Compounds containing self-immolative groups and ligand-drug conjugates containing the same

Abstract

The present invention provides a compound containing a self-immolative group and a ligand-drug conjugate containing the same. According to the present invention, an active substance can be stably delivered to a target site and rapidly released at the target site, thereby increasing the effectiveness of the active substance and preventing side effects from occurring at sites other than the target site.

Description

[Technical Field]

[0001] The present invention relates to novel compounds containing a self-immolative group and ligand-drug conjugates containing the same, and in particular to compounds containing a self-immolative group of formula 1 and ligand-drug conjugates of formula 2. [Background technology]

[0002] Biologically active agents, such as drugs and diagnostic agents, have target-specific activity in vivo: for example, drugs have an inhibitory or therapeutic effect on specific target cells, and diagnostic agents react with specific proteins in the body to perform a diagnosis.

[0003] On the other hand, since biologically active substances can be toxic to biological substances other than the target, techniques have been proposed that enable the drug effect to be selectively manifested in target cells while suppressing the side effects of the drug.

[0004] For example, antibody-drug conjugates (ADCs) are a targeting technology in which a drug or toxin is attached to an antibody that binds to an in vivo receptor, and then the drug or toxin is selectively released from target cells to exhibit the desired drug effect. ADCs release the drug or toxin only under specific conditions, selectively delivering the drug or toxin to target cells while minimizing side effects on normal cells, and therefore have better efficacy than antibody therapeutics and can significantly reduce the risk of side effects.

[0005] These antibody-drug conjugates have a common "antibody-linker-drug (toxin)" structure. The linker not only connects the antibody and the drug, but also enables the antibody-drug conjugate to stably reach target cells during circulation in the body, and the drug then separates from the antibody-drug in the target cells by dissociation of the antibody-drug in the target cells (e.g., as a result of enzymatic hydrolysis), thereby selectively exerting its effect on the target cells. Therefore, the stability of the linker has a significant impact on the efficacy and systemic toxicity of the antibody-drug conjugate (Discovery Medicine 2010, 10(53):329-39).

[0006] Linkers in antibody-drug conjugates can generally be classified into non-cleavable and cleavable types.

[0007] Thioether is commonly used as a non-cleavable linker. Instead of the bond between the drug and the linker dissociating within the cell, the bond between the linker and the antibody dissociates, and the drug bound to the linker is separated from the antibody. Thiol-maleimide linkers are commonly used, but have the disadvantages of low chemical and plasma stability and low efficacy.

[0008] As cleavable linkers, mainly linkers that can be separated by chemical methods or hydrolyzed by enzymatic reactions are used.

[0009] Linkers with chemical cleavage mechanisms typically use linkers consisting of disulfide, hydrazone, or oxime bonds, but these linkers can dissociate drugs at locations unrelated to the target site depending on the conditions in blood or cells, potentially resulting in toxic side effects.

[0010] To solve this problem, linkers that are selectively hydrolyzed in target cells by enzymatic reactions have been developed. For example, enzymatically hydrolyzable linkers are not directly linked to drugs but are linked via a self-immolative group (SIG) interposed between the drug and the linker, and the drug is released through mechanisms such as 1,6-elimination or cyclization after enzymatic hydrolysis (Clinical Cancer Res. 2005, 11, 843-852).

[0011] However, there remains a need in the art for the development of linkers that have excellent plasma and chemical stability, are capable of rapid drug release selectively within target cells, and have good versatility to form conjugates with a variety of antibodies and drugs. Summary of the Invention [Problem to be solved by the invention]

[0012] One object of the present invention is to provide compounds containing a self-immolative group of Formula 1 or Formula 1-1 and ligand-drug conjugates of Formula 2 or Formula 2-1.

[0013] Another object of the present invention is to provide a pharmaceutical composition, an imaging composition, or a detection composition comprising a compound of Formula 1 or Formula 1-1, or a ligand-drug conjugate of Formula 2 or Formula 2-1. [Effects of the Invention]

[0014] The compounds or ligand-drug conjugates of the present invention are capable of stably delivering active agents, such as drugs, toxins, fluorophores, affinity ligands, diagnostic substances, or detection probes, to a target site and rapidly releasing the active agent in the specific environment of the target site.

[0015] The compounds or ligand-drug conjugates of the present invention may have excellent stability at blood temperature and neutral conditions, and may rapidly release the active agent under acidic conditions, such as in the tumor microenvironment. [Brief explanation of the drawings]

[0016] [Figure 1] 1 is a graph showing the results of measuring the enzymatic cleavage rate of compound A-15 using E. coli β-galactosidase or E. coli β-glucuronidase. [Figure 2] 1 is a graph showing the results of measuring the enzymatic cleavage rate of compound A-23 using E. coli β-galactosidase or E. coli β-glucuronidase. [Figure 3] 1 is a graph showing the results of measuring the enzymatic cleavage rate of compound A-36 using E. coli β-galactosidase or E. coli β-glucuronidase. [Figure 4] 1 is a graph showing the results of measuring the enzymatic cleavage rate of compound A-69 using E. coli β-galactosidase or E. coli β-glucuronidase. [Figure 5] 1 is a graph showing the results of measuring the chemical stability and plasma stability of compound A-69. [Figure 6] 1 is a graph showing the results of in vivo activity analysis of ADC-1 to ADC-2. [Figure 7] 1 is a graph showing the results of in vivo activity analysis of ADC-3 to ADC-7. [Figure 8] 1 is a graph showing the results of in vivo activity analysis of ADC-11 to ADC-15. DETAILED DESCRIPTION OF THE INVENTION

[0017] Each description and embodiment disclosed in this application can also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this application are included within the scope of this application. In addition, the scope of this application should not be limited to the specific description provided below. In one aspect of the present invention, a compound of Formula 1: [Formula 1] A-(L 1 ) k -U j The present invention provides a compound containing a self-immolative group represented by the formula: or a pharmaceutically acceptable salt thereof. Additionally, in another aspect of the present invention, a compound of formula 2:

[0018] [ka] or a pharmaceutically acceptable salt thereof.

[0019] In Formula 1 or Formula 2 of the present invention, L 1 is a divalent or polyvalent linking group, k is 0 or 1, and j is 1 to 10.

[0020] In Formula 1 or Formula 2 of the present invention, A is absent, H, or a linking functional group, and A' is a divalent linking group derived from the linking functional group of A.

[0021] In formula 2 of the present invention, n is a real number between 1 and 10, and E is a ligand or protein with receptor binding properties. In the formula 1 or 2 of the present invention, U is a group represented by the following formula A:

[0022] [ka] (In Equation A, R 1 and R 2 are each independently H or C 1~8 saturated or unsaturated hydrocarbyl; PL is L with a heteroatom selected from N, O and S. 2 To, or R 1 and R 2 is an activator linked to the carbon atom to which is attached; L 2 L 2 and R 1 and R 2 The bond between the carbon atom and the2 a self-elimination linker selected to facilitate cleavage of the bond between the W is an optional substituent on the benzene ring; Z 1 and Z 3 One of them is N, NR 3 , O, S, and Se; Z 1 and Z 3 the other and Z 2 are each independently CH or N, -(L 1 ) k -A, and if present -(V) h each independently replaces H in NH or CH;

[0023] [ka] is A-(L 1 ) k - represents the bond with; R 3 is H or C 1~8 is a hydrocarbyl; V is an electron-withdrawing or electron-donating group; When T is cleaved, a 1,6-elimination reaction occurs to give PL and, if present, L. 2 is a triggering group capable of initiating the release of L 3 is an optional self-immolative spacer group which, if present, is cleaved sequentially upon cleavage of T; X and Y are each independently selected from —O—, —NH—, and S; h, i, l, x, and y are each independently 0 or 1, and p is an integer of 0 to 2. This is the part represented by Compounds containing a self-immolative group of formula 1 Fused ring containing core unit Equation 1(A-(L 1 ) k -U j ) U is represented by the following formula A:

[0024] [ka] It is expressed as:

[0025] In Equation 1, L 1 is a divalent linking group, L 1 One side of is bound to A and the other side is bound to U. In this case, one U is bound to L 1 Or, L 1 When L contains a branched or dendrimer structure (i.e., L 1 is a polyvalent linking group), L 1 Multiple U's can be bonded to L. 1 The number j of U' bonded to can be 1 to 10. In one embodiment, j is 1 to 5. In one embodiment, j is 1.

[0026] In the above formula A, Z 1 and Z 3 One of them is N, NR 3 , O, S, and Se; Z 1 and Z 3 the other and Z 2 are each independently CH or N. -(L 1 ) k -A, and if present -(V) h are each independently replaced with H in NH or CH. In this case, R 3 is H or C 1~8 It is a hydrocarbyl. In the above formula A, Z 1 ~Z 3 linked to a five-membered ring containing

[0027] [ka] is A-(L 1 ) k -Represents a bond with.

[0028] In one embodiment, Z 1 and Z3 One of them is N, NR 3 , O, S, and Se; L 1 or bonded to A and Z 1 and Z 3 the other and Z 2 are each independently H, V, L 1 , or C or N bonded to A. R 3 is H or C 1~8 In one embodiment, R 3 is H, C 1~4 Alkyl or C 1~3 It can be alkyl.

[0029] In one embodiment, Z 1 ~Z 3 Any one of may contain a heteroatom selected from the group consisting of N, O, S, and Se. 1 ~Z 3 Two or more of may each independently contain a heteroatom selected from the group consisting of N, O, S, and Se.

[0030] In one embodiment, Z 1 and Z 3 One of them is A or L 1 and Z 2 can be CH. Alternatively, Z 1 and Z 3 On the other hand, NR 3 , O, S and Se, and the other and Z 2 is CH, or A or L 1 Alternatively, Z 1 and Z 3 On the other hand, NR 3 , O and S, and the other and Z 3 One of the two can be N, and Z 1 ~Z 3 The other is CH, or A or L 1 C bonded to

[0031] In one embodiment, V is Z 1 ~Z 3When any one or more of Z is CH, it can be substituted with a carbon atom of CH. For example, Z 2 If is CH, V is Z 2 may be substituted with

[0032] In one embodiment, the compound of Formula 1 can be a derivative of indole, benzothiophene, benzofuran, benzoselenophene, indazole, benzimidazole, benzoxazole, benzisoxazole, or benzothiazole. In one embodiment, the ring of formula A

[0033] [ka] is the following group:

[0034] [ka] may be selected from:

[0035] The benzene ring of the fused ring structure of formula A above can be substituted with an optional substituent W, provided that it does not have the undesirable effect of the 1,6-elimination reaction initiated from the initiating group T. In one embodiment, the substituent W on the benzene ring is selected from the group consisting of H, C, 1~12 Saturated or unsaturated hydrocarbyl, halogen, halo-C 1~8 Alkyl, CN, NO2, OH, C 1~8 Alkoxy, Hydroxy-C 1~8 Alkyl, C 1~8 Alkoxy-C 1~8 Alkyl, SH, C 1~8 Alkylthio, mercapto-C 1~8 Alkyl, Amino, Mono C 1~8 Alkylamino, DiC 1~8 Alkylamino, Amino-C 1~8 Alkyl, C 1~8 Monoalkylamino-C 1~8 Alkyl, C 1~8 Dialkylamino-C 1~8 Alkyl, carboxy, C1~8 Alkoxycarbonyl, C 1~8 Alkoxycarbonyloxy, Carboxy-C 1~8 Alkyl, C 1~8 Alkoxycarbonyl-C 1~8 Alkyl, Carbamoyl, Mono C 1~8 Alkylcarbamoyl, diC 1~8 Alkylcarbamoyl, Carbamoyl-C 1~8 Alkyl, Mono C 1~8 Alkylcarbamoyl-C 1~8 Alkyl and diC 1~8 Alkylcarbamoyl-C 1~8 In Formula 1, p can be an integer from 0 to 2. In one embodiment, p can be 0.

[0036] In addition, Z of the fused ring of the above formula A 1 , Z 2 and Z 3 The five-membered ring comprising: may be optionally substituted with V, an electron-withdrawing group, or an electron-donating group. In Formula A, h is 0 or 1. In one embodiment, A-(L 1 ) k - is Z 2 When V is bonded to V, V is absent (h is 0).

[0037] In some embodiments, V is halogen, CN, NO, formyl, C 1~8 Alkylcarbonyl, carboxy, C 1~8 Alkoxycarbonyl, Carboxy-C 1~8 Alkyl, Carbamoyl, Mono C 1~8 Alkylcarbamoyl, diC 1~8 Alkylcarbamoyl, C 1~8 Alkyl, C 1~8 Alkenyl, OH, C 1~8 Alkoxy, SH, C 1~8 Alkylsulfanyl, NH2, Mono C 1~8 Alkylamino, DiC 1~8 Alkylamino and C 6~18 In some embodiments, V may be selected from the group consisting of carboxy, carboxy-C 1~8Alkyl or C 1~8 For example, V can be carboxy, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, carboxymethyl, carboxyethyl, or carboxypropyl.

[0038] In the present invention, in Formula A, R 1 and R 2 are each independently H or C 1~8 It may be a saturated or unsaturated hydrocarbyl.

[0039] In one embodiment, R 1 and R 2 are each independently H or C 1~8 Alkyl or C 3~8 In one embodiment, R 1 and R 2 are each independently H or C 1~4 It can be saturated or fully or partially unsaturated hydrocarbyl. For example, R 1 and R 2 may each be H. The unsaturated hydrocarbyl may include partially unsaturated or fully unsaturated hydrocarbyl. The hydrocarbyl may be straight chain, branched chain, or cyclic hydrocarbyl. Self-elimination linker In Formula 1 of the present invention, L 2 L 2 and R 1 and R 2 The bond between the carbon atom and the 2 is a self-elimination linker selected to facilitate cleavage of the bond between R and PL. 1 can be 0 or 1. When 1 is 0, PL is 1 and R 2 may be directly bonded to the carbon atom to which is bonded.

[0040] When the compound of Formula 1 contains a self-elimination linker, L 2 The group can be converted to R by a 1,6-elimination reaction induced by the inducing group T. 1 and R 2 is cleaved from the carbon atom to which it is attached, and PL - or PL-H is L2 can be released from In one embodiment, L 2 is -OC(=O)-, -S(=O)2-,

[0041] [ka] and at least one linker selected from the group consisting of: 10 ~R 12 are each independently H, C 1~8 Alkyl, Amino-C 1~8 Alkyl, mono- or di-(C 1~8 Alkyl)amino-substituted C 1~8 Alkyl, or -(CH2CH2O) g R 13 In this case, R 13 is H or C 1~4 alkyl, and g can be an integer from 1 to 10. In one embodiment, C 1~8 Alkyl is C 1~6 Alkyl, C 1~4 Alkyl or C 1~3 For example, R 10 ~R 12 may each independently comprise H, methyl, ethyl, propyl, 2-aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl, 2-(N-ethylamino)ethyl, or 2-(N,N-diethylamino)ethyl. In one embodiment, a portion of formula A is L 2 may include -OC(=O)-. Activator (PL) In Formula A of the present invention, PL is an active agent that exhibits a desired biological activity in a target cell, and L is linked to the active agent by a heteroatom selected from N, O, and S. 2 To, or R 1 and R 2 PL is linked to the carbon atom to which T is attached. PL is released from the compound of formula 1 by a 1,6-elimination reaction when T is cleaved by an enzymatic or chemical reaction.

[0042] In one embodiment, the PL can be at least one active agent selected from the group consisting of a drug, a toxin, a fluorophore, an affinity ligand, a diagnostic substance, and a detection probe. Specifically, a heteroatom selected from N, O, and S contained in the drug, toxin, fluorophore, affinity ligand, diagnostic substance, and detection probe can be R 1 and R 2 or L 2 Therefore, PL may be bonded to R 1 and R 2 or a carbon atom to which (L 2 (if present)L 2 It should be noted that the PL of the present invention can be used as long as it contains a heteroatom selected from N, O, and S that can be bonded to the above, or a functional group containing such a heteroatom can be further introduced, and the PL of the present invention is not limited to the specific active agents exemplified herein. For example, the PL may include a functional group resulting from the removal of H from a primary or secondary amine group, H from a hydroxyl group, or H from a carboxyl group, a functional group resulting from the donation of the lone pair of electrons from the nitrogen atom of a tertiary amine group, or a functional group linked to a nitrogen atom through the addition reaction of an imine group.

[0043] Drugs included erlotinib (Tarceva; Genentech / OSI Pharm.); bortezomib (VELCADE; MillenniumPharm.); fulvestrant (Faslodex; AstraZeneca); Sutent (SU11248; Pfizer); letrozole (FEMARA; Novartis); imatinib mesylate (Gleevec; Novartis); PTK787 / ZK 222584 (Novartis); oxaliplatin (Eloxatin; Sanofi); 5-fluorouracil (5-FU); leucovorin; rapamycin (sirolimus, Rapamune; Wyeth); lapatinib (TYKERB, GSK572016; GlaxoSmithKline); lonafarnib (SCH 66336); sorafenib (BAY43-9006; Bayer Labs.); gefitinib (IRESSA; Astrazeneca); AG1478, AG1571 (SU 5271; Sugen); alkylating agents (e.g., thiotepa or CYTOXAN®); cyclophosphamide); alkylsulfonates (e.g., busulfan, improsulfan, or piposulfan); aziridines (e.g., benzodopa, carboquone, meturedopa, or uredopa); ethyleneimine, methylmelamine, altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphor amides, trimethylolmelamine; acetogenins (e.g., bullatacin or bullatacinone); camptothecins, including the synthetic analog topotecan; bryostatin; kallistatin; CC-1065 (including its synthetic analogs adozelesin, carzelesin, or bizelesin); cryptophycins (e.g., cryptophycin 1 or cryptophycin 8); dolastatin; duocarmycins (including synthetic analogs KW-2189 and CB1-TM1); eleutherobin; pancratistatin; sarcodictiin; spongistatin;nitrogen mustards (e.g., chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novoenbiquine, fenesterine, prednimustine, trofosfamide, or uracil mustard); nitrousureas (e.g., carmustine, chlorozotocin, fotemustine, lomustine, nimustine, or ranimnustine); antibiotics (e.g., enediyne antibiotics, calicheamicins selected from dynemicins, including calicheamicin gamma 1I and calicheamicin omega 1I or dynemicin A; bisphosphonates (e.g., clodronate); esperamicin, neocarzinostatin chromophore or related chromoprotein enediyne antibiotic chromophore, aclacinomycin, actinomycin, anthromycin, azaserine, bleomycin, cactinomycin, carabicin, carninomycin, carzinophilin, chromomycin , dactinomycin, daunorubicin, detorubucin, 6-diazo-5-oxo-L-norleucine, adrurimycin; doxorubicin (e.g., morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubucin, liposomal doxorubicin, or deoxydoxorubicin), epirubicin, esorubicin, marcellomycin, mitomycin (e.g., mitomycin C, mycophenolic acid, nogara), mycin, olivomycin, peplomycin, potfilomycin, puromycin, chelamycin, rhodrubicin, streptomigrin, streptozocin, tubercidin, ubenimex, zinostatin, or zorubicin; antimetabolites (e.g., 5-fluorouracil (5-FU)); folic acid analogs (e.g., denopterin, methotrexate, pteropterin, or trimetrexate); purine analogs (e.g., fludarabine, 6-mercaptopurine, thiamiprine, or thiguanine);pyrimidine analogues (e.g., ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, or floxuridine); androgens (e.g., calsterone, dromostanolone propionate, epithiostanol, mepitiostane, or testolactone); antiadrenal agents (e.g., aminoglutethimide, mitotane, or trilostane); folic acid supplements (e.g., folinic acid); aceglatone; aldophosph Amidoglycosides; aminolevulinic acid; eniluracil; amsacrine; bestravcil; bisantrene; edatraxate; defofamin; demecolcine; diaziquone; elfornithine; elliptinium acetate; epothilon; etoglucide; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids (e.g., maytansine or Ansamitocins; trichothecenes (e.g., T-2 toxin, verracurin A, roridin A, or anguidine); mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; 2-ethylhydrazide; procarbazine; PSK®; polysaccharides; razoxane; rhizoxin; sizofiran; spirogermanium; tenu Azonic acid; triaziquone; 2,2',2"-trichlorotriethylamine; trichothecenes (especially T-2 toxin, veracrine A, roridin A, and anguidine); urethane; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside ("Ara-C"); cyclophosphamide; thiotepa; taxoids (e.g., TAXOL; paclitaxel (TAXOL; Bristol-Myers Squibb Oncology, Princeton, NJ), cremophor-free ABRAXANE™, albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumber, IL) or TAXOTERE;The compound may be selected from the group consisting of, but is not limited to, docetaxel (taxotere); chlorambucil; gemcitabine; 6-thioguanine; mercaptopurine; platinum analogs (e.g., cisplatin or carboplatin); vinblastine; platinum; etoposide, ifosfamide; mitoxantrone; vincristine; vinorelbine (navelbine); novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; CPT-11; the topoisomerase inhibitor RFS 2000; difluoromethylornithine (DFMO); retinoids (e.g., retinoic acid); capecitabine; and pharmaceutically acceptable salts, solvates, acids, or derivatives thereof.

[0044] Additional drugs other than those mentioned above include: (i) antihormonal drugs that regulate or inhibit hormone action in tumors, such as tamoxifen (including NOLVADEX; tamoxifen), raloxifene, droloxifene, 4-hydroxytamoxifen, trioxifene, ketoxifene, LY117018, onapristone, and FAREATON; antiestrogens and selective estrogen receptor modulators (SERMs), including toremifene; (ii) aromatase inhibitors. Aromatase inhibitors, which inhibit the enzyme aromatase and thereby regulate estrogen production in the adrenal glands, such as 4(5)-imidazole, aminoglutethimide, and MEGASE; megestrol acetate, aromasin; exemestane, femara; letrozole and ARIMIDEX; anastrozole; (iii) antiandrogens, such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; and troxacitabine (1,3-dioxolane nuclease). (iv) aromatase inhibitors; (v) protein kinase inhibitors; (vi) lipid kinase inhibitors; (vii) antisense oligonucleotides, particularly those that inhibit gene expression in signal transduction pathways associated with adhesion cells, e.g., PKC-α, Raf, H-Ras; (viii) ribozymes, e.g., VEGF inhibitors, e.g., ANGIOZYME ribozymes and HER2 expression inhibitors; (ix) vaccines, e.g., gene therapy vaccines; allovectin (ALL OVECTIN); vaccine, LEUVECTIN vaccine and VAXID vaccine; PROLEUKIN; rlL-2; LURTOTECAN; topoisomerase 1 inhibitors; ABARELIX; rmRH; (x) anti-angiogenic agents, e.g., bevacizumab (AVASTIN, Genentech); and (xi) pharmaceutically acceptable salts, solvates, acids, or derivatives thereof.

[0045] In one embodiment, the drug may be selected from a cytokine, an immunomodulatory compound, an anti-cancer agent, an anti-viral agent, an anti-bacterial agent, an anti-fungal agent, an anti-parasitic agent, or a combination thereof.

[0046] Cytokines are small cell-signaling protein molecules secreted by many cells and can be signaling molecules widely used in cell-to-cell communication. Cytokines include monokines, lymphokines, traditional polypeptide hormones, and the like. Exemplary cytokines include growth hormones (e.g., human growth hormone, N-methionyl human growth hormone, or bovine growth hormone); parathyroid hormone; thyroxine; insulin; proinsulin; relaxin; prorelaxin; glycoprotein hormones (e.g., follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), or luteinizing hormone (LH)); hepatic growth factor; fibroblast growth factor; prolactin; placental lactogen; tumor necrosis factor-α, tumor necrosis factor-β; Müllerian inhibitory substance; mouse gonadotropin-related peptide; inhibin; activin; vascular endothelial growth factor; integrins, thrombopoietin (TPO); nerve growth factor (e.g., NGF-β); platelet growth factor; transforming growth factor (TGF) (e.g., TGF-α or TG) F-β); insulin-like growth factor-I, insulin-like growth factor-II; erythropoietin (EPO); osteogenic factor; interferons (e.g., interferon-α, interferon-β, or interferon-γ); colony-stimulating factors (CSF) (e.g., macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), or granulocyte-CSF (G-CSF)); interleukins (IL) (e.g., IL-1, IL-1α, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, or IL-12); tumor necrosis factors (e.g., TNF-α or TNF-β); and polypeptide factors (e.g., LIF or kit ligand (KL)). In addition, the term "cytokine" can also include proteins from natural sources or from recombinant cell culture and biologically active equivalents of the native-sequence cytokines.

[0047] The immunomodulatory compound may be selected from the group consisting of aminocaproic acid, azathioprine, bromocriptine, chloroquine, chlorambucil, cyclosporine, cyclosporine A, danazol, DHEA (dehydroepiandrosterone), dexamethasone, etanercept, hydroxychloroquine, hydrocortisone, infliximab, meloxicam, methotrexate, cyclophosphamide, mycophenolate mofetil, prednisone, sirolimus, and tacrolimus.

[0048] Anticancer drugs include methotrexate, taxol, L-asparaginase, mercaptopurine, thioguanine, hydroxyurea, cytarabine, cyclophosphamide, ifosfamide, nitrosourea, cisplatin, carboplatin, mitomycin, dacarbazine, procarbazine, topotecan, nitrogen mustard, cytoxan, etoposide, 5-fluorouracil, BCNU (bis-chloroethylnitrosourea), irinotecan, camptothecin, exatecan, belotecan, bleomycin, doxorubicin, idarubicin, daunorubicin, dactinomycin, plicamycin, mitoxantrone, Asparaginase, vinblastine, vincristine, vinorelbine, paclitaxel, docetaxel, chlorambucil, melphalan, carmustine, lomustine, busulfan, treosulfan, dacarbazine, etoposide, teniposide, topotecan, 9-aminocamptothecin, crisnatol, mitomycin C, trimetrexate, mycophenolic acid, tiazofurin, ribavirin, EICAR (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide), hydroxyurea, deferoxamine, floxuridine, doxifluridine, raltitrexed, cytarabine (ara) C), cytosine arabinoside, fludarabine, tamoxifen, raloxifene, megestrol, goserelin, leuprolide acetate, flutamide, bicalutamide, EB1089, CB1093, KH1060, verteporfin, phthalocyanine, photosensitizer Pe4, demethoxy-hypocrelin A, interferon-α, interferon-γ, tumor necrosis factor, gemcitabine, velcade, rebamide, talamide, lovastatin, 1-methyl-4-phenylpyridinium ion, staurosporine, actinomycin D, dactinomycin, bleomycin A2, bleomycin B2, peplomycin, epirubicin, pirarubicin, zorubicin, mitoxantrone, verapamil and thapsigargin.

[0049] The antiviral agent may be selected from the group consisting of pencicyclovir, valacyclovir, gancicyclovir, foscarnet, ribavirin, idoxuridine, vidarabine, trifluridine, acyclovir, famcicyclovir, amantadine, rimantadine, cidofovir, antisense oligonucleotides, immunoglobulins, and interferons.

[0050] The antibacterial agent may be selected from the group consisting of chloramphenicol, vancomycin, metronidazole, trimethoprin, sulfamethazole, quinupristin, dalfopristin, rifampicin, spectinomycin, and nitrofurantoin.

[0051] Antifungal agents include amphotericin B, candicidin, filipin, hamycin, natamycin, nystatin, rimocidin, bifonazole, butoconazole, clotrimazole, econazole, fenticonazole, isoconazole, ketoconazole, luliconazole, miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, albaconazole, fluconazole, isavuconazole, itraconazole, posaconazole, The antiparasitic agent may be selected from the group consisting of ravuconazole, terconazole, voriconazole, abafungin, amorolfine, butenafine, naftifine, terbinafine, anidulafungin, caspofungin, micafungin, benzoic acid, ciclopirox, flucytosine, griseofulvin, haloprogin, tolnaftate, undecylenic acid, crystal violet, balsam of Peru, ciclopirox olamine, piroctone olamine, zinc pyrithione, and selenium disulfide. The antiparasitic agent may be selected from the group consisting of mebendazole, pyrantel pamoate, thiabendazole, diethylcarbamazine, ivermectin, niclosamide, praziquantel, albendazole, rifampicin, amphotericin B, melarsoprol, eflornithine, metronidazole, tinidazole, and miltefosine.

[0052] "Toxin" refers to a harmful substance produced within a living cell or organism. A toxin can be a small molecule, peptide, or protein that can cause disease upon contact with or absorption into body tissues where it interacts with biological macromolecules such as enzymes or cellular receptors. In addition, "toxin" includes plant and animal toxins. Exemplary animal toxins include, but are not limited to, diphtheria toxin, botulinum toxin, tetanus toxin, shiga toxin, cholera toxin, tetrodotoxin, brevetoxin, and ciguatoxin. Exemplary plant toxins include, but are not limited to, ricin and AM-toxin.

[0053] For example, small molecule toxins include auristatins, tubulysins, geldanamycin (Kerr et al., 1997, Bioconjugate Chem. 8(6):781-784), maytansinoids (EP 1391213, ACR 2008, 41, 98-107), calicheamicin (US 2009105461, Cancer Res. 1993, 53, 3336-3342), daunomycin, doxorubicin, methotrexate, vindesine, SG2285 (Cancer Res. 2010, 70(17), 6849-6858), dolastatins, dolastatin analogs, auristatins (U.S. Pat. No. 5,635,483), cryptophycins, camptothecins, rhizoxin derivatives, CC-1065 analogs or derivatives, duocarmycins, enediyne antibiotics, esperamicins, epothilones, PBD (pyrrolobenzodiazepine) derivatives, α-amanitin, and toxoids. Toxins can exhibit cytotoxic and cell growth inhibitory activity through tubulin binding, DNA binding, topoisomerase inhibition, and the like.

[0054] The affinity ligand may include a molecule capable of forming a complex with a target biomolecule. The affinity ligand may be a molecule that transmits a signal upon binding to a predetermined site on the target protein. The affinity ligand may be a substrate, an inhibitor, a stimulant, a neurotransmitter, or a radioisotope.

[0055] A "detection probe" can refer to a substance or portion of a substance that can be detected by spectroscopic, photochemical, biochemical, immunochemical, radioactive, or chemical means. For example, useful detection probes include: 32 P, 35 Detection probes can include S, fluorescent dyes, electron-dense reagents, enzymes (e.g., those commonly used in ELISA), biotin-streptavidin, dioxigenin, haptens, and proteins for which antisera or monoclonal antibodies are available, or nucleic acid molecules containing sequences complementary to the target. Detection probes are often capable of generating a measurable signal, such as a radioactive, chromogenic, or fluorescent signal, which can be used to quantify the amount of bound detectable moiety in a sample. Quantification of the signal can be achieved, for example, by scintillation counting, densitometry, flow cytometry, ELISA, or direct analysis of intact or subsequently digested peptides by mass spectrometry (one or more peptides can be assayed).

[0056] The above detection probes may include (i) substances capable of providing a detectable signal, (ii) substances capable of modifying the detectable signal generated by the first or second probe, such as fluorescence resonance energy transfer (FRET), by causing the first or second probe to react with each other, (iii) substances capable of stabilizing the interaction with an antigen or ligand or increasing the binding affinity, (iv) substances capable of affecting electrophoretic mobility or cell invasiveness through physical parameters such as charge, hydrophobicity, etc., and (v) substances capable of modulating ligand affinity, antigen-antibody binding, or the formation of ionic complexes. In one embodiment, the PL is selected from the group consisting of MMAF (monomethyl auristatin F), auristatin F, MMAE (monomethyl auristatin E), SN-38, p-nitrophenol, xanthenecarboxylic acid, abiraterone, gefitinib, PBD dimer, α-amanitin, seco-DUBA, doxorubicin, lapatinib, imatinib, erlotinib, exatecan, belotecan, and compounds of the formula:

[0057] [ka] The compound may be part of an active agent selected from the group consisting of compounds represented by one of the following: In one embodiment, PL has the formula:

[0058] [ka] The moiety may be selected from the group consisting of: Triggering Units In the present invention, in formula A, T, when cleaved, undergoes a 1,6-elimination reaction to give PL and, if present, L. 2 is a triggering group capable of initiating the release of

[0059] T can be selectively cleaved in vivo by a chemical or enzymatic reaction, i.e., T (or the bond between Y and T, if Y is present) can be selectively cleaved under specific conditions in vivo, thereby stably delivering PL to a target site and selectively releasing PL at the target site.

[0060] In one embodiment, T can be linked to the benzene ring through a heteroatom such as an oxygen atom, a sulfur atom, or a nitrogen atom. That is, in Formula A, Y, which connects the inducing group T to the compound moiety, can be -O-, -NH-, and S.

[0061] In one embodiment, -(Y) y -T is -β-galactosides, -β-glucuronides, -O-SO3 - , -NO2, -valine-citrulline derivatives, -valine-alanine derivatives, -OC(O)(CH2) r COR t1 , -O(CH2)-Ar 1 -NO2, -SC(O)(CH2) s COR t2 , -S(CH2)-Ar 2 -NO2 and -BR t3 Rt4 may be selected from the group consisting of:

[0062] The β-galactosides and β-glucuronides may be linked to the benzene ring through an oxygen atom bonded to the first carbon atom of the β-galactosides and β-glucuronides moieties. The valine-citrulline derivatives and valine-alanine derivatives may be linked to the benzene ring through a nitrogen atom of the valine moiety. That is, the β-galactosides, β-glucuronides, valine-citrulline derivatives, and valine-alanine derivatives herein may be moieties having the following structures:

[0063] [ka] R t1 and R t2 may each be C1-C8 alkyl, and Ar 1 and Ar 2 are C5 to C 20 may be arylene or heteroarylene, R t3 and R t4 may each independently be hydrogen, C1-C8 alkoxy, or hydroxy, and r and s may each be an integer from 1 to 5. In one embodiment, the arylene may be phenyl or naphthyl. In one embodiment, the heteroarylene may contain 1 to 3 heteroatoms (N, O, or S). For example, the heteroarylene may be furanyl, thiophenyl, or pyrrolyl.

[0064] R t5 Oh, Mono C 1~8 Alkylamino, DiC 1~8 Alkylamino or -NH(CH2CH2O) f R t6 R t6 is H or C 1~4 It can be alkyl, and f can be an integer from 1 to 10. In one embodiment, -(Y) y -T is

[0065] [ka] saccharides such as;

[0066] [ka] Peptides such as -O-SO3 - The saccharides may contain a functional group that can be selectively hydrolyzed by lysosome-specific enzymes. The above saccharides may include those in which the -OH is protected with a protecting group (e.g., acetyl) or substituted with an optional substituent. In addition, -SC(O)(CH) s COR t2 , -S(CH2)-Ar 2 -NO2, -OC(O)(CH2) r COR t1 and -O(CH2)-Ar 1 -NO2 can be cleaved under reducing conditions.

[0067] For example, Y is absent (y=0) and T is -NO2 or -BR t3 R t4 which can be cleaved under reducing and protolytic conditions, respectively. Optional self-immolative spacer unit In the formula A of the present invention, L 3 is an optional self-immolative spacer group, if present, that is sequentially cleaved upon cleavage of T. Under certain conditions in vivo, a 1,6-elimination reaction induced by cleavage of T can result in the release of L from a portion of the compound. 3 Therefore, L 3 has a structure that can transfer the electrons generated when T is cleaved to the benzene ring of formula A and PL. In one embodiment, -(X) x -L 3 -teeth,

[0068] [ka] where R8 and R 9 are each independently H, halogen, or C 1~8 It may be selected from the group consisting of alkyl, CN and NO2, and o may be an integer from 0 to 2. For example, -(X) x -L 3 - can be derived from benzyl hydroxide (PhCH2OH) and its derivatives. In one embodiment, Z 1 and Z 3 One of the -(X) can be O, and -(X) x -L 3 -teeth,

[0069] [ka] It could be.

[0070] In Formula A of the present invention, i can be 0 or 1. In one embodiment, when i is 0, the self-immolative spacer group cannot be present and -(Y) y -T may be directly linked to the benzene ring. Bonding Unit In Formula 1 of the present invention, A is absent, H, or a linking functional group. 1 When k is present (k=1), A is H or a linking functional group, and L 1 If does not exist (k=0), then A does not exist either.

[0071] The binding functional group is a functional group contained in the ligand or protein (E in Formula 2) or L in Formula 1, which can be attached by a reaction such as addition or substitution. 1 That is, the binding functional group can refer to a functional group that can be linked to a functional group contained in a linker precursor to form a linker. 1 Between or (L 1(if not present) is any functional group capable of providing a bond between U in Formula 1 and another linker. In the field of ligand-drug conjugates, various functional groups for bonding between a ligand and a linker are known in the art. Therefore, those skilled in the art can select an appropriate bonding functional group taking into account the structures and properties of the ligand and the linker, and it should be noted that the bonding functional groups of the present invention are not limited to the specific functional groups exemplified herein. For example, the bonding functional group can be bonded to a ligand or protein (E) having receptor binding properties or a linker precursor by click chemistry. In one embodiment, L in Formula 1 1 When L is absent (i.e., k is 0), the binding functionality may be further attached to a linker precursor, which may then be attached to a ligand or protein (E) having receptor binding properties through a functional group contained in the linker precursor. In this case, the compound of Formula 1 has the structure "AU" and the ligand-drug conjugate of Formula 2 has the structure "E-Linker-AU". In another embodiment, L of Formula 1 1 is present (i.e., k is 1), the linking functionality may be attached to a further linker precursor to form an extended linker, which may then be attached to a ligand having receptor binding properties through a functional group contained in the further linker precursor.

[0072] Thus, when A is a binding functionality, the compound according to Formula 1 of the present invention may be an intermediate for coupling to a further linker precursor or ligand or protein (E) having receptor binding properties, e.g., to provide a ligand-drug conjugate. On the other hand, when A is absent or H, the compound according to Formula 1 of the present invention may be a conjugate comprising an active agent (PL) that is not assumed to bind to a ligand having receptor binding properties. The conjugate may be used for various purposes, such as altering the properties (e.g., water solubility) of the active agent, targeting, etc. In one embodiment, the binding functional group is a halogen, OH, C 1~8 Alkoxy, hydroxylamino, COH, C 1~8 Alkylcarbonyl, carboxy, C1~8 Alkoxycarbonyl, tosyl, tosylate, amino, mono C 1~8 Alkylamino, DiC 1~8 Alkylamino, NHNH2, N3, haloacetamide, maleimidyl, succinimidyl, SH, SO3H, C 1~8 alkylsulfonyl,

[0073] [ka] , C 1~8 Alkoxysulfonyl, 2-pyridyl disulfide, PO3H2, OPO3H2, -N≡C, -NCS, C 4~10 Dienyl, C 2~8 Alkenyl, C 2~8 Alkynyl, C 4~10 Cycloalkynyl and C 2~8 R may comprise or consist of a functional group selected from the group consisting of alkynylcarbonyl. f are each independently H or C 1~8 In one embodiment, A is maleimidyl, hydroxylamino, carboxy, amino, N3, C 2~8 alkynyl, or

[0074] [ka] For example, maleimidyl refers to a group in which the nitrogen atom of maleimide is L of Formula 1. 1 or U. In one embodiment, C 1~8 Alkyl is C 1~6 Alkyl, C 1~4 Alkyl or C 1~3 In one embodiment, C 2~8 Alkynyl can be ethynyl, propynyl (propargyl) or butynyl.

[0075] In Formula 1 of the present invention, L 1 is Z of formula A 1 ~Z 3and k is 0 or 1.

[0076] In one embodiment, k in formula A is 1 and Z 1 or Z 3 When contains a nitrogen atom, L 1 is Z 1 or Z 3 In one embodiment, k in formula A is 1 and Z 1 ~Z 3 If at least one of the groups contains a carbon atom, L 1 may be attached to a carbon atom. For example, Z 2 If contains carbon atoms, L 1 is Z 2 may be bonded to a carbon atom of

[0077] In one embodiment, AL of Formula 1 1 The precursor of A and L 1 It can be formed by bonding between the precursor of A and the precursor of L. 1 The bond between the precursor of can be achieved through, but is not limited to, a bond via click chemistry, an amide bond, a urea bond, an ester bond, a carbamate bond, a disulfide bond, or a maleimide bond.

[0078] For example, the precursor of A may contain at least one functional group selected from the group consisting of hydroxy, amino, azido, alkynyl, conjugated dienyl, alkenyl, cyclooctynyl, maleimidyl, SO2N3, alkoxysulfinyl, oxiranyl, aziridinyl, oxo, hydrazinyl, hydroxyamino, mercapto, and 1,3-dicarbonyl. 1 The precursor of reacts chemically with the precursor of A to form AL 1 Alternatively, the structure AL 1 A linker precursor having the formula:

[0079] In one embodiment, L 1C optionally contains a divalent or polyvalent functional group in the middle of the chain selected from the group consisting of amide, sulfonamide, amino, ether, carbonyl, triazole, tetrazole, sugar-derived group, sulfoester and dendrimer; 1~200 It can be alkylene. 1~200 The alkylene group is C 1~150 Alkylene group, C 1~100 Alkylene group, C 1~80 Alkylene group, C 1~60 Alkylene group, C 1~50 Alkylene group, C 1~40 Alkylene group, C 1~30 Alkylene group, C 1~20 Alkylene group or C 1~10 The sugar-derived group may be an alkylene group. A sugar-derived group refers to any chemical structure formed by a covalent bond between a sugar molecule and another group. For example, the sugar-derived group may contain a glycosidic bond. A dendrimer refers to an ordered three-dimensional molecular structure having branching units centered around a core. In the field of ligand-drug conjugates, various dendrimer-structured linkers are known (see, for example, Lee et al., Nat. Biotechnol. 2005, 23, 1517-26; Almutairi et al., Proc. Natl. Acad. Sci. 2009, 106, 685-90), which may be beneficial, for example, to increase the ratio of ligand to drug.

[0080] In one embodiment, L 1 When L contains a polyvalent functional group, i.e., 1 When L contains a branched or dendrimer structure, 1 Multiple U's can be bonded to L. 1 The number of Us bonded to can be 1 to 10. In one embodiment, j can be 1 to 5. For example, j can be 1.

[0081] In one embodiment, Z of formula A 1 or Z 3 When contains a nitrogen atom, L 1 may be bonded to a nitrogen atom.

[0082] In one embodiment, L1 is Z 1 ~Z 3 For example, Z 2 is a carbon atom, L 1 is Z 2 In one embodiment, L 1 Functional groups (eg, carboxyl, aminocarbonyl, amino, etc.) for the -U bond may be required as substituents for the carbon atom.

[0083] In one embodiment, L 1 is C 1~10 It may include alkylene, oxyethylene, amide, triazole ring, tetrazole ring, ether, carbonyl, or a combination thereof. In one embodiment, L 1 is -(CH2) na -;-(CH2CH2O) ma -;-(CH2OCH2) mb -;-(OCH2CH2) mc -;-C(=O)-;

[0084] [ka] or a combination thereof, wherein R d is H or C 1~8 It may be alkyl, and na and ma to mc may each independently be an integer of 0 to 10. In one embodiment, na and ma to mc may each independently be an integer of 1 to 8, an integer of 1 to 6, or an integer of 1 to 4. When two or more types of functional groups described above are combined with each other, the order of the functional groups is not limited. In one embodiment, in Formula 1, k can be 1 and AL 1 - is N3-(CH2) n1 -;N3-(CH2CH2O) m1 -(CH2) n2 -;HO-(CH2CH2O) m1 -(CH2) n2 -;H2N-(CH2CH2O) m1-(CH2) n2 -;H2N-O-(CH2CH2O) m1 -(CH2) n2 -;N3-(CH2CH2O) m2 -(CH2) n3 -NR d1 CO-(CH2) n4 -;R a1 NH-(CH2) n5 -;R b1 OC(=O)-(CH2) n6 -;R c1 C≡C-(CH2OCH2) m3 -CONR d2 -(CH2) n7 -;

[0085] [ka] In this case, R a1 , R b1 , R c1 , R c2 and R d1 ~R d5 are each independently H or C 1~8 In one embodiment, n1 to n15 and m1 to m11 can each independently be an integer from 0 to 10. In one embodiment, n1 to n15 and m1 to m11 can each independently be an integer from 0 to 8, an integer from 0 to 6, or an integer from 0 to 5. In one embodiment, n1 to n15 and m1 to m11 can each independently be an integer from 1 to 8, an integer from 1 to 6, or an integer from 1 to 5. Exemplary Compounds of Formula 1 In one embodiment, the compound of the present invention represented by formula 1 may be a compound represented by the following formula:

[0086] [ka] JPEG2025525296000022.jpg197149 In the above formula, A, L 1 ,k,V,R 1 , R2 , R 3 , R 11 , R 12 and PL are as described above with respect to Equation 1.

[0087] The structure A-(L 1 ) k -, V, L 2 , -(X) x -L 3 -and-(Y) y The combinations of -T- are merely illustrative, and compounds of Formula 1 having various combinations thereof can be readily prepared based on the examples set forth below and the disclosure of this application, and it should be understood that all such compounds are within the scope of this application.

[0088] In one embodiment, the compound of the present invention represented by formula 1 may have one PL, for example, the compound of formula 1 may be selected from the group consisting of the compounds shown in the attached Table A.

[0089] In one embodiment, the DAR2 type compound may contain a functional group, such as a maleimide functional group, capable of forming a bond with a ligand, such as an antibody, to prepare a ligand-drug conjugate. Examples of these compounds are shown in the accompanying Table B. DAR4 type compound (formula 1-1) In one embodiment, the linking group L of formula 1 according to the present invention 1 When L has a branched or dendrimer structure (i.e., L 1 is a polyvalent linking group), it is possible to provide a compound of formula 1 to which two or more active agents are attached. In one embodiment, the compound represented by formula 1 can be a compound represented by the following formula 1-1:

[0090] [ka] In formula 1-1, A has the same meaning as in formula 1.

[0091] In Equation 1-1, U 1 and U2 have the same meaning as U in Formula 1, and U 1 and U 2 may be the same or different from each other.

[0092] In Equation 1-1, L 11 and L 12 is the L in Eq. 1 and L 11 and L 12 may be the same or different from each other.

[0093] In Formula 1-1, j is 1 to 10. In one embodiment, j is 1 to 5. For example, j is 1.

[0094] Formula A, L 1 Regarding A and U, the contents of Formula 1 are, if applicable, A, U in Formula 1-1, respectively. 1 and U 2 , and L 11 and L 12 can be applied to In Equation 1-1, L 1a and L 1b are each independently a direct bond;

[0095] [ka] In this case, R e is H or C 1~8 It is alkyl. In formula 1-1, q1, q2, and q3 can each independently be an integer of 0 to 10. In formula 1-1, q4 can be an integer of 1 to 10. Furthermore, L 1a but

[0096] [ka] If q2 is not 0, L 1b but

[0097] [ka] In one embodiment, when L 1a and / or L 1b is a direct bond, and q2 and q3 are 0, L 11 and L 12 linker structures, for example, C optionally containing a bivalent or polyvalent functional group selected from amide, sulfonamide, amino, ether, carbonyl, triazole, tetrazole, sugar-derived group, sulfoester and dendrimer in the middle of the chain; 1~200 The alkylene may be directly bonded to the central N atom.

[0098] In one embodiment, q1 can be an integer from 0 to 8, an integer from 1 to 8, or an integer from 1 to 6. In one embodiment, q2 and q3 can each independently be an integer from 0 to 8, an integer from 0 to 6, or an integer from 0 to 4. In one embodiment, q4 can be an integer from 1 to 8, an integer from 1 to 6, or an integer from 1 to 4. In one embodiment, the compound of formula 1-1 above

[0099] [ka] has the following structure:

[0100] [ka] (q2 and q3 are defined as above). In one embodiment, A in the above formula 1-1 is halogen, OH, C 1~8 Alkoxy, hydroxylamino, COH, C 1~8 Alkylcarbonyl, carboxy, C 1~8 Alkoxycarbonyl, tosyl, tosylate, amino, mono C 1~8 Alkylamino, DiC 1~8 Alkylamino, NHNH2, N3, haloacetamide, maleimidyl, succinimidyl, SH, SO3H, C1~8 alkylsulfonyl,

[0101] [ka] C 1~8 Alkoxysulfonyl, 2-pyridyl disulfide, PO3H2, OPO3H2, -N≡C, -NCS, C 4~10 Dienyl, C 2~8 Alkenyl, C 2~8 Alkynyl, C 4~10 Cycloalkynyl and C 2~8 R may comprise or consist of a functional group selected from the group consisting of alkynylcarbonyl. f are each independently H or C 1~8 For example, A in formula 1-1 can be maleimidyl, hydroxylamino, carboxy, amino, N3, alkynyl, or

[0102] [ka] It could be.

[0103] In one embodiment, L 11 and L 12 each independently optionally containing a divalent or polyvalent functional group in the middle of the chain selected from the group consisting of amide, sulfonamide, amino, ether, carbonyl, triazole, tetrazole, sugar-derived group, sulfoester, and dendrimer; 1~200 It can be alkylene. 1~200 The alkylene group is C 1~150 Alkylene group, C 1~100 Alkylene group, C 1~80 Alkylene group, C 1~60 Alkylene group, C 1~50 Alkylene group, C 1~40 Alkylene group, C 1~30 Alkylene group, C 1~20 Alkylene group or C 1~10 It may be an alkylene group. In one embodiment, L 11and L 12 are each independently -(CH2) na -;-(CH2CH2O) ma -;-(CH2OCH2) mb -;-(OCH2CH2) mc -;-C(=O)-;

[0104] [ka] or a combination thereof, wherein R d , na, ma-mc are as described above with respect to Equation 1. In one embodiment, L 11 and L 12 are each independently -(CH2) n1 -;-(CH2CH2O) m1 -(CH2) n2 -;-(CH2CH2O) m2 -(CH2) n3 -NR d1 CO-(CH2) n4 -;-(CH2CH2O) m10 -(CH2) n15 -CONR d5 -(CH2) n14 -; and

[0105] [ka] Here, n1, n2, n3, n4, n8, n14, and n15, and m1, m2, m8, and m10 can each independently be an integer of 1 to 8, an integer of 1 to 6, or an integer of 1 to 5. In addition, R d1 and R d5 are each independently H or C 1~8 It is alkyl. In one embodiment, the compound of formula 1-1 (j is 1) has the following formula:

[0106] [ka] (In the above formula, q1 to q4, U 1 , U 2 , n1, n3, n4, n8, n14, and n15, and m2, m8, and m10 are as described above with respect to Formula 1-1. d1 , R d5 and R e are each independently H or C 1~8 alkyl) The compound may be represented by the formula: In one embodiment, the compound of formula 1-1 has the following formula:

[0107] [ka] JPEG2025525296000035.jpg72149 The compound may be represented by the formula:

[0108] In the above formula, q1 to q4, n1, n3, n4, n14 and n15, m2 and m10, R d1 , R d5 and R e is as described above. In the above formula, PL has the same meaning as PL in formula 1. In the above formula, Z 1 is NR 3 , a heteroatom selected from O, S and Se. 3 is H or C 1~8 In the above formula, the -O-CO- group of the -O-CO-PL group is an optional self-immolative spacer group and can be absent (i.e., the -PL group is directly linked to the -CH2- group) or replaced with a functional group as described above with respect to the "optional self-immolative spacer group."

[0109] In one embodiment, the compound represented by formula 1-1 may be selected from the compounds listed in the attached Table C. Methods for preparing compounds of formula 1 The compounds containing a self-immolative group of formula 1 according to the present invention can be easily prepared by selecting appropriate solvents, starting materials, intermediates, reaction conditions, etc. based on the examples herein and the technical knowledge of those skilled in the art of organic synthesis.

[0110] In one embodiment, compounds of Formula 1 having an indole core and a β-galactoside-derived group can be prepared according to Reaction Scheme 1 below.

[0111] [ka] In step 1 of Reaction Scheme 1, an indole starting material containing COH and OBn substituted at the para position of the benzene ring is prepared, and AL 1 -X (X is halogen: Cl, Br, etc.) to form AL 1 can be introduced to the nitrogen atom of the indole. In the reaction of Step 1, an additive such as potassium carbonate can be used. Step 1 can be carried out under temperature conditions of 40°C to 100°C, 60°C to 100°C, or 60°C to 90°C.

[0112] In step 2, OBn can be converted to OH using boron trichloride. Step 2 can be carried out under low temperature conditions, for example, at -90°C to 0°C, -90°C to -10°C, -90°C to -20°C, -80°C to 0°C, -80°C to -10°C, or -80°C to -20°C.

[0113] In Step 3, galactose can be introduced when the hydroxyl group is protected with a protecting group (-PG). For example, a protected galactose group, such as an acetogalactoside group, can be introduced by reacting with a protected galactose, such as acetylated galactose or acetobromo-alpha-D-galactose. In Step 3, additives such as benzyltributylammonium chloride, HOBt, pyridine, DIPEA, etc. can be used. Additionally, additives such as silver oxide and molecular sieves can be used. Step 3 can be performed at temperatures between -40°C and 40°C, between -40°C and 30°C, between -20°C and 40°C, between -20°C and 30°C, between -10°C and 40°C, or between -10°C and 30°C.

[0114] In step 4, the COH bonded to the benzene ring can be reduced. The reduction reaction can be carried out using a reducing agent such as sodium borohydride (NaBH) at low temperatures of -40°C to 10°C, -40°C to 0°C, -30°C to 10°C, -30°C to 0°C, -20°C to 10°C, or -20°C to 0°C.

[0115] In Step 5, an -OCO- self-elimination linker structure can be introduced. Bis(4-nitrophenyl)carbonate, 4-nitrophenylchloroformate, etc. can be used as a precursor for the -OCO- linking group. In the reaction of Step 5, additives such as DIPEA and pyridine can be used. Step 5 can be carried out under low-temperature conditions such as -40°C to 10°C, -40°C to 0°C, -30°C to 10°C, -30°C to 0°C, -20°C to 10°C, or -20°C to 0°C.

[0116] In Step 6, PL can be introduced. For example, PL can be introduced by replacing the leaving group (e.g., p-nitrophenyl) linked to -OCO- with a precursor such as PL-H. In the reaction of Step 6, additives such as HOBt, pyridine, and DIPEA can be used depending on the type of PL. Step 6 can be carried out under low-temperature conditions such as -40°C to 10°C, -40°C to 0°C, -30°C to 10°C, -30°C to 0°C, -20°C to 10°C, or -20°C to 0°C.

[0117] In Step 7, the protecting group of the protected galactoside can be deprotected through hydrolysis, thereby converting it to a galactoside. Hydrolysis can be carried out with an acid such as hydrochloric acid or a base such as potassium carbonate, sodium hydroxide, or lithium hydroxide. Step 7 can be carried out at temperatures between -40°C and 40°C, between -40°C and 30°C, between -20°C and 40°C, between -20°C and 30°C, between -10°C and 40°C, or between -10°C and 30°C.

[0118] Each step in Reaction Scheme 1 can be carried out in a suitable solvent selected from the group consisting of organic solvents such as methanol, DMF, MC, ACN, THF, EA, and distilled water. In addition, after the reaction is completed in each step, the product can be purified through dilution, extraction, and chromatography using a suitable solvent. In one embodiment, each step in Reaction Scheme 1 can be carried out under a nitrogen atmosphere.

[0119] In one embodiment, P.L., A., L. 1 Depending on the formula and V, some steps in Reaction Scheme 1 can be omitted. For example, if PL can react with a hydroxymethyl group directly linked to a benzene ring even in the absence of -OCO- or can be bonded to a methyl group, step 5 can be omitted. A ligand-drug conjugate represented by formula 2 In one aspect of the present invention, a compound of Formula 2:

[0120] [ka] (In Formula 2, E is a ligand or protein with receptor binding properties) or a pharmaceutically acceptable salt thereof. The compounds of Formula 1 according to the present invention can be conjugated to a ligand or protein (E) having receptor binding properties to provide a ligand-drug conjugate of Formula 2. The ligand or protein (E) can be optionally modified to conjugate to the binding functional group of the compound of Formula 1. In one embodiment, when the ligand E is an antibody, -SH of cysteine, -NH2 of lysine, -C(=O)NH2 of glutamine, -CH4-OH of tyrosine, -SeH of selenocysteine, and -N3 and -N4 of unnatural amino acids present at specific positions of the antibody can be used.

[0121] [ka] and the linking functional group of the compound of Formula 1 may be linked to one another. In the field of ligand-drug conjugates, the types and modifications of functional groups on the ligand for linking linker-drug moieties to the ligand or protein are known in the art.

[0122] The ligand may be selected from the group consisting of a peptide, a tumor cell-specific peptide, a tumor cell-specific aptamer, a tumor cell-specific carbohydrate, a tumor cell-specific monoclonal or polyclonal antibody, and an antibody fragment.

[0123] In one embodiment, the protein is C 1~20 It may be selected from the group consisting of a hydrocarbyl, an oligopeptide, a polypeptide, an antibody, a fragment of an antigenic polypeptide, and an artificial antibody (Repebody). In one embodiment, the C-terminus of the protein may be a light or heavy chain of an antibody.

[0124] In one embodiment, the antibody may be selected from the group consisting of an intact polyclonal antibody, an intact monoclonal antibody, an antibody fragment, a single-chain Fv (scFv) variant, a multispecific antibody, a bispecific antibody, a chimeric antibody, a humanized antibody, a human antibody, a fusion protein comprising an antigenic determinant of an antibody, and other modified immunoglobulin molecules comprising an antigen recognition site.

[0125] In one embodiment, the antibody is selected from the group consisting of muromonab-CD3, abciximab, rituximab, daclizumab, palivizumab, infliximab, trastuzumab (herceptin), etanercept, basiliximab, gemtuzumab, alemtuzumab, ibritumomab, adalimumab, alefacept, omalizumab, efalizumab, tositumomob-I131, cetuximab, bevacizumab, natalizumab, ranibizumab, panitumumab, eculizumab, rilonacept, certolizumab pegol, romiplostim, AMG-531 (romiplostim), CNTO-148 (golimumab), CNTO-1275 (ustekinumab), ABT874 (briakinumab), LEA-29Y (belatacept), belimumab, TACI-Ig (transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin), second-generation anti-CD20, ACZ-885 (canakinumab), tocilizumab, atlizumab, mepolizumab, pertuzumab, Humax CD20 (ofatumumab), tremelimumab (CP-675 206), ticilimumab, MDX-010 (ipilimumab), IDEC-114 (galiximab), inotuzumab, Humax EGFR (zalutumumab), aflibercept (VEGF Trap-Eye), Humax-CD4 (zanolimumab), Ala-Ala (hOKT3 gamma 1), otelixizumab (ChAglyCD3; TRX4), catumaxomab, MT-201 (adecatumumab), pregovomab (Pr egovomab), CH-14.18 (dinutuximab), WXG250 (dilentuximab), AMG-162 (denosumab), AAB-001 (bapineuzumab), motavizumab, MEDI524 (motavizumab), Efumgumab, Aurograb®, raxibacumab, third generation anti-CD20, LY2469298 (ocaratuzumab), and veltuzumab.

[0126] In one embodiment, the antibody may be a monoclonal antibody (mAb).

[0127] In Formula 2 above, A' is a divalent linking group derived from the linking functionality (A) of Formula 1. For example, A' may include a functional group formed by an addition reaction of a double bond contained in the linking functionality. In one embodiment, when the linking functionality is maleimidyl, A' may be a functional group formed by participating in an addition reaction of a double bond in the five-membered ring of maleimidyl. The subject matter discussed above regarding the linking functionality (A) of Formula 1 can be similarly applied to A', if applicable.

[0128] In one embodiment, the ligand E can be an antibody. For example, the antibody can contain a functional group that binds to A in Formula 1 to form the E-A' bond structure in Formula 2. If necessary, the functional group for the above-mentioned binding can be introduced into the antibody, and the types of such functional groups and methods for introducing functional groups are known in the art. In one embodiment, the bond structure of ligands E and A′ can be represented by a moiety represented by one of the following formulas: * can be the remainder of the antibody. In the formula below, * The S, NH, CONH, CH-OH, Se, and triazole ring moieties that directly bind to the ligand E are -SH of cysteine, -NH2 of lysine, -C(=O)NH2 of glutamine, -CH-OH of tyrosine, -SeH of selenocysteine, and -N3 and -N4 of unnatural amino acids present at specific positions in the ligand E.

[0129] [ka] It can come from parts like:

[0130] [ka] In Equation 2, n can be a real number from 1 to 10. For example, n can be a real number from 1 to 6, a real number from 1 to 4, or a real number from 1 to 2.

[0131] In Equation 2, U and L 1 , k and j are U, L in Eq. 1, k, and j in the above formula 1. 1 , k and j, where applicable, are the U, L of Equation 2. 1 , k, and j. In one embodiment, when E in the above formula 2 is an antibody and PL of U is a drug, the compound represented by formula 2 can be provided as an antibody-drug conjugate. In one embodiment, the conjugate represented by Formula 2 has the following formula:

[0132] [ka] The conjugate may be selected from the group consisting of:

[0133] In the above formula, mAb represents an antibody moiety. In the above formula, m5, m6, m9, m10, n9, n10, n13, n14, and n15 can each independently be an integer of 1 to 10. In one embodiment, m5, m6, m9, m10, n9, n10, n13, n14, and n15 can each independently be an integer of 1 to 8, an integer of 1 to 6, an integer of 1 to 5, an integer of 1 to 4, or an integer of 1 to 3. In the above formula, R d3 and R d5 are each independently H or C 1~8 It is alkyl. In the above formula, Z 1 is NR 3 , a heteroatom selected from O, S and Se. 3 is H or C 1~8 In the above formula, PL has the same meaning as PL in Formula 1. In the above formula, the -O-CO- group of the -O-CO-PL group is an optional self-immolative spacer group and may be absent (i.e., the -PL group is directly linked to the -CH2- group), or may be -S(=O)2-,

[0134] [ka] (In the above formula, R 10 ~R12 are each independently H, C 1~8 Alkyl, Amino-C 1~8 Alkyl, mono- or di-(C 1~8 Alkyl)amino-substituted C 1~8 Alkyl, or -(CH2CH2O) g R 13 and R 13 is H or C 1~4 alkyl, and g is an integer of 1 to 10).

[0135] In the above formula, n is a real number from 1 to 10. In one embodiment, n can be a real number from 1 to 8, a real number from 1 to 6, a real number from 1 to 4, or a real number from 1 to 2. In one embodiment, the conjugate represented by Formula 2 has the following formula:

[0136] [ka] JPEG2025525296000044.jpg169149 The conjugate may be selected from the group consisting of:

[0137] In the above formula, mAb represents an antibody portion. In the above formula, n is a real number from 1 to 10. In one embodiment, n can be a real number from 1 to 8, a real number from 1 to 6, a real number from 1 to 4, or a real number from 1 to 2. Exemplary DAR2 Type Ligand-Drug Conjugates In one embodiment, the compound represented by Formula 2 can be selected from the compounds listed in the attached Table D. The specific n values listed in Table D can vary from real numbers between 1 and 10. For example, n can be a real number between 1 and 8, a real number between 1 and 6, a real number between 1 and 4, or a real number between 1 and 2. DAR4-type ligand-drug conjugate (Formula 2-1) In one embodiment, the linking group L of formula 2 according to the present invention 1 When L has a branched or dendrimer structure (i.e., L 1is a polyvalent linking group), a ligand-drug conjugate of formula 2 can be provided to which multiple active agents are attached. In one embodiment, the compound of formula 2 can be represented by the following formula 2-1:

[0138] [ka] The ligand-drug conjugate may be represented by the formula:

[0139] In Formula 2-1, E is a ligand or protein with receptor binding properties, and A' is a divalent linking group derived from the binding functionality (A) of Formula 1. With respect to E and A', the subject matter described in Formula 2 can also be similarly applied to Formula 2-1.

[0140] In Equation 2-1, U 1 and U 2 have the same meaning as U in Formula 1, and U 1 and U 2 may be the same or different. 11 and L 12 is the L in Eq. 1 and L 11 and L 12 may be the same or different from each other.

[0141] In formula 2-1, j is 1 to 10. In one embodiment, j is 1 to 5. For example, j is 1.

[0142] Formula A, L 1 Regarding U, the subject matter described in Formula 1 is A, U in Formula 2-1, respectively. 1 and U 2 , and L 11 and L 12 In addition, U 1 and U 2 , and L 11 and L 12 With respect to the above, the subject matter described in formula 1-1 can be similarly applied to formula 2-1. In Equation 2-1, L1a and L 1b are each independently a direct bond;

[0143] [ka] In this case, R e is H or C 1~8 It is alkyl. In formula 2-1, q1, q2, and q3 can each independently be an integer of 0 to 10. In formula 2-1, q4 can be an integer of 1 to 10. Furthermore, L 1a but

[0144] [ka] If q2 is not 0, L 1b but

[0145] [ka] If , then q3 is not 0.

[0146] In one embodiment, q1 can be an integer from 0 to 8, an integer from 1 to 8, or an integer from 1 to 6. In one embodiment, q2 and q3 can each independently be an integer from 0 to 8, an integer from 0 to 6, or an integer from 0 to 4. In one embodiment, q4 can be an integer from 1 to 8, an integer from 1 to 6, or an integer from 1 to 4.

[0147] L 1a and L 1b , q1, q2, q3, and q4, the subject matter described in Equation 1-1 can be similarly applied to Equation 2-1.

[0148] In Formula 2-1, n can be a real number from 1 to 10. In one embodiment, n can be a real number from 1 to 6, a real number from 1 to 4, or a real number from 1 to 2. In one embodiment, the ligand-drug conjugate represented by formula 2-1 has the following formula:

[0149] [ka] (In the above formula, mAb is the antibody portion. In the above formula, q1-q4, n, U 1 and U 2 , R d1 , R d5 , R e , n1, n3, n4, n8, n14 and n15, m2, m8 and m10 are as described above with respect to Formula 1-1 or Formula 2-1). The conjugate may be represented by the formula: In one embodiment, the ligand-drug conjugate represented by formula 2-1 has the following formula:

[0150] [ka] JPEG2025525296000051.jpg74149 The conjugate may be represented by the formula:

[0151] In the above formula, mAb is the antibody moiety. In the above formula, q1 to q4, n1, n3, n4, n14 and n15, m2 and m10, R d1 , R d5 and R e is as described above with respect to Formula 1-1. In the above formula, PL has the same meaning as PL in Formula 1. In the above formula, Z 1 is a heteroatom selected from N, O, S, and Se. In the above formula, the -O-CO- group of the -O-CO-PL group is an optional self-immolative spacer group and can be absent (i.e., the -PL group is directly linked to the -CH2- group) or replaced with a functional group as described above with respect to the "optional self-immolative spacer group."

[0152] In one embodiment, the ligand-drug conjugate represented by Formula 2-1 can be selected from the compounds listed in the attached Table E. The specific n values listed in Table E can vary between real numbers ranging from 1 to 10. For example, n can be between 1 and 6, between 1 and 4, or between 1 and 2. definition As used herein, the term "hydrocarbyl" refers to a functional group composed of carbon and hydrogen and refers to a saturated, partially unsaturated, or fully unsaturated straight-chain, branched-chain, or cyclic hydrocarbon. Hydrocarbyls can include alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, etc. Non-limiting examples of hydrocarbyls can include methyl, ethyl, propyl, butyl, ethenyl, propenyl, butenyl, ethynyl, propynyl, butynyl, etc.

[0153] The term "alkyl" refers to a fully saturated branched or unbranched (or straight or linear) hydrocarbon. Alkyl can be substituted or unsubstituted alkyl. 1~8 Alkyl can be C1-C6, C1-C5, C1-C4, C1-C3, or C1-C2 alkyl. Non-limiting examples of alkyl can include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, n-pentyl, isopentyl, neopentyl, isoamyl, or n-hexyl.

[0154] The term "alkenyl" includes straight- or branched-chain alkenyl having 2 to 6 carbon atoms, 2 to 5 carbon atoms, or 2 to 4 carbon atoms, including one or more double bonds at any position. For example, alkenyl can include vinyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, and the like.

[0155] The term "alkynyl" refers to a straight or branched hydrocarbon chain having at least one triple bond. Alkynyl is preferably a straight or branched chain having 2 to 8 carbon atoms, and examples of alkynyl may include 2-propynyl, 3-butynyl, 2-butynyl, 4-pentynyl, 3-pentynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 3-octynyl, etc.

[0156] The term "alkoxy" refers to an alkyl linked to an oxygen atom. For example, a C1-C8 alkoxy can be a C1-C6, C1-C5, C1-C4, C1-C3, or C1-C2 alkoxy. An alkoxy can be methoxy, ethoxy, or propoxy.

[0157] The term "cycloalkyl" includes mono- or polycyclic saturated carbocyclic rings containing 3 to 8 carbon atoms. Examples may include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like.

[0158] The term "cycloalkenyl" includes non-aromatic monocyclic or polycyclic rings having from 3 to 8 carbon atoms and containing at least one carbon-carbon double bond. Examples can include cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and the like.

[0159] The term "cycloalkynyl" refers to a monocyclic or polycyclic unsaturated hydrocarbon ring having 4 to 10 carbon atoms and containing at least one triple bond. Examples include monocyclic alkynyl groups such as cyclooctynyl and cyclodecynyl. In its broadest sense, "cycloalkynyl" includes structures in which one or more carbon atoms of a hydrocarbon ring containing at least one triple bond between carbon atoms are replaced with a heteroatom such as N.

[0160] The term "dienyl" refers to an unsaturated branched or unbranched C alkyl group having two double bonds between two adjacent carbon atoms. 4~10Refers to an aliphatic substituent. Examples include, but are not limited to, 2,4-pentadienyl, 2,4-hexadienyl, 4-methyl-2,4-pentadienyl, and the like.

[0161] The term "halogen" refers to atoms in Group 17 of the periodic table. Halogen atoms include fluorine, chlorine, bromine, and iodine.

[0162] The term "haloalkyl" refers to an alkyl substituted with one or more halogen atoms.

[0163] The term "hydroxy" refers to an OH functional group (hydroxyl group).

[0164] The term "mercapto" refers to an SH functionality.

[0165] The term "cyano" is CN and refers to a functional group consisting of a triple bond between a carbon atom and a nitrogen atom.

[0166] The term "oxo" refers to =O and "oxo-substituted" means that a carbon atom has an =O substituent in the form -C(=O)-.

[0167] The term "nitro" refers to NO2.

[0168] The term "amino" refers to -NH2.

[0169] The term "alkylamino" refers to a functional group in which one or two hydrogen atoms of an amino (-NH2) are replaced with one or two of the alkyls described above, and includes both monoalkylamino and dialkylamino, where the two alkyls in a dialkylamino may be the same or different. Specifically, monoC 1~8 Alkylamino is an amino (-NH2) group in which one hydrogen atom is C 1~8 may be substituted with alkyl, diC 1~8 Alkylamino is an amino (-NH2) group in which the two hydrogen atoms are the same or different C 1~8It may be substituted with alkyl. For example, mono C 1~8 Alkylamino (-NH(C 1~8 Alkyl)) can include methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino, tert-butylamino, pentylamino, hexylamino, and the like. 1~8 Alkylamino (-N(C 1~8 Alkyl)2) can include, for example, dimethylamino, diethylamino, dipropylamino, methylethylamino, methylpropylamino, methylisopropylamino, methylbutylamino, methylisobutylamino, ethylpropylamino, ethylisopropylamino, ethylisobutylamino, isopropylisobutylamino, methylhexylamino, ethylhexylamino, and the like.

[0170] The term "carboxy" refers to --COOH.

[0171] The term "carbamoyl" refers to -CONH2.

[0172] The term "N-mono C 1~8 Alkylcarbamoyl" and "N,N-diC 1~8 "Alkylcarbamoyl" refers to a group in which one or both hydrogen atoms bonded to the nitrogen atom of carbamoyl (-CONH2) are C 1~8 Refers to alkyl-substituted N,N-diC 1~8 In alkylcarbamoyl, two C 1~8 The alkyls may be the same or different from each other.

[0173] The term "alkanoyl" refers to an alkyl, as defined above, with the specified number of carbon atoms attached through a carbonyl bridge (i.e., -(C=O)-alkyl). For example, alkanoyl includes methanoyl (formyl: -COH), ethanoyl (acetyl: -COCH), propanoyl (-COCHCH), butanoyl (-CO(CH)CH), and the like.

[0174] The term "alkanoylamino" refers to an amino substituted with an alkanoyl group (i.e., -NH(C=O)-alkyl). The nitrogen atom of an alkanoylamino can be substituted with a further substituent, such as an alkyl group. For example, alkanoylamino includes formylamino (-NHCOH), acetylamino (-NHCOCH), propanoylamino (-NHCOCHCH), butanoylamino (-NHCO(CH)CH), and the like.

[0175] The term "cyano-C" 1~8 Alkyl, Halo-C 1~8 Alkyl, Hydroxy-C 1~8 Alkyl," "C 1~8 Alkoxy-C 1~8 Alkyl," "C 1~8 Alkoxy-C 1~8 Alkoxy-C 1~8 Alkyl, Carboxy-C 1~8 Alkyl, Amino-C 1~8 Alkyl, Carbamoyl-C 1~8 Alkyl, N-mono C 1~8 Alkylcarbamoyl-C 1~8 Alkyl" and "N,N-diC 1~8 Alkylcarbamoyl-C 1~8 "Alkyl" refers to C substituted at the end or in the middle with cyano, halogen, hydroxy, alkoxy, carboxy, amino, carbamoyl, 1~8 Refers to alkyl. N-mono C 1~8 Alkylcarbamoyl and N,N-diC 1~8 Alkylcarbamoyl.

[0176] The term "glycosidyl" refers to a functional group formed in the condensation reaction of sugar molecules.

[0177] The term "heterocyclyl" refers to a saturated or partially unsaturated cyclic hydrocarbon containing at least one heteroatom. Heterocyclyl ring groups can be monocyclic or bicyclic. Bicyclic heterocyclyls can be spiro, bridged, or fused ring groups. Heterocyclyls can contain 3 to 20 ring atoms, 3 to 10 ring atoms, 3 to 8 ring atoms, 3 to 7 ring atoms, 3 to 6 ring atoms, 4 to 9 ring atoms, 4 to 8 ring atoms, 4 to 7 ring atoms, or 4 to 6 ring atoms. The heteroatom can be any one or more selected from the group consisting of N, O, and S. The heteroatom can be 1 to 3, 1, or 2 heteroatoms selected from the group consisting of N, O, and S.

[0178] Non-limiting examples of heterocyclyl can include aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, dihydropyridinyl, tetrahydropyridinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dihydrofuranyl, dihydropyranyl, tetrahydrothiophenyl, morpholinyl, thiomorpholinyl, azepanyl, diazepanyl, oxazepanyl, thiazepanyl, and the like.

[0179] The term "heterocyclyloxy" refers to a functional group in which an oxygen atom is directly attached to the ring of a heterocycle.

[0180] The term "heteroaryl" or "heteroarylene" refers to a monocyclic or bicyclic aromatic moiety containing one or more heteroatoms selected from the group consisting of N, O, and S, with the remaining ring atoms being carbon. A heteroaryl group can contain, for example, 1 to 4 heteroatoms, 1 to 3 heteroatoms, or 1 or 2 heteroatoms. A heteroaryl group can contain 5 to 10 ring elements, 5 to 7 ring elements, or 5 or 6 ring elements. A heteroaryl can be a 5- to 6-membered heteroaryl containing one or two N, O, or S atoms. A heteroaryl group can be a monocyclic, bicyclic, or tricyclic group. A bicyclic group can be a spirocyclic, bridged, or fused ring group.

[0181] Non-limiting examples of "heteroaryl" include pyrrolyl, imidazolyl, pyrazolyl, pyridazinyl, furanyl, pyranyl, thienyl, thiophenyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, oxazol-2-yl, and oxazol-4-yl. -yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, tetrazolyl, pyrid-2-yl, pyrid-3-yl, 2-pyrazin-2-yl, pyrazin-4-yl, pyrazin-5-yl, 2-pyrimidin-2-yl, 4-pyrimidin-2-yl, 5-pyrimidin-2-yl, indolyl, and the like.

[0182] The term "binding functionality" refers to a functional group that can form a covalent bond through addition, substitution, condensation reaction, etc. with a functional group contained in a ligand or protein, or a functional group contained in a linker precursor.

[0183] As used herein, the term "moiety" refers to the portion of a compound that corresponds to the parent compound of the moiety when the parent compound is attached to a compound of Formula 1 or a conjugate of Formula 2. Even when a portion of a whole compound is referred to herein as a compound or active agent, it is understood in the context that this refers to a "portion" of the compound or active agent.

[0184] In the present invention, "precursor" refers to a compound as a reactant that ultimately provides a desired moiety through chemical reaction or the like.

[0185] In the present invention, the term "linker precursor" refers to a compound that forms a desired linker structure or a part thereof through a chemical reaction. For example, various PEG linkers are known, such as hydroxy-PEG linkers, alkynyl-PEG linkers, bromo-PEG linkers, DBCO-PEG linkers, azide-PEG linkers, amino-PEG linkers, and maleimide-PEG linkers. In addition, linker compounds such as aminooxy-PEG linkers, tetrazine-PEG linkers, tosylate-PEG linkers, thiol-PEG linkers, aldehyde-PEG linkers, phosphonate-PEG linkers, hydrazide-PEG linkers, iodo-PEG linkers, and carboxyl-PEG linkers are also widely used in related fields. As another example, various linkers having a DBCO (dibenzocyclooctyne) group are known, such as amine-reactive DBCO (DBCO-NHS, DBCO-sulfo-NHS ester, DBCO-PEG-NHS ester, DBCO-NHCO-PEG-NHS ester, etc.), carboxyl / carbonyl-reactive DBCO (DBCO-amine, DBCO-PEG-amine, etc.), -SH group-reactive DBCO (DBCO-maleimide, DBCO-PEG-maleimide, etc.), DBCO-PEG-t-butyl ester, DBCO-alcohol, DBCO-PEG-alcohol, DBCO-PEG-DBCO, and bis-DBCO-PEG. The linker precursor of the present invention includes various linkers known in the field of ligand-conjugates and is not limited to the linker structures exemplified herein. Usable linker precursors, preparation methods, reaction conditions, etc. are well known in the relevant fields.

[0186] The term "dendrimer" refers to an ordered three-dimensional molecular structure with branching units centered around a core.

[0187] The term "1,6-elimination reaction" refers to a reaction in which the cleavage of a covalent bond occurs at a specific position in the molecular structure of a compound, resulting in the cleavage of the covalent bond at a distance of five atoms (1,6 relationship).

[0188] In one embodiment, compounds of Formula 1 having an indole core and a β-galactoside inducing group can undergo PL synthesis via a 1,6-elimination reaction when β-galactose is separated from galactosidase. - Or it can release PL-H.

[0189] [ka] Additionally, when the compound of Formula 1 contains the optional self-immolative group T, the β-galactose and 4-hydroxybenzyl alcohol can be separated to form PL by, for example, a 1,6-elimination reaction as shown in Reaction Scheme B below. - Or it can release PL-H.

[0190] [ka] Additionally, when the compound of Formula 1 contains a self-eliminating linker such as -OCO-, the β-galactose and CO2 can be separated to form PL via a 1,6-elimination reaction, for example, as shown in Reaction Scheme C below. - Or it can release PL-H.

[0191] [ka] In this application, the term "click chemistry" refers to a general term for molecular assembly reactions using modular reactants that specifically react with each other even under mild conditions, such as room temperature and pressure. The types of click chemistry reactions and the functional groups involved in click chemistry reactions are generally well known. For example, click chemistry reactions include, but are not limited to, [3 + 2] cycloadditions, thiol-ene reactions, Diels-Alder reactions, inverse electron demand Diels-Alder reactions, [4 + 1] cycloadditions, etc. More specifically, click chemistry reactions include, but are not limited to, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), strain-promoted azide-alkyne cycloaddition (SPAAC), strain-promoted alkyne-nitrone cycloaddition (SPANC), [3 + 2] cycloadditions of alkenes and azides, inverse electron demand Diels-Alder reactions of alkenes and tetrazines, photoclick reactions of alkenes and tetrazoles, and Huisgen cycloadditions of azides and alkynes. Click chemistry functional groups include, but are not limited to, alkynes, cycloalkynes, cyclooctynes, and cyclononynes (e.g., cycloalkynes such as bicyclo[6.1.0]-non-4-yn-9-ylmethanol), trans-cyclooctene, nitrones, nitrile oxides, azides, conjugated dienes, dienophiles, and cycloalkynes such as cyclooctynes, cyclononynes, dibenzocyclooctynes (DIBO), BARAC (biarylazacyclooctynone), ALO (aryllessoctyne), DIFO (difluorinated cyclooctyne), MOFO (monofluorinated), DIBAC (dibenzo-aza-cyclooctyne), and DIMAC (dimethoxyazacylooctyne). For example, click chemistry functional groups can include acetylene, transcyclooctene, cyclooctyne, diarylcyclooctyne, methyl ester phosphine, norbornene, tetrazine, methylcyclopropene, azetine, cyanide, azide, dibenzocyclooctyne, and the like. Medical Uses and Pharmaceutical Compositions The compound of formula 1 or the ligand-drug conjugate of formula 2 of the present invention can have excellent stability in various blood environments, i.e., the active agent can maintain a stable binding state in the plasma environments of mice, rats, dogs, and humans, thereby minimizing blood toxicity.

[0192] In addition, the compounds of Formula 1 or the ligand-drug conjugates of Formula 2 of the present invention can exhibit excellent target cell selectivity and excellent active agent release properties. The compounds and conjugates of the present invention can rapidly dissociate and release the active agent by reacting with enzymes such as galactosidase and glucuronidase under pH conditions of 4 to 5. Therefore, the compounds of the present invention can effectively release the active agent in the environment within target cells (e.g., tumor lysosomes).

[0193] In one aspect of the present invention, there is provided a pharmaceutical composition comprising a compound comprising a self-immolative group of Formula 1 or Formula 1-1 or a Ligand-Drug Conjugate of Formula 2 or Formula 2-1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0194] In another aspect of the present invention, there is provided an imaging or detecting composition comprising a compound comprising a self-immolative group of Formula 1 or Formula 1-1 or a ligand-drug conjugate of Formula 2 or Formula 2-1, or a pharmaceutically acceptable salt thereof.

[0195] A compound according to the present invention comprising a self-immolative group of Formula 1 or Formula 1-1 and a ligand-drug conjugate of Formula 2 or Formula 2-1 can be mixed with a solvent and provided as a composition.

[0196] The composition can be prepared in an injectable form as a liquid solution or suspension. In addition, the composition can be prepared in a solid form suitable for injection as an emulsion or a polypeptide encapsulated in a liposome. The compound or ligand-drug conjugate of the present invention can be combined with a pharmaceutically acceptable carrier, including any carrier that does not induce the production of antibodies harmful to the subject receiving the carrier. Suitable carriers can typically include slowly metabolized macromolecules such as proteins, polysaccharides, polylactic acids, polyglycolic acids, amino acid polymers, amino acid copolymers, lipid aggregates, etc. Proteins can be formulated into vaccines in neutral or salt form.

[0197] The composition may contain a diluent such as water, saline, glycerol, ethanol, etc. Auxiliary substances such as wetting or emulsifying agents, pH buffering agents, etc. may be added to the composition. The composition may be administered parenterally by injection, or via subcutaneous or intramuscular injection. Further formulations may be provided, for example, as suppositories or oral preparations. Oral compositions may be provided as solutions, suspensions, tablets, pills, capsules, or sustained-release formulations.

[0198] The composition can be administered in a manner compatible with the dosage form. The composition comprises a therapeutically effective amount of a compound or ligand-drug conjugate according to the present invention. A therapeutically effective amount refers to a dose, either in a single dose or in a multiple administration schedule, that is effective for treating or preventing a disease or disorder. The dose administered is determined by the type of active agent contained in the compound or ligand-drug conjugate of the present invention and / or the type of ligand or protein that binds to the receptor. In addition, the dose administered may vary depending on the health and physical condition of the subject being treated, the desired degree of protection, and other relevant factors.

[0199] For example, a therapeutically effective amount of a compound or ligand-drug conjugate of the present invention or a pharmaceutical composition comprising the same can be used to treat or prevent a proliferative disease, an autoimmune disease, or an infectious disease.

[0200] For example, the compositions can be used to treat cancer or tumors. For example, the compositions can be administered to a patient to treat or prevent infection by a pathogen (e.g., a virus, bacteria, fungus, parasite, etc.). These methods include administering to a mammal a therapeutic or prophylactic amount of a compound or conjugate sufficient to treat the disease or disorder or a symptom thereof, under conditions such that the disease or disorder is prevented or treated.

[0201] In the above-mentioned compositions, the compound or conjugate of the present invention may be administered in the form of its pharmaceutically acceptable salt, hydrate, or solvate. In one embodiment, it may be administered with a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and / or a pharmaceutically acceptable additive. The pharmaceutically effective amount and type of pharmaceutically acceptable salt or solvate, excipient, and additive can be determined using standard methods (see Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, 18th Edition, 1990).

[0202] As used herein, the term "pharmaceutically acceptable salt" includes organic and inorganic salts. Examples include, but are not limited to, hydrochloride, hydrobromide, iodate, sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantonate, bitartrate, ascorbate, succinate, maleate, genticinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and pamoate (i.e., 1,1'-methylene-bis(2-hydroxy-3-naphthoate)) salts. A pharmaceutically acceptable salt may contain another molecule, such as an acetate ion, a succinate ion, or other counterion, and may also contain one or more charged atoms or one or more counter ion.

[0203] Exemplary solvates that can be used in the pharmaceutically acceptable solvates of the above compounds include, but are not limited to, solvates of water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid, or ethanolamine. [Example]

[0204] The present invention will be described in more detail below through examples, but these examples are for illustrative purposes only and do not limit the scope of the present invention to these examples. Abbreviations used herein are as follows, and abbreviations not listed in the abbreviation list below have their meanings commonly used in the field of organic synthesis: AcO: acetyl AcOH: acetic acid EA: Ethyl acetate MC: methylene chloride DMF: dimethylformamide EDCI: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide EDC: N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride HOBt: 1-hydroxybenzotriazole hydrate ACN: acetonitrile THF: tetrahydrofuran DCC: N,N'-dicyclohexylcarbodiimide DMAP: 4-dimethylaminopyridine NHS: N-hydroxysuccinimide DIPEA: Disopropylethylamine TEA: Triethylamine Boc: tert-butyloxycarbonyl LAH: Lithium aluminum hydride TFA: Trifluoroacetic acid AgOTf: silver trifluoromethanesulfonate KO t Bu: potassium tert-butoxide MMAF-OMe: Monomethyl auristatin F methyl ester PPTS: Pyridinium p-toluenesulfonate TBAI: Tetrabutylammonium iodide Preparation Example 1: Preparation of Linker P-1

[0205] [ka] Step 1: Preparation of Compounds P-1b and P-1c Compound P-1a (tetraethylene glycol, Daejung Chemicals & Metals, CAS No. 112-60-7, 30 g, 154.46 mmol) was dissolved in MC (300 mL) at 0 °C under a nitrogen atmosphere. 4-Methylbenzenesulfonyl chloride (14.7 g, 77.23 mmol) and potassium hydroxide (4.3 g, 77.23 mmol) were then added, and the mixture was stirred at room temperature for 16 h. After completion of the reaction, the organic layer was extracted twice with MC (500 mL) and distilled water (500 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compounds P-1b and P-1c, respectively, in the form of colorless oils (P-1b: 4.4 g, 11%, P-1c: 15.1 g, 56%). P-1b: 1 H-NMR(400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 4H),7.34 (d, J = 8.0 Hz, 4H), 4.16 - 4.14 (m, 4H), 3.69 - 3.66 (m, 4H), 3.57 - 3.55(m, 8H), 2.44 (s, 6H). P-1c: 1 H-NMR(400 MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H),7.34 (d, J = 8.0 Hz, 2H), 4.18 - 4.15 (m, 2H), 3.72 - 3.59 (m, 14H), 2.45 (s,3H). Step 2: Preparation of compound P-1d Compound P-1b (8.78 g, 17.48 mmol) was dissolved in DMF (50 mL) at room temperature under a nitrogen atmosphere, and then sodium azide (3.41 g, 52.44 mmol) was added, and the mixture was stirred at 60 °C for 16 h. After completion of the reaction, the mixture was cooled to room temperature, and EA (500 mL) and saturated aqueous sodium bicarbonate solution (500 mL) were added to extract the organic layer twice. The organic layer obtained was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound P-1d (4.17 g, 97%) in the form of a colorless liquid. 1 H-NMR(400 MHz, CDCl3) δ 3.69 - 3.66 (m, 12H),3.40 - 3.37 (m, 4H). Step 3: Preparation of linker P-1 Compound P-1d (4.17 g, 17.06 mmol) was dissolved in EA (32 mL), diethyl ether (32 mL), and 5% aqueous hydrochloric acid (64 mL) under a nitrogen atmosphere at 0 °C. Triphenylphosphine (4.47 g, 17.06 mmol) was then added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the mixture was concentrated under reduced pressure to remove the organic layer. The process of adding MC (100 mL) to the aqueous layer and washing the aqueous layer was then repeated three times. The resulting aqueous layer was concentrated under reduced pressure to obtain linker P-1 in the form of a colorless liquid (4.12 g, 95%). 1 H-NMR(400 MHz, CDCl3) δ 8.27 (brs, 2H), 3.86 -3.83 (m, 2H), 3.72 - 3.68 (m, 10H), 3.47 - 3.45 (m, 2H), 3.26 - 3.24 (m, 2H). Preparation Example 2: Preparation of Linker P-2

[0206] [ka] Step 1: Preparation of compound P-2a Compound P-1c (15.1 g, 43.34 mmol) prepared in Step 1 of Preparation Example 1 was dissolved in DMF (100 mL) at room temperature under a nitrogen atmosphere. Sodium azide (4.2 g, 65.01 mmol) was then added, and the mixture was stirred at 60 °C for 16 hours. After completion of the reaction, the mixture was cooled to room temperature, and EA (800 mL) and distilled water (800 mL) were added to extract the organic layer five times. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound P-2a (6.11 g, 64%) in the form of a colorless liquid. 1 H-NMR(400 MHz, CDCl3) δ 3.73 - 3.66 (m, 12H),3.62 - 3.60 (m, 2H), 3.41 - 3.39 (m, 2H). Step 2: Preparation of compound P-2b Compound P-2a (3.82 g, 17.44 mmol) was dissolved in THF (50 mL) at 0° C. under a nitrogen atmosphere, and then KO t Bu (2.93 g, 26.16 mmol) was added, and the mixture was stirred at 0 ° C. for 20 minutes. Then, propargyl bromide (5.2 g, 34.88 mmol) was added, and the mixture was stirred for 16 hours while the temperature was gradually raised from 0 ° C. to room temperature. After completion of the reaction, the reaction solution was diluted with EA (200 mL), extracted by adding distilled water (250 mL) to the solution, and filtered using Celite filter material. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was subjected to column chromatography to obtain compound P-2b in the form of an orange liquid (2.97 g, 66%). 1 H-NMR(400 MHz, CDCl3) δ 4.21 (d, J = 2.4 Hz, 2H),3.70 - 3.67 (m, 14H), 3.40 - 3.38 (m, 2H), 2.43 (t, J = 2.4 Hz, 1H). Step 3: Preparation of linker P-2 Compound P-2b (2.97 g, 11.54 mmol) was dissolved in EA (24 mL), diethyl ether (24 mL), and 5% aqueous hydrochloric acid (48 mL) under a nitrogen atmosphere at 0° C., and then triphenylphosphine (3.03 g, 11.54 mmol) was added. The mixture was stirred for 16 hours while gradually increasing the temperature from 0° C. to room temperature. After completion of the reaction, the reaction solution was concentrated under reduced pressure to remove the organic solvent. Then, MC (100 mL) was added to the remaining aqueous solution to extract and remove the organic layer. The resulting aqueous layer was concentrated under reduced pressure to obtain linker P-2 in the form of a yellow liquid (2.66 g, 86%). 1 H-NMR(400 MHz, DMSO-d6) δ 7.93 (brs, 2H), 4.14(d, J = 2.4 Hz, 2H), 3.62 - 3.52 (m, 14H), 3.44 (t, J = 2.4 Hz, 1H), 2.96 -2.95 (m, 2H). Preparation Example 3: Preparation of Linker P-3

[0207] [ka] Step 1: Preparation of compound P-3a Compound P-2a (2.27 g, 10.35 mmol) prepared in Step 1 of Preparation Example 2 was dissolved in MC (52 mL) at room temperature under a nitrogen atmosphere. Then, TEA (4.3 mL, 31.06 mmol) and 4-methylbenzenesulfonyl chloride (3.95 g, 20.71 mmol) were added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted three times with MC (100 mL) and distilled water (100 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound P-3a in the form of a yellow liquid (2.52 g, 65%). 1H-NMR(400 MHz, CDCl3) δ 7.80 (d, J = 8.0 Hz, 2H),7.34 (d, J = 8.0 Hz, 2H), 4.16 (t, J = 4.8 Hz, 2H), 3.70 - 3.59 (m, 12H), 3.37(t, J = 4.8 Hz, 2H), 2.45 (s, 3H). Step 2: Preparation of linker P-3 Compound P-3a (2.52 g, 6.76 mmol) was dissolved in THF (33 mL) at room temperature under a nitrogen atmosphere, and then lithium bromide (1.76 g, 20.29 mmol) was added. The mixture was refluxed and stirred for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, and EA (150 mL) and aqueous sodium bicarbonate solution (150 mL) were added to extract the organic layer twice. The organic layer obtained was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound P-3 in the form of a yellow liquid (1.8 g, 94%). 1 H-NMR (400MHz, CDCl3) δ 3.81 (t, J = 6.4 Hz, 2H),3.69-3.67 (m, 10H), 3.47 (t, J = 6.4 Hz, 2H), 3.39 (m, 2H). Preparation Example 4: Preparation of Linker P-4

[0208] [ka] Step 1: Preparation of compound P-4b Compound P-4a (pentaethylene glycol, Merck, CAS No. 4792-15-8, 10 g, 41.97 mmol) was dissolved in MC (60 mL) at 0 °C under a nitrogen atmosphere, and then 4-methylbenzenesulfonyl chloride (17.60 g, 92.33 mmol) and lithium hydroxide monohydrate (8.80 g, 209.85 mmol) were added, and the mixture was stirred at room temperature for 12 h. After completion of the reaction, the organic layer was extracted twice with MC (200 mL) and distilled water (200 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound P-4b in the form of a colorless oil (22.5 g, 98%). 1 H-NMR(400 MHz, CDCl3) δ 7.79 (d, J = 8.0 Hz, 4H),7.34 (d, J = 8.0 Hz, 4H), 4.14 (t, J = 4.8 Hz, 4H), 3.68 (t, J = 4.8 Hz, 4H),3.60 (s, 4H), 3.58 (s, 8H), 2.44 (s, 6H). Step 2: Preparation of compound P-4c Compound P-4b (22.5 g, 41.16 mmol) was dissolved in ACN (200 mL) at room temperature under a nitrogen atmosphere, and then sodium azide (6.69 g, 102.89 mmol) was added, and the mixture was stirred at 80 ° C. for 15 hours. After completion of the reaction, the mixture was cooled to room temperature, the precipitate was removed by filtration using diethyl ether (100 mL), and the remaining filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound P-4c in the form of a colorless liquid (8.72 g, 73.5%). 1 H-NMR (400MHz, CDCl3) δ 3.69-3.66 (m, 16H), 3.39 (t, J =4.8 Hz, 4H). Step 3: Preparation of linker P-4 Compound P-4c (8.72 g, 30.25 mmol) was dissolved in EA (48 mL) and diethyl ether (48 mL) at 0 °C under a nitrogen atmosphere, and then 5% aqueous hydrochloric acid (96 mL) and triphenylphosphine (8.73 g, 33.28 mmol) were added dropwise in succession. The reaction solution was stirred for 15 hours while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, the organic layer was removed, and the remaining aqueous layer was washed again with EA (50 mL). The resulting aqueous layer was concentrated under reduced pressure to give linker P-4 in the form of a colorless oil (7.8 g, 86.3%). 1 H-NMR(400 MHz, CDCl3) 8.21 (brs, 2H), 3.90 (t, J = 4.8 Hz, 2H), 3.74-3.66(m, 14H), 3.51 (t, J = 4.8 Hz, 2H), 3.21 (m, 2H). Preparation Example 5: Preparation of Linker P-5

[0209] [ka] Step 1: Preparation of compound P-5a Linker P-1 (3.36 g, 13.19 mmol) was dissolved in 1,4-dioxane (44 mL) at 0 °C under a nitrogen atmosphere. Sodium bicarbonate (2.21 g, 26.38 mmol) and di-tert-butyl ether (Boc anhydride, 3.45 g, 15.83 mmol) dissolved in distilled water (22 mL) were then added, and the mixture was stirred at room temperature for 5 h. After completion of the reaction, EA (350 mL) and distilled water (300 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound P-5a in the form of a colorless liquid (3.68 g, 87%). 1H-NMR(400 MHz, CDCl3) δ 5.02 (brs, 1H), 3.70 -3.60 (m, 10H), 3.54 (t, J = 5.2 Hz, 2H), 3.39 (t, J = 5.2 Hz, 2H), 3.32 - 3.31(m, 2H), 1.44 (s, 9H). Step 2: Preparation of compound P-5b THF (70 mL) was added dropwise to sodium hydride (60% dispersion in mineral oil, 924 mg, 23.10 mmol) at 0 °C under a nitrogen atmosphere. Compound P-5a (3.68 g, 11.55 mmol) dissolved in THF (30 mL) was slowly added to the reaction solution, and the mixture was stirred at 0 °C for 30 min. Iodomethane (7.19 mL, 115.52 mmol) was slowly added to the reaction solution, and the mixture was stirred for 30 min. The temperature was then gradually raised to room temperature and stirred for another 16 h. After completion of the reaction, the mixture was cooled to 0 °C, and distilled water (350 mL) and EA (350 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound P-5b (3.74 g, 97%) in the form of a yellow liquid. 1 H-NMR(400 MHz, CDCl3) δ 3.69 - 3.62 (m, 12H),3.41 - 3.38 (m, 4H), 2.91 (s, 3H), 1.45 (s, 9H). Step 3: Preparation of linker P-5 Compound P-5b (3.74 g, 11.27 mmol) was dissolved in MC (20 mL) under a nitrogen atmosphere at 0 °C, and then a 4 M hydrochloric acid solution (4 M HCl in 1,4-dioxocane, 40 mL) was added, and the mixture was stirred at room temperature for 1.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure to obtain linker P-5 in the form of a yellow liquid (3.33 g, 99%). 1H-NMR(400 MHz, CDCl3) δ 9.45 (brs, 1H), 3.91 (t,J = 5.2 Hz, 2H), 3.72 - 3.68 (m, 10H), 3.44 (t, J = 5.2 Hz, 2H), 3.20 - 3.17(m, 2H), 2.76 (t, J = 5.2 Hz, 3H). Preparation Example 6: Preparation of Linker P-6

[0210] [ka] Compound P-6a (triethylene glycol monomethyl ether, TCI, CAS number 112-35-6, 1 g, 6.09 mmol) was dissolved in THF (10 mL) at 0° C. under a nitrogen atmosphere, followed by KO t Bu (1 g, 9.13 mmol) was added, and the mixture was stirred at 0 °C for 20 min. Propargyl bromide (1.3 mL, 12.18 mmol) was added to the reaction solution, and the mixture was stirred for 16 h while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, the reaction solution was diluted with EA (200 mL), extracted by adding distilled water (250 mL) to the solution, and filtered using Celite. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain linker P-6 (820 mg, 66%). 1 H-NMR(400 MHz, CDCl3) δ 4.21 (d, J = 2.4 Hz, 2H),3.71 - 3.63 (m, 10H), 3.56 - 3.54 (m, 2H), 3.38 (s, 3H), 2.42 (t, J = 2.4 Hz,1H). Preparation Example 7: Preparation of Linker P-7

[0211] [ka] Step 1: Preparation of compound P-7b Sodium hydride (60% dispersion in mineral oil, 411 mg, 10.29 mmol) was added to THF (10 mL) under a nitrogen atmosphere at 0 °C. Compound P-7a (tetraethylene glycol, Merck, CAS No. 112-60-7, 6.0 g, 30.89 mmol) dissolved in THF (20 mL) was slowly added dropwise, and the mixture was then stirred for 5 min. Propargyl bromide (80% in toluene, 1.146 mL, 10.29 mmol) was added to the reaction solution, and the mixture was stirred for another 2 h at 0 °C. After completion of the reaction, MC (200 mL) and distilled water (100 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound P-7b in the form of an oil (1.9 g, 79.8%). 1 H-NMR(400 MHz, CDCl3) δ 4.21 (d, J = 2.4 Hz, 2H),3.72-3.67 (m, 14H), 3.61 (t, J = 4.4 Hz, 2H), 2.61 (brs, 1H), 2.43 (t, J = 2.4Hz, 1H). Step 2: Preparation of compound P-7c Compound P-7b (1.0 mg, 4.3 mmol) was dissolved in acetone (30 mL), and Jones reagent (Merck, CAS No. 65272-70-0, 3 mL) was then slowly added at -5 °C. The mixture was stirred at room temperature for 3 h. After completion of the reaction, the green inorganic salts were removed by filtration, and the remaining filtrate was extracted with MC (100 mL) and distilled water (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound P-7c (630 mg, 59.4%). 1 EI-MS m / z: 246[M+H] + . Step 3: Preparation of linker P-7 Compound P-7c (90 mg, 0.365 mmol) was dissolved in MC (5 mL) under a nitrogen atmosphere at 0 °C, and then NHS (46.2 mg, 0.40 mmol) and DCC (83 mg, 0.40 mmol) were added, and the mixture was stirred for 16 hours. After completion of the reaction, EA / n-pentane (volume ratio 1:1, 20 mL) was added, and the resulting precipitate was removed by filtration. The filtrate was concentrated, and then EA / n-pentane (volume ratio 1:1, 20 mL) solution was added again, the resulting precipitate was removed, and the filtrate was concentrated under reduced pressure. The resulting linker P-7 (100 mg, 80%) was used in the next reaction without further purification. 1 H-NMR(400 MHz, CDCl3) δ 4.53 (s, 2H), 4.20 (d, J= 2.4 Hz, 2H), 3.81-3.79 (m, 2H), 3.75-3.67 (m, 10H), 2.85 (s, 4H), 2.43 (t, J= 2.4 EI-MS m / z: 366 [M+Na] + . Preparation Example 8: Preparation of Linker P-8

[0212] [ka] P-8a (2-[2-(2-aminoethoxy)ethoxy]acetic acid, TCI, CAS number 134978-97-5, 1.28 g, 7.87 mmol) was dissolved in 1,4-dioxane (30 mL) at 0 °C under a nitrogen atmosphere. Sodium bicarbonate (1.32 g, 15.74 mmol) and di-tert-butyl ether (Boc anhydride, 2.06 g, 9.44 mmol) dissolved in distilled water (15 mL) were then added sequentially. The mixture was stirred for 16 h while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, the organic layer was extracted five times with EA (200 mL), distilled water (150 mL), and 2 N aqueous hydrochloric acid (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to give linker P-8 in the form of a colorless liquid (2.32 g, quantitatively obtained). 1 H-NMR(400 MHz, CDCl3) δ 4.93 (brs, 1H), 4.17 (s,2H), 3.78 - 3.76 (m, 2H), 3.68 - 3.65 (m, 2H), 3.62 - 3.56 (m, 2H), 3.38 - 3.32(m, 2H), 1.45 (s, 9H). Preparation Example 9: Preparation of auristatin F-OMe

[0213] [ka] The compound MMAF-OMe (CAS No. 863971-12-4, 1 g, 1.34 mmol) was dissolved in DMF (7 mL) at room temperature under a nitrogen atmosphere. Then, 37% aqueous formaldehyde solution (37% by weight in HO, 299 μL, 4.02 mmol) and acetic acid (1.53 mL, 26.81 mmol) were added sequentially, and the mixture was stirred at room temperature for 30 min. Sodium cyanoborohydride (NaCNBH, 168.5 mg, 2.68 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 2.5 h. After completion of the reaction, saturated aqueous sodium bicarbonate solution was slowly added dropwise until the pH of the reaction solution reached 9. EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give auristatin F-OMe in the form of a white solid (892 mg, 88%); EI-MS m / z: 761.0 [M+H] + . Preparation Example 10: Preparation of Compound L3-1

[0214] [ka] Step 1: Preparation of compound L3-1b Compound L3-1a (4-hydroxybenzaldehyde, CAS No. 123-08-0, 300 mg, 2.46 mmol) was dissolved in ACN (10 mL) at 0 °C under a nitrogen atmosphere. Then, acetobromo-alpha-D-galactose (Merck, CAS No. 3068-32-4, 1.1 g, 2.70 mmol), molecular sieves (100 mg), and silver(I) oxide (1.42 g, 6.14 mmol) were added sequentially, and the mixture was stirred at room temperature for 3 h. After completion of the reaction, the reaction solution was diluted with EA (100 mL), filtered through Celite, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound L3-1b in the form of a white solid (951 mg, 86%). 1 H-NMR(400 MHz, CDCl3) δ 9.93 (s, 1H), 7.86 (d, J= 8.4 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 5.47 (m, 2H), 5.15 (m, 2H), 4.17 (m,3H), 2.19 (s, 3H), 2.07 (s, 6H), 2.02 (s, 3H). Step 2: Preparation of compound L3-1c Compound L3-1b (951 mg, 2.1 mmol) was dissolved in THF (20 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (159 mg, 4.2 mmol) was added, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, distilled water (100 mL) was added to quench the reaction, and EA (100 mL) was added to extract the organic layer three times. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound L3-1c in the form of a white solid (695 mg, 73%). 1 H-NMR(400 MHz, CDCl3) 7.31 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H),5.46 (m, 2H), 5.04 (m, 2H), 4.66 (s, 2H), 4.17 (m, 3H), 2.19 (s, 3H), 2.07 (s,6H), 2.01 (s, 3H). Step 3: Preparation of compound L3-1 Compound L3-1c (800 mg, 1.76 mmol) was dissolved in MC (10 mL) at 0 °C under a nitrogen atmosphere, and then thionyl chloride (191 μL, 2.64 mmol) was added. The mixture was stirred for 2 h while the temperature was raised from 0 °C to room temperature. After completion of the reaction, the mixture was diluted by adding MC (10 mL) and then concentrated under reduced pressure. The organic layer of the residue obtained by concentration under reduced pressure was extracted twice with EA (50 mL) and distilled water (50 mL). The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to obtain compound L3-1 in the form of a colorless viscous oil (831 mg, 99%). 1 H-NMR(400 MHz, CDCl3) 7.32 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H),5.51 - 5.45 (m, 2H), 5.11 (dd, J = 10.4, 3.6 Hz, 1H), 5.04 (d, J = 7.6 Hz, 1H),4.56 (s, 2H), 4.25 - 4.14 (m, 3H), 2.18 (s, 3H), 2.06 (s, 6H), 2.01 (s, 3H). Preparation Example 11: Preparation of Compound PL-1

[0215] [ka] Step 1: Preparation of compound PL-1b A solution of compound PL-1a (carbobenzyloxy-L-valine, Z-Val-OH, Merck, CAS number 1149-26-4, 5 g, 19.9 mmol) dissolved in THF (20 mL) was slowly added to a reaction solution of 60% sodium hydride (60% dispersion in mineral oil, 3.4 g, 85.56 mmol) in THF (50 mL) under a nitrogen atmosphere at 0 °C. The mixture was stirred at 0 °C for 20 min. Iodomethane (12.38 mL, 198.98 mmol) was then slowly added, and the mixture was stirred at room temperature for 20 h. The reaction solution was cooled to 0 °C, and the reaction was quenched by the addition of distilled water (150 mL). The organic layer was extracted twice with EA (200 mL) and 2 N aqueous hydrochloric acid (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to column chromatography to give compound PL-1b (3.7 g, 70%). 1 H-NMR(400 MHz, DMSO-d6) δ 7.36-7.30 (m, 5H), 5.11(s, 2H), 4.22-412 (m, 1H), 2.84-81 (m, 3H), 2.11 (m, 1H), 0.95 (m, 3H), 0.82 (m,3H). Step 2: Preparation of compound PL-1d Compound PL-1b (600 mg, 2.26 mmol) and compound PL-1c (N-methylaniline, Merck, CAS number 100-61-8, 361 mg, 3.39 mmol) were dissolved in MC (12 mL) at 0 °C under a nitrogen atmosphere. DCC (700 mg, 3.39 mmol), DMAP (55.2 mg, 0.46 mmol), and DIPEA (0.78 mL, 4.52 mmol) were then added sequentially, and the mixture was stirred at 0 °C for 20 min. The reaction mixture was stirred for an additional 16 h. After completion of the reaction, the reaction solution was diluted with EA (100 mL), and the filtered solution was extracted with 2 N aqueous hydrochloric acid (100 mL). The organic layer obtained by adding 2 N aqueous sodium hydroxide (100 mL) was extracted again and then washed with saturated aqueous sodium chloride (100 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound PL-1d (429 mg, 53%) in the form of a colorless oil. 1 H-NMR(400 MHz, CDCl3) δ 7.41 - 7.24 (m, 6H), 7.09- 7.02 (m, 4H), 5.01-4.96 (m, 2H), 4.40-4.28 (m, 1H), 3.25 (s, 3H), 2.91-2.87(m, 3H), 2.33 (m, 1H), 0.90 (d, J = 6.8 Hz, 3H), 0.74-0.65 (m, 3H). Step 3: Preparation of compound PL-1 Compound PL-1d (429 mg, 1.21 mmol) was dissolved in methanol (50 mL) at room temperature under a nitrogen atmosphere, and then 5% palladium on carbon (5% Pd / C, 150 mg) was added, and the mixture was stirred under a hydrogen atmosphere for 2 hours. After completion of the reaction, the reaction solution was diluted with EA (100 mL), filtered through Celite filter material, and concentrated under reduced pressure to give compound PL-1 (264.3 mg, 99%) as a colorless oil. 1H-NMR(400 MHz, CDCl3) δ 7.45 - 4.41 (m, 2H), 7.37- 7.34 (m, 1H), 7.02 - 7.18 (m, 2H), 3.31 (s, 3H), 2.85 (d, J = 6.4 Hz, 1H),2.31 (s, 3H), 1.71 (m, 1H), 0.85 (d, J = 6.8 Hz, 3H), 0.80 (d, J = 6.8 Hz, 3H). Preparation Example 12: Preparation of Compound PL-2

[0216] [ka] Compound PL-2a (SN-38, 7-ethyl-10-hydroxycamptothecin, ASTATECH, CAS No. 86639-52-3, 30.0 mg, 0.076 mmol) was dissolved in MC (6.0 mL) under a nitrogen atmosphere, and then 4-nitrophenyl chloroformate (23.1 mg, 0.114 mmol), DIPEA (13.3 μL, 0.076 mmol), and pyridine (18.4 μL, 0.229 mmol) were added sequentially. The mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL). The reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL). The mixture was then separated and purified using preparative HPLC and lyophilized to obtain compound PL-2 in the form of a white solid (7.5 mg, 17%); EI-MS m / z: 558 [M+H]. + . Preparation Example 13: Preparation of Compound PL-3

[0217] [ka] Compound PL-3a (abiraterone, TCI, CAS number 154229-19-3, 30.0 mg, 0.086 mmol) was dissolved in THF (3.0 mL) under a nitrogen atmosphere, and then carbonyldiimidazole (CDI, Alfa Aesar, CAS number 530-62-1, 17.2 mg, 0.105 mmol) was added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, EA (10 mL) and distilled water (10 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound PL-3 in the form of a white solid (16.0 mg, 42%). 1 H-NMR (400MHz, CDCl3) δ 8.62 (s, 1H), 8.46 (d, J = 4.8Hz, 1H), 8.13 (s, 1H), 8.13 (s, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H),7.22 (dd, J = 8.0 Hz, J = 4.8 Hz, 1H), 7.06 (s, 1H), 6.00 (s, 1H), 5.49 (d, J =4.8 Hz, 1H), 4.85 - 4.83 (m, 1H), 2.54 - 2.52 (m, 2H), 2.29 - 2.25 (m, 1H),2.08 - 2.04 (m, 4H), 1.97 - 1.81 (m, 1H), 1.80 - 1.48 (m, 9H), 1.26 - 1.22 (m,1H), 1.13 (s, 3H), 1.06 (s, 3H). Preparation Example 14: Preparation of Core C-1

[0218] [ka] Step 1: Preparation of compound C-1b Compound C-1a (2-benzyloxybenzaldehyde, CAS number 5896-17-3, 5.48 g, 25.8 mmol) was dissolved in methanol (55 mL) at −30° C. under a nitrogen atmosphere, and then ethyl azidoacetate (CAS number 637-81-0, TCI, 28.2 mL, 258.20 mmol) and sodium methoxide (25% by weight in MeOH, 44.6 mL, 206.4 mmol) were added slowly. The mixture was stirred at −30° C. for 3 hours, and then distilled water (100 mL) was added dropwise to quench the reaction. EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give compound C-1b (7.74 g, 97%). The resulting compound C-1b was used in the next reaction without further purification. Step 2: Preparation of compound C-1c Compound C-1b (7.74 g, 25.02 mmol) was dissolved in xylene (200 mL) at room temperature under a nitrogen atmosphere, and the mixture was then stirred at 150° C. for 3 hours. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-1c (510.8 mg, 22.7%). 1 H-NMR (400MHz, CDCl3) δ 8.82 (brs, 1H), 7.51-7.49 (m,2H), 7.42-7.33 (m, 4H), 7.22 (t, J = 8 Hz, 1H), 7.02 (d, J = 8 Hz, 1H), 6.58(d, J = 8 Hz, 1H), 5.22 (s, 2H), 3.92 (s, 3H). Step 3: Preparation of compound C-1d Compound C-1c (1.14 g, 4.05 mmol) was dissolved in DMF (35 mL) at room temperature under a nitrogen atmosphere. Potassium carbonate (1.68 g, 12.15 mmol) and iodomethane (0.65 mL, 10.53 mmol) were then added sequentially, and the mixture was stirred for 12 hours. After completion of the reaction, EA (100 mL) and distilled water (100 mL) were added to extract the organic layer. Distilled water (300 mL) was added to extract the resulting organic layer again. The organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-1d (912.7 mg, 76%). 1 H-NMR(400 MHz, CDCl3) δ 7.50-7.47 (m, 3H),7.42-7.33 (m, 3H), 7.25 (m, 1H), 6.99 (d, J = 8 Hz, 1H), 6.57 (d, J = 8 Hz,1H), 5.22 (s, 2H), 4.06 (s, 3H), 3.89 (s, 3H). Step 4: Preparation of compound C-1e C-1d (800 mg, 2.70 mmol) was dissolved in MC (40 mL) at −50 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (735 μL, 8.10 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 8.1 mL, 8.1 mmol) were then added sequentially and slowly. The mixture was stirred for 2 h while maintaining the temperature. After completion of the reaction, the reaction was quenched by the dropwise addition of chilled distilled water (100 mL). EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-1e (392 mg, 44.8%). 1H-NMR(400 MHz, CDCl3) δ 10.10 (s, 1H), 7.81 (d, J= 8.4 Hz, 1H), 7.44 (s, 1H), 7.49-7.47 (m, 2H), 7.44-7.36 (m, 3H), 6.69 (d, J =8.4 Hz, 1H), 5.39 (s, 2H), 4.36 (s, 3H), 3.90 (s, 3H). Step 5: Preparation of Core C-1 Compound C-1e (393.2 mg, 1.22 mmol) was dissolved in MC (20 mL) at -50 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl3 in MC, 6 mL, 6.08 mmol) was slowly added, and the mixture was stirred for 1.5 h while the temperature was gradually raised to -30 °C. After completion of the reaction, distilled water (100 mL) was slowly added dropwise to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction mixture. MC (100 mL) was added to the mixture to extract the organic layer four times. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-1 in the form of a pale orange solid (239.7 mg, 84%). 1 H-NMR(400 MHz, DMSO-d6) δ 9.99 (s, 1H), 7.79 (m,1H), 7.43 (s, 1H), 6.55 (m, 1H), 4.22 (s, 3H), 3.84 (s, 3H). Preparation Example 15: Preparation of Core C-2

[0219] [ka] Step 1: Preparation of compound C-2b Compound C-2a (2-nitro-m-cresol, TCI, CAS number 4920-77-8, 20 g, 130.59 mmol) was dissolved in ACN (250 mL) at 0 °C under a nitrogen atmosphere, and then benzyl chloride (15.78 mL, 137.12 mmol) and potassium carbonate (22.56 g, 163.24 mmol) were added, and the mixture was stirred at 80 °C for 16 h. After completion of the reaction, EA (200 mL) and distilled water (300 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-2b in the form of a light yellow oil (31.76 g, 99%). 1 H-NMR(400 MHz, CDCl3) δ 7.37-7.31 (m, 5H), 7.24(m, 1H), 6.89-6.83 (m, 2H), 5.15 (s, 2H), 2.31 (s, 3H). Step 2: Preparation of compound C-2c KO t Bu (15.35 g, 136.82 mmol) was dissolved in THF (100 mL) and diethyl ether (300 mL) at room temperature under a nitrogen atmosphere, and diethyl oxalate (Merck, CAS No. 95-92-1, 19.46 mL, 143.34 mmol) was added. The mixture was then stirred for 15 minutes. Compound C-2c (31.7 g, 31.7 mmol) dissolved in THF (50 mL) was slowly added to the above reaction solution, and the mixture was stirred at room temperature for 19 hours and then at 80 °C for another 3 hours. After completion of the reaction, the reaction solution was cooled to room temperature, and diethyl ether (200 mL) was added dropwise. The resulting precipitate was filtered, washed with diethyl ether (100 mL), and then dried to obtain compound C-2c in the form of a light orange solid (41.5 g, 83%). 1H-NMR(400 MHz, DMSO-d6) δ 8.66 (d, J = 8 Hz, 1H),7.40-7.30 (m, 5H), 7.04 (t, J = 8 Hz, 1H), 6.50 (d, J = 8 Hz, 1H), 5.15 (s,1H), 5.10 (s, 2H), 3.99 (q, J = 7.2 Hz, 2H), 1.17 (t, J = 7.2 Hz, 3H). Step 3: Preparation of compound C-2d Iron powder (57.1 g, 1.02 mol) was slowly added to acetic acid (200 mL) at room temperature under a nitrogen atmosphere. Compound C-2c (39 g, 102.24 mmol) dissolved in acetic acid (150 mL) was added with stirring, and the mixture was stirred at 80 °C for 6 h. After completion of the reaction, the temperature of the reaction solution was lowered to 45 °C, EA (500 mL) was added dropwise, and the mixture was stirred for another 30 min. The filtrate obtained through celite filtration was concentrated under reduced pressure. EA (300 mL) was added to the concentrate thus obtained, and the resulting precipitate was filtered again. The filtrate was concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound C-2d in the form of a light yellow solid (22.18 g, 73%). 1 H-NMR(400 MHz, CD3OD-d4) 7.57-7.55 (m, 2H), 7.43-7.39 (m, 2H),7.36-7.32 (m, 1H), 7.23 (d, J = 8 Hz, 1H), 7.15 (s, 1H), 6.98 (t, J = 8 Hz,1H), 6.83 (d, J = 7.6 Hz, 1H), 5.29 (s, 2H), 4.39 (q, J = 7.2 Hz, 2H), 1.42 (t,J = 7.2 Hz, 3H). Step 4: Preparation of compound C-2e Compound C-2d (6 g, 20.31 mmol) was dissolved in DMF (30 mL) at 0 °C under a nitrogen atmosphere. Potassium carbonate (4.21 g, 30.46 mmol) and iodomethane (1.64 mL, 26.40 mmol) were then added sequentially, and the mixture was stirred at 0 °C for 1 h. The reaction temperature was raised to room temperature, and the mixture was stirred for 12 h. The mixture was then stirred at 60 °C for an additional 3 h to complete the reaction. The reaction solution was cooled to room temperature, and EA (200 mL) and distilled water (400 mL) were added to extract the organic layer. Distilled water (300 mL) was added to extract the organic layer again. The extracted organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The obtained C-2e (6.28 g, 99%) was used in the next reaction without further purification. 1 H-NMR(400 MHz, CDCl3) δ 7.49-7.47 (m, 2H),7.42-7.39 (m, 2H), 7.37-7.33 (m, 1H), 7.25-7.23 (m, 2H), 6.99 (t, J = 8 Hz,1H), 6.77 (d, J = 7.6 Hz, 1H), 5.18 (s, 2H), 4.37 (s, 3H), 4.35 (q, J = 7.2 Hz,2H), 1.40 (t, J = 7.2 Hz, 3H). Step 5: Preparation of compound C-2f Compound C-2e (500 mg, 1.61 mmol) was dissolved in MC (20 mL) at −30 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (Merck, CAS No. 4885-02-3, 438 μL, 4.83 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 4.85 mL, 4.83 mmol) were then added sequentially and slowly. The mixture was stirred for 1 h while maintaining the temperature. After completion of the reaction, chilled distilled water (100 mL) was slowly added dropwise to quench the reaction, and EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-2f (495 mg, 94%). 1H-NMR(400 MHz, CD3OD-d4) δ 9.96 (s,1H), 7.91 (s, 1H), 7.67 (d, J = 8 Hz, 1H), 7.57-7.55 (m, 2H), 7.47-7.37 (m,3H), 7.08 (d, J = 8 Hz, 1H), 5.37 (s, 2H), 4.39-4.36 (m, 5H), 1.42 (t, J = 7.2Hz, 3H). Step 6: Preparation of Core C-2 Compound C-2f (300 mg, 0.89 mmol) was dissolved in ethanol (8 mL) and THF (4 mL) at room temperature. Lithium hydroxide monohydrate (75 mg, 1.78 mmol) dissolved in distilled water (3 mL) was then slowly added dropwise, and the mixture was stirred at 50 °C for 30 min. The reaction solution was cooled, and then 1N aqueous hydrochloric acid (10 mL), distilled water (50 mL), and EA (100 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to obtain core C-2 (275 mg, 99%), which was used in the next reaction without further purification. 1 H-NMR (400 MHz, acetone-d₄) δ 10.06 (s, 1H), 8.03 (s, 1H), 7.71 (d, J = 8 Hz, 1H), 7.65-7.63 (m, 2H), 7.49-7.38 (m, 3H), 7.15 (d, J = 8 Hz, 1H), 5.45 (s, 2H), 4.41 (s, 3H). Preparation Example 16: Preparation of Core C-3

[0220] [ka] Step 1: Preparation of compound C-3b Compound C-3a (benzo[b]thiophen-4-ol, Ambeed, CAS No. 3610-02-4, 500 mg, 3.35 mmol) was dissolved in 10% aqueous potassium hydroxide solution (410 mg in 4 mL of HO) at 0 °C under a nitrogen atmosphere. Glyoxylic acid monohydrate (300 mg) was then added, and the mixture was stirred for 7 h. After completion of the reaction, the mixture was diluted with distilled water (2 mL), and 2 N aqueous hydrochloric acid was slowly added dropwise to adjust the pH of the reaction solution to 7. The organic layer was extracted with diethyl ether (10 mL) and removed. 2 N aqueous hydrochloric acid was slowly added dropwise to the aqueous layer to adjust the pH to 2, and the mixture was extracted three times with diethyl ether (100 mL). The organic layer was collected, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to give compound C-3b (460 mg, 61.6%). 1 H-NMR(400 MHz, CDCl3) δ 7.51 (d, J = 5.6 Hz, 1H),7.36 (d, J = 5.6 Hz, 1H), 7.24 (d, J = 8 Hz, 1H), 6.72 (d, J = 8 Hz, 1H), 5.41(s, 1H). Step 2: Preparation of Core C-3 Compound C-3b (450 mg, 2.0 mmol) was dissolved in ethanol (0.8 mL) at room temperature under a nitrogen atmosphere. Ferric sulfate hydrate (923 mg, 2.3 mmol) and 0.4 N aqueous sulfuric acid (3.8 mL) were then added sequentially, and the mixture was stirred at 60 °C for 1 hour. After completion of the reaction, the reaction temperature was lowered to room temperature, and the reaction solution was filtered using EA (100 mL). Distilled water (100 mL) was added to the filtrate to extract the organic layer, which was then dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-3 (210 mg, 58%). 1 H-NMR(400 MHz, CDCl3) δ 10.01 (s, 1H), 7.74 (d, J= 8 Hz, 1H), 7.60 (d, J = 5.6 Hz, 1H), 7.52 (d, J = 5.6 Hz, 1H), 6.88 (d, J = 8Hz, 1H). Preparation Example 17: Preparation of Core C-4

[0221] [ka] Step 1: Preparation of compound C-4b Compound C-4a (benzo[b]thiophen-4-ol, Ambeed, CAS No. 3610-02-4, 1.14 g, 7.63 mmol) was dissolved in ACN (50 mL) at 0 °C under a nitrogen atmosphere. Potassium carbonate (2.63 g, 19.07 mmol) and benzyl bromide (1 mL, 8.39 mmol) were then added slowly, and the mixture was stirred at 0 °C for 30 min. The reaction temperature was raised to room temperature, and the mixture was stirred for another 16 h. After completion of the reaction, EA (350 mL) and distilled water (350 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-4b (1.87 g, 99%) in the form of a light orange oil. 1 H-NMR(400 MHz, CDCl3) δ 7.57 (d, J = 5.6 Hz, 1H),7.50 - 7.47 (m, 3H), 7.42 - 7.38 (m, 2H), 7.35 - 7.32 (m, 2H), 7.27 - 7.23 (m,1H), 6.81 (d, J = 8 Hz, 1H), 5.22 (s, 2H). Step 2: Preparation of compound C-4c Compound C-4b (1.87 g, 7.8 mmol) was dissolved in THF (60 mL) at room temperature under a nitrogen atmosphere. The solution was cooled to -78 °C, and then n-butyllithium solution (2.5 M n-BuLi in hexane, 1.42 mL, 3.56 mmol) was slowly added dropwise. The mixture was stirred at the same temperature for 30 min. DMF (0.78 mL) was slowly added to the mixture, and the mixture was stirred at the same temperature for another 30 min. Distilled water (300 mL) was added to the mixture at the same temperature to quench the reaction, and then EA (300 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-4c (1.36 g, 65%) in the form of a light yellow oil. 1 H-NMR(400 MHz, CDCl3) δ 10.06 (s, 1H), 8.25 (s,1H), 7.50 - 7.37 (m, 7H), 6.85 (d, J = 7.6 Hz, 1H), 5.24 (s, 2H). Step 3: Preparation of Core C-4 Compound C-4c (300 mg, 1.11 mmol) was dissolved in MC (20 mL) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl in MC, 2.2 mL, 2.20 mmol) was slowly added, and the mixture was stirred for 30 min. After completion of the reaction, EA (10 mL) and distilled water (10 mL) were slowly added dropwise at −50 °C to quench the reaction. EA (100 mL) and distilled water (100 mL) were added at room temperature to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-4 in the form of a light tan solid (174 mg, 87.4%). 1 H-NMR(400 MHz, DMSO-d6) δ 10.62 (brs, 1H), 8.41(s, 1H), 7.46 (d, J = 8 Hz, 1H), 7.39 (t, J = 8 Hz, 1H), 6.82 (d, J = 8 Hz,1H). Preparation Example 18: Preparation of Core C-5

[0222] [ka] Step 1: Preparation of compound C-5a Compound C-4c (1.36 g, 5.09 mmol) prepared in Step 2 of Preparation Example 17 was dissolved in methanol (65 mL) at 0 °C under a nitrogen atmosphere. Potassium hydroxide (713 mg, 12.72 mmol) dissolved in methanol (15 mL) and iodine (1.67 g, 6.61 mmol) dissolved in methanol (15 mL) were then added sequentially and slowly. The mixture was then stirred at room temperature for 1 hour. After completion of the reaction, the organic layer was extracted with EA (500 mL) and distilled water (500 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound C-5a (1.43 g, 94%) in the form of an ivory solid. 1 H-NMR(400 MHz, CDCl3) δ 8.28 (s, 1H), 7.49 - 7.47(m, 2H), 7.44 - 7.34 (m, 5H), 6.82 (d, J = 7.6 Hz, 1H), 5.21 (s, 2H), 3.93 (s,3H). Step 2: Preparation of compound C-5b Compound C-5a (240 mg, 0.80 mmol) was dissolved in MC (15 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (218 μL, 2.41 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 2.41 mL, 2.41 mmol) were then added sequentially and slowly. The mixture was stirred for 1 h while maintaining the temperature. After completion of the reaction, distilled water (100 mL) was slowly added dropwise to quench the reaction. EA (100 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-5b (206.7 mg, 79%). 1H-NMR(400 MHz, CDCl3) δ 10.07 (s, 1H), 8.34 (s,1H), 7.93 (d, J = 8 Hz, 1H), 7.50 - 7.39 (m, 5H), 7.00 (d, J = 8 Hz, 1H), 5.34(s, 2H), 3.95 (s, 3H). Step 3: Preparation of Core C-5 Compound C-5b (82.5 mg, 0.25 mmol) was dissolved in MC (5 mL) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl3 in MC, 2.78 mL, 2.78 mmol) was slowly added, and the mixture was stirred for 5 h while the temperature was gradually raised to −30 °C. After completion of the reaction, distilled water (50 mL) was slowly added dropwise to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction mixture. MC (50 mL) was added to the mixture to extract the organic layer three times. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-5 (32.8 mg, 55%) in the form of an ivory solid. 1 H-NMR(400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.23 (s,1H), 8.12 (d, J = 8 Hz, 1H), 7.02 (d, J = 8 Hz, 1H), 3.90 (s, 3H). Preparation Example 19: Preparation of Core C-6

[0223] [ka] Step 1: Preparation of compound C-6b Compound C-6a (3-fluorophenol, TCI, CAS number 372-20-3, 10 g, 89.2 mmol) was dissolved in anhydrous ACN (200 mL) at 0 °C under a nitrogen atmosphere, and then benzyl bromide (12.7 mL, 107 mmol) and potassium carbonate (18.5 g, 7.98 mmol) were added, and the mixture was stirred at room temperature for 20 h. After completion of the reaction, the organic layer was extracted twice with EA (350 mL) and distilled water (350 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-6b in the form of a white solid (15 g, 83%). 1 H-NMR(400 MHz, CDCl3) δ 7.43 - 7.37 (m, 4H), 7.35- 7.32 (m, 1H), 7.25 - 7.19 (m, 1H), 6.75 (dd, J = 8.4, 2.4 Hz, 1H), 6.71 -6.64 (m, 2H), 5.04 (s, 2H). Step 2: Preparation of compound C-6c Compound C-6b (15 g, 74.1 mmol) was added to THF (495 mL) at room temperature under a nitrogen atmosphere. The mixture was cooled to −78 °C, and then n-butyllithium solution (2.5 M n-BuLi in hexane, 35.6 mL, 89.0 mmol) was slowly added dropwise. The mixture was stirred for 30 min while maintaining the temperature at −78 °C. DMF (17.2 mL) was then slowly added dropwise, and the mixture was stirred for another 30 min. After 30 min, the temperature was gradually increased, and the mixture was stirred at 0 °C for 1 h. After completion of the reaction, the mixture was cooled again to −20 °C, and distilled water (300 mL) was added dropwise to quench the reaction. The reaction solution was extracted twice with EA (500 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-6c (14.5 g, 85%) in the form of a white solid. 1H-NMR(400 MHz, CDCl3) δ 10.51 (s, 1H), 7.44 -7.40 (m, 6H), 6.83 (d, J = 8.4 Hz, 1H), 6.74 (t, J = 8.4 Hz, 1H), 5.20 (s, 2H). Step 3: Preparation of compound C-6d Compound C-6c (14.5 g, 62.9 mmol) was dissolved in DMF (150 mL) at room temperature under a nitrogen atmosphere. Methyl thioglycolate (Merck, CAS No. 2365-48-2, 8.44 mL, 94.4 mmol) and triethylamine (22.1 mL, 157.4 mmol) were then added, and the mixture was stirred at 100 °C for 16 h. After completion of the reaction, the reaction solution was cooled to room temperature, and the organic layer was extracted twice with EA (400 mL) and distilled water (400 mL). The resulting organic layer was washed with an aqueous sodium chloride solution. The washed organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-6d (7.2 g, 38%) in the form of a white solid. 1 H-NMR(400 MHz, CDCl3) δ 8.28 (s, 1H), 7.49 - 7.47(m, 2H), 7.45 - 7.29 (m, 5H), 6.81 (d, J = 7.6 Hz, 1H), 5.21 (s, 2H), 3.92 (s,3H). Step 4: Preparation of compound C-6e Compound C-6d (1 g, 3.35 mmol) was dissolved in MC (65 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (Merck, CAS No. 4885-02-3, 910 μL, 10.05 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 10.05 mL, 10.05 mmol) were then added sequentially and slowly. The mixture was stirred for 3 h while maintaining the temperature. After completion of the reaction, distilled water (250 mL) was slowly added dropwise to quench the reaction. MC (250 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-6e (733 mg, 67%). 1 H-NMR(400 MHz, CDCl3) δ 10.07 (s, 1H), 8.34 (s,1H), 7.93 (d, J = 8 Hz, 1H), 7.50 - 7.39 (m, 5H), 7.00 (d, J = 8 Hz, 1H), 5.34(s, 2H), 3.95 (s, 3H). Step 5: Preparation of Core C-6 Compound C-6e (1.37 g, 4.19 mmol) was dissolved in ethanol (45 mL) and THF (45 mL) at room temperature under a nitrogen atmosphere. Lithium hydroxide monohydrate (352.2 mg, 8.39 mmol) dissolved in distilled water (17 mL) was then slowly added dropwise, and the mixture was stirred at room temperature for 1 h. The mixture was stirred at 60 °C for an additional 3 h. After completion of the reaction, EA (300 mL) and 2 N aqueous hydrochloric acid (250 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to give core C-6 (1.3 g, 99%). 1 H-NMR(400 MHz, DMSO-d6) δ 10.08 (s, 1H), 8.26 (d,J = 8.4 Hz, 1H), 8.09 (s, 1H), 7.56 (m, 2H), 7.46 - 7.35 (m, 4H), 5.47 (s, 2H). Preparation Example 20: Preparation of Core C-7

[0224] [ka] Step 1: Preparation of compound C-7a Compound C-4c (2.1 g, 7.82 mmol) prepared in Step 2 of Preparation Example 17 was dissolved in MC (40 mL) at room temperature under a nitrogen atmosphere. Ethyl (triphenylphosphoranylidene)acetate (5.45 g, 15.6 mmol) was then added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted twice with MC (100 mL) and distilled water (100 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-7a in the form of a white solid (2.5 g, 95%). 1 H-NMR(400 MHz, CDCl3) δ 7.85 (d, J = 15.6 Hz,1H), 7.69 (s, 1H), 7.48 - 7.46 (m, 2H), 7.43 - 7.35 (m, 4H), 7.31 - 7.27 (m,1H), 6.79 (d, J = 7.6 Hz, 1H), 6.25 (d, J = 15.6 Hz, 1H), 5.21 (s, 2H), 4.26(q, J = 7.2 Hz, 2H), 1.33 (t, J = 7.2 Hz, 3H). Step 2: Preparation of compound C-7b Compound C-7a (4.7 g, 13.3 mmol) was dissolved in THF (150 mL) and methanol (500 mL) at room temperature under a nitrogen atmosphere, and 5% palladium on carbon (5% Pd / C, 5.67 g) was added. The mixture was then reacted under a hydrogen atmosphere for 1 hour. After completion of the reaction, the solution was filtered using Celite and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound C-7b (4.3 g, 91%) in the form of a white solid. 1H-NMR(400 MHz, CDCl3) δ 7.48 - 7.41 (m, 1H), 7.42- 7.34 (m, 4H), 7.26 - 7.25 (m, 1H), 7.18 (t, J = 8 Hz, 1H), 6.77 (d, J = 7.6Hz, 1H), 5.19 (s, 2H), 4.15 (q, J = 7.2 Hz, 2H), 3.22 (t, J = 8.0 Hz, 2H), 2.74(t, J = 8.0 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H). Step 3: Preparation of compound C-7c Compound C-7b (485 mg, 1.42 mmol) was dissolved in MC (30 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (Merck, CAS No. 4885-02-3, 400 μL, 4.27 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 4.3 mL, 4.27 mmol) were then added sequentially and slowly. The mixture was stirred for 2 h while maintaining the temperature. After completion of the reaction, distilled water (250 mL) was slowly added dropwise to quench the reaction. MC (250 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-7c (290 mg, 55%). 1 H-NMR(400 MHz, CDCl3) δ 10.03 (s, 1H), 7.74 (d, J= 8.4 Hz, 1H), 7.49 - 7.35 (m, 6H), 6.94 (d, J = 8.4 Hz, 1H), 5.30 (s, 2H),4.15 (q, J = 7.2 Hz, 2H), 3.27 (t, J = 7.6 Hz, 2H), 2.78 (t, J = 7.6 Hz, 2H),1.24 (t, J = 7.2 Hz, 3H). Step 4: Preparation of Core C-7 Compound C-7c (290 mg, 0.79 mmol) was dissolved in ethanol (5 mL) and THF (5 mL) at room temperature under a nitrogen atmosphere. Lithium hydroxide monohydrate (66 mg, 1.57 mmol) dissolved in distilled water (2.5 mL) was then slowly added dropwise, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, EA (300 mL) and 2N aqueous hydrochloric acid (250 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to give core C-7 (278 mg, 99%). 1 H-NMR(400 MHz, CDCl3) δ 10.03 (s, 1H), 7.75 (d, J= 8.4 Hz, 1H), 7.49 - 7.35 (m, 6H), 6.94 (d, J = 8.4 Hz, 1H), 5.31 (s, 2H),3.28 (t, J = 7.6 Hz, 2H), 2.85 (t, J = 7.6 Hz, 2H); EI-MS m / z: 341(M + ). Preparation Example 21: Preparation of Core C-8

[0225] [ka] Compound C-7c (279 mg, 0.81 mmol) was dissolved in MC (16 mL) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl3 in MC, 2.44 mL, 2.44 mmol) was slowly added, and the mixture was stirred for 1.5 h. After completion of the reaction, the temperature was raised to −50 °C, and then distilled water (15 mL) was added dropwise to quench the reaction. The temperature was raised to 0 °C, and 2 N aqueous sodium hydroxide solution (5 mL) was added dropwise. The organic layer was extracted twice from the mixture using MC (30 mL). The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-8 in the form of a white solid (150 mg, 66%). 1H-NMR(400 MHz, CDCl3) δ 10.02 (s, 1H), 7.67 (d, J= 7.6 Hz, 1H), 6.84 (d, J = 8 Hz, 1H), 5.94 (s, 1H), 4.16 (q, J = 6.8 Hz, 2H),3.29 (t, J = 7.6 Hz, 2H), 2.79 (t, J = 7.6 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H). Preparation Example 22: Preparation of Core C-9

[0226] [ka] Compound C-9a (2-iodoresorcinol, CAS No. 41046-67-7, TCI, 1 g, 4.23 mmol) was dissolved in ACN (150 mL) under a nitrogen atmosphere at 0 °C. Methyl 5-hexynoate (CAS No. 77758-51-1, Thermoscientific, 600 μL), PdCl(TPP) (100 mg), CuI (40 mg), and TEA (5.9 mL, 42.3 mmol) were added sequentially, and the mixture was stirred at room temperature for 1 h. The mixture was stirred at 60 °C for an additional 16 h, followed by the addition of EA (100 mL) and 2 N aqueous hydrochloric acid (100 mL) to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give core C-9 (340 mg, 34.2%). 1 H-NMR(400 MHz, CDCl3) δ 7.08-7.01 (m, 2H), 6.59(m, 1H), 6.47 (s, 1H), 5.15 (s, 1H), 3.67 (s, 3H), 2.82 (t, J = 7.2 Hz, 2H),2.41 (t, J = 7.2 Hz, 2H), 2.08 (m, 2H). Preparation Example 23: Preparation of Core C-10

[0227] [ka] Step 1: Preparation of compound C-10a Core C-9 (690 mg, 2.94 mmol) was dissolved in ACN (20 mL) at 0 °C under a nitrogen atmosphere, and then potassium carbonate (1.01 g, 7.36 mmol) and benzyl bromide (420 μL, 3.53 mmol) were added slowly. The mixture was stirred at 0 °C for 30 min, and then at room temperature for 16 h. After completion of the reaction, EA (300 mL) and distilled water (300 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-10a in the form of a yellow oil (894 mg, 93%). 1 H-NMR(400 MHz, CDCl3) δ 7.48 - 7.46 (m, 2H), 7.41- 7.32 (m, 3H), 7.13 - 7.04 (m, 2H), 6.69 (d, J = 8 Hz, 1H), 6.55 (s, 1H), 5.18(s, 2H), 3.66 (s, 3H), 2.81 (t, J = 7.2 Hz, 2H), 2.41 (t, J = 7.2 Hz, 2H), 2.07(p, J = 7.2 Hz, 2H). Step 2: Preparation of compound C-10b Compound C-10a (894 mg, 2.75 mmol) was dissolved in MC (50 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (748 μL, 8.27 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 8.27 mL, 8.27 mmol) were then added sequentially and slowly. The mixture was stirred for 1.5 h while maintaining the temperature. After completion of the reaction, distilled water (250 mL) was slowly added dropwise to quench the reaction. MC (250 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound C-10b (511 mg, 53%) in the form of a yellow oil. 1H-NMR(400 MHz, CDCl3) δ 10.25 (s, 1H), 7.68 (d, J= 8.4 Hz, 1H), 7.47 - 2.27 (m, 5H), 6.81 (d, J = 8.4 Hz, 1H), 6.61 (s, 1H),5.27 (s, 2H), 3.67 (s, 3H), 2.89 (t, J = 7.2 Hz, 2H), 2.43 (t, J = 7.2 Hz, 2H),2.11 (p, J = 7.2 Hz, 2H). Step 3: Preparation of Core C-10 Compound C-10b (511 mg, 1.45 mmol) was dissolved in MC (30 mL) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl3 in MC, 4.35 mL, 4.35 mmol) was slowly added, and the mixture was stirred for 1.5 h. After completion of the reaction, distilled water (150 mL) was slowly added dropwise to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction mixture. MC (150 mL) was added to the mixture to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-10 in the form of a white solid (200.2 mg, 52%). 1 H-NMR(400 MHz, DMSO-d6) δ 10.04 (s, 1H), 7.61 (d,J = 8.4 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 6.71 (s, 1H), 3.58 (s, 3H), 2.82 (t,J = 7.2 Hz, 2H), 2.43 (t, J = 7.2 Hz, 2H), 1.95 (p, J = 7.2 Hz, 2H). Preparation Example 24: Preparation of Core C-11

[0228] [ka] Core C-9 (200.2 mg, 0.76 mmol) was dissolved in ethanol (5 mL) and THF (5 mL) at room temperature under a nitrogen atmosphere. Lithium hydroxide monohydrate (64 mg, 1.53 mmol) dissolved in distilled water (2.5 mL) was then slowly added dropwise, and the mixture was stirred at room temperature for 2.5 hours. After completion of the reaction, EA (150 mL) and 2N aqueous hydrochloric acid (150 mL) were added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to give Core C-11 in the form of a black solid (210 mg, 99%). 1 H-NMR(400 MHz, DMSO-d6) δ 11.08 (s, 1H), 10.05(s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 6.71 (s, 1H), 2.82(t, J = 7.2 Hz, 2H), 2.33 (t, J = 7.2 Hz, 2H), 1.90 (p, J = 7.2 Hz, 2H). Preparation Example 25: Preparation of Core C-12

[0229] [ka] Step 1: Preparation of compound C-12b Compound C-12a (10 g, 90.8 mmol) was dissolved in ACN (200 mL) at room temperature under a nitrogen atmosphere, and then benzyl bromide (7.18 mL, 60.5 mmol) was added. The mixture was then cooled to 0 °C. Potassium carbonate (20.9 g, 151.2 mmol) was added, and the mixture was stirred at room temperature for 20 h. After completion of the reaction, the organic layer was extracted twice with EA (400 mL) and distilled water (500 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-12b in the form of a yellow solid (6.6 g, 54%). 1H-NMR(400 MHz, CDCl3) δ 7.43 - 7.36 (m, 4H), 7.34- 7.32 (m, 1H), 7.13 (t, J = 8.4 Hz, 1H), 6.56 (dd, J = 2.4, 0.8 Hz, 1H), 6.48(t, J = 2.4 Hz, 1H), 6.43 (dd, J = 2.4, 0.8 Hz, 1H), 5.03 (s, 2H), 4.97 (s,1H). Step 2-1: Preparation of compound C-12c Compound C-12b (1.0 g, 4.99 mmol) was dissolved in ACN (25 mL) at room temperature under a nitrogen atmosphere. Chloromethyl methyl ether (CAS No. 107-30-2, 7.18 mL, 5.99 mmol) and potassium carbonate (1.37 g, 9.98 mmol) were then added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted twice with EA (100 mL) and distilled water (100 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-12c in the form of a white solid (908 mg, 74%). 1 H-NMR(400 MHz, CDCl3) δ 7.44 - 7.42 (m, 2H), 7.39- 7.36 (m, 2H), 7.33 - 7.31 (m, 1H), 7.18 (t, J = 8.4 Hz, 1H), 6.70 - 6.69 (m,1H), 6.66 - 6.62 (m, 2H), 5.15 (s, 2H), 5.04 (s, 2H), 3.47 (s, 3H). Step 3-1: Preparation of compound C-12d Compound C-12c (900 mg, 3.68 mmol) was added to THF (30 mL) at room temperature under a nitrogen atmosphere. The mixture was cooled to -40 °C, and then n-butyllithium solution (2.5 M n-BuLi in hexane, 1.76 mL, 4.42 mmol) was added dropwise. The temperature of the mixture was raised to -20 °C, and then DMF (0.85 mL) was added dropwise. The temperature was gradually raised to room temperature, and the mixture was stirred for 1 h. After completion of the reaction, distilled water (30 mL) was added dropwise to quench the reaction. The organic layer was extracted twice with EA (30 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-12d (300 mg, 30%) in the form of a white solid. 1 H-NMR(400 MHz, CDCl3) δ 10.60 (s, 1H), 7.46 -7.45 (m, 2H), 7.41 - 7.34 (m, 3H), 7.32 - 7.30 (m, 1H), 6.80 (d, J = 8.4 Hz,1H), 6.67 (d, J = 8.4 Hz, 1H), 5.26 (s, 2H), 5.18 (s, 2H), 3.50 (s, 3H). Step 4-1: Preparation of Compound C-12g (Method 1) Compound C-12d (300 mg, 1.10 mmol) was dissolved in ethanol (10 mL) at room temperature under a nitrogen atmosphere. 2N aqueous hydrochloric acid (1.1 mL) was then added, and the mixture was stirred for 16 hours. After completion of the reaction, distilled water (50 mL) was added dropwise to quench the reaction, and the organic layer was extracted twice with EA (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-12g in the form of a white solid (150 mg, 60%). 1H-NMR(400 MHz, CDCl3) δ 11.95 (s, 1H), 10.41 (s,1H), 7.41 - 7.35 (m, 6H), 6.54 (d, J = 8.4 Hz, 1H), 6.45 (d, J = 8.4 Hz, 1H),5.14 (s, 2H), 3.88 (td, J = 10.8, 3.2 Hz, 1H), 3.63 - 3.60 (m, 1H), 2.05 - 1.98(m, 1H), 1.97 - 1.86 (m, 2H), 1.73 - 1.60 (m, 3H). Step 2-2: Preparation of Compound C-12e Compound C-12b (22 g, 109.8 mmol) was dissolved in MC (200 mL) at room temperature under a nitrogen atmosphere. 3,4-Dihydro-2H-pyran (CAS No. 110-87-2, 12.0 mL, 131.8 mmol) and PPTS (2.76 g, 10.9 mmol) were then added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted twice with MC (500 mL) and distilled water (500 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound A-24e in the form of a white solid (23.9 g, 76%). 1 H-NMR(400 MHz, CDCl3) δ 7.44 - 7.42 (m, 2H), 7.40- 7.36 (m, 2H), 7.33 - 7.29 (m, 1H), 7.17 (t, J = 8.4 Hz, 1H), 6.72 (t, J = 2.4Hz, 1H), 6.66 (dd, J = 2.4, 0.8 Hz, 1H), 6.61 (dd, J = 2.4, 0.8 Hz, 1H), 5.39(t, J = 3.6 Hz, 1H), 5.04 (s, 2H), 3.94 - 3.88 (m, 1H), 3.62 - 3.57 (m, 1H),2.04 - 1.95 (m, 1H), 1.86 - 1.82 (m, 2H), 1.69 - 1.53 (m, 3H). Step 3-2: Preparation of compound C-12f Compound C-12e (7.7 g, 27.0 mmol) was dissolved in THF (200 mL) at room temperature under a nitrogen atmosphere. The mixture was then cooled to 0 °C, and n-butyllithium solution (2.5 M n-BuLi in hexane, 13.0 mL, 32.4 mmol) was added dropwise. The reaction solution was stirred for 30 min, and then DMF (6.3 mL) was added dropwise. The temperature was gradually raised to room temperature, and the mixture was stirred for another 1 h. After completion of the reaction, distilled water (500 mL) was added dropwise to quench the reaction. The organic layer was extracted twice with EA (500 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-12f (2.5 g, 27%) in the form of a white solid. 1 H-NMR(400 MHz, CDCl3) δ 10.62 (s, 1H), 7.47 -7.46 (m, 2H), 7.40 - 7.36 (m, 3H), 7.35 - 7.31 (m, 1H), 6.82 (d, J = 8.4 Hz,1H), 6.64 (d, J = 8.4 Hz, 1H), 3.88 (td, J = 10.8, 3.2 Hz, 1H), 3.63 - 3.60 (m,1H), 2.05 - 1.98 (m, 1H), 1.97 - 1.86 (m, 2H), 1.73 - 1.60 (m, 3H). Step 4-2: Preparation of Compound C-12g (Method 2) Compound C-12f (3.98 g, 12.7 mmol) was dissolved in ethanol (80 mL) at room temperature under a nitrogen atmosphere, and then PPTS (2.76 g, 10.9 mmol) was added. The mixture was stirred at 60 °C for 2 hours. After completion of the reaction, distilled water (300 mL) was added dropwise to quench the reaction. EA (300 mL) was added to the reaction solution to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-12g in the form of a white solid (2.6 g, 89%). 1H-NMR(400 MHz, CDCl3) δ 11.97 (s, 1H), 10.41 (s,1H), 7.42 - 7.38 (m, 6H), 6.54 (d, J = 8.4 Hz, 1H), 6.45 (d, J = 8.4 Hz, 1H),5.14 (s, 2H), 3.88 (td, J = 10.8, 3.2 Hz, 1H), 3.63 - 3.60 (m, 1H), 2.05 - 1.98(m, 1H), 1.97 - 1.86 (m, 2H), 1.73 - 1.60 (m, 3H). Step 5: Preparation of compound C-12h Compound C-12g (2.5 g, 10.9 mmol) was dissolved in DMF (50 mL) at room temperature under a nitrogen atmosphere. Ethyl chloroacetate (1.40 mL, 13.1 mmol) and potassium carbonate (3.02 g, 21.9 mmol) were then added, and the mixture was stirred at 80 °C for 2 h. After completion of the reaction, distilled water (300 mL) was added dropwise to quench the reaction. EA (300 mL) was added to the reaction solution to extract the organic layer twice, and aqueous hydrochloric acid was added to the resulting organic layer to extract the organic layer again. The washed organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-12h in the form of a white solid (2.7 g mg, 77%). 1 H-NMR(400 MHz, CDCl3) δ 10.63 (s, 1H), 7.46 -7.45 (m, 2H), 7.40 - 7.36 (m, 3H), 7.33 - 7.32 (m, 1H), 6.68 (d, J = 8.4 Hz,1H), 6.45 (d, J = 8.4 Hz, 1H), 5.18 (s, 2H), 4.72 (s, 2H), 4.26 (q, J = 7.2 Hz,2H), 1.28 (d, J = 7.2 Hz, 3H). Step 6: Preparation of compound C-12i Compound C-12h (2.7 g, 8.59 mmol) was dissolved in DMF (50 mL) at room temperature under a nitrogen atmosphere. Potassium carbonate (1.78 g, 12.9 mmol) was then added, and the mixture was stirred at 100 °C for 2 h. After completion of the reaction, distilled water (200 mL) was added dropwise to quench the reaction. The organic layer was extracted twice from the reaction solution using EA (300 mL), and the resulting organic layer was washed by adding an aqueous sodium chloride solution. The washed organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-12i in the form of a white solid (2.1 g mg, 82%). 1 H-NMR(400 MHz, CDCl3) δ 7.67 (s, 1H), 7.48 - 7.46(m, 2H), 7.43 - 7.39 (m, 2H), 7.37 - 7.32 (m, 2H), 7.20 (d, J = 8.4 Hz, 1H),6.75 (d, J = 8.4 Hz, 1H), 5.21 (s, 2H), 4.42 (q, J = 7.2 Hz, 2H), 1.42 (t, J =7.2 Hz, 3H). Step 7: Preparation of compound C-12j Compound C-12i (910 mg, 3.07 mmol) was dissolved in MC (60 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (833 μL, 9.21 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 9.2 mL, 9.21 mmol) were then added sequentially and slowly. The mixture was stirred for 2 h while maintaining the temperature. After completion of the reaction, distilled water (100 mL) was slowly added dropwise to quench the reaction, and EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-12j (270 mg, 26.7%). 1H-NMR(400 MHz, CDCl3) δ 10.43 (s, 1H), 7.95 (d, J= 8.4 Hz, 1H), 7.71 (s, 1H), 7.47-7.38 (m, 5H), 6.88 (d, J = 8.4 Hz, 1H), 5.30(s, 2H), 4.44 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H). Step 8: Preparation of Core C-12 Compound C-12j (250 mg, 0.77 mmol) was dissolved in MC (15 mL) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl in MC, 4.3 mL, 4.3 mmol) was slowly added, and the mixture was stirred for 1 h. After completion of the reaction, distilled water (50 mL) was slowly added dropwise at −50 °C to quench the reaction. EA (100 mL) and distilled water (100 mL) were further added at room temperature to extract the organic layer. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-12 in the form of a white solid (150 mg, 83%). 1 H-NMR(400 MHz, CDCl3) δ 10.37 (s, 1H), 7.85 (d, J = 8.4 Hz,1H), 7.76 (s, 1H), 6.81 (d, J = 8.4 Hz, 1H), 4.44 (q, J = 7.2 Hz, 2H), 1.43 (t,J = 7.2 Hz, 3H). Preparation Example 26: Preparation of Core C-13

[0230] [ka] Step 1: Preparation of compound C-13a LAH (2.65 g, 69.77 mmol) was added to THF (350 mL) under a nitrogen atmosphere at 0 °C. Compound C-12i (8.27 g, 27.91 mmol) prepared in Step 6 of Preparation 25 was dissolved in THF (50 mL) and slowly added. The mixture was stirred at 0 °C for 1 hour. After completion of the reaction, distilled water (300 mL) was added to quench the reaction. The reaction solution was diluted with EA (300 mL) and filtered through Celite. The resulting solution was concentrated under reduced pressure to remove the organic layer. EA (500 mL) was then added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain C-13a in the form of a white solid (6.99 g, 98%). 1 H-NMR(400 MHz, CDCl3) δ 7.47 - 7.45 (m, 2H), 7.41- 7.37 (m, 2H), 7.35 (m, 1H), 7.18 (t, J = 8 Hz, 1H), 7.10 (d, J = 8 Hz, 1H),6.80 (s, 1H), 6.71 (d, J = 8 Hz, 1H), 5.19 (s, 2H), 4.73 (d, J = 6 Hz, 2H),1.88 (t, J = 6 Hz, 1H). Step 2: Preparation of compound C-13b Dess-Martin reagent (CAS No. 87413-09-0, 7.02 g, 16.56 mmol) was added to MC (25 mL) under a nitrogen atmosphere at 0 °C. Compound C-13a (3.5 g, 13.80 mmol) dissolved in MC (10 mL) was then slowly added, and the mixture was stirred at 0 °C for 30 min. The mixture was stirred for another 3 h while the temperature was raised to room temperature. After completion of the reaction, the reaction solution was diluted with MC (200 mL), filtered using Celite, and the organic layer was extracted twice with distilled water (200 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain C-13b in the form of a pale yellow solid (3.31 g, 95%). 1H-NMR(400 MHz, CDCl3) δ 9.80 (s, 1H), 7.71 (s,1H), 7.48 - 7.36 (m, 6H), 7.20 (d, J = 8 Hz, 1H), 6.77 (d, J = 8 Hz, 1H), 5.22(s, 2H). Step 3: Preparation of compound C-13c Compound C-13b (3.31 g, 13.12 mmol) was dissolved in MC (65 mL) at room temperature under a nitrogen atmosphere, and then (carbethoxymethylene)triphenylphosphorane (Merck, CAS No. 1099-45-2, 9.14 g, 26.24 mmol) was added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound C-13c in the form of a white solid (4.24 g, 99%). cis form: 1 H-NMR(400 MHz, CDCl3) δ 8.03 (s, 1H), 7.48 - 7.46(m, 2H), 7.41 - 7.33 (m, 3H), 7.23 (m, 1H), 7.07 (d, J = 8 Hz, 1H), 6.85 (d, J= 13.2 EI-MS m / z: 323 [M+H] + . trans form: 1H-NMR (400 MHz, CDCl3) δ 7.52 (d,J = 15.6 Hz, 1H), 7.48 - 7.45 (m, 2H), 7.42 - 7.35 (m, 3H), 7.24 (m, 1H), 7.10(d, J = 8 Hz, 1H), 7.07 EI-MSm / z: 323 [M+H] + . Step 4: Preparation of compound C-13d Compound C-13c (4.24 g, 13.15 mmol) was dissolved in THF (160 mL) and methanol (480 mL) at room temperature under a nitrogen atmosphere, and then 5% palladium on carbon (5% Pd / C, 2.1 g) was added, and the mixture was stirred under a hydrogen atmosphere for 3 hours. After completion of the reaction, the reaction solution was diluted with EA (350 mL) and filtered through Celite. The filtered solution was concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound C-13d in the form of a white solid (2.93 g, 95%). 1 H-NMR(400 MHz, CDCl3) δ 7.08 - 7.00 (m, 2H), 6.59(dd, J = 7.6, 0.8 Hz, 1H), 6.49 (d, J = 0.8 Hz, 1H), 5.41 (s, 1H), 4.16 (q, J =7.2 Hz, EI-MS m / z: 235 [M+H] + . Step 5: Preparation of compound C-13e Compound C-13d (2.93 g, 12.51 mmol) was dissolved in ACN (100 mL) at room temperature under a nitrogen atmosphere. Potassium carbonate (4.3 g, 31.27 mmol) and benzyl bromide (1.9 mL, 16.26 mmol) were then added, and the mixture was stirred at 80 °C for 16 h. After completion of the reaction, EA (500 mL), distilled water (450 mL), and 2 N aqueous hydrochloric acid (50 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-13e (3.99 g, 98%) in the form of a colorless oil. 1 H-NMR(400 MHz, CDCl3) δ 7.47 - 7.45 (m, 2H), 7.41- 7.37 (m, 2H), 7.33 (m, 1H), 7.12 (t, J = 8 Hz, 1H), 7.05 (d, J = 8 Hz, 1H),7.68 (d, J = 8 Hz, 1H), 6.57 (s, 1H), 5.18 (s, 2H), 4.16 (q, J = 7.2 Hz, 2H),3.10 (t, J = 7.2 Hz, 2H), 2.74 (t, J = 7.2 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H);EI-MS m / z: 325 [M+H] + . Step 6: Preparation of compound C-13f Compound C-13e (3.99 g, 12.3 mmol) was dissolved in MC (240 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (3.3 mL, 36.9 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 36.9 mL, 36.9 mmol) were then added sequentially and slowly. The mixture was stirred for 1.5 h while maintaining the temperature. After completion of the reaction, distilled water (500 mL) was slowly added dropwise to quench the reaction, and MC (350 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound C-13f (2.3 g, 53%) in the form of a yellow solid. 1H-NMR(400 MHz, CDCl3) δ 10.24 (s, 1H), 7.68 (d, J= 8.4 Hz, 1H), 7.46 - 7.34 (m, 5H), 6.80 (d, J = 8.4 Hz, 1H), 6.62 (s, 1H),5.26 (s, 2H), 4.17 (q, J = 7.2 Hz, 2H), 3.18 (t, J = 7.2 Hz, 2H), 2.78 (t, J =7.2 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H). Step 7: Preparation of Core C-13 Compound C-13f (2.3 g, 6.53 mmol) was dissolved in ethanol (40 mL) and THF (40 mL) under a nitrogen atmosphere at 0 °C. Lithium hydroxide monohydrate (821 mg, 19.58 mmol) dissolved in distilled water (20 mL) was then slowly added dropwise, and the mixture was stirred at room temperature for 1.5 h. After completion of the reaction, the organic layer was extracted with EA (300 mL) and 2 N aqueous hydrochloric acid (200 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-13 in the form of a green solid (2.4 g, 99%). 1 H-NMR(400 MHz, DMSO-d6) δ 10.11 (s, 1H), 7.76 (d,J = 8.4 Hz, 1H), 7.53 - 7.51 (m, 2H), 7.44 - 7.36 (m, 3H), 7.08 (d, J = 8.4 Hz,1H), 6.74 (s, 1H), 5.37 (s, 2H), 3.04 (t, J = 7.2 Hz, 2H), 2.71 (t, J = 7.2 Hz,2H). Preparation Example 27: Preparation of Core C-14

[0231] [ka] Compound C-13b (1 g, 3.96 mmol) prepared in Step 2 of Preparation 26 was dissolved in MC (80 mL) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl3 in MC, 11.89 mL, 11.89 mmol) was slowly added, and the mixture was stirred at −78 °C for 2 h. After completion of the reaction, distilled water (250 mL) was slowly added dropwise to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction mixture. MC (250 mL) was added to the mixture to extract the organic layer three times. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-14 in the form of a yellow solid (580 mg, 90%). 1 H-NMR(400 MHz, DMSO-d6) δ 10.61 (brs, 1H), 9.78(s, 1H), 7.97 (s, 1H), 7.38 (t, J = 8.4 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 6.71(d, J = 8.4 Hz, 1H). Preparation Example 28: Preparation of Core C-15

[0232] [ka] Step 1: Preparation of compound C-15b Compound C-15a (2-chloro-6-hydroxybenzaldehyde, Merck, CAS No. 18362-30-6, 500 mg, 3.19 mmol) was dissolved in ACN (10 mL) at 0 °C under a nitrogen atmosphere, and then benzyl bromide (400 μL, 3.35 mmol) and potassium carbonate (1.1 g, 7.98 mmol) were added, and the mixture was stirred at room temperature for 16 h. After completion of the reaction, EA (100 mL) and distilled water (100 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-15b in the form of a white solid (750 mg, 95%). 1H-NMR(400 MHz, CDCl3) δ 10.57 (s, 1H), 7.45 -7.34 (m, 6H), 7.04 (d, J = 8 Hz, 1H), 6.96 (d, J = 8.8 Hz, 1H), 5.19 (s, 2H). Step 2: Preparation of compound C-15c Selenium powder (256 mg, 3.24 mmol) was added to THF (10 mL) at room temperature under a nitrogen atmosphere. The mixture was cooled to 0 °C, and then n-butyllithium solution (2.5 M n-BuLi in hexane, 1.42 mL, 3.56 mmol) was slowly added dropwise. The mixture was stirred at 0 °C for 40 min, and then compound C-15b (800 mg, 3.24 mmol) dissolved in DMF (2 mL) was added, and the mixture was stirred at room temperature for 12 h. After completion of the reaction, the mixture was cooled to 0 °C, and distilled water (100 mL) was slowly added dropwise to quench the reaction. EA (100 mL) was added to the reaction solution, followed by extraction. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-15c (900 mg, 80%) in the form of a bright yellow solid. 1 H-NMR(400 MHz, CDCl3) δ 10.70 (s, 1H), 7.42-7.33(m, 6H), 7.04 (d, J = 8 Hz, 1H), 6.81 (d, J = 8.8 Hz, 1H), 5.18 (s, 2H), 2.85(t, J = 7.6 Hz, 2H), 1.75 (qui, J = 7.6 Hz, 2H), 1.51 (m, 2H), 0.95 (t, J = 7.6Hz, 3H). Step 3: Preparation of compound C-15d Compound C-15c (900 mg, 2.59 mmol) was dissolved in DMF (10 mL) at room temperature under a nitrogen atmosphere, and then ethyl bromoacetate (574 μL, 6.48 mmol) was added, and the mixture was stirred at 120° C. for 12 hours. After completion of the reaction, the reaction solution was cooled to room temperature and used in the next reaction without further purification. Step 4: Preparation of compound C-15e Potassium carbonate (716 mg, 6.48 mmol) was added to the reaction solution under a nitrogen atmosphere, and the mixture was stirred at 120° C. for 2.5 hours. After completion of the reaction, EA (100 mL) and distilled water (200 mL) were added to extract the organic layer. The organic layer was further washed by adding distilled water (200 mL) again to the obtained organic layer, and the organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound C-15e in the form of a white solid (840 mg, 90%). 1 H-NMR(400 MHz, CDCl3) δ 8.55 (s, 1H), 7.49-7.47(m, 3H), 7.43-7.29 (m, 4H), 6.84 (d, J = 8 Hz, 1H), 5.21 (s, 2H), 4.37 (q, J =7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 3H); EI-MS m / z: 361 [M+H] + . Step 5: Preparation of compound C-15f Compound C-15e (400 mg, 1.11 mmol) was dissolved in MC (30 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (300 μL, 3.33 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 3.33 mL, 3.33 mmol) were then added sequentially and slowly. The mixture was stirred for 2 h while maintaining the temperature. After completion of the reaction, distilled water (100 mL) was slowly added dropwise to quench the reaction, and EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound C-15f (310 mg, 72%). 1H-NMR(400 MHz, CDCl3) δ 10.09 (s,1H), 8.62 (s,1H), 7.89 (d, J = 8 Hz, 1H), 7.49-7.38 (m, 5H), 7.03 (d, J = 8 Hz, 1H), 5.34(s, 2H), 4.39 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz, 3H); EI-MS m / z: 388[M+H] + . Step 6: Preparation of Core C-15 Compound C-15f (300 mg, 0.77 mmol) was dissolved in MC (15 mL) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl in MC, 4.62 mL, 4.62 mmol) was slowly added, and the mixture was stirred for 1.5 h. After completion of the reaction, distilled water (100 mL) was slowly added dropwise to quench the reaction, and EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-15 in the form of a white solid (185 mg, 80%). 1 H-NMR(400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.47 (s,1H), 8.09 (d, J = 8 Hz, 1H), 7.05 (d, J = 8 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H),1.34 (t, J = 7.2Hz, 3H). Preparation Example 29: Preparation of Core C-16

[0233] [ka] Compound C-2d (3.0 g, 10.15 mmol) was dissolved in MC (180 mL) at -30 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (Merck, CAS No. 4885-02-3, 2.76 mL, 30.45 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 30.45 mL, 30.45 mmol) were then added sequentially and slowly. The mixture was stirred for 2 h while maintaining the temperature. After completion of the reaction, chilled distilled water (100 mL) was slowly added dropwise to quench the reaction, and EA (300 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain core C-16 (2.76 g, 84%). 1 H-NMR(400 MHz, CDCl3) δ10.07 (S ,1H), 9.28 (brs,1H), 7.94 (d, J = 2.0 Hz, 1H), 7.61 (d, J = 8 Hz, 1H), 7.49 - 7.40 (m, 5H),6.90 (d, J = 8 Hz, 1H), 5.31 (s, 2H), 4.41 (q, J = 7.2 Hz, 2H), 1.41 (t, J =7.2 Hz, 3H). Preparation Example 30: Preparation of Linker Q-1

[0234] [ka] Linker P-2 (172 mg, 0.64 mmol) was dissolved in saturated aqueous sodium bicarbonate (3.5 mL) at 0 °C under a nitrogen atmosphere, and the mixture was stirred at 0 °C for 15 min. Q-1a (N-methoxycarbonylmaleimide, TCI, CAS No. 55750-48-6, 100 mg, 0.64 mmol) was gradually added to the mixture, and the mixture was stirred at the same temperature for 1.5 h. After completion of the reaction, EA (50 mL) and distilled water (50 mL) were added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure at a temperature below 20 °C. The residue thus obtained was subjected to column chromatography to obtain linker Q-1 in the form of a colorless oil (137.3 mg, 68%). 1 H-NMR(400 MHz, CDCl3) δ 6.70 (s, 2H), 4.20 (d, J= 2.4 Hz, 2H), 3.74 - 3.59 (m, 16H), 2.42 (t, J = 2.4 Hz, 1H). Preparation Example 31: Preparation of Linker Q-2

[0235] [ka] Compound Q-2a (Mal-PEG2-acid, CAS No. 1374666-32-6, TCI, 100 mg, 0.388 mmol) was dissolved in MC (5 mL) at 0 °C under a nitrogen atmosphere, and then NHS (49.2 mg, 0.427 mmol) and DCC (88.2 mg, 0.427 mmol) were added, and the mixture was stirred for 15 hours. After completion of the reaction, EA / n-hexane (1:1 volume ratio, 20 mL) was added, and the resulting precipitate was removed by filtration. The filtrate was concentrated, and then EA / n-hexane (1:1 volume ratio, 20 mL) was added again, and the resulting precipitate was removed. The filtrate was concentrated under reduced pressure to give linker Q-2 (139 mg, 99%). 1H-NMR(400 MHz, CDCl3) δ 6.70 (s, 2H), 3.81 (t, J= 6.4 Hz, 2H), 3.72 (m, 2H), 3.65-3.58 (m, 6H), 2.87 (t, J = 6.4 Hz, 2H), 2.84(s 4H); EI-MS m / z: 355 [M+H] + . Preparation Example 32: Preparation of Linker Q-3

[0236] [ka] Step 1: Preparation of Compound Q-3b Compound Q-3a (diethanolamine, Daejung Chemicals & Metals, CAS No. 111-42-2, 10 g, 95.12 mmol) was dissolved in 1,4-dioxane (320 mL) at 0 °C under a nitrogen atmosphere. Sodium bicarbonate (16 g, 190.24 mmol) and di-tert-butyl ether (Boc anhydride, 25 g, 114.14 mmol) dissolved in distilled water (160 mL) were then added sequentially. The mixture was stirred for 48 h while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, the organic layer was extracted five times with EA (500 mL), distilled water (400 mL), and 2 N aqueous hydrochloric acid (100 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to give compound Q-3b (17.89 g, 91%) in the form of a colorless liquid. 1 H-NMR(400 MHz, DMSO-d6) δ 4.67 (brs, 2H), 3.49 -3.42 (m, 4H), 3.25 - 3.19 (m, 4H), 1.38 (s, 9H). Step 2: Preparation of compound Q-3c Compound Q-3b (1.02 g, 4.97 mmol) was dissolved in DMF (16 mL) at 0 °C under a nitrogen atmosphere. Then, propargyl bromide (2.2 mL, 19.88 mmol) and potassium hydroxide (1.11 g, 19.88 mmol) were added, and the mixture was stirred for 16 h while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, the organic layer was extracted twice with EA (250 mL), distilled water (150 mL), and 2 N aqueous hydrochloric acid (100 mL). The obtained organic layer was washed with saturated aqueous sodium chloride (250 mL). The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound Q-3c (806 mg, 57%) in the form of a light yellow liquid. 1 H-NMR(400 MHz, CDCl3) δ 4.14 (d, J = 2 Hz, 4H),3.67 - 3.61 (m, 4H), 3.51 - 3.43 (m, 4H), 2.43 - 2.40 (m, 2H), 1.46 (s, 9H). Step 3: Preparation of compound Q-3d Compound Q-3c (806 mg, 2.86 mmol) was dissolved in dichloromethane (5 mL) at 0° C. under a nitrogen atmosphere, then a 4N hydrochloric acid solution (4 M HCl in dioxane, 10 mL) was added, and the mixture was stirred at 0° C. for 1 hour, and then the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the mixture was concentrated under reduced pressure to give compound Q-3d in the form of an ivory solid (618 mg, 99%). 1 H-NMR(400 MHz, CDCl3) δ 9.46 (brs, 1H), 4.26 (d,J = 2.4 Hz, 4H), 3.98 (t, J = 5.2 Hz, 4H), 3.38 - 3.30 (m, 4H), 2.50 (t, J =2.4 Hz, 2H). Step 4: Preparation of Compound Q-3e Compound Q-3d (618 mg, 2.84 mmol) and linker P-8 (747 mg, 2.84 mmol) were dissolved in DMF (15 mL) at 0 °C under a nitrogen atmosphere. EDCI hydrochloride (816 mg, 4.26 mmol), HOBt (384 mg, 2.84 mmol), DMAP (35 mg, 0.28 mmol), and DIPEA (1.48 mL, 8.51 mmol) were added sequentially. The mixture was stirred for 16 h while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, the organic layer was extracted twice with EA (150 mL), distilled water (100 mL), and 2 N aqueous hydrochloric acid (50 mL). Saturated aqueous sodium chloride (200 mL) was added to the resulting organic layer to wash the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give Q-3e in the form of a yellow oil (887 mg, 73%). 1 H-NMR(400 MHz, CDCl3) δ 5.08 (brs, 1H), 4.30 (s,2H), 4.16 - 4.11 (m, 4H), 3.73 - 3.68 (m, 4H), 3.68 - 3.63 (m, 4H), 3.62 - 3.58(m, 4H), 3.57 - 3.52 (m, 2H), 3.35 - 3.29 (m, 2H), 2.45 - 2.40 (m, 2H), 1.44(s, 9H); EI-MS m / z: 427(M + ). Step 5: Preparation of compound Q-3f Compound Q-3e (887 mg, 2.08 mmol) was dissolved in dichloromethane (4 mL) at 0° C. under a nitrogen atmosphere, then a 4N hydrochloric acid solution (4 M HCl in dioxane, 8 mL) was added, and the mixture was stirred at 0° C. for 1 hour, and then the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the mixture was concentrated under reduced pressure to give compound Q-3f in the form of an ivory solid (824 mg, quantitatively obtained). 1H-NMR(400 MHz, CDCl3) δ 8.42 (brs, 2H), 4.35 (s,2H), 4.18 - 4.14 (m, 4H), 3.92 (t, J = 4.8 Hz, 2H), 3.76 - 3.73 (m, 2H), 3.72 -3.64 (m, EI-MS m / z: 327 [M+H] + . Step 6: Preparation of Compound Q-3 Compound Q-3f (147 mg, 0.40 mmol) was dissolved in saturated aqueous sodium bicarbonate (sodium bicarbonate, 2 mL) at 0 °C under a nitrogen atmosphere, and the mixture was stirred at 0 °C for 15 minutes. Q-1a (N-methoxycarbonylmaleimide, TCI, CAS number 55750-48-6, 63 mg, 0.40 mmol) was gradually added to the mixture, and the mixture was stirred at the same temperature for 1.5 hours. After completion of the reaction, EA (50 mL) and distilled water (50 mL) were added to extract the organic layer three times. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure at a temperature below 15 °C. The residue thus obtained was subjected to column chromatography to give Q-3 (55.1 mg, 33%) in the form of a colorless oil. 1 H-NMR(400 MHz, CDCl3) δ 6.69 (s, 2H), 4.27 (s,2H), 4.16 - 4.11 (m, 4H), 3.75 - 3.68 (m, 4H), 3.67 - 3.62 (m, 8H), 3.61 - 3.57(m, 4H), 2.45 - 2.41 (m, 2H); EI-MS m / z: 407 [M+H] + . Preparation Example 33: Preparation of Linker Q-4

[0237] [ka] Step 1: Preparation of compound Q-4a Compound P-1a (tetraethylene glycol, Daejung Chemicals & Metals, CAS No. 112-60-7, 5 g, 25.74 mmol) was dissolved in THF (60 mL) under a nitrogen atmosphere at room temperature. Sodium hydride (60% NaH dispersion in mineral oil, 16.5 mg, 0.41 mmol) was then added, and the mixture was stirred at room temperature for 30 minutes. tert-Butyl acrylate (Merck, CAS No. 1663-39-4, 1.5 mL, 10.30 mmol) was gradually added to the reaction solution over 2 hours, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, saturated aqueous sodium chloride solution (20 mL) was added to quench the reaction, and the organic solvent was removed by concentration under reduced pressure. MC (60 mL) was added to the remaining aqueous sodium chloride solution to extract the organic layer. The resulting organic layer was then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to column chromatography to give compound Q-4a in the form of a pale pink oil (1.39 g, 42%). 1 EI-MS m / z:345 [M+Na] + . Step 2: Preparation of compound Q-4b Compound Q-4a (1.39 g, 4.31 mmol) was dissolved in ACN (7.5 mL) at 0 °C under a nitrogen atmosphere, and then pyridine (4 mL) was added slowly. A solution of 4-methylbenzenesulfonyl chloride (p-toluenesulfonyl chloride, 1.1 g, 5.77 mmol) dissolved in ACN (10.5 mL) was then added slowly over 30 min, and the mixture was stirred at room temperature for 6.5 h. After completion of the reaction, the organic layer was extracted twice with EA (200 mL), distilled water (150 mL), and 2 N aqueous hydrochloric acid (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound Q-4b (1.78 g, 86%) in the form of a colorless oil. 1H-NMR(400 MHz, CDCl3) δ 7.80 (d, J = 8 Hz, 2H),7.34 (d, J = 8 Hz, 2H), 4.16 (t, J = 4.8 Hz, 2H), 3.73 - 3.65 (m, 4H), 3.65 -3.57 (m, 12H), 2.50 (t, J = 6.4 Hz, 2H), 2.45 (s, 3H), 1.44 (s, 9H); EI-MS m / z:499 [M+Na] + . Step 3: Preparation of compound Q-4c Compound Q-4b (1.78 g, 3.73 mmol) was dissolved in DMF (20 mL) at room temperature under a nitrogen atmosphere. Sodium azide (NaN3, 364 mg, 5.60 mmol) was then added, and the mixture was stirred at 60 °C for 16 h. After completion of the reaction, the mixture was cooled to room temperature, and the organic layer was extracted twice with EA (200 mL) and distilled water (200 mL). The obtained organic layer was washed three times with saturated aqueous sodium chloride solution (200 mL). The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound Q-4c (1.25 g, 96%) in the form of a colorless oil. 1 EI-MS m / z:348 [M+H] + . Step 4: Preparation of compound Q-4d Compound Q-4c (500 mg, 1.44 mmol) was dissolved in 1,4-dioxane (8 mL) at room temperature under a nitrogen atmosphere, and then 5% palladium on carbon (5% Pd / C, 153 mg, 0.07 mmol) was added. The mixture was then stirred at 60° C. under a hydrogen atmosphere for 4 hours. After completion of the reaction, the reaction solution was diluted with EA (50 mL), filtered using Celite filter material, and the solution was concentrated under reduced pressure. The residue obtained was subjected to column chromatography to obtain compound Q-4d (92.5 mg, 20%) in the form of a colorless oil. 1 H-NMR(400 MHz, CDCl3) δ 3.71 (t, J = 6.4 Hz, 4H),3.65 - 3.56 (m, 28H), 2.81 (t, J = 5.6 Hz, 4H), 2.50 (t, J = 6.4 Hz, 4H), 1.44(s, 18H); EI-MS m / z: 626 [M+H] + . Step 5: Preparation of compound Q-4e Compound Q-4d (92.5 mg, 0.15 mmol) was dissolved in MC (2 mL) under a nitrogen atmosphere at 0 °C, and then linker Q-2 (68.1 mg, 0.19 mmol), pyridine (11.9 μL), and DIPEA (5.1 μL) were added dropwise, and the mixture was stirred at room temperature for 2 h. After completion of the reaction, the reaction solution was subjected to column chromatography without extraction to obtain compound Q-4e (83.6 mg, 65%) in the form of an orange oil. 1 H-NMR(400 MHz, CDCl3) δ 6.70 (s, 2H), 3.76 - 3.69(m, 8H), 3.65 - 3.54 (m, 38H), 2.66 (t, J = 6.8 Hz, 2H), 2.50 (t, J = 6.4 Hz,4H), 1.44 (s, 18H); EI-MS m / z: 866 [M+H] + . Step 6: Preparation of compound Q-4f Compound Q-4e (92.5 mg, 0.15 mmol) was dissolved in MC (3 mL) at 0° C. under a nitrogen atmosphere, then TFA (0.3 mL) was added slowly, and the mixture was stirred for 6 hours while the temperature was gradually raised from 0° C. to 15° C. After completion of the reaction, the mixture was diluted by adding MC (20 mL), and then concentrated under reduced pressure at low temperature to give compound Q-4f in the form of a colorless oil (41.2 mg, 99%). 1 EI-MS m / z: 753 [M+H] + . Step 7: Preparation of Compound Q-4 Compound Q-4f (40.5 mg, 0.054 mmol) was dissolved in MC (3 mL) at 0 °C under a nitrogen atmosphere, and then NHS (13 mg, 0.113 mmol) and DCC (24.4 mg, 0.118 mmol) were added. The mixture was stirred for 16 hours while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, EA / n-hexane (1:1 volume ratio, 20 mL) was added, and the resulting precipitate was removed by filtration. The filtrate was concentrated, and then EA / n-hexane (1:1 volume ratio, 20 mL) was added again. The resulting precipitate was removed, and the filtrate was concentrated under reduced pressure to give linker Q-4 (17.4 mg, 43%). 1 H-NMR(400 MHz, CDCl3) δ 6.70 (s, 2H), 3.85 (t, J= 6.4 Hz, 4H), 3.76 - 3.69 (m, 4H), 3.66 - 3.52 (m, 38H), 2.90 (t, J = 6.4 Hz,4H), 2.85 - 2.80 (m, 8H), 2.66 (t, J = 6.8 Hz, 2H); EI-MS m / z: 947 [M+H] + . Preparation Example 34: Preparation of Linker Q-5

[0238] [ka] Linker P-1 (164 mg, 0.64 mmol) was dissolved in saturated aqueous sodium bicarbonate (3.5 mL) at 0 °C under a nitrogen atmosphere, and the mixture was stirred at 0 °C for 20 min. Q-1a (N-methoxycarbonylmaleimide, TCI, CAS No. 55750-48-6, 100 mg, 0.64 mmol) was gradually added to the mixture, and the mixture was stirred at the same temperature for 1.5 h. EA (50 mL) and distilled water (50 mL) were added to extract the organic layer three times. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure at a temperature below 10 °C. The residue thus obtained was subjected to column chromatography to obtain linker Q-5 (77 mg, 40%) in the form of a colorless oil. 1 H-NMR(400 MHz, CDCl3) δ 6.70 (s, 2H), 3.76 - 3.71(m, 2H), 3.69 - 3.60 (m, 12H), 3.39 (t, J = 5.2 Hz, 2H). Preparation Example 35: Preparation of Linker Q-6

[0239] [ka] Step 1: Preparation of compound Q-6a Linker Q-2 (70 mg, 0.198 mmol) was dissolved in THF (3 mL) at 0 °C under a nitrogen atmosphere, and then 3,3'-iminodipropionic acid (TCI, CAS number 505-47-5, 28.6 mg, 0.177 mmol), distilled water (300 μL), and DIPEA (41.3 μL) were added dropwise, and the mixture was stirred at room temperature for 12 hours. After completion of the reaction, the reaction solution was diluted with ACN (1 mL) containing 0.1% formic acid and distilled water (1 mL), separated and purified using preparative HPLC, and then lyophilized to obtain compound Q-6a (3 mg, 4%); MS m / z: 401 [M+H]. + . Step 2: Preparation of compound Q-6 Compound Q-6a (3 mg, 0.0074 mmol) was dissolved in MC (1 mL) at 0 °C under a nitrogen atmosphere, and then NHS (1.9 mg, 0.0148 mmol) and DCC (3.24 mg, 0.0155 mmol) were added, and the mixture was stirred for 2 hours. After completion of the reaction, EA / n-hexane (1:1 volume ratio, 20 mL) was added, and the resulting precipitate was removed by filtration. The filtrate was concentrated, and then EA / n-hexane (1:1 volume ratio, 20 mL) was added again, and the resulting precipitate was removed. The filtrate was concentrated under reduced pressure to give linker Q-6 (4.5 mg, 99%); EI-MS m / z: 595 [M+H]. + . Preparation Example 36: Preparation of Linker Q-7

[0240] [ka] Step 1: Preparation of compound Q-7a Compound P-1a (20 g, 102.97 mmol) was dissolved in ethanolic THF (80 mL) at 0 °C under a nitrogen atmosphere. Sodium hydride (60% NaH dispersion in mineral oil, 823 mg, 34.3 mmol) was then added, and the mixture was stirred at 0 °C for 20 min. Propargyl bromide (1.96 mL, 20.6 mmol) was added, and the mixture was stirred at 0 °C for 1 h. The mixture was then stirred at room temperature for 16 h. After completion of the reaction, the reaction mixture was extracted with EA (100 mL), distilled water (100 mL), and saturated aqueous sodium chloride solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give Q-7a (3.5 g, 74%) in the form of a yellow oil. 1 H-NMR(400 MHz, CDCl3) δ 4.20 (d, J = 2.0 Hz, 2H),3.72 - 3.67 (m, 15H), 3.62 - 3.60 (m, 2H), 2.51 (s, 1H), 2.42 (t, J = 2.0 Hz,1H). Step 2: Preparation of compound Q-7b Compound Q-7a (1.0 g, 4.30 mmol) was dissolved in MC (50 mL) at room temperature under a nitrogen atmosphere, and then DMP (Dess-Martin reagent, 2.73 g, 6.45 mmol) was added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction solution was extracted with MC (100 mL), aqueous sodium thiosulfate solution (50 mL), and aqueous sodium bicarbonate solution (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain Q-7b (570 mg, 57%) in the form of a colorless oil. 1 H-NMR(400 MHz, CDCl3) δ 9.73 (s, 1H), 4.20 (d, J= 2.0 Hz, 2H), 4.15 (s, 2H), 3.74 - 3.66 (m, 12H), 2.42 (t, J = 2.0 Hz, 1H). Step 3: Preparation of compound Q-7c Compound Q-7b (1.23 g, 5.34 mmol) was dissolved in methanol (100 mL) at room temperature under a nitrogen atmosphere, and then compound P-2 (1.23 g, 5.34 mmol) and acetic acid (0.3 mL, 5.34 mmol) were added, and the mixture was stirred for 10 minutes. Sodium cyanoborohydride (671 mg, 10.68 mmol) was added, and the mixture was stirred for 3 hours. After completion of the reaction, the mixture was concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound Q-7c (90 mg, 3.8%) in the form of a colorless oil. 1 EI-MSm / z: 446 [M+H] + . Step 4: Preparation of compound Q-7 Compound Q-7c (40 mg, 0.089 mmol) was dissolved in MC (5 mL) under a nitrogen atmosphere at room temperature. Compound Q-2 (47.7 mg, 0.134 mmol), DIPEA (7.7 μL, 0.044 mmol), and pyridine (7.3 μL, 0.089 mmol) were then added sequentially, and the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL). The reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound Q-7 (10.9 mg, 17%) in the form of a colorless oil. Example I-1: Preparation of Compounds A-1 and A-2

[0241] [ka] Step 1: Preparation of Compound A-1a Core C-16 (1.76 g, 5.46 mmol) was dissolved in DMF (27 mL) at room temperature under a nitrogen atmosphere, then linker P-3 (1.8 g, 6.38 mmol) and potassium carbonate (2.26 g, 16.38 mmol) were added, and the mixture was stirred at 80 °C for 16 h. After completion of the reaction, EA (250 mL) and 2N aqueous hydrochloric acid (250 mL) were added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound A-1a in the form of a yellow liquid (2.86 g, 99%). 1H-NMR(400 MHz, CDCl3) δ 10.05 (s, 1H), 8.04 (s,1H), 7.57 (d, J = 8 Hz, 1H), 7.50 - 7.36 (m, 5H), 6.90 (d, J = 8 Hz, 1H), 5.17- 5.13 (m, 2H), 4.36 (q, J = 7.2 Hz, 2H), 3.71 - 3.67 (m, 2H), 3.59 (t, J = 4.8Hz, 2H), 3.53 - 3.38 (m, 8H), 3.33 (t, J = 5.2 Hz, 2H), 1.41 (t, J = 7.2Hz,3H). Step 2: Preparation of Compound A-1b Compound A-1a (2.83 g, 5.39 mmol) was dissolved in MC (95 mL) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl3 in MC, 43.15 mL, 43.15 mmol) was slowly added, and the mixture was stirred for 8 hours while the temperature was gradually raised to −50 °C. After completion of the reaction, distilled water (300 mL) was slowly added dropwise to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction mixture. MC (300 mL) was added to the mixture to extract the organic layer three times. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-1b (1.68 mg, 71%) in the form of a brown liquid. 1 H-NMR(400 MHz, CDCl3) δ 10.03 (s, 1H), 9.24 (brs,1H), 8.12 (s, 1H), 7.56 (d, J = 8 Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 4.95 -4.92 (m, 2H), 4.37 (q, J = 7.2 Hz, 2H), 4.15 - 4.09 (m, 2H), 3.73 - 3.71 (m,2H), 3.61 - 3.58 (m, 4H), 3.57 - 3.51 (m, 4H), 3.33 (t, J = 5.2 Hz, 2H), 1.42(t, J = 7.2 Hz, 3H). Step 3: Preparation of Compound A-1c Compound A-lb (1.68 mg, 3.87 mmol) was dissolved in MC (130 mL) at 0 °C under a nitrogen atmosphere, and then acetobromo-alpha-D-galactose (183 mg, 0.44 mmol) and benzyltributylammonium chloride (1.2 g, 3.87 mmol) were added. 5N aqueous sodium hydroxide solution (2.32 mL, 11.60 mmol) was slowly added to the reaction solution, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted three times with MC (150 mL) and distilled water (150 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-lc (1.9 g, 64%) in the form of a brown viscous gum. 1 H-NMR(400 MHz, CDCl3) δ 10.10 (s, 1H), 8.02 (s,1H), 7.57 (d, J = 8.4 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 5.59 (dd, J =10.4, 8Hz, 1H), 5.50 (d, J =3.2 Hz, 1H), 5.43 (d, J = 8 Hz, 1H), 5.21 - 5.17 (m, 2H),5.01 (m, 1H), 4.37 (q, J = 7.2 Hz, 2H), 4.23 - 4.11 (m, 3H), 3.69 - 3.67 (m,2H), 3.58 (t, J = 5.2 Hz, 2H), 3.50 - 3.47 (m, 2H), 3.43 - 3.32 (m, 8H), 2.21(s, 3H), 2.19 (s, 3H), 2.14 (s, 3H), 2.04 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H). Step 4: Preparation of Compound A-1d Compound A-1c (1.9 g, 2.49 mmol) was dissolved in THF (40 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (188.6 mg) was added, and the mixture was stirred for 2.5 hours. After completion of the reaction, distilled water (200 mL) was added to quench the reaction, and then EA (200 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-1d in the form of a yellow solid (1.55 g, 81%). 1 H-NMR(400 MHz, CDCl3) δ 7.38 (s, 1H), 7.01 (d, J= 7.6 Hz, 1H), 6.86 (d, J = 8 Hz, 1H), 5.55 (dd, J =10.4, 8 Hz, 1H), 5.48 (d, J=3.2 Hz, 1H), 5.31 (d, J = 8 Hz, 1H), 5.21 - 5.14 (m, 2H), 5.01 - 4.95 (m, 1H),4.90 (d, J = 5.2 Hz, 2H), 4.35 (q, J = 7.2 Hz, 2H), 4.23 - 4.09 (m, 3H), 3.71 -3.66 (m, 2H), 3.58 (t, J = 5.2 Hz, 2H), 3.51 - 3.34 (m, 10H), 2.21 (s, 3H),2.07 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H), 1.76 (t, J = 5.6 Hz, 1H), 1.41 (t, J= 7.2 Hz, 3H). Step 5: Preparation of Compound A-1e Compound A-1d (160 mg, 0.2 mmol) was dissolved in DMF (4 mL) at 0 °C under a nitrogen atmosphere, and then bis(4-nitrophenyl)carbonate (127 mg, 0.4 mmol) and DIPEA (54.5 μL, 0.3 mmol) were added sequentially, and the mixture was stirred for 1 h. The reaction mixture was stirred at room temperature for another 5 h and then extracted with EA (50 mL) and distilled water (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-1e (162 mg, 83%) in the form of a light yellow oil. 1 H-NMR(400 MHz, CDCl3) δ 8.27 (d, J = 9.2 Hz, 2H),7.37 (d, J = 9.2 Hz, 2H), 7.35 (s, 1H), 7.13 (d, J = 8 Hz, 1H), 6.87 (d, J = 8Hz, 1H), 5.56 (dd, J = 10.4, 8 Hz, 1H), 5.52 (s, 2H), 5.49 (d, J =3 .2 Hz, 1H),5.34 (d, J = 8 Hz, 1H), 5.21 - 5.15 (m, 2H), 5.03 - 4.98 (m, 1H), 4.38 (q, J =7.2 Hz, 2H), 4.24 - 4.10 (m, 3H), 3.71 - 3.68 (m, 2H), 3.60 (t, J = 5.2 Hz,2H), 3.54 - 3.42 (m, 8H), 3.35 (m, 2H), 2.21 (s, 3H), 2.07 (s, 3H), 2.05 (s,3H), 2.03 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H); EI-MS m / z: 795 [M+H] + . Step 6: Preparation of Compound A-1f Compound A-1e (30 mg, 0.032 mmol) was dissolved in DMF (0.2 mL) at room temperature under a nitrogen atmosphere, and then MMAF-OMe (24 mg, 0.032 mmol), HOBt (6.5 mg, 0.048 mmol), and DIPEA (14 μL, 0.08 mmol) were added sequentially. The mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1 mL). The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL). The solution was then separated and purified using preparative HPLC and lyophilized to obtain compound A-1f in the form of a white solid (12.1 mg, 24%); EI-MS m / z: 1539 [M+H]. + . Step 7: Preparation of Compounds A-1 and A-2 Compound A-1f (12.1 mg, 0.008 mmol) was dissolved in methanol (1 mL) at 0 °C, and then lithium hydroxide monohydrate (4.3 mg, 0.1 mmol) dissolved in distilled water (250 μL) was slowly added dropwise, and the mixture was stirred at room temperature for 1.5 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1 mL). The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL). Then, the reaction solution was separated and purified using preparative HPLC and lyophilized to obtain compounds A-1 and A-2 in the form of a white solid (A-1: 1.4 mg, 13%, A-2: 1.8 mg, 17%); EI-MS m / z: A-1: 1357 [M+H]. + , A-2: 1328 [M+H] + . Example I-2: Preparation of Compound A-3

[0242] [ka] Step 1: Preparation of Compound A-3a Triphenylphosphine (65.6 mg, 0.24 mmol) and carbon tetrabromide (CBr4, 173 mg, 0.50 mmol) were dissolved in MC (5 mL) at 0 °C under a nitrogen atmosphere, and the mixture was stirred for 30 minutes. Compound A-1d (160 mg, 0.20 mmol) prepared in Step 4 of Example I-1 was dissolved in MC (2 mL) and added to the above reaction solution, and the mixture was stirred for 1 hour. After completion of the reaction, EA (100 mL) and distilled water (100 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound A-3a (30 mg, 17%); EI-MS m / z: 761 [M+H]. + . Step 2: Preparation of Compound A-3b Compound A-3a (30 mg, 0.036 mmol) was dissolved in DMF (2 mL) at 0° C. under a nitrogen atmosphere, and then auristatin F-OMe (30 mg, 0.04 mmol) prepared in Preparation Example 9 and DIPEA (18.9 μL, 0.11 mmol) were added sequentially, and the mixture was stirred at 60° C. for 3 hours. After completion of the reaction, the reaction solution was cooled to room temperature, and the reaction solution containing compound A-3b was used in the next reaction without further processing; EI-MS m / z: 1509 [M+H] + . Step 3: Preparation of Compound A-3 To the above reaction solution, lithium hydroxide monohydrate (15.2 mg, 0.36 mmol) was slowly added dropwise, and the mixture was stirred for 3 hours. After completion of the reaction, 2N aqueous hydrochloric acid (0.1 mL) was slowly added dropwise to quench the reaction, and the reaction solution was diluted with ACN (1 mL) and distilled water (1 mL). Then, it was separated and purified using preparative HPLC, and lyophilized to obtain compound A-3 in the form of a white solid (7.9 mg, 16%); EI-MS m / z: 1299 [M+H] + . Example I-3: Preparation of Compound A-4

[0243] [ka] Step 1: Preparation of Compound A-4a Compound A-1b (300 mg, 0.69 mmol) prepared in Step 2 of Example I-1 was dissolved in DMF (5 mL) at room temperature under a nitrogen atmosphere. Potassium carbonate (286 mg, 2.07 mmol) and compound L3-1 (424 mg, 0.90 mmol) prepared in Preparation Example 10 were then added sequentially, and the mixture was stirred at 70 °C for 4 hours. After completion of the reaction, the temperature of the reaction solution was lowered to room temperature, and EA (100 mL) and distilled water (200 mL) were added to extract the organic layer. Distilled water (300 mL) was added to extract the resulting organic layer again. The extracted organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-4a (580 mg, 96%) in the form of a light yellow oil. 1 H-NMR(400 MHz, CDCl3) δ 10.05 (s, 1H), 8.04 (s,1H), 7.57 (d, J = 8 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz,2H), 6.88 (d, J = 8 Hz, 1H), 5.52 (m. 2H), 5.25 (s, 2H), 5.15-5.08 (m, 4H),4.36 (q, J = 7.2 Hz, 2H), 4.26-4.22 (m, 1H), 4.19-4.07 (m, 2H), 3.69 (t, J = 6Hz, 2H), 3.59 (m ,2H), 3.53-3.51 (m, 2H), 3.48-3.43 (m, 4H), 3.41-3.39(m, 2H),3.44 (m, 2H), 2.19 (s, 3H), 2.08 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H), 1.41 (t,J = 7.2 Hz, 3H). Step 2: Preparation of Compound A-4b Compound A-4a (580 mg, 0.66 mmol) was dissolved in THF (10 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (63 mg, 1.65 mmol) was added, and the mixture was stirred for 3 h. After completion of the reaction, distilled water (100 mL) was added to quench the reaction, and EA (100 mL) was added to extract the organic layer. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-4b (370 mg, 63%). 1 H-NMR (400MHz, CDCl3) δ 7.42-7.40 (m, 3H), 7.04-6.98 (m,3H), 6.73 (d, J = 8 Hz, 1H), 5.52-5.47(m, 2H), 5.15-5.07 (m, 6H), 4.89 (m ,2H),4.35 (q, J = 7.2 Hz, 2H), 4.23 (m, 1H), 4.17 (m, 1H), 4.09 (m, 1H), 3.70 (m,2H), 3.59 (m, 2H), 3.53-3.41 (m, 8H), 3.33 (m, 2H), 2.19 (s, 3H), 2.08 (s, 3H),2.05 (s, 3H), 2.02 (s, 3H), 1.40 (t, J = 7.2 Hz, 3H). Step 3: Preparation of compound A-4c Compound A-4b (150 mg, 0.17 mmol) was dissolved in DMF (3 mL) at 0 °C under a nitrogen atmosphere, and then bis(4-nitrophenyl)carbonate (104.5 mg, 0.34 mmol) and DIPEA (60 μL, 0.34 mmol) were added sequentially. The mixture was stirred at room temperature for 2 hours. After completion of the reaction, the organic layer was diluted with EA (50 mL). Distilled water (50 mL) and 2N aqueous hydrochloric acid (10 mL) were added to extract the organic layer. The extracted organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography to give Compound A-4c (115 mg, 67%). 1H-NMR (400MHz, CDCl3) δ 8.20 (d, J = 8 Hz, 2H), 7.41 (d,J = 8.8 Hz, 2H), 7.29 (s, 1H), 7.07-7.02 (m, 5H), 6.75 (d, J = 8 Hz, 1H),5.52-5.46 (m, 2H), 5.34 (s, 2H), 5.16 (s, 2H), 5.14-5.07 (m, 4H), 4.35 (q, J =7.2 Hz, 2H), 4.23 (m, 1H), 4.19-4.08 (m, 2H), 3.72 (m, 2H), 3.61 (t, J = 7.2Hz, 2H), 3.52-3.42 (m, 8H), 3.43 (m, 2H), 2.19 (s, 3H), 2.08 (s, 3H), 2.05 (s,3H), 2.02 (s, 3H), 1.39 (t, J=7.2 Hz, 3H); EI-MS m / z: 1016 [M+Na] + . Step 4: Preparation of Compound A-4 Compound A-4c (22.3 mg, 0.022 mmol) was dissolved in methanol (1 mL) and THF (1 mL) at 0 ° C., and then lithium hydroxide monohydrate (4.7 mg, 0.112 mmol) dissolved in distilled water (200 μL) was slowly added dropwise, and the mixture was stirred at 0 ° C. for 10 minutes. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1 mL), and the reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-4 in the form of an ivory solid (8.9 mg, 48%). 1H-NMR (400MHz, DMSO-d6) δ 8.24 (d, J = 9.2 Hz, 2H), 7.49(d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.28 (d, J = 9.2 Hz, 2H), 7.20 (d, J = 7.6Hz, 1H), 7.08 (d, J = 8.8 Hz, 2H), 6.99 (d, J = 7.6 Hz, 1H), 5.48 (s, 2H), 5.21(s, 2H), 5.18 (m, 1H), 5.03 - 5.01 (m, 2H), 4.89 - 4.84 (m, 2H), 4.67 (m, 1H),4.53 (m, EI-MS m / z: 848 [M+Na] + . Example I-4: Preparation of Compound A-5

[0244] [ka] Compound A-4c (23.5 mg, 0.024 mmol) prepared in Step 3 of Example I-3 was dissolved in methanol (1.5 mL) and THF (0.4 mL) at 0 °C. Lithium hydroxide monohydrate (24.8 mg, 0.59 mmol) dissolved in distilled water (500 μL) was then slowly added dropwise, and the mixture was stirred at 0 °C for 1 hour. The reaction mixture was stirred at room temperature for another 2 hours. After completion of the reaction, 2N aqueous hydrochloric acid (1 mL) was added to quench the reaction. The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-5 in the form of a white solid (10 mg, 53%). 1H-NMR (400MHz, DMSO-d6) δ 8.21 (d, J = 9.2 Hz, 2H), 7.47(d, J = 8.4 Hz, 2H), 7.26 (d, J = 9.2 Hz, 2H), 7.18 (s, 1H), 7.12 (d, J = 8 Hz,1H), 7.06 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 8 Hz, 1H), 5.43 (s, 2H), 5.19 (s,2H), 5.17 (m, 1H), 5.03 - 5.01 (m, 2H), 4.90 - 4.83 (m, 2H), 4.65 (m, 1H), 4.51(m, 1H), 3.71 (m, 1H), 3.61 - 3.46 (m, 15H); EI-MS m / z: 820 [M+Na] + . Example I-5: Preparation of Compound A-6

[0245] [ka] Step 1: Preparation of Compound A-6a Compound A-4b (50 mg, 0.057 mmol) prepared in Step 2 of Example I-3 was dissolved in MC (2.5 mL) under a nitrogen atmosphere at 0 °C. Thionyl chloride (5 μL, 0.069 mmol) was then added, and the mixture was stirred at 0 °C for 3 hours. After completion of the reaction, EA (50 mL) and distilled water (50 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound A-6a (50 mg, 98%); EI-MS m / z: 891 [M+H]. + . Step 2: Preparation of Compound A-6b Compound A-6a (50 mg, 0.056 mmol) was dissolved in DMF (2 mL) at 0° C. under a nitrogen atmosphere, and then auristatin F-OMe (46.9 mg, 0.061 mmol) prepared in Preparation Example 9, DIPEA (24.4 μL, 0.14 mmol), and TBAI (2 mg, 0.005 mmol) were added sequentially. The mixture was stirred at 40° C. for 15 hours to prepare compound A-6b; EI-MS m / z: 1615 [M+H] + . Step 3: Preparation of Compound A-6 The reaction solution containing compound A-6b obtained in step 2 above was cooled to room temperature, and methanol (1 mL) was added. 6N aqueous sodium hydroxide solution (0.1 mL) and distilled water (1 mL) were added sequentially at 0°C, and the mixture was stirred for 30 minutes, then stirred at room temperature for another 2 hours. 2N aqueous hydrochloric acid solution (0.1 mL) was slowly added dropwise to quench the reaction. The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-6 (2 mg, 2%); EI-MS m / z: 1405 [M+H]. + . Example I-6: Preparation of Compound A-7

[0246] [ka] Step 1: Preparation of Compound A-7a Core C-1 (99.1 mg, 0.42 mmol) was dissolved in MC (15 mL) at 0 °C under a nitrogen atmosphere, and then acetobromo-alpha-D-galactose (192 mg, 0.46 mmol) and benzyltributylammonium chloride (132 mg, 0.42 mmol) were added. A 5N aqueous solution of sodium hydroxide (255 μL, 1.27 mmol) was gradually added to the reaction solution, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted three times with MC (50 mL) and distilled water (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-7a (131.3 mg, 55%) in the form of an ivory solid. 1 H-NMR (400MHz, CDCl3) δ 10.19 (s, 1H), 7.82 (d, J = 8 Hz,1H), 7.38 (s, 1H), 6.80 (d, J = 8 Hz, 1H), 5.64 (dd, J =10.4, 8 Hz, 1H), 5.50(d, J =3.2 Hz, 1H), 5.29 (d, J = 8 Hz, 1H), 5.16 (dd, J =10.4, 3.2 Hz, 1H),4.34 (s, 3H), 4.26 - 4.09 (m, 3H), 3.93 (s, 3H), 2.21 (s, 3H), 2.08 (s, 3H),2.06 (s, 3H), 2.05 (s, 3H). Step 7: Preparation of Compound A-7b Compound A-7a (131.3 mg, 0.23 mmol) was dissolved in THF (3 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (26.5 mg, 0.70 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, distilled water (50 mL) was added to quench the reaction, and EA (50 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-7b (101.5 mg, 77%) in the form of a yellow solid. 1H-NMR(400 MHz, CDCl3) δ 7.32 (s, 1H), 7.12 (d, J= 8 Hz, 1H), 6.63 (d, J = 8 Hz, 1H), 5.61 (dd, J = 10.4, 8 Hz, 1H), 5.48 (d, J= 2.8 Hz, 1H), 5.16 - 5.12 (m, 2H), 4.99 - 4.97 (m, 2H), 4.41 (s, 3H), 4.28 -4.08 (m, 3H), 3.91 (s, 3H), 2.20 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.04 (s,3H). Step 8: Preparation of Compound A-7c Compound A-7b (101.5 mg, 0.18 mmol) was dissolved in MC (5 mL) at 0 °C under a nitrogen atmosphere, and then 4-nitrophenyl chloroformate (108.5 mg, 0.54 mmol) and DIPEA (156 μL, 0.89 mmol) were added sequentially, and the mixture was stirred for 20 h. After completion of the reaction, EA (30 mL) and distilled water (30 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-7c (44.1 mg, 36%). 1 H-NMR(400 MHz, CDCl3) δ 8.25 (d, J = 9.2 Hz, 2H),7.35 (s, 1H), 7.23 (d, J = 8 Hz, 1H), 7.08 (d, J = 9.2 Hz, 2H), 6.69 (d, J = 8Hz, 1H), 5.62 (dd, J =10.4, 8 Hz, 1H), 5.49 (d, J = 2.8 Hz, 1H), 5.44 (m, 2H),5.18 (d, J = 8 Hz, 1H), 5.15 (dd, J = 10.4, 3.6 Hz, 1H), 4.27 (m, 1H), 4.24 (s,3H), 4.20 - 4.09 (m, 2H), 3.91 (s, 3H), 2.21 (s, 3H), 2.06 (m, 6H), 2.04 (s,3H). Step 9: Preparation of Compound A-7 Compound A-7c (37.2 mg, 0.054 mmol) was dissolved in methanol (1.5 mL) and ACN (1.5 mL) under a nitrogen atmosphere at 0° C., and then potassium carbonate (52.4 mg, 0.38 mmol) was added. The mixture was stirred for 1.5 hours while the temperature was raised from 0° C. to room temperature. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1 mL). The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-7 in the form of a white solid (5 mg, 18%). 1 H-NMR(400 MHz, DMSO-d6) δ 8.25 (d, J = 9.2 Hz,2H), 7.47 (s, 1H), 7.38 (d, J = 8 Hz, 1H), 7.32 (d, J = 9.2 Hz, 2H), 6.76 (d, J= 8 Hz, 1H), 5.59 (s, 2H), 5.33 (m, 1H), 4.94 - 4.92 (m, 2H), 4.68 (m, 1H),4.57 (m, 1H), 4.18 (s, 3H), 3.85 (s, 3H), 3.73 (m, 1H), 3.64 (m, 1H). Example I-7: Preparation of Compound A-8

[0247] [ka] Step 1: Preparation of Compound A-8a Core C-2 (2.4 g, 7.75 mmol) was dissolved in DMF (25 mL) at 0 °C under a nitrogen atmosphere. EDC (CAS No. 25952-53-8, 2.23 g, 11.63 mmol), HOBt (1.05 g, 8.14 mmol), DMAP (95 mg, 0.77 mmol), DIPEA (4 mL, 23.25 mmol), and linker P-1 (1.98 g, 7.75 mmol) were added sequentially, and the mixture was stirred for 30 min. The reaction mixture was stirred at room temperature for an additional 16 h and then extracted with EA (300 mL) and 1N aqueous hydrochloric acid (400 mL). 1N aqueous sodium hydroxide solution (5 mL) and distilled water (300 mL) were added to the resulting organic layer to extract the organic layer. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-8a in the form of a light yellow oil (2.57 g, 65%). 1 H-NMR(400 MHz, CDCl3) δ 10.01 (s, 1H), 7.67 (s,1H), 7.54 (d, J = 8 Hz, 1H), 7.48-7.37 (m, 5H), 6.88-6.84 (m, 2H), 5.30 (s,2H), 4.33 (s, 3H), 3.71-3.60 (m, 14H), 3.32 (t, J = 5.2 Hz, 2H); EI-MS m / z: 510[M+H] + . Step 2 to Step 7: Preparation of Compound A-8 Compound A-8a was used as the starting material in the same manner as in Steps 2 to 7 of Example I-1 to obtain compound A-8 in the form of a white solid (3.1 mg, 39%); EI-MS m / z: 1341 [M+H] + . Example I-8: Preparation of Compound A-9

[0248] [ka] Using compound A-8b as the starting material in the same manner as in Example I-3, compound A-9 was obtained in the form of an ivory solid (21.5 mg, 72%). 1 H-NMR (400MHz, DMSO-d6) δ 8.50 (t, J = 5.2 Hz, 1H), 8.22(d, J = 9.2 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 9.2 Hz, 2H), 7.13 -7.11 (m, 2H), 7.06 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8 Hz, 1H), 5.38 (s, 2H),5.18 (s, 2H), 5.16 (m, 1H), 4.84 - 4.82 (m, 2H), 4.64 (m, 1H), 4.51 (m, 1H),4.20 (s, 3H), 3.70 (m, 1H), 3.56 - 3.51 (m, 15H), 3.40 (m, 2H). Example I-9: Preparation of Compound A-10

[0249] [ka] Step 1: Preparation of Compound A-10a Core C-3 (160 mg, 0.89 mmol) was dissolved in ACN (12 mL) at 0 °C under a nitrogen atmosphere, and then acetobromo-alpha-D-galactose (406 mg, 0.98 mmol), silver(I) oxide (520 mg, 2.22 mmol), and molecular sieves (70 mg) were added sequentially. The mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction solution was diluted with EA (100 mL), filtered using a Celite filter, and extracted with distilled water (100 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-10a (400 mg, 87.7%) in solid form. 1H-NMR (400MHz, CDCl3) δ 10.13 (s, 1H), 7.84 (d, J = 8 Hz,1H), 7.59 (d, J = 5.6 Hz, 1H), 7.49 (d, J = 5.6 Hz, 1H), 7.09 (d, J = 8 Hz,1H), 5.67 (dd, J = 10.4, 8 Hz, 1H), 5.52 (d, J = 3.2 Hz, 1H), 5.30 (d, J = 8Hz, 1H), 5.19 (dd, J =10.4, 3.6 Hz, 1H), 4.29 (m, 1H), 4.21-4.17 (m, 2H), 2.21(s, 3H), 2.10(s, 3H), 2.04 (s, 6H). Step 2: Preparation of Compound A-10b Compound A-10a (183 mg, 0.36 mmol) was dissolved in THF (10 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (34 mg, 0.90 mmol) was added. The mixture was stirred at 0 °C for 1 hour, and then at room temperature for 2.5 hours. After completion of the reaction, distilled water (50 mL) was added to quench the reaction, and EA (50 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-10b (137.2 mg, 75%) in the form of a white solid. 1 H-NMR (400MHz, CDCl3) δ 7.45 (d, J = 5.6 Hz, 1H), 7.40(d, J = 5.6 Hz, 1H), 7.28 (d, J = 8 Hz, 1H), 6.95 (d, J = 8 Hz, 1H), 5.63 (dd,J = 10.4, 8 Hz, 1H), 5.50 (d, J = 2.8 Hz, 1H), 5.17 - 5.14 (m, 2H), 4.92 (d, J= 5.6 Hz, 2H), 4.29 - 4.11 (m, 3H), 2.20 (s, 3H), 2.08 (s, 3H), 2.05 (s, 3H),2.03 (s, 3H), 1.79 (t, J = 6 Hz, 1H). Step 3: Preparation of Compound A-10c Compound A-10b (137.2 mg, 0.18 mmol) was dissolved in MC (10 mL) at 0 °C under a nitrogen atmosphere, and then 4-nitrophenyl chloroformate (81.2 mg, 0.40 mmol) and DIPEA (140 μL, 0.81 mmol) were added sequentially. The mixture was stirred for 16 h while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, EA (50 mL) and distilled water (50 mL) were added to extract the organic layer. The organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography to give compound A-10c (114.7 mg, 63%) in the form of a white solid. 1 H-NMR(400 MHz, CDCl3) δ 8.27 (d, J = 9.2 Hz, 2H),7.48 (d, J = 5.6 Hz, 1H), 7.44 (d, J = 5.6 Hz, 1H), 7.39 - 7.36 (m, 3H), 6.97(d, J = 8 Hz, 1H), 5.64 (dd, J = 10.4, 8 Hz, 1H), 5.24 (s, 2H), 5.51 (d, J =3.2 Hz, 1H), 5.19 - 5.14 (m, 2H), 4.29 - 4.13 (m, 3H), 2.21 (s, 3H), 2.08 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H). Step 4: Preparation of Compound A-10d Compound A-10c (64 mg, 0.094 mmol) was dissolved in DMF (3 mL) at 0 °C under a nitrogen atmosphere, and then compound PL-1 (25 mg, 0.113 mmol), HOBt (20 mg, 0.141 mmol), pyridine (500 μL), and DIPEA (41 μL, 0.235 mmol) were added sequentially, and the mixture was stirred at room temperature for 12 h. After completion of the reaction, extraction was carried out using EA (50 mL) and 1N aqueous hydrochloric acid (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-10d (49 mg, 68.3%). 1 H-NMR (400MHz, CDCl3) δ 7.46 - 7.39 (m, 2H), 7.34 (m,1H), 7.28 - 7.22 (m, 2H), 7.16 - 7.03 (m, 3H), 7.01 - 6.65 (m, 2H), 5.63 (m,1H), 5.50 (m, 1H), 5.17 - 4.93 (m, 4H), 4.63 - 4.09 (m, 4H), 3.26 - 3.22 (m,3H), 2.88 - 3.87 (m, 3H), 2.32 (m, 1H), 2.20 (s, 3H), 2.08 - 2.07 (m, 3H), 2.05- 2.03 (m, 6H), 0.90 - 0.87 (m, 3H), 0.72 - 0.55 (m, 3H); MS m / z: 757 [M+H] + . Step 5: Preparation of Compound A-10 Compound A-10d (49 mg, 0.065 mmol) was dissolved in methanol (2 mL) at 0 ° C., and then lithium hydroxide monohydrate (13.6 mg, 0.324 mmol) dissolved in distilled water (400 μL) was slowly added dropwise, and the mixture was stirred at 0 ° C. for 10 minutes. After completion of the reaction, 2N aqueous hydrochloric acid solution (1 mL) was added to terminate the reaction, and the reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-10 in the form of a white solid (28.5 mg, 74%). 1H-NMR (400MHz, DMSO-d6) δ 7.72 (m, 0.5H), 7.68 - 7.65 (m,1H), 7.58 (m, 0.5H), 7.31 - 7.21 (m, 3H), 7.15 - 7.02 (m, 4H), 5.31 (m, 1H),5.10 - 4.91 (m, 3H), 4.68 (m, 1H), 4.55 (m, 1H), 4.24 (m, 1H), 3.73 - 3.44 (m,3H), 3.14 (s, 3H), 2.72 (m, 3H), 2.16 (m, 1H), 0.83 - 0.77 (m, 3H), 0.63 - 0.43(m, 3H); EI-MS m / z: 589 [M+H] + . Example I-10: Preparation of Compound A-11

[0250] [ka] Compound A-11 was obtained in the same manner as in Example I-9, except that MMAF-OMe was used instead of compound PL-1 in step 4 of Example I-9 (10.4 mg, 65%) in the form of a white solid; EI-MS m / z: 1101 [M+H] + . Example I-11: Preparation of Compound A-12

[0251] [ka] Using core C-5 as the starting material in the same manner as in Example I-9, except that MMAF-OMe was used instead of compound PL-1 in step 4 of Example I-9, compound A-12 was obtained in the form of a white solid (11.7 mg, 64%); EI-MS m / z: 1145 [M+H] + . Example I-12: Preparation of Compound A-13

[0252] [ka] Step 1: Preparation of Compound A-13a Core C-6 (192 mg, 0.61 mmol) was dissolved in DMF (5 mL) at 0 °C under a nitrogen atmosphere, followed by the sequential addition of EDCI (177 mg, 0.92 mmol), HOBt (83.1 mg, 0.61 mmol), DMAP (7.5 mg, 0.06 mmol), and DIPEA (322 μL, 1.85 mmol). Linker P-4 (azido-PEG-amine, TCI, CAS No. 951671-92-4, 184 mg, 0.61 mmol) dissolved in DMF (3 mL) was then added, and the mixture was stirred at 0 °C for 3 h. The mixture was stirred for an additional 16 h while the temperature was allowed to rise to room temperature. After completion of the reaction, the organic layer was extracted with EA (100 mL) and 2 N aqueous hydrochloric acid (100 mL). The organic layer was extracted with 2N aqueous sodium hydroxide (5 mL) and distilled water (50 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain Compound A-13a (184.9 mg, 54%) in the form of a brown oil. 1 H-NMR (400MHz, CDCl3) δ 10.07 (s, 1H), 8.12 (s, 1H), 7.89(d, J = 8.4 Hz, 1H), 7.50 - 7.37 (m, 5H), 7.00 (d, J = 8 Hz, 1H), 6.96 (m, 1H),5.33 (s, 2H), 3.68 - 3.58 (m, 18H), 3.31 (t, J = 5.2 Hz, 2H); EI-MS m / z: 557[M+H] + . Step 2: Preparation of Compound A-13b Compound A-13a (184.9 mg, 0.33 mmol) was dissolved in MC (10 mL) at −50 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl in MC, 2.99 mL, 2.99 mmol) was slowly added, and the mixture was stirred for 3.5 h while the temperature was gradually raised to −30 °C. After completion of the reaction, distilled water (100 mL) was slowly added dropwise to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction mixture. MC (100 mL) was added to the mixture to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-13b (75.9 mg, 49%) in the form of a bright orange solid. 1 H-NMR(400 MHz, CDCl3) δ 10.02 (s, 1H), 8.41 (s,1H), 7.84 (d, J = 8 Hz, 1H), 7.32 (brs, 1H), 6.98 (d, J = 8 Hz, 1H), 3.82 -3.64 (m, 16H), 3.55 (t, J = 5.2 Hz, 2H), 3.28 (t, J = 5.2 Hz, 2H). Steps 3-7: Preparation of compound A-13 Compound A-13 was obtained in the same manner as in Example I-9, except that MMAF-OMe was used instead of compound PL-1 in step 4 of Example I-9 (25.7 mg, 66%) in the form of a white solid; EI-MS m / z: 1389 [M+H] + . Example I-13: Preparation of Compound A-14

[0253] [ka] Compound A-14 was obtained in the same manner as in Example I-12, except that linker P-5 was used instead of linker P-4 in step 1 of Example I-12 (22.4 mg, 67%) in the form of a white solid; EI-MS m / z: 1358 [M+H] + . Example I-14: Preparation of Compound A-15

[0254] [ka] Step 1: Preparation of Compound A-15a Core C-7 (278 mg, 0.81 mmol) and linker P-1 (208 mg, 0.81 mmol) were dissolved in DMF (5 mL) at 0 °C under a nitrogen atmosphere. EDCI hydrochloride (235 mg, 1.22 mmol), DMAP (10 mg, 0.08 mmol), and DIPEA (430 μL, 2.45 mmol) were added sequentially, and the mixture was stirred for 16 h while the temperature was gradually raised to room temperature. After completion of the reaction, the organic layer was extracted twice with EA (250 mL) and 2 N aqueous hydrochloric acid (250 mL). Saturated aqueous sodium chloride solution (250 mL) was added to the obtained organic layer, and the organic layer was extracted. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-15a (207 mg, 47%) in the form of a yellow oil. 1 H-NMR (400MHz, CDCl3) δ 10.03 (s, 1H), 7.74 (d, J = 8 Hz,1H), 7.49 - 7.34 (m, 6H), 6.94 (d, J = 8 Hz, 1H), 6.18 (m, 1H), 5.30 (s, 2H),3.65 - 3.60 (m, 6H), 3.57 - 3.55 (m, 2H), 3.52 - 3.48 (m, 4H), 3.44 (t, J = 5.2Hz, 2H), 3.35 (t, J = 5.2 Hz, 2H), 3.31 (t, J = 7.6 Hz, 2H), 2.64 (t, J = 7.6Hz, 2H); EI-MS m / z: 541 [M+H] + . Step 2: Preparation of Compound A-15b Compound A-15a (207 mg, 0.38 mmol) was dissolved in MC (10 mL) at −55 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl in MC, 2.3 mL, 2.3 mmol) was slowly added, and the mixture was stirred for 2.5 h while the temperature was gradually raised to −40 °C. After completion of the reaction, distilled water (100 mL) was slowly added dropwise to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction solution. MC (100 mL) was added to the mixture, and the organic layer was extracted twice. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-15b (97.5 mg, 56%) in the form of a yellow viscous gum. 1 H-NMR(400 MHz, CDCl3) δ 9.98 (s, 1H), 7.66 (d, J= 8 Hz, 1H), 7.44 (s, 1H), 6.89 (d, J = 8 Hz, 1H), 6.36 (brs, 1H), 3.66 (m,4H), 3.64 - 3.58 (m, 4H), 3.55 - 3.52 (m, 2H), 3.49 - 3.43 (m, 4H), 3.35 - 3.30(m, 4H), 2.68 (t, J = 7.2 Hz, 2H); EI-MS m / z: 451 [M+H] + . Step 3: Preparation of Compound A-15c Compound A-15b (97.5 mg, 0.21 mmol) was dissolved in MC (7 mL) at 0 °C under a nitrogen atmosphere, and then acetobromo-alpha-D-galactose (142 mg, 0.34 mmol) and benzyltributylammonium chloride (67.5 mg, 0.21 mmol) were added. 5N aqueous sodium hydroxide solution (0.13 mL, 0.65 mmol) was slowly added to the reaction solution, and the mixture was stirred for 20 hours while the temperature was gradually raised to room temperature. After completion of the reaction, the organic layer was extracted three times with MC (150 mL) and distilled water (150 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-15c (42.3 mg, 25%). 1 H-NMR (400MHz, CDCl3) δ 10.08 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H),7.18 (s, 1H), 6.05 (d, J = 8.4 Hz, 1H), 6.14 (m, 1H), 5.59 (dd, J = 10.4, 8 Hz,1H), 5.52 (d, J = 3.2 Hz, 1H), 5.27 (d, J = 8 Hz, 1H), 5.18 (dd, J = 10.4, 3.2Hz, 1H), 4.27 (m, 1H), 4.20 - 4.15 (m, 2H), 3.67 - 3.65 (m, 6H), 3.61 - 3.59(m, 2H), 3.57 - 3.52 (m, 4H), 3.48 - 3.45 (m, 2H), 3.37 (t, J = 5.2 Hz, 2H),3.16 (t, J = 7.6 Hz, 2H), 2.63 (t, J = 7.6 Hz, 2H), 2.21 (s, 3H), 2.09 (s, 3H),2.06 (s, 3H), 2.04 (s, 3H). Step 4: Preparation of Compound A-15d Compound A-15c (42.3 mg, 0.054 mmol) was dissolved in THF (3 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (5.1 mg, 0.135 mmol) was added. The mixture was stirred for 2.5 hours while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, distilled water (50 mL) was added to quench the reaction, and EA (50 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-15d in the form of a white solid (30.6 mg, 72%); EI-MS m / z: 783 [M+H]+. Step 5: Preparation of Compound A-15e Compound A-15d (30.6 mg, 0.039 mmol) was dissolved in MC (2 mL) at 0 °C under a nitrogen atmosphere, and then 4-nitrophenyl chloroformate (11.8 mg, 0.058 mmol) and DIPEA (17 μL, 0.098 mmol) were added sequentially. The mixture was stirred for 16 hours while the temperature was raised from 0 °C to room temperature. After completion of the reaction, MC (50 mL) and distilled water (50 mL) were added to extract the organic layer twice. The organic layer obtained was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography to obtain compound A-15e in the form of a white solid (22.2 mg, 60%); EI-MS m / z: 948 [M+H]. + . Step 6: Preparation of Compound A-15f Compound A-15e (22.2 mg, 0.023 mmol) was dissolved in DMF (0.5 mL) at 0 °C under a nitrogen atmosphere, and then MMAF-OMe (17.5 mg, 0.023 mmol), HOBt (4.7 mg, 0.035 mmol), pyridine (500 μL), and DIPEA (10.2 μL, 0.058 mmol) were added sequentially, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted twice with EA (50 mL) and 2N aqueous hydrochloric acid (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-15f in the form of a colorless solid (23.6 mg, 65%); EI-MS m / z: 1555 [M+H]. + . Step 7: Preparation of Compound A-15 Compound A-15f (23.6 mg, 0.015 mmol) was dissolved in methanol (0.6 mL) and THF (0.3 mL) at 0 °C, and then lithium hydroxide monohydrate (6.3 mg, 0.152 mmol) dissolved in distilled water (0.2 mL) was slowly added dropwise. The mixture was stirred for 2.5 hours while the temperature was gradually raised from 0 °C to room temperature. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1 mL). The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC, followed by lyophilization to obtain compound A-15 in the form of a white solid (10.1 mg, 48%); EI-MS m / z: 1373 [M+H] + . Example I-15: Preparation of Compound A-16

[0255] [ka] Using core C-8 as the starting material in the same manner as in Example I-9, except that MMAF-OMe was used instead of compound PL-1 in step 4 of Example I-9, compound A-16 was obtained in the form of a white solid (7.7 mg, 60%); EI-MS m / z: 1172 [M+H] + . Example I-16: Preparation of Compound A-17

[0256] [ka] Step 1: Preparation of Compound A-17a Core C-4 (174 mg, 0.976 mmol) was dissolved in MC (30 mL) at room temperature under a nitrogen atmosphere, followed by the sequential addition of acetobromo-alpha-D-galactose (440 mg, 1.07 mmol) and benzyltributylammonium chloride (Sigma-Aldrich, CAS No. 23616-79-7, 304 mg, 0.976 mmol). A 5N aqueous solution of sodium hydroxide (586 μL, 2.93 mmol) was added to the reaction solution, and the mixture was stirred for 5 hours. After completion of the reaction, MC (100 mL) and distilled water (100 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography to obtain compound A-17a (250 mg, 50.4%). 1 H-NMR(400 MHz, CDCl3) δ 10.09 (s, 1H), 8.09 (s,1H), 7.59 (d, J = 8 Hz, 1H), 7.44 (t, J = 8 Hz, 1H), 6.95 (d, J = 8 Hz, 1H),5.64 (dd, J =10.4, 8 Hz, 1H), 5.50 (d, J = 3.2 Hz, 1H), 5.23 (d, J = 8 Hz, 1H),5.18 (dd, J =10.4, 8 Hz, 1H), 4.27 (m, 1H), 4.20-4.11 (m, 2H), 2.21 (s, 3H),2.06 (s, 6H), 2.05 (s, 3H). Step 2: Preparation of Compound A-17b Compound A-17a (250 mg, 0.49 mmol) was dissolved in THF (10 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (46.5 mg, 1.225 mmol) was added, and the mixture was stirred for 1 h. After completion of the reaction, distilled water (50 mL) was added to quench the reaction, and EA (50 mL) was added to extract the organic layer. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-17b (230 mg, 92%). 1 H-NMR (400MHz, CDCl3) δ 7.53 (d, J = 8 Hz, 1H), 7.28-7.22(m, 2H), 6.93 (d, J = 8 Hz, 1H), 5.60 (dd, J =10.4, 8 Hz, 1H), 5.48 (d, J = 2.4Hz, 1H), 5.16-5.12 (m, 2H), 4.91 (d, = 5.2 Hz, 2H), 4.31 (dd, J =11.2, 7.2 Hz,1H), 4.16-4.10 (m, 2H), 2.21 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H). Step 3: Preparation of compound A-17c Compound A-17b (300 mg, 0.58 mmol) was dissolved in concentrated hydrochloric acid (8 mL) at 0° C. under a nitrogen atmosphere, and the mixture was then stirred at 0° C. for 1 hour. After completion of the reaction, EA (50 mL) and distilled water (50 mL) were added to extract the organic layer, which was then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give compound A-17c in the form of a white solid (300 mg, 96.7%); MS m / z: 529 [M+H] + . Step 4: Preparation of Compound A-17d Compound A-17c (300 mg, 0.56 mmol) was dissolved in DMF (15 mL) at room temperature under a nitrogen atmosphere. Sodium azide (55 mg, 0.84 mmol) was then added, and the mixture was stirred at 60 °C for 2 hours. After completion of the reaction, EA (100 mL) and distilled water (200 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-17d (230 mg, 75.6%). 1 H-NMR (400MHz, CDCl3) δ 7.52 (d, J = 8 Hz, 1H), 7.32 (s,1H), 7.28 (t, J = 8 Hz, 1H), 6.94 (d, J = 8 Hz, 1H), 5.61 (dd, J = 10.4, 8 Hz,1H), 5.50 (d, J = 2.4 Hz, 1H), 5.17-5.14 (m, 2H), 4.60 (d, J = 14.4 Hz, 1H),4.52 (d, J = 14.4 Hz, 1H), 4.26 (dd, J =11.2, 6.8 Hz, 1H), 4.20-4.11 (m, 2H),2.20 (s, 3H), 2.07 (s, 3H), 2.05(s, 3H), 2.04 (s, 3H); MS m / z: 558 [M+Na] + . Step 5: Preparation of Compound A-17e A-17d (230 mg, 0.42 mmol) was dissolved in MC (15 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (116 μL, 1.26 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 1.28 mL, 1.26 mmol) were then added sequentially and slowly. The mixture was stirred for 1 h while maintaining the temperature. After completion of the reaction, cooled distilled water (100 mL) was slowly added dropwise to quench the reaction, and EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-17e (130 mg, 53.7%) in the form of a white solid. 1 H-NMR(400 MHz, CDCl3) δ 10.11 (s, 1H), 7.84 (d, J= 8 Hz, 1H), 7.40 (s, 1H), 7.08 (d, J = 8 Hz, 1H), 5.66 (dd, J =10.4, 8 Hz,1H), 5.52 (d, J = 3.2 Hz, 1H), 5.29 (d, J = 8 Hz, 1H), 5.19 (dd, J =10.4, 3.2Hz, 1H), 4.65 (d, J = 14.4 Hz, 1H), 4.52 (d, J = 14.4 Hz, 1H), 4.31-4.17 (m,3H), 2.21 (s, 3H), 2.09 (s, 3H), 2.05 (s, 6H); MS m / z: 586 [M+Na] + . Step 6: Preparation of Compound A-17f Compound A-17e (130 mg, 0.23 mmol) was dissolved in THF (10 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (22 mg, 0.575 mmol) was added, and the mixture was stirred for 1 h. After completion of the reaction, distilled water (100 mL) was added to quench the reaction, and EA (100 mL) was added to extract the organic layer. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-17f (120 mg, 92.3%). 1H-NMR (400MHz, CDCl3) δ 7.36 (s, 1H), 7.28 (d, J = 8 Hz,1H), 6.94 (d, J = 8 Hz, 1H), 5.61 (dd, J =10.4, 8 Hz, 1H), 5.49 (d, J = 2.8 Hz,1H), 5.17-5.14 (m, 2H), 4.89 (d, J = 5.6 Hz, 2H), 4.61 (d, J = 14.4 Hz, 1H),4.54 (d, J = 14.4 Hz, 1H), 4.26 (dd, J = 11.2, 6.8 Hz, 1H), 4.20-4.11 (m, 2H),2.20 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 1.79 (t, J = 5.6 Hz,1H). Step 7: Preparation of Compound A-17g Compound A-17f (120 mg, 0.21 mmol) was dissolved in MC (3 mL) at 0 °C under a nitrogen atmosphere, and then 4-nitrophenyl chloroformate (85 mg, 0.42 mmol), pyridine (51 μL, 0.63 mmol), and DIPEA (55 μL, 0.32 mmol) were added sequentially. The mixture was stirred at 0 °C for 30 minutes and at room temperature for 2 hours. After completion of the reaction, the reaction solution was diluted with MC (50 mL), and 2N aqueous hydrochloric acid (50 mL) was added to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography to give compound A-17g (116.3 mg, 75%). 1H-NMR (400MHz, CDCl3) δ 8.27 (d, J = 9.2 Hz, 2H), 7.39 -7.37 (m, 4H), 6.96 (d, J = 8 Hz, 1H), 5.62 (dd, J = 10.4, 8 Hz, 1H), 5.50 (d, J= 3.2 Hz, 1H), 5.48 (s, 2H), 5.19 - 5.15 (m, 2H), 4.63 (d, J = 14.4 Hz, 1H),4.57 (d, J = 14.4 Hz, 1H), 4.26 (m, 1H), 4.20 - 4.11 (m, 2H), 2.21 (s, 3H),2.07 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H). Step 8: Preparation of compound A-17h Compound A-17g (18.7 mg, 0.025 mmol) and compound PL-1 (6.7 mg, 0.031 mmol) were dissolved in DMF (500 μL) at 0 °C under a nitrogen atmosphere. HOBt (5.2 mg, 0.038 mmol), pyridine (500 μL), and DIPEA (11.1 μL, 0.064 mmol) were then added sequentially, and the mixture was stirred at room temperature for 16 h. After completion of the reaction, the organic layer was extracted twice with EA (50 mL) and 2 N aqueous hydrochloric acid (50 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-17h (17.9 mg, 86%) in the form of a white solid. 1H-NMR(400 MHz, CDCl3) δ 7.37 - 7.32 (m, 1H), 7.28- 7.22 (m, 2H), 7.19 - 6.85 (m, 5H), 5.61 (m, 1H), 5.50 (m, 1H), 5.18 - 5.09(m, 4H), 4.64 - 4.48 (m, 3H), 4.39 - 4.13 (m, 3H), 3.25 -3.23 (m, 3H), 2.90 -2.88 (m, 3H), 2.32 (m, 1H), 2.20 (s ,3H), 2.07 - 2.04 (m, 9H), 0.98 - 0.83 (m,3H), 0.72 - 0.55 (m, 3H); EI-MS m / z: 812 [M+H] + . Step 9: Preparation of Compound A-17 Compound A-17h (17.9 mg, 0.022 mmol) was dissolved in methanol (1 mL) and THF (0.5 mL) under a nitrogen atmosphere at 0° C., and then potassium carbonate (21.3 mg, 0.154 mmol) was added, and the mixture was stirred at 0° C. for 40 minutes. After completion of the reaction, 2N aqueous hydrochloric acid (1 mL) was added to quench the reaction, and the reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-17 in the form of a white solid (7.5 mg, 53%); EI-MS m / z: 644 [M+H] + . Example I-17: Preparation of Compound A-18

[0257] [ka] Compound A-18 was obtained as a white solid (22 mg, 71%) in the same manner as in Example I-16, except that MMAF-OMe was used instead of compound PL-1 in step 8 of Example I-16 and lithium hydroxide monohydrate was used instead of potassium carbonate in step 9. EI-MS m / z: 1156 [M+H] + . Example I-18: Preparation of Compound A-19

[0258] [ka] Compound A-18 (4.3 mg, 0.0037 mmol) was dissolved in DMSO (200 μL) at 0 °C under a nitrogen atmosphere. Then, 70 μL of a solution of linker P-6 (16.7 mg) dissolved in DMSO (1 mL) was added to the reaction mixture. Distilled water (2 mL), DMSO (0.4 mL), copper(II) sulfate pentahydrate (CuSO 5H O, 1 mg), and sodium ascorbate (1.47 mg) were added sequentially to the reaction mixture, and the mixture was stirred at room temperature for 30 min. After completion of the reaction, the reaction mixture was diluted with distilled water (1 mL), separated and purified using preparative HPLC, and then lyophilized to obtain compound A-19 (3.6 mg, 72%); MS m / z: 1358 [M+H]. + . Example I-19: Preparation of Compound A-20

[0259] [ka] Compound A-18 (17.8 mg, 0.0154 mmol) was dissolved in THF (1 mL) at room temperature under a nitrogen atmosphere. Triphenylphosphine (4.4 mg, 0.017 mmol) and distilled water (0.3 mL) were then added sequentially, and the mixture was stirred for 12 hours. 2N aqueous sodium hydroxide solution (10 μL) was added to the above reaction solution at room temperature, and the mixture was stirred for 30 minutes. 2N aqueous hydrochloric acid solution was then added dropwise to adjust the pH of the reaction solution to 3. The reaction solution was separated and purified using preparative HPLC, and then lyophilized to obtain compound A-20 (11.3 mg, 65%); MS m / z: 1130 [M+H]. + . Example I-20: Preparation of Compound A-21

[0260] [ka] Compound A-20 (4.7 mg, 0.0041 mmol) was dissolved in THF (2 mL) at 0 °C under a nitrogen atmosphere, and then linker P-7 (2.7 mg, 0.0078 mmol), DIPEA (10 μL), and distilled water (200 μL) were added dropwise, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was diluted with ACN (2 mL) containing 0.1% formic acid, separated and purified using preparative HPLC, and then lyophilized to give compound A-21 (2.9 mg, 51%); MS m / z: 1358 [M+H]. + . Example I-21: Preparation of Compound A-22

[0261] [ka] Using core C-10 as the starting material in the same manner as in Example I-15, compound A-22 was obtained in the form of a white solid (8 mg, 58%); EI-MS m / z: 1171 [M+H] + . Example I-22: Preparation of Compound A-23

[0262] [ka] Step 1: Preparation of Compound A-23a Core C-11 (189 mg, 0.76 mmol) and linker P-1 (233 mg, 0.91 mmol) were dissolved in DMF (5 mL) at 0 °C under a nitrogen atmosphere. EDCI hydrochloride (219 mg, 1.14 mmol), DMAP (9.3 mg, 0.07 mmol), and DIPEA (400 μL, 2.29 mmol) were added sequentially, and the mixture was stirred for 16 h while the temperature was gradually raised to room temperature. After completion of the reaction, the organic layer was extracted twice with EA (150 mL) and 2 N aqueous hydrochloric acid (150 mL). Saturated aqueous sodium chloride (100 mL) was added to the resulting organic layer, and the organic layer was extracted. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-23a in the form of an orange solid (47.5 mg, 14%); EI-MS m / z: 449 [M+H] + . Steps 2-6: Preparation of Compound A-23 Compound A-23a was used as the starting material in the same manner as in Example I-9, except that MMAF-OMe was used instead of compound PL-1 in step 4 of Example I-9, to give compound A-23 in the form of a white solid (16.8 mg, 69%); EI-MS m / z: 1371 [M+H] + . Example I-23: Preparation of Compound A-24

[0263] [ka] Using core C-12 as the starting material in the same manner as in steps 3 to 7 of Example I-1, compound A-24 was obtained in the form of a white solid (12.1 mg, 68%); EI-MS m / z: 1129 [M+H] + . Example I-24: Preparation of Compound A-25

[0264] [ka] Using core C-13 as the starting material in the same manner as in Example I-14, compound A-25 was obtained in the form of a white solid (18.6 mg, 65%); EI-MS m / z: 1342 [M+H] + . Example I-25: Preparation of Compound A-26

[0265] [ka] Using core C-14 as a starting material in the same manner as in Example I-16, except that compound PL-1 in step 8 of Example I-16 was replaced with MMAF-OMe, and lithium hydroxide monohydrate was used instead of potassium carbonate in step 9, compound A-26 was obtained in the form of a white solid (21.3 mg, 61%); EI-MS m / z: 1140 [M+H] + . Example I-26: Preparation of Compound A-27

[0266] [ka] Compound A-26 (15.7 mg, 0.013 mmol) was dissolved in THF (1 mL) at room temperature under a nitrogen atmosphere, and then triphenylphosphine (5.4 mg, 0.0195 mmol) and distilled water (0.3 mL) were added sequentially. The mixture was stirred for 16 hours. 2N aqueous sodium hydroxide solution (10 μL) was added to the above reaction solution at room temperature, and the mixture was stirred for another hour. 2N aqueous hydrochloric acid solution was then added dropwise to adjust the pH of the reaction solution to 3. The reaction solution was separated and purified using preparative HPLC, and then lyophilized to obtain compound A-27 in the form of a white solid (10.5 mg, 65%); MS m / z: 1113 [M+H]. + . Example I-27: Preparation of Compound A-28

[0267] [ka] Compound A-27 (3 mg, 0.0026 mmol) was dissolved in THF (2 mL) at 0 °C under a nitrogen atmosphere, and then linker P-7 (1.4 mg, 0.0039 mmol), DIPEA (10 μL), and distilled water (200 μL) were added dropwise, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, 2 N aqueous hydrochloric acid (20 μL) was added, and the reaction solution was diluted with ACN (2 mL) containing 0.1% formic acid. The mixture was separated and purified using preparative HPLC, and then lyophilized to give compound A-28 (2.2 mg, 61%); MS m / z: 1341 [M+H]. + . Example I-28: Preparation of Compound A-29

[0268] [ka] Using core C-15 as a starting material in the same manner as in Example I-9, except that IPA and chloroform were used as solvents instead of THF in step 2 of Example I-9, silica gel was added together with sodium borohydride, and MMAF-OMe was used instead of compound PL-1 in step 4, compound A-29 was obtained in the form of a white solid (15.9 mg, 64%); EI-MS m / z: 1192 [M+H] + . Example I-29: Preparation of Compound A-33

[0269] [ka] Step 1: Preparation of Compound A-33a Compound A-12b (180 mg, 0.31 mmol) from Example I-11 was dissolved in MC (20 mL) at 0 ° C under a nitrogen atmosphere, and then thionyl chloride (48.2 μL, 0.65 mmol) was added slowly, and the mixture was stirred at 0 ° C for 2 hours. After the reaction was completed, the mixture was diluted by adding MC (50 mL) and then concentrated under reduced pressure. The residue was solidified by adding n-hexane (50 mL), and then concentrated under reduced pressure to obtain compound A-33a in the form of a white solid. The obtained compound was used in the next reaction without further purification (185 mg, 99%). 1 H-NMR (400MHz, CDCl3) δ 8.12 (s, 1H), 7.41 (d, J = 8 Hz,1H), 6.98 (d, J = 8 Hz, 1H), 5.62 (dd, J = 10.8, 8 Hz, 1H), 5.48 (d, J = 2.8Hz, 1H), 5.17 - 5.13 (m, 2H), 4.80 (s, 2H), 4.22 (m, 1H), 4.18 (m, 1H), 4.12(m, 1H), 3.96 (s,3H), 2.21 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H);EI-MS m / z: 587 [M+H] + . Steps 2 and 3: Preparation of Compound A-33 Compound A-33a (30 mg, 0.051 mmol) was dissolved in DMF (3 mL) at 0° C. under a nitrogen atmosphere. Compound auristatin F-OMe (42.7 mg, 0.056 mmol), DIPEA (26.7 μL, 0.153 mmol), and TBAI (2 mg, 0.005 mmol) were then added to the reaction solution in that order, and the mixture was stirred at 40° C. for 16 hours. After completion of the reaction, the resulting compound A-33b (EI-MS m / z: 1311 [M+H] +The reaction solution containing ) was cooled to room temperature, and lithium hydroxide hydrate (21.4 mg, 0.51 mmol) dissolved in distilled water (1 mL) was slowly added at 0 °C, and the mixture was stirred for 2 hours. 2N aqueous hydrochloric acid (0.3 mL) was slowly added dropwise to the reaction solution to quench the reaction. The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC, followed by lyophilization to obtain compound A-33 (1.1 mg, 2%); EI-MS m / z: 1115 [M+H] + . Example I-30: Preparation of Compound A-34

[0270] [ka] Step 1: Preparation of Compound A-34a Compound A-33a (135 mg, 0.229 mmol) from Example I-29 was dissolved in ACN (5 mL) at room temperature under a nitrogen atmosphere, and then potassium thioacetate (31.5 mg, 0.275 mmol) was added, and the mixture was stirred for 3 hours. After completion of the reaction, EA (50 mL) and distilled water (50 mL) were added to extract the organic layer. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-34a (140 mg, 97%). 1 H-NMR(400 MHz, CDCl3) δ 8.11 (s, 1H), 7.40 (d, J= 8 Hz, 1H), 6.95 (d, J = 8 Hz, 1H), 5.60 (dd, J = 10.4, 8 Hz, 1H), 5.47 (d, J= 2.8 Hz, 1H), 5.15 - 5.12 (m, 2H), 4.31 (d, J = 5.2 Hz, 1H), 4.25 - 4.08 (m,3H), 3.95 (s, 3H), 2.36 (s ,3H), 2.20 (s ,3H), 2.08 (s ,2H), 2.06 (s, 3H), 2.03(s ,3H); EI-MS m / z: 627 [M+H] + . Step 2: Preparation of Compound A-34b N-chlorosuccinimide (NCS, 120 mg, 0.88 mmol) was added to a mixture of 2N aqueous hydrochloric acid (60 μL) and ACN (300 μL) at 0°C under a nitrogen atmosphere, followed by the addition of compound A-34a (140 mg, 0.22 mmol) dissolved in ACN (100 μL). The reaction solution was stirred at 0°C for 3 hours. After completion of the reaction, diethyl ether (100 mL) and distilled water (100 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to obtain compound A-34b in the form of a white solid (35 mg, 24%), which was used in the next reaction without further purification. Steps 3 and 4: Preparation of Compound A-34 Compound A-34b (35 mg, 0.053 mmol) was dissolved in DMF (3 mL) at 0 °C under a nitrogen atmosphere. SN-38 (CAS No. 86639-52-3, 21 mg, 0.053 mmol) and TEA (18.7 μL, 0.132 mmol) were then added sequentially, and the mixture was stirred at 0 °C for 1 h. After completion of the reaction, EA (50 mL), 2N aqueous hydrochloric acid (10 mL), and distilled water (100 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to obtain compound A-34c. The resulting compound A-34c was dissolved in methanol (2 mL) and THF (1 mL). Lithium hydroxide hydrate (22.5 mg, 0.53 mmol) was then dissolved in distilled water (0.5 mL) and slowly added at 0 °C. The mixture was stirred for 30 min. The mixture was stirred at room temperature for another 30 minutes, and then 2N aqueous hydrochloric acid (0.3 mL) was added dropwise to quench the reaction. The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to give compound A-34 (0.4 mg, 1%); EI-MS m / z: 825 [M+H]. + . Example I-31: Preparation of Compound A-35

[0271] [ka] Step 1: Preparation of Compound A-35a Core C-9 (572.6 mg, 2.44 mmol) was dissolved in MC (80 mL) at 0 °C under a nitrogen atmosphere, and then acetobromo-alpha-D-galactose (1.1 g, 2.69 mmol) and benzyltributylammonium chloride (762.5 mg, 2.44 mmol) were added. A 5N aqueous solution of sodium hydroxide (1.46 mL, 7.33 mmol) was gradually added to the reaction solution, and the mixture was stirred for 16 hours while the temperature was gradually raised to room temperature. After completion of the reaction, the organic layer was extracted three times with MC (200 mL) and distilled water (200 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-35a (1.017 g, 74%) in solid form. 1 H-NMR (400MHz, CDCl3) δ 7.17 - 7.10 (m, 2H), 6.80 (dd, J= 7.6, 0.8 Hz, 1H), 6.42 (s, 1H), 5.57 (dd, J = 10.4, 8 Hz, 1H), 5.48 (d, J =3.2 Hz, 1H), 5.15 - 5.10 (m, 2H), 4.28 - 4.23 (m, 1H), 4.20 - 4.16 (m, J = 1H),4.10 - 4.07 (m, 1H), 3.67 (s, 3H), 2.81 (t, J = 7.2 Hz, 2H), 2.39 (t, J = 7.2Hz, 2H), 2.20 (s, 3H), 2.10 - 2.05 (m, 8H), 2.03 (s, 3H). Step 2: Preparation of Compound A-35b Compound A-35a (700 mg, 1.23 mmol) was dissolved in MC (40 mL) at −30 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (450 μL, 4.92 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 4.9 mL, 4.92 mmol) were then added sequentially and slowly. The mixture was stirred for 2 h while maintaining the temperature at −10 °C. After completion of the reaction, distilled water (100 mL) was slowly added dropwise to quench the reaction, and EA (100 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-35b (190 mg, 25.8%). 1 H-NMR (400MHz, CDCl3) δ 10.33 (s, 1H), 7.69 (d, J = 8.4Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), 6.49 (s, 1H), 5.59 (dd, J = 10.4, 8 Hz, 1H),5.49 (d, J = 3.6 Hz, 1H), 5.23 (d, J = 8 Hz, 1H), 5.16 (dd, J =10.4, 3.6 Hz,1H), 4.27-4.14 (m, 3H), 3.68 (s, 3H), 2.89 (t, J = 7.2 Hz, 2H), 2.42 (t, J =7.2 Hz, 2H), 2.20 (s, 3H), 2.11 (m, 2H), 2.07 (s, 3H), 2.06 (s, 3H), 2.03 (s,3H). Step 3: Preparation of Compound A-35c Compound A-35b (190 mg, 0.32 mmol) was dissolved in anhydrous THF (3 mL) at room temperature under a nitrogen atmosphere. Zn powder (CAS No. 7440-66-6, DAEJUNG, 105 mg, 3.2 mmol), 1,2-diiodoethane (CAS No. 624-73-7, Alfa Aesar, 90.4 mg, 0.32 mmol), and propargyl bromide (80% in toluene, 45.5 μL, 0.525 mmol) were added sequentially. The mixture was then sonicated in an ultrasonic cleaner (PowerSonic 410) for 30 minutes. After completion of the reaction, the reaction solution was diluted with EA (50 mL), filtered through Celite, and extracted with distilled water (50 mL) and 2N aqueous hydrochloric acid (0.7 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-35c in the form of a white solid (167 mg, 82.6%). 1 H-NMR (400MHz, CDCl3) δ 7.21 (m, 1H), 6.81-6.79(m, 1H),6.44 (s, 1H), 5.55 (dd, J = 10.4, 8 Hz, 1H), 5.47 (d, J = 3.2 Hz, 1H), 5.27 (m,1H), 5.15-5.09 (m, 2H), 4.26-4.13 (m, 2H), 4.09 (m, 1H), 3.67 (s ,3H),2.86-2.78 (m, 4H), 2.57 (dd, J = 9.2, 4.8 Hz, 1H), 2.40 (m, 2H), 2.19 (s ,3H),2.08-2.04 (m, 8H), 2.20 (s, 3H); MS m / z: 655 [M+Na] + . Step 4: Preparation of Compound A-35d Compound A-35c (42 mg, 0.066 mmol) was dissolved in MC (2 mL) at 0 °C under a nitrogen atmosphere. 4-Nitrophenyl chloroformate (27 mg, 0.132 mmol), pyridine (16 μL, 0.2 mmol), and DIPEA (11.6 μL, 0.066 mmol) were added sequentially, and the mixture was stirred for 1 h. After completion of the reaction, the reaction solution was diluted with EA (50 mL). Distilled water (50 mL) and 2 N aqueous hydrochloric acid (2 mL) were added to extract the organic layer. The extracted organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography to give compound A-35d (51 mg, 96.4%). 1 H-NMR (400MHz, CDCl3) δ 8.26 (d, J = 9.2 Hz, 2H), 7.38(d, J = 9.2 Hz, 2H), 7.25 (m, 1H), 6.81 (dd, J = 8.4, 2.4 Hz, 1H), 6.46 (s,1H), 6.25 (m, 1H), 5.56 (dd, J = 10.4, 8 Hz, 1H), 5.48 (d, J = 2.8 Hz, 1H),5.15-5.12 (m, 2H), 4.27-4.08 (m, 3H), 3.67 (s, 3H), 3.17-3.01 (m, 2H), 2.84 (t,J = 7.2 Hz, MS m / z: 820 [M+Na] + . Step 5: Preparation of Compound A-35e Compound A-35d (32 mg, 0.040 mmol) was dissolved in DMF (3 mL) at 0 °C under a nitrogen atmosphere, and then compound PL-1 (13.2 mg, 0.06 mmol), HOBt (5.4 mg, 0.04 mmol), pyridine (300 μL), and DIPEA (14 μL, 0.08 mmol) were added sequentially. The mixture was stirred for 30 minutes and then at room temperature for another 12 hours. After completion of the reaction, extraction was carried out using EA (50 mL) and 1N aqueous hydrochloric acid (50 mL). The organic layer obtained was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-35e in the form of a white solid (27 mg, 77%); MS m / z: 901 [M+Na]. + . Step 6: Preparation of Compound A-35 Compound A-35e (27 mg, 0.031 mmol) was dissolved in methanol (1 mL) and THF (0.5 mL) at 0° C., and then lithium hydroxide hydrate (19 mg, 0.461 mmol) dissolved in distilled water (0.2 mL) was added dropwise. The mixture was stirred for 2.5 hours while the temperature was gradually raised from 0° C. to room temperature. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1 mL). The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-35 in the form of a white solid (5.8 mg, 27%); EI-MS m / z: 719 [M+Na] + . Example I-32: Preparation of Compound A-36

[0272] [ka] Step 1: Preparation of Compound A-36a Compound A-25b (277 mg, 0.64 mmol) from Example I-24 was dissolved in MC (21 mL) at 0 °C under a nitrogen atmosphere. Then, acetobromo-α-D-glucuronic acid methyl ester (TCI, CAS No. 21085-72-3, 405 mg, 1.02 mmol), benzyltributylammonium chloride (199 mg, 0.64 mmol), and 5N aqueous sodium hydroxide solution (0.53 mL, 2.55 mmol) were slowly added. The mixture was stirred at 0 °C for 30 minutes and then at room temperature for another 48 hours. After completion of the reaction, the reaction solution was neutralized with 2N aqueous hydrochloric acid, and the organic layer was extracted twice with MC (100 mL) and distilled water (100 mL). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-36a in the form of a yellow viscous gum (144 mg, 30%); EI-MS m / z: 751 [M+H] + . Step 2: Preparation of Compound A-36b Compound A-36a (144 mg, 0.19 mmol) was dissolved in THF (10 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (18 mg, 0.48 mmol) was added, and the mixture was stirred at 0 °C for 3 hours. After completion of the reaction, distilled water (50 mL) was added to quench the reaction, and EA (50 mL) was added to extract the organic layer twice. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-36b in the form of a colorless viscous gum (93.5 mg, 65%); EI-MS m / z: 753 [M+H] + . Step 3: Preparation of Compound A-36c Compound A-36b (93.5 mg, 0.12 mmol) was dissolved in MC (5 mL) at 0 °C under a nitrogen atmosphere, and then 4-nitrophenyl chloroformate (50.1 mg, 0.25 mmol), pyridine (30 μL, 0.37 mmol), and DIPEA (32.4 μL, 0.18 mmol) were added sequentially. The mixture was stirred at 0 °C for 30 minutes and then at room temperature for another 2.5 hours. After completion of the reaction, the reaction solution was diluted with EA (50 mL), and 2N aqueous hydrochloric acid (50 mL) was added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography to give compound A-36c (80.3 mg, 70%); EI-MS m / z: 918 [M+H]. + . Step 4: Preparation of Compound A-36d Compound A-36c (80.3 mg, 0.087 mmol) was dissolved in DMF (1 mL) at 0 °C under a nitrogen atmosphere, and then MMAE (monomethyl auristatin E, CAS number 474645-27-7, 62.8 mg, 0.087 mmol), HOBt (17.7 mg, 0.131 mmol), DIPEA (38.1 μL, 0.218 mmol), and pyridine (1 mL) were added sequentially, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted twice with EA (50 mL) and 2N aqueous hydrochloric acid (50 mL). The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was separated and purified using preparative HPLC, followed by lyophilization to give compound A-36d in the form of a white solid (42 mg, 32%); EI-MS m / z: 1497 [M+H]. + . Step 5: Preparation of Compound A-36 Compound A-36d (42 mg, 0.028 mmol) was dissolved at −20° C. by mixing and adding methanol (0.7 mL), distilled water (0.35 mL), and THF (0.14 mL). Lithium hydroxide (2.9 mg, 0.07 mmol) dissolved in distilled water (0.35 mL) was then added dropwise. The mixture was stirred for 1 hour while the temperature was gradually raised from −20° C. to −5° C. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (0.2 mL). The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL). The solution was then separated and purified using preparative HPLC and lyophilized to obtain compound A-36 (29.1 mg, 76%) in the form of a white solid; EI-MS m / z: 1357 [M+H] + . Example I-33: Preparation of Compound A-37

[0273] [ka] Step 1: Preparation of Compound A-37a Compound A-33a (20 mg, 0.034 mmol) was dissolved in DMF (2 mL) at room temperature under a nitrogen atmosphere. Gefitinib (CAS No. 18447535-2, 15.2 mg, 0.034 mmol), potassium iodide (KI, 1.7 mg, 0.01 mmol), and DIPEA (14.83 μL, 0.085 mmol) were then added sequentially to the reaction mixture, and the mixture was stirred at 60 °C for 15 hours. After completion of the reaction, the reaction mixture was neutralized by adding 2N aqueous hydrochloric acid (10 μL). The reaction mixture was diluted with ACN (1 mL) and distilled water (1 mL). The mixture was then separated and purified using preparative HPLC and lyophilized to obtain compound A-37a (8.4 mg, 24%); EI-MS m / z: 998 [M+H]. + . Step 2: Preparation of Compound A-37 Compound A-37a (3.6 mg, 0.0035 mmol) was dissolved in methanol (1 mL) and THF (0.5 mL) at 0° C., and then lithium hydroxide hydrate (1.5 mg, 0.035 mmol) dissolved in distilled water (0.3 mL) was added dropwise, and the mixture was stirred at 0° C. for 30 minutes. After completion of the reaction, 2N aqueous hydrochloric acid (10 μL) was added to quench the reaction. The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-37 (1.5 mg, 50%); EI-MS m / z: 830 [M+H]. + . Example I-34: Preparation of Compound A-38

[0274] [ka] Step 1: Preparation of Compound A-38a Compound A-10c (20.0 mg, 0.029 mmol) was dissolved in MC (3.0 mL) at 0 °C under a nitrogen atmosphere, and then N,N'-dimethylethylenediamine (TCI, CAS No. 110-70-3, 31 μL, 0.29 mmol) was added dropwise, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, 2N aqueous hydrochloric acid was slowly added dropwise to adjust the pH of the reaction solution to 7. The reaction solution was then separated and purified using preparative HPLC and lyophilized to obtain compound A-38a (8.5 mg, 24%) in the form of a white solid; EI-MS m / z: 625 [M+H] + . Step 2: Preparation of Compound A-38b Compound A-38a (8.5 mg, 0.013 mmol) was dissolved in DMF (2.0 mL) at 0 °C under a nitrogen atmosphere, and then compound PL-2 (7.5 mg, 0.013 mmol) and DIPEA (2.37 μL, 0.013 mmol) were added sequentially, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, EA (10 mL) and distilled water (10 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-38b in the form of a clear oil (10.0 mg, 71%); EI-MS m / z: 1044 [M+H]. + . Step 3: Preparation of Compound A-38 Compound A-38b (8.5 mg, 0.013 mmol) was dissolved in methanol (1.0 mL) at 0° C. under a nitrogen atmosphere, and then potassium carbonate (9.27 mg, 0.067 mmol) dissolved in distilled water (500 μL) was slowly added dropwise, and the mixture was stirred at 0° C. for 2 hours. After completion of the reaction, 2N aqueous hydrochloric acid solution (1.0 mL) was added to terminate the reaction, and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-38 in the form of a white solid (1.5 mg, 18%); EI-MS m / z: 875 [M+H] + . Example I-35: Preparation of Compound A-39

[0275] [ka] Step 1: Preparation of Compound A-39a Core C-3 (55.0 mg, 0.308 mmol) was dissolved in ACN (5.0 mL) at 0 °C under a nitrogen atmosphere, and then 2-(bromomethyl)-5-nitrofuran (Sigma Aldrich, CAS No. 20782-91-6, 76.3 mg, 0.370 mmol) and potassium carbonate (85.1 mg, 0.616 mmol) were added sequentially, and the mixture was stirred at room temperature for 16 h. After completion of the reaction, EA (10 mL) and distilled water (10 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-39a in the form of a yellow solid (90.0 mg, 96%). 1 H-NMR (400MHz, CDCl3) δ 10.11 (s, 1H), 7.86 (d, J = 8.0Hz, 1H), 7.58 (s, 2H), 7.33 (d, J = 3.6 Hz, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.74(d, J = 3.6 Hz, 1H), 5.36 (s, 2H). Step 2: Preparation of Compound A-39b Compound A-39a (90.0 mg, 0.297 mmol) was dissolved in THF (10.0 mL) at 0 °C under a nitrogen atmosphere, and then sodium borohydride (28.0 mg, 0.742 mmol) was added, and the mixture was stirred at 0 °C for 3 hours. After completion of the reaction, EA (30 mL) and distilled water (30 mL) were added to extract the organic layer. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-39b (30.0 mg, 33%) in the form of a yellow solid. 1H-NMR (400MHz, CDCl3) δ 7.54 (d, J = 5.6 Hz, 1H), 7.41(d, J = 5.6 Hz, 1H), 7.31 - 7.28 (m, 2H), 6.81 (d, J = 8.0 Hz, 1H), 6.67 (d, J= 3.6 Hz, 1H), 5.25 (s, 2H), 4.92 (d, J = 5.6 Hz, 2H), 1.73 (t, J = 5.6 Hz,1H). Step 3: Preparation of Compound A-39 Compound A-39b (20.0 mg, 0.065 mmol) and xanthene-9-carboxylic acid (Alfa Aesar, CAS number 82-07-5, 16.3 mg, 0.072 mmol) were dissolved in DMF (3.0 mL) at 0° C. under a nitrogen atmosphere, and then EDCI hydrochloride (18.8 mg, 0.098 mmol), DMAP (0.8 mg, 0.006 mmol), and DIPEA (34.0 μL, 0.196 mmol) were added sequentially. The mixture was stirred for 16 hours while the temperature was gradually raised from 0° C. to room temperature. After completion of the reaction, 2N aqueous hydrochloric acid solution (1.0 mL) was added to terminate the reaction, and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC, and lyophilized to obtain compound A-39 in the form of an ivory solid (2.3 mg, 6.8%). 1 H-NMR(400 MHz, DMSO) δ 7.73 - 7.71 (m, 2H), 7.51 (d, J = 5.6Hz, 1H), 7.39 -7.32 (m, 4H), 7.26 (d, J = 8.0 Hz, 1H), 7.18 (d, J = 8.0 EI-MS m / z: 536[M+Na] + . Example I-36: Preparation of Compound A-40

[0276] [ka] Compound A-39b (9.1 mg, 0.029 mmol) was dissolved in THF (2.0 mL) under a nitrogen atmosphere at 0 ° C., and then compound PL-3 and sodium hydride (60% dispersion in mineral oil, 1.44 mg, 0.036 mmol) were added sequentially, and the mixture was stirred at 0 ° C. for 7 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL), and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-40 in the form of a white solid (5.1 mg, 2.5%). 1 H-NMR (400MHz, CDCl3) δ 8.49 (s, 1H), 8.33 (s, 1H), 7.51(d, J = 8.0 Hz, 1H), 7.41 (d, J = 5.6 Hz, 1H), 7.28 (d, J = 5.6 Hz, 1H), 7.22 -7.18 (m, 2H), 7.13 - 7.09 (m, 1H), 6.68 (d, J = 8.0 Hz, 1H), 6.55 (d, J = 3.6Hz, 1H), 5.86 (s, 1H), 5.31 - 5.30 (m, 1H), 5.24 (s, 2H), 5.12 (s, 2H), 4.40 -4.37 (m, EI-MS m / z: 681 [M+H] + . Example I-37: Preparation of Compound A-41

[0277] [ka] Step 1: Preparation of Compound A-41a Compound A-10c (20.0 mg, 0.029 mmol) was dissolved in DMF (3.0 mL) at 0 °C under a nitrogen atmosphere, and then doxorubicin (Sigma Aldrich, CAS No. 23214-92-8, 19.3 mg, 0.035 mmol) and DIPEA (7.6 μL, 0.043 mmol) were added sequentially, and the mixture was stirred at 0 °C for 4 hours. After completion of the reaction, EA (20 mL) and distilled water (20 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-41a in the form of a red solid (12.0 mg, 38%); EI-MS m / z: 1102 [M+Na] + . Step 2: Preparation of Compound A-41 Compound A-41a (12.0 mg, 0.011 mmol) was dissolved in methanol (1.0 mL) and THF (0.5 mL) under a nitrogen atmosphere at 0° C., and then potassium carbonate (10.7 mg, 0.077 mmol) dissolved in distilled water (200.0 μL) was slowly added dropwise, and the mixture was stirred at 0° C. for 2 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL). The reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-41 in the form of a red solid (0.3 mg, 2.9%); EI-MS m / z: 934 [M+Na] + . Example I-38: Preparation of Compound A-42

[0278] [ka] Step 1: Preparation of Compound A-42a Compound A-10c (18.2 mg, 0.027 mmol) was dissolved in DMF (2.0 mL) under a nitrogen atmosphere, and then lapatinib (TCI, CAS No. 231277-92-2, 15.6 mg, 0.027 mmol) and DIPEA (12.0 μL, 0.067 mmol) were added dropwise in succession, and the mixture was stirred at room temperature for 48 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL). The reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-42a in the form of a white solid (7.0 mg, 23%); EI-MS m / z: 1118 [M+H]. + . Step 2: Preparation of Compound A-42 Compound A-42a (7.0 mg, 0.006 mmol) was dissolved in methanol (1.0 mL) and THF (0.5 mL) under a nitrogen atmosphere at 0° C., and then potassium carbonate (6.0 mg, 0.044 mmol) dissolved in distilled water (200.0 μL) was slowly added dropwise, and the mixture was stirred at 0° C. for 30 minutes. After completion of the reaction, 2N aqueous hydrochloric acid (1.0 mL) was added to terminate the reaction, and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-42 in the form of a white solid (3.7 mg, 62%); EI-MS m / z: 949 [M+H] + . Example I-39: Preparation of Compound A-43

[0279] [ka] Step 1: Preparation of Compound A-43a Compound A-10b (69.0 mg, 0.135 mmol) was dissolved in MC (2.0 mL) under a nitrogen atmosphere at 0 °C, and then thionyl chloride (21.6 μL, 0.296 mmol) was added dropwise slowly, and the mixture was stirred at 0 °C for 3 hours. After completion of the reaction, MC (20 mL) and distilled water (20 mL) were added to extract the organic layer. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-43a (62.0 mg, 87%) in the form of a white solid. 1 H-NMR (400MHz, CDCl3) δ 7.46 - 7.42 (m, 2H), 7.30 (d, J =8.0 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 5.63 (dd, J = 10.4 Hz, J = 8.0 Hz, 1H),5.50 (d, J = 3.2 Hz 1H), 5.17 - 5.13 (m, 2H), 4.83 (s, 2H), 4.28 - 4.24 (m,1H), 4.21 - 4.18(m, 1H), 4.16 - 4.11 (m, 1H), 2.20 (s, 3H), 2.08 (s, 3H), 2.04(s, 3H), 2.03 (s, 3H). Step 2: Preparation of Compound A-43b Compound A-43a (21.0 mg, 0.040 mmol) was dissolved in DMF (1.0 mL) under a nitrogen atmosphere at 0 ° C., and then erlotinib (Sigma-Aldrich, CAS No. 183319-69-9, 20.6 mg, 0.048 mmol) and potassium iodide (0.6 mg, 0.004 mmol) were added dropwise in succession, and the mixture was stirred at 80 ° C. for 16 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL), and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-43b in the form of a white solid (2.2 mg, 62%). 1H-NMR (400MHz, DMSO) δ 8.25 (s, 1H), 7.80 (d, J = 5.6 Hz, 1H), 7.64(s, 1H), 7.40 (d, J = 4.4 Hz, 1H), 7.27 - 7.23 (m, 2H), 7.12 (s, 1H), 7.07 -7.04 (m, 3H), 6.77 (s, 1H), 5.57 - 5.53 (m, 3H), 5.39 - 5.31 (m, 3H), 4.47 (t,J = 6.4 Hz, 1H), 4.13 - 4.12 (m, 4H), 4.07 (s, 1H), 3.94 (t, J = 4.4 Hz, EI-MS m / z: 887 [M+H] + . Step 3: Preparation of Compound A-43 Compound A-43b (5.0 mg, 0.0056 mmol) was dissolved in methanol (1.0 mL) at 0 °C under a nitrogen atmosphere, and then potassium carbonate (5.45 mg, 0.039 mmol) dissolved in distilled water (200.0 μL) was slowly added dropwise, and the mixture was stirred at 0 °C for 2 hours. After completion of the reaction, 2N aqueous hydrochloric acid solution (1.0 mL) was added to quench the reaction, and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-43 in the form of a white solid (2.2 mg, 54%). 1H-NMR (400MHz, DMSO) δ 8.29 (s, 1H), 8.26 (s, 1H), 7.71 (d, J = 5.6Hz, 1H), 7.66 - 7.63 (m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 5.67 (t, J = 8.0 Hz,1H), 7.13 - 7.09 (m, 2H), 7.08 - 7.03 (m, 2H), 6.81 - 6.77 (m, 1H), 5.55 (s,2H), 4.89 (d, J = 8.0 Hz, 1H), 4.11 (t, J = 4.4 Hz, 2H), 4.06 (s, 1H), 3.93 (t,J = 4.4 Hz, 2H), 3.73 - 3.44 (m, 9H), 3.29 (s, 3H), 3.18 (s, 3H); EI-MS m / z:719 [M+H] + . Example I-40: Preparation of Compound A-44

[0280] [ka] Step 1: Preparation of Compound A-44a Compound A-43a (36.2 mg, 0.068 mmol) was dissolved in DMF (1.0 mL) at 0 ° C under a nitrogen atmosphere, and then imatinib (TCI, CAS No. 152459-95-5, 40.5 mg, 0.082 mmol) and potassium iodide (1.1 mg, 0.006 mmol) were added dropwise in succession, and the mixture was stirred at 80 ° C for 16 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL), and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-44a in the form of a white solid (18.0 mg, 26%). 1H-NMR (400MHz, DMSO) δ 10.24 (s, 1H), 9.27 (d, J = 3.2 Hz, 1H), 8.99(s, 1H), 8.68 (dd, J = 8.0 Hz, J = 3.2 Hz 1H), 8.54 (s, 1H), 8.51 (d, J = 5.6Hz, 1H), 8.47 (dt, J = 8.0 Hz, J = 3.2 Hz, 1H), 8.08 (s, 1H), 7.96 (d, J = 8.0Hz, 2H), 7.89 (d, J = 5.6 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.53 - 7.42 (m,5H), 7.29 (d, J = 5.6 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H), 7.15 (d, J = 8.4 Hz,1H), 5.65 (d, J = 10.8 Hz, 1H), 5.40 - 5.35 (m, 3H), 4.86 (s, 2H), 4.55 (t, J =6.4 Hz, 1H), 4.16 - 4.13 (m, 2H), 3.71 (s, 2H), 3.65 - 3.62 (m, 2H), 3.51 -3.48 (m, 2H), 3.06 (s, 3H), 2.91 - 2.88 (m, 2H), 2.74 - 2.68 (m, 2H), 2.22 (s,3H), 2.16 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H); EI-MS m / z: 988 [M+H] + ,494 1 / 2 [M+H] + . ステップ2: Preparation of compound A-44 Compound A-44a (18.0 mg, 0.018 mmol) was dissolved in methanol (1.0 mL) under a nitrogen atmosphere at 0 ° C., and then potassium carbonate (17.6 mg, 0.127 mmol) dissolved in distilled water (200.0 μL) was slowly added dropwise, and the mixture was stirred at 0 ° C. for 30 minutes. After completion of the reaction, 2N aqueous hydrochloric acid solution (1.0 mL) was added to quench the reaction, and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-44 in the form of a white solid (7.0 mg, 46%). 1 H-NMR (400MHz, DMSO) δ 10.23 (s, 1H), 9.27 (d, J =1.6 Hz, 1H), 8.98(s, 1H), 8.68 (dd, J = 5.6 Hz, J = 1.6 Hz, 1H), 8.51 (d, J = 5.6 Hz, 1H), 8.48- 8.46 (m, 2H), 8.08 (s, 1H), 7.96 (d, J = 5.6 Hz, 2H), 7.80 (d, J = 5.6 Hz,1H), 7.66 (d, J = 5.6 Hz, 1H), 7.56 - 7.42 (m, 5H), 7.23 - 7.18 (m, 2H), 4.99(d, J = 7.6 Hz, 1H), 4.85 (s, 2H), 3.76 - 3.46 (m, 15H), 3.05 (s, 3H), 2.91 -2.88 (m, 2H), 2.74 - 2.69 (m, 2H), 2.22 (s, 3H), 3.17 (s, 2H), 3.65 - 3.62 (m,2H), 3.51 - 3.48 (m, 2H), 3.06 (s, 3H), 2.91 - 2.88 (m, 2H), 2.74 - 2.68 (m,2H), 2.22 (s, 3H); EI-MS m / z: 987 [M+H] + , 494 1 / 2 [M+H] + . Example I-41: Preparation of Compounds A-45 and A-50

[0281] [ka] Compound A-25 (13.5 mg, 0.01 mmol) was dissolved in THF (1 mL) at room temperature under a nitrogen atmosphere. Triphenylphosphine (3.95 mg, 0.015 mmol) and distilled water (0.3 mL) were then added sequentially, and the mixture was stirred for 12 hours. 2N aqueous sodium hydroxide solution (10 μL) was added to the above reaction solution at room temperature, and the mixture was stirred for 30 minutes. 2N aqueous hydrochloric acid was then added dropwise to adjust the pH of the reaction solution to 3. The reaction solution was separated and purified using preparative HPLC, and then lyophilized to obtain compounds A-45 and A-50, respectively (A-45: 1 mg, 7%, A-50: 7.8 mg, 59%); MS m / z: A-45 = 1317 [M+H]. + , A-50 = 1318 [M+H] + . Example I-42: Preparation of Compound A-46

[0282] [ka] Step 1: Preparation of compound A-46a Compound A-26g (50.0 mg, 0.070 mmol) was dissolved in DMF (2.0 mL) at 0 °C under a nitrogen atmosphere, and then MMAE (50.0 mg, 0.070 mmol), HOBt (14.0 mg, 0.105 mmol), DIPEA (30.0 μL, 0.175 mmol), and pyridine (1.0 mL) were added sequentially, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, extraction was carried out using distilled water (50 mL), 2N aqueous hydrochloric acid (50 mL), and EA (100 mL). The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-46a in the form of a white solid (75.0 mg, 83%); EI-MS m / z: 1294 [M+H]. + . Step 2: Preparation of Compound A-46 Compound A-46a (62.0 mg, 0.048 mmol) was dissolved in methanol (1.0 mL) at 0° C. under a nitrogen atmosphere, and then potassium carbonate (46.3 mg, 0.335 mmol) dissolved in distilled water (1.0 mL) was slowly added dropwise, and the mixture was stirred at 0° C. for 1 hour. After completion of the reaction, 2N aqueous hydrochloric acid (1.0 mL) was added to terminate the reaction, and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-46 in the form of a white solid (29.0 mg, 59%); EI-MS m / z: 1126 [M+H] + . Example I-43: Preparation of Compound A-47

[0283] [ka] Compound A-46 (12.4 mg, 0.011 mmol) was dissolved in THF (2 mL) at room temperature under a nitrogen atmosphere, and then triphenylphosphine (4.33 mg, 0.0165 mmol) and distilled water (0.1 mL) were added sequentially, and the mixture was stirred for 48 hours. After completion of the reaction, the reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC, followed by lyophilization to obtain compound A-47 (3 mg, 24.8%); EI-MS m / z: 1100 [M+H] + . Example I-44: Preparation of Compound A-48

[0284] [ka] Step 1: Preparation of Compound A-48a Compound A-26g (43.0 mg, 0.060 mmol) was dissolved in MC (6.0 mL) at 0 °C under a nitrogen atmosphere, and then N,N'-dimethylethylenediamine (TCI, CAS number 110-70-3, 64 μL, 0.6 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL). The reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-48a in the form of a white solid (28.5 mg, 71%); EI-MS m / z: 664 [M+H]. + . Step 2: Preparation of Compound A-48b Compound A-48a (28.5 mg, 0.043 mmol) was dissolved in DMF (1.0 mL) at 0 °C under a nitrogen atmosphere, and then compound PL-2 (24 mg, 0.043 mmol) and DIPEA (7.5 μL, 0.043 mmol) were added sequentially. The mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1.0 mL). The reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL). It was then separated and purified using preparative HPLC and lyophilized to obtain compound A-48b (26.5 mg, 57%) in the form of a white solid; EI-MS m / z: 1083 [M+H]. + . Step 3: Preparation of Compound A-48 Compound A-48b (26.5 mg, 0.024 mmol) was dissolved in methanol (1.0 mL) and THF (0.5 mL) under a nitrogen atmosphere at 0° C., and then potassium carbonate (23.6 mg, 0.171 mmol) dissolved in distilled water (200.0 μL) was slowly added dropwise, and the mixture was stirred at 0° C. for 2 hours. After completion of the reaction, 2N aqueous hydrochloric acid solution (1.0 mL) was added to terminate the reaction, and the reaction solution was diluted with ACN (1.0 mL) and distilled water (1.0 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-48 in the form of a white solid (16.5 mg, 73%); EI-MS m / z: 914 [M+H] + . Example I-45: Preparation of Compound A-49

[0285] [ka] Step 1: Preparation of Compound A-49a LAH (2.25 g, 59.29 mmol) was added to THF (300 mL) at room temperature under a nitrogen atmosphere, and the mixture was then cooled to 0 °C. Compound C-15e (8.53 g, 23.74 mmol) was dissolved in THF (75 mL) and slowly added, and the mixture was stirred at 0 °C for 5 minutes. After completion of the reaction, the reaction was quenched by adding 2 N aqueous sodium hydroxide solution (36 mL), and the reaction solution was diluted with THF (150 mL) and filtered through Celite. The resulting solution was concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-49a (7.2 g, 96%) in the form of an ivory solid. 1 H-NMR(400 MHz, CDCl3) δ 7.66 (s, 1H), 7.48 - 7.33(m, 6H), 7.19 (t, J = 8 Hz, 1H), 6.83 (d, J = 8 Hz, 1H), 5.19 (s, 2H), 4.93 (d,J = 6 Hz, 2H), 1.92 (t, J = 6 Hz, 1H); EI-MS m / z: 318 [M+H] + . Step 2: Preparation of Compound A-49b Compound A-49a (4.66 g, 14.69 mmol) was added to MC (93 mL) under a nitrogen atmosphere at room temperature, followed by the addition of TEMPO (Alfa Aesar, CAS No. 2564-83-2, 230 mg, 1.47 mmol) and TBAI (543 mg, 1.47 mmol). Sodium bicarbonate (4.2 g, 0.5 mol) and potassium carbonate (691 mg, 0.05 mol) dissolved in 100 mL of water were then added, followed by the addition of NCS (N-chlorosuccinimide, Merck, CAS No. 128-09-6, 2.16 g, 16.18 mmol). The mixture was stirred at room temperature for 2 hours. After completion of the reaction, the organic layer was extracted twice with MC (100 mL) and distilled water (100 mL). The organic layer was washed with saturated aqueous sodium chloride (100 mL), and then the resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain Compound A-49b (4.35 g, 94%) in the form of a yellow solid. 1 EI-MS m / z: 316[M+H] + . Step 3: Preparation of Compound A-49c Compound A-49b (4.35 g, 13.80 mmol) was dissolved in MC (70 mL) at room temperature under a nitrogen atmosphere, and then (carbethoxymethylene)triphenylphosphorane (Merck, CAS No. 1099-45-2, 9.16 g, 27.59 mmol) was added, and the mixture was stirred at room temperature for 1.5 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-49c (5.12 g, 96%) in the form of an ivory solid. 1H-NMR (400MHz, CDCl3) δ 7.94 (s, 1H), 7.86 (d, J = 15.2Hz, 1H), 7.48 - 7.34 (m, 6H), 6.82 (d, J = 8 Hz, 1H), 6.10 (d, J = 15.2 Hz,1H), 5.20 (s, 2H), 4.26 (q, J = 7.2 Hz, 2H), 1.33 (t, J = 7.2 Hz, 3H); EI-MSm / z: 386 [M+H] + . Step 4: Preparation of Compound A-49d Compound A-49c (5.12 g, 13.29 mmol) was dissolved in EA (147 mL) and methanol (441 mL) at room temperature under a nitrogen atmosphere. Five percent palladium on carbon (5% Pd / C, 5.12 g) was then added, and the mixture was stirred under a hydrogen atmosphere for 16 hours. After completion of the reaction, the reaction solution was diluted with MC (800 mL) and filtered through Celite. The filtered solution was concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-49d (4.53 g, 88%) in the form of a pale brown oil. 1 H-NMR (400MHz, CDCl3) δ 7.50 - 7.3 (m, 7H), 7.14 (t, J =8 Hz, 1H), 6.81 (d, J = 8 Hz, 1H), 5.12 (s, 2H), 4.16 (q, J = 7.2 Hz, 2H), 3.25(t, J EI-MSm / z: 388 [M+H] + . Step 5: Preparation of Compound A-49e Compound A-49d (3.88 g, 10.01 mmol) was dissolved in MC (287 mL) at −78 °C under a nitrogen atmosphere. Dichloromethyl methyl ether (Merck, CAS No. 4885-02-3, 2.72 mL, 30.01 mmol) and titanium tetrachloride solution (1 M TiCl4 in MC, 30 mL, 30 mmol) were then added sequentially and slowly. The mixture was stirred for 2 h while maintaining the temperature. After completion of the reaction, distilled water (250 mL) was slowly added dropwise to quench the reaction, and MC (250 mL) was added to extract the organic layer twice. The organic layer was washed with saturated aqueous sodium chloride solution (250 mL), and then the resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-49e (2.59 g, 62%) in the form of a yellow oil. 1 H-NMR (400MHz, CDCl3) δ 10.05 (s, 1H), 7.72 (d, J = 8.4Hz, 1H), 7.58 (s, 1H), 7.49 - 7.36 (m, 5H), 6.99 (d, J = 8.4 Hz, 1H), 5.30 (s,2H), 4.17 (q, J = 7.2 Hz, 2H), 3.32 (t, J = 7.6 Hz, 2H), 2.76 (t, J = 7.6 Hz,2H), 1.25 (t, J = 7.2 Hz, 3H); EI-MS m / z: 416 [M+H] + . Step 6: Preparation of Compound A-49f Compound A-49e (2.85 g, 6.86 mmol) was dissolved in ethanol (17 mL) and THF (17 mL) at 0 °C under a nitrogen atmosphere. Lithium hydroxide monohydrate (864 mg, 20.59 mmol) dissolved in distilled water (8.5 mL) was then slowly added dropwise, and the mixture was stirred at room temperature for 1.5 h. After completion of the reaction, 2N aqueous hydrochloric acid (15 mL) was added to quench the reaction, and EA (85 mL) and distilled water (85 mL) were added to extract the organic layer. The organic layer was washed with saturated aqueous sodium chloride (250 mL), and then the resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-49f (2.56 g, 96%) in the form of an orange solid. 1 H-NMR (400MHz, CDCl3) δ 10.05 (s, 1H), 7.73 (d, J = 8 Hz,1H), 7.60 (s, 1H), 7.52 - 7.36 (m, 5H), 6.99 (d, J = 8.4 Hz, 1H), 5.31 (s, EI-MS m / z: 388 [M+H] + . Step 7: Preparation of Compound A-49g Compound A-49f (2.56 g, 6.61 mmol) was dissolved in DMF (22 mL) at 0 °C under a nitrogen atmosphere. EDC (1.9 g, 9.91 mmol), HOBt (894 mg, 6.61 mmol), DMAP (81 mg, 0.66 mmol), and DIPEA (3.45 mL, 19.81 mmol) were added sequentially, and the mixture was stirred for 1.5 h. Furthermore, linker P-1 (1.68 g, 6.60 mmol) dissolved in DMF (11 mL) was slowly added dropwise. The reaction mixture was stirred at room temperature for 16 h and then extracted with EA (100 mL) and distilled water (100 mL). The resulting organic layer was washed with saturated aqueous sodium chloride (50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-49g in the form of a brown oil (2.24 g, 58%). 1 H-NMR (400MHz, CDCl3) δ 10.04 (s, 1H), 7.71 (d, J = 8.4Hz, 1H), 7.58 (s, 1H), 7.49 - 7.36 (m, 5H), 6.98 (d, J = 8 Hz, 1H), 6.14 (brs,1H), 5.30 (s, 2H), 3.71 - 3.49 (m, 14H), 3.47 - 3.44 (m, 2H), 3.36 - 3.33 (m,4H), 2.61 (t, J = 7.6 Hz, 2H); EI-MS m / z: 588 [M+H] + . Step 8: Preparation of compound A-49h Compound A-49g (2.23 g, 3.80 mmol) was dissolved in MC (76 mL) at −78 °C under a nitrogen atmosphere, and then pentamethylbenzene (Alfa Aesar CAS No. 700-12-9, 1.69 g, 11.40 mmol) was added. Boron trichloride solution (1 M BCl3 in MC, 22.8 mL, 22.8 mmol) was slowly added. The mixture was stirred for 1 h while the temperature was gradually raised to −55 °C. After completion of the reaction, distilled water (150 mL) was slowly added dropwise to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction solution. MC (150 mL) and distilled water (150 mL) were added to the mixture, and the organic layer was extracted twice. The resulting organic layer was washed with saturated aqueous sodium chloride solution (150 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-49h in the form of a light brown solid (1.33 g, 71%). 1 H-NMR (400MHz, CDCl3) δ 10.01 (s, 1H), 8.42 (brs, 1H),7.66 - 7.64 (m, 2H), 6.94 (d, J = 8 Hz, 1H), 6.32 (brs, 1H), 3.66 - 3.59 (m,8H), 3.53 - 3.52 (m, 2H), 3.48 - 3.44 (m, 4H), 3.38 - 3.33 (m, 4H), 2.66 (t, J= 7.2 Hz, 2H); EI-MS m / z: 498 [M+H] + . Step 9: Preparation of Compound A-49i Compound A-49h (500 mg, 1.01 mmol) was dissolved in MC (33 mL) at 0 °C under a nitrogen atmosphere. Then, acetobromo-α-D-glucuronic acid methyl ether (TCI, 838 mg, 2.11 mmol), benzyltributylammonium chloride (314 mg, 1.01 mmol), and 5N aqueous sodium hydroxide solution (1 mL, 5.00 mmol) were slowly added. The mixture was stirred at 0 °C for 30 minutes and then at room temperature for an additional 16 hours. After completion of the reaction, the reaction solution was neutralized with 2N aqueous hydrochloric acid and extracted with MC (165 mL) and distilled water (165 mL). The resulting organic layer was washed with saturated aqueous sodium chloride solution (165 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to give compound A-49i in the form of an ivory-colored viscous gum (200 mg, 25%). 1 H-NMR (400MHz, CDCl3) δ 10.10 (s, 1H), 7.73 (d, J = 8 Hz,1H), 7.39 (s, 1H), 7.09 (d, J = 8.4 Hz, 1H), 6.16 (brs, 1H), 5.44 - 5.37 (m,4H), EI-MS m / z: 814 [M+H] + . Step 10: Preparation of Compound A-49j Compound A-49i (198 mg, 0.24 mmol) was dissolved in THF (13.3 mL) at 0 °C under a nitrogen atmosphere. Sodium borohydride (NaBH, 27.6 mg, 0.73 mmol) was then added, and the mixture was stirred at 0 °C for 5 h. After completion of the reaction, distilled water (13 mL) was added to quench the reaction. EA (53 mL) and distilled water (27 mL) were added to extract the organic layer twice. The obtained organic layer was washed by adding saturated aqueous sodium chloride solution (53 mL), then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-49j (146 mg, 74%) in the form of a white viscous gum. 1 H-NMR(400 MHz, CDCl3) δ 7.34 (s, 1H), 7.14 (d, J= 8 Hz, 1H), 6.93 (d, J = 8 Hz, 1H), 6.22 (brs, 1H), 5.39 - 5.35 (m, 3H), 5.19(m, 1H), 4.81 (d, J = 5.6 Hz, 2H), 4.20 (m, 1H), 3.74 (s, 3H), 3.65 - 3.43 (m,14H), 3.38 - 3.28 (m, 4H), 2.61 (m, 2H), 2.07 (s, 3H), 2.05 (s, 6H); EI-MS m / z:816 [M+H] + . Step 11: Preparation of Compound A-49k Compound A-49j (171 mg, 0.21 mmol) was dissolved in MC (5.1 mL) at 0 °C under a nitrogen atmosphere, and then 4-nitrophenyl chloroformate (85 mg, 0.42 mmol), pyridine (50.7 μL, 0.63 mmol), and DIPEA (54.8 μL, 0.32 mmol) were added sequentially. The mixture was stirred at 0 °C for 30 min and then at room temperature for another 2.5 h. After completion of the reaction, the reaction solution was diluted with EA (25 mL), and 2N aqueous hydrochloric acid (25 mL) was added to extract the organic layer. The resulting organic layer was washed with saturated aqueous sodium chloride (25 mL), then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography to obtain compound A-49k (158 mg, 77%) in the form of a transparent viscous foam. 1 H-NMR (400MHz, CDCl3) δ 8.27 (d, J = 8.8 Hz, 1H), 7.41 -7.37 (m, 3H), 6.95 (d, J = 8.4 Hz, 1H), 6.20 (brs, 1H), 5.43 - 5.37 (m, 5H),5.24 - 5.23 (m, 1H), 4.23 - 4.21 (m, 1H), 3.73 (s, 3H), 3.66 - 3.54 (m, 12H),3.51 - 3.47 (m, 2H), 3.37 - 3.34 (m, 4H), 2.60 (d, J = 7.6 Hz, 2H), 2.08 - 2.06(m, 9H); EI-MS m / z: 981 [M+H] + . Step 12: Preparation of Compound A-49L Compound A-49k (41.1 mg, 0.042 mmol) was dissolved in DMF (1 mL) at 0 °C under a nitrogen atmosphere, and then MMAE (30 mg, 0.042 mmol), HOBt (8.5 mg, 0.063 mmol), DIPEA (18.2 μL, 0.104 mmol), and pyridine (1 mL) were added sequentially, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted twice with EA (20 mL) and 2N aqueous hydrochloric acid (20 mL). The obtained organic layer was washed by adding saturated aqueous sodium chloride (20 mL), then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-49L in the form of a white solid (47.7 mg, 73%); EI-MS m / z: 1560 [M+H]. + , 780 1 / 2 [M+H] + . Step 13: Preparation of Compound A-49 Compound A-49L (47.7 mg, 0.031 mmol) was dissolved at −20° C. by mixing and adding methanol (0.76 mL), distilled water (0.1 mL), and THF (0.48 mL). Lithium hydroxide (5.1 mg, 0.12 mmol) dissolved in distilled water (0.44 mL) was then added dropwise, and the mixture was stirred at −20° C. for 1 hour. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (1 mL). The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-49 in the form of a white solid (28.2 mg, 65%); EI-MS m / z: 1420 [M+H]. + , 710 1 / 2 [M+H] + . Example I-46: Preparation of Compound A-51

[0286] [ka] Step 1: Preparation of Compound A-51a Compound A-49k (37 mg, 0.038 mmol) was dissolved in DMF (1 mL) at 0 °C under a nitrogen atmosphere, and then MMAF-OMe (28 mg, 0.038 mmol), HOBt (7.6 mg, 0.056 mmol), DIPEA (16.4 μL, 0.094 mmol), and pyridine (1 mL) were added sequentially, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was extracted twice with EA (20 mL) and 2N aqueous hydrochloric acid (20 mL). The obtained organic layer was washed by adding saturated aqueous sodium chloride (20 mL), then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-51a in the form of a transparent viscous foam (45 mg, 75%); EI-MS m / z: 1588 [M+H]. + , 794 1 / 2 [M+H] + . Step 2: Preparation of Compound A-51 Compound A-51a (45 mg, 0.028 mmol) was dissolved at −20° C. by mixing and adding methanol (0.71 mL), distilled water (0.11 mL), and THF (0.14 mL). Lithium hydroxide (8.9 mg, 0.212 mmol) dissolved in distilled water (0.6 mL) was then added dropwise, and the mixture was stirred for 3 hours while the temperature was gradually raised from −20° C. to −5° C. After completion of the reaction, the reaction was quenched by adding 2N aqueous hydrochloric acid (0.5 mL). The reaction solution was diluted with ACN (1 mL) and distilled water (1 mL), and then separated and purified using preparative HPLC and lyophilized to obtain compound A-51 in the form of a white solid (22.2 mg, 55%); EI-MS m / z: 1434 [M+H]. + , 717 1 / 2 [M+H] + . Example I-47: Preparation of Compound A-52

[0287] [ka] Step 1: Preparation of Compound A-52a Compound A-49b (8 g, 25.38 mmol) was dissolved in MC (242 mL, 0.105 M) at −78 °C under a nitrogen atmosphere. Then, boron trichloride solution (1 M BCl3 in MC, 76.14 mL, 76.14 mmol) was slowly added, and the mixture was stirred for 2 h. After completion of the reaction, distilled water (200 mL) was added to quench the reaction, and 2 N aqueous sodium hydroxide solution was added at 0 °C to neutralize the reaction solution. 2 N aqueous hydrochloric acid solution was slowly added dropwise to the mixture to adjust the pH of the reaction solution to 7. MC (200 mL) was added to the mixture to extract the organic layer twice. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was subjected to column chromatography to obtain compound A-52a (4.9 g, ...

Claims

1. Formula 1 below: [Formula 1] A-(L １ ) ｋ -U ｊ [In Equation 1, L １ is a divalent or polyvalent linking group; k is 0 or 1 and j is 1 to 10; A is absent, H or a bonding functionality; U is of the following formula A: 【Chemical 1】 (In formula A, R １ and R ２ are each independently H or C １～８ is a saturated or unsaturated hydrocarbyl; PL is a heteroatom selected from N, O and S. ２ to, or R １ and R ２ is an active agent linked to the carbon atom to which is attached; L ２ Is, L ２ and R １ and R ２ The bond between the carbon atom to which L is bonded is broken. ２ a self-elimination linker selected to facilitate cleavage of the bond between and PL; W is an optional substituent on the benzene ring; Z １ and Z ３ One of them is N, NR ３ , O, S, and Se; Z １ and Z ３ the other and Z ２ are each independently CH or N, -(L １ ) ｋ -A, and if present -(V) ｈ each independently replaces an H in NH or CH; 【Chemistry 2】 is A-(L １ ) ｋ represents a bond with -; R ３ is H or C １～８ is a hydrocarbyl; V is an electron-withdrawing or electron-donating group; When T is cleaved, it undergoes a 1,6-elimination reaction to give PL and, if present, L. ２ is a triggering group capable of initiating the release of L ３ is an optional self-immolative spacer group which, if present, is cleaved sequentially upon cleavage of T; X and Y are each independently selected from —O—, —NH—, and S; h, i, l, x, and y are each independently 0 or 1, and p is an integer from 0 to 2. is the part represented by A compound containing a self-immolative group represented by the formula: or a pharmaceutically acceptable salt thereof.

2. The ring of formula A above 【Chemistry 3】 But the following group: 【Chemistry 4】 2. A compound containing a self-immolative group according to claim 1, selected from:

3. V is halogen, CN, NO ２ , Formyl, C １～８ Alkylcarbonyl, carboxy, C １～８ Alkoxycarbonyl, carboxy-C １～８ Alkyl, carbamoyl, mono C １～８ Alkylcarbamoyl, diC １～８ Alkylcarbamoyl, C １～８ Alkyl, C １～８ Alkenyl, OH, C １～８ Alkoxy, SH, C １～８ Alkylsulfanyl, NH ２ , Mono C １～８ Alkylamino, DiC １～８ Alkylamino and C ６～１８ aryl, A compound comprising the self-immolative group of claim 1.

4. W is H, C １～１２ Saturated or unsaturated hydrocarbyl, halogen, halo-C １～８ Alkyl, CN, NO ２ , O.H., C. １～８ Alkoxy, hydroxy-C １～８ Alkyl, C １～８ Alkoxy-C １～８ Alkyl, SH, C １～８ Alkylthio, mercapto-C １～８ Alkyl, amino, mono C １～８ Alkylamino, DiC １～８ Alkylamino, amino-C １～８ Alkyl, C １～８ Monoalkylamino-C １～８ Alkyl, C １～８ Dialkylamino-C １～８ Alkyl, carboxy, C １～８ Alkoxycarbonyl, C １～８ Alkoxycarbonyloxy, carboxy-C １～８ Alkyl, C １～８ Alkoxycarbonyl-C １～８ Alkyl, carbamoyl, mono C １～８ Alkylcarbamoyl, diC １～８ Alkylcarbamoyl, carbamoyl-C １～８ Alkyl, mono C １～８ Alkylcarbamoyl-C １～８ Alkyl and diC １～８ Alkylcarbamoyl-C １～８ selected from the group consisting of alkyl, A compound comprising the self-immolative group of claim 1.

5. -(Y) ｙ -T is, 【Chemistry 5】 -O-SO ３ － ;-NO ２ ;-OC(O)(CH ２ ) ｒ COR ｔ１ ; -O(CH ２ )-Ar １ -NO ２ ;-SC(O)(CH ２ ) ｓ COR ｔ２ ; -S(CH ２ )-Ar ２ -NO ２ and -BR ｔ３ R ｔ４ [In the formula, 【Chemistry 6】 may include a form in which the —OH group is protected with a protecting group or substituted with a substituent; R ｔ１ and R ｔ２ However, each C １ ~C ８ alkyl, and Ar １ and Ar ２ However, each C ５ ~C ２０ arylene or heteroarylene; R ｔ３ and R ｔ４ are each independently hydrogen, C １ ~C ８ alkoxy or hydroxy; R ｔ５ But, oh, Mono C １～８ Alkylamino, DiC １～８ Alkylamino or -NH(CH ２ CH ２ O) ｆ R ｔ６ (In the formula, R ｔ６ is H or C １～４ alkyl); f is an integer from 1 to 10, and r and s are each an integer from 1 to 5. and wherein the moiety is selected from the group consisting of: A compound comprising the self-immolative group of claim 1.

6. -(X) ｘ -L ３ -but, 【Chemistry 7】 and R ８ and R ９ are each independently H, halogen, or C １～８ Alkyl, CN and NO ２ wherein o is an integer from 0 to 2; A compound comprising the self-immolative group of claim 1.

7. PL is an active agent selected from a drug, a toxin, a fluorophore, an affinity ligand, a diagnostic agent, or a detection probe; A compound comprising the self-immolative group of claim 1.

8. the drug is selected from a cytokine, an immunomodulatory compound, an anti-cancer agent, an antiviral agent, an antibacterial agent, an antifungal agent, an antiparasitic agent, or a combination thereof; A compound comprising the self-immolative group of claim 7.

9. PL, 【Chemistry 8】 selected from the group consisting of A compound comprising the self-immolative group of claim 1.

10. L ２ Yes, -OC(=O)-, -S(=O) ２ -、 【Chemistry 9】 is selected from the group consisting of R １０ ~R １２ are each independently H, C １～８ Alkyl, amino-C １～８ Alkyl, mono- or di-(C １～８ C substituted with alkyl)amino １～８ Alkyl, or -(CH ２ CH ２ O) ｇ R １３ and R １３ is H or C １～４ alkyl, and g is an integer from 1 to 10; A compound comprising the self-immolative group of claim 1.

11. the binding functional group is a functional group capable of binding to a ligand or protein having receptor binding properties, or a linker precursor, by click chemistry; A compound comprising the self-immolative group of claim 1.

12. The binding functional group is halogen, OH, C １～８ Alkoxy, hydroxylamino, COH, C １～８ Alkylcarbonyl, carboxy, C １～８ Alkoxycarbonyl, tosyl, tosylate, amino, mono C １～８ Alkylamino, DiC １～８ Alkylamino, NHNH ２ , N ３ , haloacetamide, maleimidyl, succinimidyl, SH, SO ３ H, C １～８ alkylsulfonyl, 【Chemistry 10】 , C １～８ Alkoxysulfonyl, 2-pyridyl disulfide, PO ３ H ２ , O.P.O. ３ H ２ , -N≡C, -NCS,C ４～１０ Dienyl, C ２～８ Alkenyl, C ２～８ Alkynyl, C ４～１０ Cycloalkynyl and C ２～８ alkynylcarbonyl; R ｆ is H or C １～８ is alkyl, A compound comprising the self-immolative group of claim 1.

13. A-L １ But the precursor of A and L １ and the precursor of A is formed by a bond between the precursor of A and a group selected from the group consisting of hydroxy, amino, azido, alkynyl, conjugated dienyl, alkenyl, cyclooctynyl, maleimidyl, SO ２ N ３ , alkoxysulfinyl, oxiranyl, aziridinyl, oxo, hydrazinyl, hydroxyamino, mercapto, and 1,3-dicarbonyl, and said L １ The precursor of A chemically reacts with the precursor of A to form A-L １ containing bond-forming functional groups, A compound comprising the self-immolative group of claim 1.

14. L １ optionally containing a divalent or polyvalent functional group in the middle of the chain selected from the group consisting of amide, sulfonamide, amino, ether, carbonyl, triazole, tetrazole, sugar-derived group, sulfoester and dendrimer; １～２００ is alkylene, A compound comprising the self-immolative group of claim 1.

15. L １ が、-(CH ２ ) ｎａ -;-(EH ２ CH ２ O) ｍａ -;-(EH ２ OCH ２ ) ｍｂ -;-(OCH ２ CH ２ ) ｍｃ -;-C(=O)-; 【Chemistry 11】 or a combination thereof, R ｄ is H or C １～８ alkyl, and na and ma to mc are each independently an integer of 0 to 10; A compound comprising the self-immolative group of claim 1.

16. A-L １ -が、N ３ -(CH ２ ) ｎ１ -;N ３ -(CH ２ CH ２ O) ｍ１ -(CH ２ ) ｎ２ -;HO-(CH ２ CH ２ O) ｍ１ -(CH ２ ) ｎ２ -;H ２ N-(CH ２ CH ２ O) ｍ１ -(CH ２ ) ｎ２ -;H ２ N-O-(CH ２ CH ２ O) ｍ１ -(CH ２ ) ｎ２ -;N ３ -(CH ２ CH ２ O) ｍ２ -(CH ２ ) ｎ３ -NR ｄ１ CO-(CH ２ ) ｎ４ -;R ａ１ NH-(CH ２ ) ｎ５ -;R ｂ１ OC(=O)-(CH ２ ) ｎ６ -;R ｃ１ C≡C-(CH ２ OCH ２ ) ｍ３ -CONR ｄ２ -(CH ２ ) ｎ７ -; 【Chemistry 12】 is selected from the group consisting of R ａ１ , R ｂ１ , R ｃ１ , R ｃ２ and R ｄ１ ~R ｄ５ are each independently H or C １～８ is alkyl, n1 to n15 and m1 to m11 each independently represent an integer of 0 to 10. A compound comprising the self-immolative group of claim 1.

17. The compound of formula 1 has the following formula: 【Chemistry 13】 【change】 (In the above formula, A, L １ ,k,V,R １ , R ２ , R ３ , R １１ , R １２ and PL are as defined in any one of claims 1 to 16), and wherein the compound is selected from the group consisting of compounds represented by A compound comprising the self-immolative group of claim 1.

18. The compound represented by formula 1 is represented by the following formula 1-1: 【Chemistry 14】 (In Equation 1-1, A has the same meaning as defined in claim 1; U １ and U ２ each has the same meaning as U defined in claim 1, and U １ and U ２ may be the same or different from each other; j is 1 to 10; L １１ and L １２ is L as defined in claim 1 １ and L １１ and L １２ may be the same or different from each other; L １ａ and L １ｂ are each independently a direct bond; 【Chemistry 15】 and R ｅ is H or C １～８ is alkyl; q1, q2, and q3 each independently represent an integer of 0 to 10, and q4 represents an integer of 0 to 10; However, L １ａ but 【Chemistry 16】 If q2 is not 0, L １ｂ but 【Chemistry 17】 (q3 is not 0 if is a compound represented by A compound comprising the self-immolative group of claim 1.

19. The above formula 1-1 【Chemistry 18】 but has the following structure: 【Chemistry 19】 (In the above formula, the definitions of q2 and q3 are as defined in claim 18.) Selected from:

19. A compound comprising the self-immolative group of claim 18.

20. L １１ and L １２ are each independently -(CH ２ ) ｎ１ -;-(CH ２ CH ２ O) ｍ１ - (CH ２ ) ｎ２ -;-(CH ２ CH ２ O) ｍ２ - (CH ２ ) ｎ３ -NR ｄ１ CO-(CH ２ ) ｎ４ -;-(CH ２ CH ２ O) ｍ１０ - (CH ２ ) ｎ１５ -CONR ｄ５ - (CH ２ ) ｎ１４ -; and 【Chemistry 20】 Selected from: R ｄ１ and R ｄ５ are each independently H or C １～８ is alkyl, n1, n2, n3, n4, n8, n14 and n15, and m1, m2, m8 and m10 each independently represent an integer of 1 to 8.

19. A compound comprising the self-immolative group of claim 18.

21. The compound represented by formula 1-1 has the following formula: 【Chemical 21】 (In the above formula, q1 to q4, U １ and U ２ is as defined in claim 18, R ｄ１ , R ｄ５ and R ｅ are each independently H or C １～８ is alkyl, n1, n3, n4, n8, n14 and n15, m2, m8 and m10 each independently represent an integer of 1 to 8. and wherein the compound is selected from the group consisting of compounds represented by 19. A compound comprising the self-immolative group of claim 18.

22. Formula 2 below: 【Chemical 22】 (In Equation 2, E is a ligand or protein with receptor binding properties; A' is a divalent linking group derived from the binding functionality of A; n is a real number from 1 to 10; A, U, L １ , k and j are as defined in claim 1) or a pharmaceutically acceptable salt thereof.

23. the ligand is selected from the group consisting of a peptide, a tumor cell-specific peptide, a tumor cell-specific aptamer, a tumor cell-specific carbohydrate, a tumor cell-specific monoclonal or polyclonal antibody, and an antibody fragment; The protein is C １～２０ Selected from the group consisting of hydrocarbyls, oligopeptides, polypeptides, fragments of antigenic polypeptides, and artificial antibodies (repebodies); 23. The ligand-drug conjugate of claim 22.

24. The antibody is selected from the group consisting of an intact polyclonal antibody, an intact monoclonal antibody, an antibody fragment, a single-chain Fv (scFv) variant, a multispecific antibody, a bispecific antibody, a chimeric antibody, a humanized antibody, a human antibody, a fusion protein containing an antigenic determinant of an antibody, and other modified immunoglobulin molecules containing an antigenic recognition site.

24. The ligand-drug conjugate of claim 23.

25. The antibody is selected from the group consisting of muromonab-CD3, abciximab, rituximab, daclizumab, palivizumab, infliximab, trastuzumab (Herceptin), etanercept, basiliximab, gemtuzumab, alemtuzumab, ibritumomab, adalimumab, alefacept, omalizumab, efalizumab, tositumomab-I131, cetuximab, bevacizumab, natalizumab, ranibizumab, panitumumab, eculizumab, rilonacept, certolizumab pegol, romiplostim, AMG-531 (Ro miplostim), CNTO-148 (golimumab), CNTO-1275 (ustekinumab), ABT874 (briakinumab), LEA-29Y (belatacept), belimumab, TACI-Ig (transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin), second generation anti-CD20, ACZ-885 (canakinumab), tocilizumab, atlizumab, mepolizumab, pertuzumab, Humax CD20 (ofatumumab), tremelimumab (CP-675 206), ticilimumab, MDX-010 (ipilimumab), IDEC-114 (galiximab), inotuzumab, Humax-EGFR (zalutumumab), aflibercept (VEGF trap-eye), Humax-CD4 (zanolimumab), Ala-Ala (hOKT3 gamma 1), otelixizumab (ChAglyCD3; TRX4), catumaxomab, MT-201 (adecatumumab) tuximab), pregovomab, CH-14.18 (dinutuximab), WXG250 (dilentuximab), AMG-162 (denosumab), AAB-001 (bapineuzumab), motavizumab, MEDI524 (motavizumab), efamgumab, Aurograb®, raxibacumab, third generation anti-CD20, LY2469298 (ocaratuzumab), and veltuzumab; 24. The ligand-drug conjugate of claim 23.

26. E is an antibody, and the E-A' bond structure of Formula 2 is 【Chemical 23】 (In the formula, ＊ is the remainder of the antibody), 23. The ligand-drug conjugate of claim 22.

27. The conjugate of formula 2 is the following conjugate: 【Chemistry 24】 (In the above formula, mAb represents the antibody moiety; m5, m6, m9, m10, n9, n10, n13, n14, and n15 each independently represent an integer of 1 to 10; R ｄ３ and R ｄ５ are each independently H or C １～８ is alkyl; Z １ is NR ３ , a heteroatom selected from O, S, and Se; R ３ is H or C １～８ is a hydrocarbyl; PL is the active agent moiety; n is a real number between 1 and 10) Selected from:

23. The ligand-drug conjugate of claim 22.

28. The ligand-drug conjugate of formula 2 has the following formula: 【Chemistry 25】 【change】 (In the above formula, mAb is a portion of an antibody and n is a real number between 1 and 10.) and wherein the conjugate is selected from the group consisting of:

28. The ligand-drug conjugate of claim 27.

29. The compound represented by formula 2 is represented by the following formula 2-1: 【Chemical 26】 (In Equation 2-1, E is a ligand or protein with receptor binding properties; A' is a divalent linking group derived from the linking functional group of A defined in claim 1; U １ and U ２ each has the same meaning as U defined in claim 1, and U １ and U ２ may be the same or different from each other; j is 1 to 10; L １１ and L １２ is L as defined in claim 1 １ and L １１ and L １２ may be the same or different from each other; L １ａ and L １ｂ are each independently a direct bond; 【Chemical 27】 and R ｅ is H or C １～８ is alkyl; q1, q2, and q3 each independently represent an integer of 0 to 10, and q4 represents an integer of 0 to 10; However, L １ａ but 【Chemical 28】 If q2 is not 0, L １ｂ but 【Chemical 29】 If q3 is not 0; n is a real number between 1 and 10) is a compound represented by 23. The ligand-drug conjugate of claim 22.

30. The conjugate represented by formula 2-1 has the following formula: 【Chemistry 30】 (In the above formula, mAb is the antibody moiety; q1 to q4, n, U １ and U ２ is as defined in claim 29, R ｄ１ , R ｄ５ and R ｅ are each independently H or C １～８ is alkyl, n1, n3, n4, n8, n14 and n15, m2, m8 and m10 each independently represent an integer of 1 to 8. and wherein the conjugate is selected from the group consisting of:

30. The ligand-drug conjugate of claim 29.

31. The conjugate represented by formula 2-1 has the following formula: 【Chemical 31】 【change】 (In the above formula, mAb is a portion of an antibody and n is a real number between 1 and 10.) and wherein the conjugate is selected from the group consisting of:

30. The ligand-drug conjugate of claim 29.

32. A pharmaceutical composition comprising the ligand-drug conjugate of any one of claims 22 to 31 and a pharmaceutically acceptable carrier or excipient.

33. for the treatment or prevention of a proliferative disease, an autoimmune disease, or an infectious disease, 33. The pharmaceutical composition of claim 32.

34. An imaging composition comprising the ligand-drug conjugate of any one of claims 22 to 31.

35. A composition for detection comprising the ligand-drug conjugate of any one of claims 22 to 31.

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