O^d ^0     1 0^ d 0 HN O-Rd'2         u-10 yd-1 X h3co O® H3C\d     OCH3 .-=, NH         x\fJ \_0"(   / \ / \ vd ddd? d 0 HO iodk 1 ? 0             11-11 Rd-2 ~X     HO 0=< h3C Xd OH -^3 NH      \ x\LJ. \__O'"(   / \ v / d dddd 0' 0 HO id HN-           11-12 yd-1 ~^O      HO O=( H3Cxdd oh == NH / =3 / 3 / 7 \_0-(   / \ / 3 VJdd Md 0' 0 HO i(dd >° °d L rG J°x'~ cd *= 11-13 HO 0=( H3C          oh ,-=3  NH   >=\ / [J / \_='  o-<   / \ / \ \_ / ^d dddd 6 O HO =od\ >° °v°d - O HN-Yd‘1        IM4 Rd’2 -^0       HO 0=( H3C\JU° oh == NH        / \fj \_O"(   / \ vj2 \-=( 0'  0 HO =odk >0  OVO?J-O 0 3 HN O-Rd’2         n-15 yd-1HO 0=( HA\        0H =x  NH v / v^ VjOA / o' O HO =o'Yn y y 0             11-16 Rd2 O I y= /   / ^o 0=( H3C   L / P OH ,=. nh Ax / V-Z d 0 HO i GT! 6 A HN          H-17 yd-1 O 1 )= /   / ^0 O=( H3C         OH = NH / \ / / J Y-S 0"'(   / \ o' O HO ;OT) )=o °v°X / -0      1°^ y__y     Yd-1 11-18 O 1 o=\ h3c _XzP oh \ ■'  O'"(   / \ / \ d  0 HO =0M )=o °y°jL / -°     lo^ o 0 o HN-Yd'1          II-19 Rd'2 Q Ao O=< H3C         OH =x nh r=\ / \fJ \_O'"(   / \ / \ 6' o ho =o'T1 )=° °v°X r~Q      X°^' A 0 HN O-Rd'2         H-20 yd-1 O A 0=< HA JLy° oh / =\ NH / x / V-Z o' o HO =A vX o s O            1121 Rd'2or, the compound represented by Formula I is a compound represented by Formula I-a, I-b,or I-c:

3. The compound represented by Formula I or the pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein Y is -C(=O)Rb; the Rb is C1-C6 alkyl, C1-C6 alkoxy, -ORb-1, C6-C10 aryl, -C(=O)OH, or 3- to 8-membered heteroalkyl; the C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, and 3- to 8-membered heteroalkyl are optionally substituted with one or more Rb-1; each Rb-1 is independently C1-C6 alkyl, C6-C10 aryl, halogen, -NRfRf, 3- to 8-membered heterocycloalkyl, or -C(=O)OH; the C1-C6 alkyl, C6-C10 aryl, and 3- to 8-membered heterocycloalkyl are optionally substituted with one or more Rb-1-1; each Rf is independently C1-C6 alkyl; each Rb-1-1 is independently halogen;or,Rb is N(C1-C6 alkyl)(C1-C6 alkyl)C1-C6 alkyl, C1-C10 alkyl, C1-C6 alkyl substituted with 1-3 halogens, 3- to 8-membered heterocycloalkyl-C1-C6 alkyl, C6-C10 aryl substituted with 1-3 halogens, C(=O)OH-C0-C6 alkyl, C1-C10 alkoxy, C6-C10 aryl-C1-C6 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, or C(=O)OH-3- to 8-membered heteroalkyl.

4. The compound represented by Formula I or the pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein Yd-1 is -C(=O)Rd-1; Rd-1 is C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or -ORd-1-1; the C1-C6 alkyl, C6-C10 aryl, and C1-C6 alkoxy are optionally substituted with one or more Rd-1-1; each Rd-1-1 is independently C1-C6 alkyl, C6-C10 aryl, or halogen; the C1-C6 alkyl and C6-C10 aryl are optionally substituted with one or more Rd-1-1-1; each Rd-1-1-1 is independently halogen;or,Rd-1 is C1-C10 alkyl, C6-C10 aryl-C1-C6 alkyl substituted with 1-3 halogens, C1-C6 alkyl substituted with 1-3 halogens, C6-C10 aryl substituted with 1-3 halogens, or C1-C10 alkoxy.

5. The compound represented by Formula I or the pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein Rd-2 is C1-C6 alkyl.

6. The compound represented by Formula I according to claim 1, wherein the compound represented by Formula I is any one of the following compounds:or7. A pharmaceuticalcomposition comprising the compound or the pharmaceuticallyacceptable salt thereof according to any one of claims 1-6, and a pharmaceutically acceptablecarrier.

8. Use of a compound in the manufacture of a medicament, wherein the compound is the compound or the pharmaceutically acceptable salt thereof according to any one of claims 1-6, or the pharmaceutical composition according to claim 7, and the medicament is used for treating and / or preventing cancer; the cancer may be selected from a solid tumor and a hematologic malignancy; the solid tumor may be selected from breast cancer and prostate cancer.

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