Compounds, compositions and methods

Abstract

The present invention relates to anti-cancer compounds comprising, but not limited to, antibody-drug conjugates using anti-cancer compounds, these compounds and ACDs thereof being useful in the treatment of cancer.

Description

Cross - reference to related applications This application claims the benefit of International Patent Application No. PCT / CN2022 / 124073, filed on October 9, 2022, the entire content of which is incorporated herein by reference. Background Art Antibody-drug conjugates (ADCs) are a class of complex molecules that contain an antibody conjugated to a bioactive cytotoxic payload and are designed as a targeted therapy for the treatment of cancer. Different from traditional chemotherapy, ADCs are designed to target and kill tumor cells while protecting healthy cells. The concept of targeted delivery of active pharmaceutical agents to selected specific cell locations is an effective method for the treatment of various diseases and has many beneficial aspects compared to systemic administration of the same drug. Although ADC therapies have been approved by the FDA, there is still a need for effective and targeted therapies for the treatment of cancer. Summary of the Invention The present disclosure relates to an anticancer compound, including but not limited to antibody-drug conjugates using the anticancer compound, and these compounds and their ACDs are suitable for the treatment of cancer. The present disclosure provides in one embodiment a compound of Formula I: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein, A 1 is -NHR 1 , wherein R 1 is hydrogen, -C6 aryl-C 1-6 alkyl-NH2, -C(O)R 5 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 2 and A 3 are both hydrogen; or A 2 is -NHR 2 , wherein R 2 is hydrogen, -C6 aryl-C 1-6 alkyl-NH2, -C(O)R 5 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 1 and A 3 are both hydrogen; or A 3 is -NHR 3 , wherein R 3 is hydrogen, -C6 aryl-C 1-6Alkyl-NH2, -C(O)R 5 or -C6 aryl-C 1-6 Alkyl-NHC(O)R 5 ; and A 1 and A 2 are both hydrogen; R 4 is -C 1-6 alkyl; provided that when A 1 is -NHR 1 then R 4 is not methyl; R 5 is -L-R 6 ; L is a linker moiety; and R 6 is hydrogen or a heterocyclic group, wherein said heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. The present invention also provides a pharmaceutical composition comprising a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. The present invention also provides a method for treating cancer in a patient in need thereof, comprising administering to said patient a therapeutically acceptable amount of a compound as described herein, or a stereoisomer or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound. Exemplary cancers include, but are not limited to, lung cancer, kidney cancer, urothelial cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer, and esophageal cancer. The present invention also provides a method for treating, preventing or inhibiting tumor growth in a patient in need thereof, comprising administering to said patient a therapeutically acceptable amount of a compound as described herein, or a stereoisomer or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1A shows the binding of a HER2 antibody-drug conjugate to NCI-N87 cells. Figure 1B shows the binding of a HER2 antibody-drug conjugate to SK-BR-3 cells. Figure 1C shows the binding of a HER2 antibody-drug conjugate to BT-474 cells. Figure 1D shows the binding of a HER2 antibody-drug conjugate to JIMT-1 cells. Figure 1E shows the binding of a HER2 antibody-drug conjugate to MDA-MB-468 cells. Figure 2A shows the binding of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) to NCI-N87 cells. Figure 2B shows the binding of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) to SK-BR-3 cells. Figure 2C shows the binding of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) to BT-474 cells. Figure 2D shows the binding of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) to JIMT-1 cells. Figure 2E shows the binding of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) to MDA-MB-231 cells. Figure 2F shows the binding of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) to MDA-MB-468 cells. Figure 3A shows the cytotoxicity of HER2 antibody-drug conjugates in NCI-N87 cells. Figure 3B shows the cytotoxicity of HER2 antibody-drug conjugates in SK-BR-3 cells. Figure 3C shows the cytotoxicity of HER2 antibody-drug conjugates in BT-474 cells. Figure 3D shows the cytotoxicity of HER2 antibody-drug conjugates in JIMT-1 cells. Figure 3E shows the cytotoxicity of HER2 antibody-drug conjugates in MDA-MB-468 cells.

[0025] Figure 4A shows the cytotoxicity of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) in NCI-N87 cells. Figure 4B shows the cytotoxicity of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) in SK-BR-3 cells. Figure 4C shows the cytotoxicity of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) in BT-474 cells. Figure 4D shows the cytotoxicity of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) in JIMT-1 cells. Figure 4E shows the cytotoxicity of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) in MDA-MB-231 cells. Figure 4F shows the cytotoxicity of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) in MDA-MB-468 cells. Figures 5A and 5B show the bystander killing effect of HER2 antibody-drug conjugates on human HER2-negative MDA-MB-468 cells. Figures 6A and 6B show the bystander effect of HER2 antibody-drug conjugates with drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) on human HER2-negative MDA-MB-468 cells. Figure 7 Shows the comparison of ADC-2 with trastuzumab-DXd in the JIMT-1 CDX model. Detailed Description Definitions The following description sets forth exemplary embodiments of the present technology. However, it should be recognized that such description is not intended to limit the scope of the present disclosure, but rather as a description of exemplary embodiments. The following words, phrases, and symbols used in this specification generally are intended to have the meanings set forth below, unless the context in which they are used indicates otherwise. A dash (“-”) not between two letters or symbols is used to indicate the point of attachment of a substituent. For example, -C(O)NH2 is attached through the carbon atom. Dashes at the front or end of a chemical group are for convenience, and a chemical group may be depicted with or without one or more dashes without losing its ordinary meaning. A wavy line drawn through a structural line indicates the point of attachment of a group. Unless chemistry or structure requires it, the order of writing or naming of chemical groups does not indicate or imply any directionality. The prefix “C u-v ” indicates that the following group has u to v carbon atoms. For example, “C 1-6"Alkyl" indicates that the alkyl group has 1 to 6 carbon atoms. As used herein, "about" a value or parameter includes (and describes) embodiments that are directed to that value or parameter itself. In certain embodiments, the term "about" includes the indicated amount ± 10%. In other embodiments, the term "about" includes the indicated amount ± 5%. In certain other embodiments, the term "about" includes the indicated amount ± 1%. Additionally, the term "about X" includes a description of "X". Additionally, the singular forms "a" and "the" include the plural unless the context clearly dictates otherwise. Thus, for example, reference to "a compound" includes a plurality of such compounds, and reference to "a detection method" includes one or more detection methods known to those of skill in the art and their equivalent methods. "Alkyl" refers to a straight-chain or branched-chain saturated hydrocarbon chain. As used herein, alkyl has 1 to 20 carbon atoms (i.e., C 1-20 alkyl), 1 to 8 carbon atoms (i.e., C 1-8 alkyl), 1 to 6 carbon atoms (i.e., C 1-6 alkyl) or 1 to 4 carbon atoms (i.e., C 1-4 alkyl). Examples of alkyl include methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl and 3-methylpentyl. When an alkyl residue having a specific number of carbon atoms is named by a chemical name or identified by a molecular formula, it may include all positional isomers having that number of carbon atoms. Thus, for example, "butyl" includes n-butyl (i.e., -(CH2)3CH3), sec-butyl (i.e., -CH(CH3)CH2CH3), isobutyl (i.e., -CH2CH(CH3)2) and tert-butyl (i.e., -C(CH3)3), and "propyl" includes n-propyl (i.e., -(CH2)2CH3) and isopropyl (i.e., -CH(CH3)2). "Alkenyl" refers to an alkyl group that contains at least one carbon-carbon double bond and has 2 to 20 carbon atoms (i.e., C 2-20 alkenyl), 2 to 8 carbon atoms (i.e., C 2-8 alkenyl), 2 to 6 carbon atoms (i.e., C 2-6 alkenyl) or 2 to 4 carbon atoms (i.e., C 2-4 alkenyl). Examples of alkenyl include vinyl, propenyl, butadienyl (including 1,2-butadienyl and 1,3-butadienyl). "Alkynyl" refers to an alkyl group that contains at least one carbon-carbon triple bond and has 2 to 20 carbon atoms (i.e., C 2-20 alkyl), 2 to 8 carbon atoms (i.e., C 2-8 alkyl), 2 to 6 carbon atoms (i.e., C 2-6 alkyl) or 2 to 4 carbon atoms (i.e., C 2-4An alkyl group of the (alkyl). The term "alkynyl" also includes a group having one triple bond and one double bond. "Alkoxy" refers to the group "alkyl-O-". Examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentyloxy, n-hexyloxy, and 1,2-dimethylbutoxy. "Haloalkyl" refers to a straight-chain or branched alkyl group as defined above, wherein one or more hydrogen atoms are replaced by a halogen. For example, when a residue is replaced by more than one halogen, a prefix corresponding to the number of attached halogens may be used to indicate. Dihaloalkyl and trihaloalkyl refer to an alkyl group substituted by two ("di-") or three ("tri-") halo groups, which may or may not be the same halogen. Examples of haloalkyl groups include difluoromethyl (-CHF2) and trifluoromethyl (-CF3). "Haloalkoxy" refers to an alkoxy group as defined above, wherein one or more hydrogen atoms are replaced by a halogen. "Alkylthio" refers to the group "alkyl-S-". "Acyl" refers to the group -C(O)R, wherein R is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroalkyl, or heteroaryl; as defined herein, each of the above groups may be optionally substituted. Examples of acyl groups include formyl, acetyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, and benzoyl. "Amido" refers to both the "C-amido" group (i.e., the group -C(O)NR y R z ), and the "N-amido" group (i.e., the group -NR y C(O)R z ), wherein R y and R z are independently selected from the group consisting of hydrogen, alkyl, aryl, haloalkyl, or heteroaryl, and each of the above groups may be optionally substituted. "Amino" refers to the group -NR y R z , wherein R y and R z are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, or heteroaryl, and each of the above groups may be optionally substituted. "Aryl" refers to an aromatic carbocyclic group having a single ring (such as monocyclic) or multiple rings (such as bicyclic or tricyclic, including fused systems). As used herein, aryl has 6 to 20 ring carbon atoms (i.e., C 6-20 aryl), 6 to 12 carbocyclic atoms (i.e., C 6-12 aryl), or 6 to 10 carbocyclic atoms (i.e., C 6-10aryl). Examples of aryl include phenyl, naphthyl, fluorenyl, and anthracenyl. However, aryl does not in any way include heteroaryl as defined below or overlap with heteroaryl as defined below. If one or more aryl groups are fused to a heteroaryl group, the resulting ring system is heteroaryl. If one or more aryl groups are fused to a heterocyclic group, the resulting ring system is heterocyclic. "Carbamoyl" refers to both an "O-carbamoyl" group (i.e., the group –O-C(O)NR y R z ), and an "N-carbamoyl" group (i.e., the group -NR y C(O)OR z ), where R y and R z are independently selected from the group consisting of hydrogen, alkyl, aryl, haloalkyl, or heteroaryl, each of which may be optionally substituted. "Carboxylate" refers to both -OC(O)R and -C(O)OR, where R is hydrogen, alkyl, cycloalkyl, heterocyclic, aryl, heteroalkyl, or heteroaryl; as defined herein, each of the above groups may be optionally substituted. "Cycloalkyl" refers to a saturated or partially unsaturated cyclic alkyl having a monocyclic or polycyclic (including fused, bridged, and spiro ring systems). The term "cycloalkyl" includes cycloalkenyl (i.e., a cyclic group having at least one double bond). As used herein, cycloalkyl has from 3 to 20 ring carbon atoms (i.e., C 3-20 cycloalkyl), from 3 to 12 ring carbon atoms (i.e., C 3-12 cycloalkyl), from 3 to 10 ring carbon atoms (i.e., C 3-10 cycloalkyl), from 3 to 8 ring carbon atoms (i.e., C 3-8 cycloalkyl), or from 3 to 6 ring carbon atoms (i.e., C 3-6 cycloalkyl). Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. "Imino" refers to the group -C(NR)R, where each R is independently alkyl, cycloalkyl, heterocyclic, aryl, heteroalkyl, or heteroaryl, each of which may be optionally substituted as defined herein. "Halogen" or "halo" includes fluorine, chlorine, bromine, and iodine. "Heteroalkyl" means an alkyl group in which one or more carbon atoms (and any associated hydrogen atoms) are each independently substituted by the same or different heteroatom groups (e.g., C2 heteroalkyl has one carbon atom and one heteroatom). The term "heteroalkyl" includes straight-chain or branched-chain saturated chains having carbon atoms and heteroatoms. By way of example, 1, 2 or 3 carbon atoms may be independently substituted by the same or different heteroatom groups. Heteroatom groups include, but are not limited to, -NR-, -O-, -S-, -S(O)-, -S(O)2-, etc., where R is hydrogen, alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl or heterocyclic group, each of which may optionally be substituted. Examples of heteroalkyl groups include -OCH3, --CH2OCH3, -SCH3, -CH2SCH3, -NRCH3 and -CH2NRCH3, where R is hydrogen, alkyl, aryl, aralkyl, heteroalkyl or heteroaryl, each of which may optionally be substituted. As used herein, heteroalkyl contains 1 to 10 carbon atoms, 1 to 8 carbon atoms or 1 to 4 carbon atoms and contains 1 to 3 heteroatoms, 1 to 2 heteroatoms or 1 heteroatom. "Heteroalkylene" refers to a divalent heteroalkyl group. The "heteroalkylene" group must have at least one carbon atom and at least one heteroatom group in the chain. The term "heteroalkylene" includes straight-chain or branched-chain saturated chains having carbon atoms and heteroatoms. By way of example, one, two or three carbon atoms may each independently be substituted by the same or different heteroatom groups. Heteroatom groups include, but are not limited to, -NR-, -O-, -S-, -S(O)-, -S(O)2-, etc., where R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroalkyl or heteroaryl, as defined herein, and each of the foregoing groups may optionally be substituted. Examples of heteroalkylene include, for example, -CH2OCH2-, -CH(CH3)OCH2-, -CH2CH2OCH2-, -OCH2-, -CH(CH3)O-, -CH2CH2O-, -CH2CH2OCH2CH2OCH2-, -CH2CH2OCH2CH2O-, -CH2SCH2-, -CH(CH3)SCH2-, -CH2CH2SCH2-, -CH2CH2SCH2CH2SCH2-, -SCH2-, -CH(CH3)S-, -CH2CH2S-, -CH2CH2SCH2CH2S-, -CH2S(O)2CH2-, -CH(CH3)S(O)2CH2-, -CH2CH2S(O)2CH2-, -CH2CH2S(O)2CH2CH2OCH2-, -CH2NRCH2-, -CH(CH3)NRCH2-, -CH2CH2NRCH2-, -CH2CH2NRCH2CH2NRCH2-, etc., where each R is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroalkyl or heteroaryl, as defined herein, and each of the foregoing groups may optionally be substituted. As used herein, heteroalkylene contains from 1 to 10 carbon atoms, from 1 to 8 carbon atoms or from 1 to 4 carbon atoms and contains from 1 to 3 heteroatoms, from 1 to 2 heteroatoms or 1 heteroatom. "Heteroaryl" refers to an aromatic group having a monocyclic, polycyclic or multiple fused-ring structure, the aromatic group having one or more ring heteroatoms independently selected from nitrogen, oxygen and sulfur. As used herein, heteroaryl contains from 1 to 20 ring carbon atoms (i.e., C 1-20 heteroaryl), from 3 to 12 ring carbon atoms (i.e., C 3-12 heteroaryl) or from 3 to 8 carbon ring atoms (i.e., C 3-8a heteroaryl group) and contains 1 to 5 heteroatoms, 1 to 4 heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, oxygen, and sulfur. Examples of heteroaryl groups include pyrimidinyl, purinyl, pyridyl, pyridazinyl, benzothiazolyl, and pyrazolyl. Examples of fused heteroaryl rings include, but are not limited to, benzothiazolyl, quinolinyl, isoquinolinyl, benzothiophenyl, indazolyl, benzimidazolyl, pyrazolo[1,5-a]pyridyl, and imidazo[1,5-a]pyridyl, wherein the heteroaryl group can be attached through any ring of the fused system. Any aromatic ring having a single or multiple fused rings and containing at least one heteroatom, whether or not attached to the remainder of the molecule (i.e., through any one of the fused rings), is considered a heteroaryl group. A heteroaryl group does not include an aryl group as defined above and does not overlap with an aryl group. "Heterocyclic group" refers to a saturated or unsaturated cyclic alkyl group having one or more ring heteroatoms independently selected from nitrogen, oxygen, and sulfur. The term "heterocyclic group" includes heterocyclic alkenyl groups (i.e., heterocyclic groups having at least one double bond), bridged heterocyclic groups, fused heterocyclic groups, and spiro heterocyclic groups. The heterocyclic group can be monocyclic or polycyclic, wherein multiple rings can be fused, bridged, or spiro. Any non-aromatic ring containing at least one heteroatom, regardless of its attachment mode (i.e., it can be attached through a carbon atom or a heteroatom), is considered a heterocycle. In addition, the term "heterocyclic group" is intended to cover any non-aromatic ring containing at least one heteroatom that can be fused to an aryl or heteroaryl ring, regardless of its connection mode to the remainder of the molecule. As used herein, the heterocyclic group contains 2 to 20 ring carbon atoms (i.e., C 2-20 heterocyclic group), 2 to 12 ring carbon atoms (i.e., C 2-12 heterocyclic group), 2 to 10 ring carbon atoms (i.e., C 2-10 heterocyclic group), 2 to 8 ring carbon atoms (i.e., C 2-8 heterocyclic group), 3 to 12 ring carbon atoms (i.e., C 3-12 heterocyclic group), 3 to 8 ring carbon atoms (i.e., C 3-8 heterocyclic group) or 3 to 6 ring carbon atoms (i.e., C 3-6(heterocyclic group) and having 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms or 1 ring heteroatom, and these heteroatoms are independently selected from nitrogen, sulfur or oxygen. Examples of heterocyclic groups include pyrrolidinyl, piperidinyl, piperazinyl, oxetanyl, dioxolanyl, azetidinyl and morpholinyl. As used herein, the term "bridged heterocyclic group" refers to a cyclic moiety having 4 to 10 members, which cyclic moiety is connected at two non-adjacent atoms of the heterocyclic group to one or more (e.g., 1 or 2) cyclic moieties having 4 to 10 members and having at least one heteroatom, wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur. As used herein, bridged heterocyclic groups include bicyclic and tricyclic ring systems. Also as used herein, the term "spiro heterocyclic group" refers to a ring system in which a 3- to 10-membered heterocyclic group has one or more additional rings, wherein the one or more additional rings are 3- to 10-membered cycloalkyl groups or 3- to 10-membered heterocyclic groups, and a single atom in the one or more additional rings is also an atom of the 3- to 10-membered heterocyclic group. Examples of spiro heterocyclic group rings include bicyclic and tricyclic ring systems such as 2-oxa-7-azaspiro[3.5]nonyl, 2-oxa-6-azaspiro[3.4]octyl and 6-oxa-1-azaspiro[3.3]heptyl. Examples of fused heterocyclic group rings include, but are not limited to, 1,2,3,4-tetrahydroisoquinolinyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridinyl, indolinyl and isoindolinyl, wherein the heterocyclic group can be connected through any one of the rings in the fused system. "Sulfonyl" refers to the group -S(O)2R, where R is alkyl, haloalkyl, heterocyclic group, cycloalkyl, heteroaryl or aryl. Examples of sulfonyl groups are methylsulfonyl, ethylsulfonyl, phenylsulfonyl and toluenesulfonyl. "Alkylsulfonyl" refers to the group -S(O)2R, where R is alkyl. "Alkylsulfinyl" refers to the group -S(O)R, where R is alkyl. Certain commonly used alternative chemical names can be used. For example, divalent groups such as divalent "alkyl" groups, divalent "aryl" groups, etc. can also be referred to as "alkylene" groups or "alkylene" groups, "arylene" groups or "arylene" groups, respectively. In addition, unless otherwise expressly stated, when groups are combined and referred to as a molecule (such as aralkyl) herein, the last-mentioned group includes the atom by which the molecule is attached to the remainder of the molecule. The term "optional" or "optionally" means that the subsequent described event or circumstance may or may not occur, and the description encompasses both the case where the event or circumstance occurs and the case where it does not occur. In addition, the term "optionally substituted" means that any one or more hydrogen atoms on a specified atom or group may or may not be substituted by a moiety other than hydrogen. As used herein, the term "compound" refers to all stereoisomers, geometric isomers, allotropes, and isotopes of the depicted structure. Unless otherwise indicated, a compound identified by name or structure as a specific isomeric form herein is intended to include other isomeric forms. Certain compounds exist in isomeric forms. Isomers are in equilibrium with each other. For example, an amide-containing compound may be in equilibrium with its imidic acid homolog. Regardless of which isomer is shown and regardless of the nature of the equilibrium between isomers, one of ordinary skill in the art will understand that such compounds include both the amide and imidic acid isomers. Thus, amide-containing compounds are understood to include their imidic acid homologs. Similarly, imidic acid-containing compounds also include their amide homologs. Any formula or structure given herein is also intended to represent both the unlabeled form and the isotopically labeled form of a compound. An isotopically labeled compound has the structure depicted by the formula given herein, except that one or more atoms are replaced by atoms having a selected atomic mass or mass number. Isotopes that can be incorporated into the compounds of the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine such as, but not limited to 2 H (deuterium, D), 3 H (tritium), 11 C, 13 C, 14 C, 15 N, 18 F, 31 P, 32 P, 35 S, 36 Cl and 125 I. Various isotopically labeled compounds of the present disclosure are, for example, compounds that incorporate radioactive isotopes such as 3 H, 13 C, and 14 C. Such isotopically labeled compounds may be useful in metabolic studies, reaction kinetics studies, detection, or imaging techniques such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) including determination of the tissue distribution of a drug or a substrate, or may play a role in the radioactive treatment of patients. The present disclosure also includes “tritiated analogs” of the compounds of Formula I, wherein from 1 to n hydrogens attached to carbon atoms are replaced by tritium, where n is the number of hydrogens in the molecule. Such compounds have increased resistance to metabolism and can thus be used to extend the half-life of any compound of Formula I when administered to mammals, particularly humans. See, for example, Foster, “Deuterium Isotope Effects in Studies of Drug Metabolism,” Trends Pharmacol. Sci. 5(12):524-527 (1984). Such compounds can be synthesized by methods well known in the art, for example, using starting materials in which one or more hydrogen atoms have been replaced by deuterium. Deuterium-labeled or -substituted therapeutic compounds in the present disclosure may have improved drug metabolism and pharmacokinetics (DMPK) properties, which are related to the absorption, distribution, metabolism, and excretion (ADME) of drugs. Substitution with a heavier isotope such as deuterium may confer certain therapeutic advantages due to higher metabolic stability, such as an extended half-life in vivo, reduced dosing requirements, and / or an improved therapeutic index. 18 Compounds labeled with F may be useful for positron emission tomography (PET) or single photon emission computed tomography (SPECT) studies. The isotopically labeled compounds and prodrugs thereof in the present disclosure can generally be prepared by carrying out the steps disclosed in the following schemes or in the examples and preparation methods, simply by replacing a non-isotopically labeled reagent with an easily available isotopically labeled reagent. It should be understood that in the context of this disclosure, deuterium is considered a substituent in the compounds of Formula I. In many cases, the compounds of the present disclosure are capable of forming acid and / or base salts due to the presence of amino and / or carboxyl or similar groups. Also provided are pharmaceutically acceptable salts, hydrates, solvates, isomers, polymorphs, and prodrugs of the compounds described herein. “Pharmaceutically acceptable” or “physiologically acceptable” refers to compounds, salts, compositions, dosage forms, and other materials that can be used to prepare pharmaceutical compositions suitable for veterinary or human medicine. The term "pharmaceutically acceptable salt" of a given compound refers to salts that retain the biological activity and properties of the given compound and are not biologically or otherwise undesirable. "Pharmaceutically acceptable salts" or "physiologically acceptable salts" include, for example, salts formed with inorganic acids and salts formed with organic acids. Further, if the compounds described herein are obtained in the form of acid addition salts, the free base can be obtained by basifying a solution of the acid addition salt. Conversely, if the product is the free base, addition salts, particularly pharmaceutically acceptable addition salts, can be prepared by dissolving the free base in a suitable organic solvent and treating the solution with an acid according to conventional methods for preparing acid addition salts from basic compounds. Those skilled in the art will recognize the various synthetic methods available for preparing non-toxic pharmaceutically acceptable addition salts. Pharmaceutically acceptable acid addition salts can be prepared from inorganic acids and organic acids. Salts derived from inorganic acids include, for example, hydrochlorides, hydrobromides, sulfates, nitrates, phosphates, and the like. Salts derived from organic acids include, for example, acetates, propionates, gluconates, glycolates, pyruvates, oxalates, malates, malonates, succinates, maleates, fumarates, tartrates, citrates, benzoates, cinnamates, mandelates, mesylates, esylates, tosylates, salicylates, and the like. Similarly, pharmaceutically acceptable base addition salts can be prepared from inorganic bases and organic bases. Salts derived from inorganic bases include, by way of example only, sodium salts, potassium salts, lithium salts, aluminum salts, ammonium salts, calcium salts, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts formed from ammonia, or primary, secondary, or tertiary amines such as salts derived from nitrogen-containing heterocycles, nitrogen-containing heteroaryls, or amines of the general formula N(RN)3 (e.g., HN + (RN)3 or (alkyl)N + (RN)3), where each R N is independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl, and where each R N may optionally be substituted, for example, by one or more (such as 1 to 5 or 1 to 3) substituents (such as halogen, cyano, hydroxy, amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, or haloalkoxy). Specific examples of suitable amines include, by way of illustration, isopropylamine, trimethylamine, diethylamine, tri(isopropyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, and the like. The term "substituted" means that any one or more hydrogen atoms on a specified atom or group are replaced by one or more substituents other than hydrogen, provided that the normal valence of the specified atom is not exceeded. One or more substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amino, amido, amidino, aryl, azido, carbamoyl, carboxyl, carboxylate, cyano, guanidino, halogen, haloalkyl, haloalkoxy, heteroalkyl, heteroaryl, heterocyclic, hydroxy, hydrazino, imino, carbonyl, nitro, alkanesulfinyl, sulfonic acid, alkanesulfonyl, thiocyanate, mercapto, thione, or combinations thereof. Polymers or similar indeterminate structures defined by infinitely appending further substituents to define a substituent (e.g., a substituted aryl having a substituted alkyl which itself is substituted with a substituted aryl which is further substituted with a substituted heteroalkyl, etc.) are not intended to be included herein. Unless otherwise specified, the maximum number of consecutive substitutions in the compounds described herein is three. For example, the case of a substituted aryl being consecutively substituted with two other substituted aryls is limited to ((substituted aryl) substituted aryl) substituted aryl. Similarly, the above definitions are not intended to include non-permissible substitution patterns (e.g., a methyl group substituted with five fluorine atoms, or a heteroaryl group having two adjacent oxygen ring atoms). Such non-permissible substitution patterns are well known to those skilled in the art. When used to modify a chemical group, the term "substituted" may describe other chemical groups as defined herein. Unless otherwise specified, when a group is described as optionally substituted, any substituent of that group itself is unsubstituted. For example, in some embodiments, the term "substituted alkyl" refers to an alkyl group having one or more substituents (including hydroxy, halogen, alkoxy, cycloalkyl, heterocyclic, aryl, and heteroaryl). In other embodiments, said one or more substituents may be further substituted with halogen, alkyl, haloalkyl, hydroxy, alkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl, where each substituent itself is also substituted. In other embodiments, said substituent may be further substituted with halogen, alkyl, haloalkyl, alkoxy, hydroxy, cycloalkyl, heterocyclic, aryl, or heteroaryl, where each substituent itself is unsubstituted. As used herein, "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents and absorption delaying agents, etc. The use of such media and agents in pharmaceutical active substances is well known in the art. Unless any conventional medium or formulation is incompatible with the active ingredient, it may be considered for use in a therapeutic composition. Supplementary active ingredients can also be added to the composition. As used herein, the term "pharmaceutically acceptable" means that the compound or its salt or composition is chemically and / or toxicologically compatible with the other components of the formulation and / or the subject to which it is administered for treatment. The terms "administering" or "administration" refer to the methods of applying a dose of a compound or pharmaceutical composition to a vertebrate or invertebrate (including mammals, birds, fish or amphibians). The methods of administration may vary depending on a variety of factors, such as the components of the pharmaceutical composition, the site of the disease occurrence, and the severity of the disease, etc. As used herein, the term "effective amount" or "effective dose" or "pharmaceutically effective amount" or "therapeutically effective amount" means a sufficient amount of a chemical entity (e.g., a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof) that is administered, which will, to some extent, alleviate one or more symptoms of the disease or disorder being treated, and may include curing the disease. "Curing" means eliminating the symptoms of an active disease. The results include alleviating and / or relieving the signs, symptoms or causes of the disease, or any other desired change in a biological system. For example, an "effective amount" for therapeutic use means an amount of a composition containing the compounds disclosed herein that is sufficient to cause a clinically significant reduction in the symptoms of the disease. In any individual case, a suitable "effective" amount is determined by using any suitable technique (e.g., dose escalation studies). In some embodiments, a "therapeutically effective amount" of a compound provided herein means an amount of the compound that is effective as a monotherapy or in combination therapy. The term "excipient" or "pharmaceutically acceptable excipient" refers to a pharmaceutically acceptable material, composition, or vehicle such as a liquid or solid filler, diluent, carrier, solvent, or encapsulating material. In some embodiments, each component is "pharmaceutically acceptable" in the sense of being compatible with the other components of the pharmaceutical formulation, and each component is suitable for use in contact with the tissues or organs of humans and animals without producing excessive toxicity, irritation, allergic responses, immunogenicity, or other problems or complications and conforms to a reasonable benefit / risk ratio. See, e.g., Remington: The Science and Practice of Pharmacy, 21st ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2005; Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et al., Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed.; CRC Press LLC: Boca Raton, FL, 2009. The term "pharmaceutical composition" refers to a mixture of a compound of formula I provided herein, or a pharmaceutically acceptable salt or solvate thereof, with other chemical components (collectively referred to herein as "adjuvants"), such as carriers, stabilizers, diluents, dispersants, suspending agents, and / or thickening agents. The pharmaceutical composition facilitates the administration of the compound to a living organism. There are a variety of techniques for administering compounds in the art, including but not limited to rectal administration, oral administration, intravenous administration, aerosol administration, parenteral administration, ocular administration, pulmonary administration, and topical administration. Compound In one aspect, provided herein is a compound of formula I: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein, A 1 is -NHR 1 wherein R 1 is hydrogen, -C(O)R 5, -C6 aryl-C 1-6 alkyl-NH2 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 2 and A 3 are both hydrogen; or A 2 is -NHR 2 , where R 2 is hydrogen, -C(O)R 5 , -C6 aryl-C 1-6 alkyl-NH2 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 1 and A 3 are both hydrogen; or A 3 is -NHR 3 , where R 3 is hydrogen, -C(O)R 5 , -C6 aryl-C 1-6 alkyl-NH2 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 1 and A 2 are both hydrogen; R 4 is -C 1-6 alkyl; provided that when A 1 is -NHR 1 , R 4 is not methyl; R 5 is -L-R 6 ; L is a linker moiety; and R 6 is hydrogen or a heterocyclic group, wherein the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, A 1 is -NHR 1 , where R 1 is hydrogen, -C(O)R 5 , -C6 aryl-C 1-6 alkyl-NH 2、 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 2 and A 3 are both hydrogen. Thus, in some embodiments, a compound of formula II is provided: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein R 4 is -C 2-6 alkyl, and A 1 is independently as defined herein. In some embodiments, A 1 is -NH2, and A 2 and A 3 are both hydrogen. In some embodiments, A 1 is -NH-C(O)R 5 and A 2 and A 3 are both hydrogen. In some embodiments, A 1 is -NH-C6 aryl-C 1-6 alkyl-NH2, and A 2 and A 3 are both hydrogen. In some embodiments, A 1 is -NH-C6 aryl-CH2-NH2, and A 2 and A 3 are both hydrogen. In some embodiments, A 1 is -NH-C6 aryl-C 1-6 alkyl-NHC(O)R 5 and A 2 and A 3 are both hydrogen. In some embodiments, A 1 is -NH-C6 aryl-CH2-NHC(O)R 5 and A 2 and A 3 are both hydrogen. In some embodiments, A 2 is -NHR 2 wherein R 2 is hydrogen, -C(O)R 5 -C6 aryl-C 1-6 alkyl-NH2, or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 and A 1 and A 3 are both hydrogen. Thus, in some embodiments, there is provided a compound of formula III: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein A 2 and R 4 are each independently as defined herein. In some embodiments, A 2 is -NH2, and both A 1 and A 3 are hydrogen. In some embodiments, A 2 is -NH-C(O)R 5 and both A 1 and A 3 are hydrogen. In some embodiments, A 2 is -NH-C6 aryl-C 1-6 alkyl-NH2, and both A 1 and A 3 are hydrogen. In some embodiments, A 2 is -NH-C6 aryl-CH2-NH2, and both A 1 and A 3 are hydrogen. In some embodiments, A 2 is -NH-C6 aryl-C 1-6 alkyl-NHC(O)R 5 and both A 1 and A 3 are hydrogen. In some embodiments, A 2 is -NH-C6 aryl-CH2-NHC(O)R 5 and both A 1 and A 3 are hydrogen. In some embodiments, A 3 is -NHR 3 wherein R 3 is hydrogen, -C(O)R 5 -C6 aryl-C 1-6 alkyl-NH2, or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 and both A 1 and A 2 are hydrogen. Thus, in some embodiments, a compound of formula IV is provided: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein A 3 and R 4 are each independently as defined herein. In some embodiments, A 3 is -NH2, and both A 1 and A 2 are hydrogen. In some embodiments, A 3is -NH-C(O)R 5 and A 1 and A 2 are both hydrogen. In some embodiments, A 3 is -NH-C6 aryl-C 1-6 alkyl-NH2, and A 1 and A 2 are both hydrogen. In some embodiments, A 3 is -NH-C6 aryl-CH2-NH2, and A 1 and A 2 are both hydrogen. In some embodiments, A 3 is -NH-C6 aryl-C 1-6 alkyl-NHC(O)R 5 and A 1 and A 2 are both hydrogen. In some embodiments, A 3 is -NH-C6 aryl-CH2-NHC(O)R 5 and A 1 and A 2 are both hydrogen. In some embodiments, R 4 is methyl, ethyl or isopropyl. In some embodiments, R 4 is ethyl or isopropyl. In some embodiments, R 4 is methyl. In some embodiments, R 4 is ethyl. In some embodiments, R 4 is isopropyl. In some embodiments, there is provided a compound of formula IIA: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein A 1 is independently as defined herein. In some embodiments, there is provided a compound of formula IIB: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein A 1 is independently as defined herein. In some embodiments, there is provided a compound of formula IIIA: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein A 2 is independently as defined herein. In some embodiments, there is provided a compound of formula IVA: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein A 3 is independently as defined herein. In some embodiments, provided is a compound having the formula IIC: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein R 5 is independently as defined herein. In some embodiments, provided is a compound of formula IID: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein R 5 is independently as defined herein. In some embodiments, provided is a compound of formula IIIB: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein R 5 is independently as defined herein. In some embodiments, provided is a compound of formula IVB: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein R 5 is independently as defined herein. In some embodiments, when R 1 、R 2 、or R 3 is not hydrogen, the compound comprises a linking moiety L that covalently links R 6 to the remainder of the compound. In some embodiments, L is an uncleavable linker. In some embodiments, L is a cleavable linker. In some embodiments, L comprises from 1 to 100 linking atoms, from 1 to 50 linking atoms, or from 5 to 50 linking atoms, or from 10 to 50 linking atoms, or from 1 to 40 linking atoms, or from 1 to 30 linking atoms, or from 1 to 20 linking atoms, or from 5 to 30 linking atoms, or from 10 to 30 linking atoms, or from 5 to 40 linking atoms, or from 5 to 50 linking atoms, or from 10 to 50 linking atoms, or from 20 to 50 linking atoms, or from 20 to 40 linking atoms, or from 20 to 30 linking atoms. In some embodiments, L contains one or more chain heteroatoms and contains one or more alkylene, alkenylene, alkynylene, arylene, heteroarylene, cycloalkylene, or heterocycloalkylene moieties, wherein each alkylene, alkenylene, alkynylene, arylene, heteroarylene, cycloalkylene, or heterocycloalkylene moiety may independently optionally be substituted with one to five substituents independently selected from oxo, halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, and benzyl. In some embodiments, L is an alkylene linker optionally containing one or more -O-, -S-, amine, ester, amide, carbamate, carbonate, succinimide, or ketone functional groups. In some embodiments, L includes one or more amino acids. In some embodiments, L contains one or more straight-chain or branched, natural or non-natural amino acids. In some embodiments, L contains a polypeptide. In some embodiments, L contains one or more polyethylene glycol units (e.g., PEG having an average molecular weight from 300 g / mol to 10,000 g / mol). In some embodiments, L is -L 1 -(AA) n -L 2 -R 6 wherein each L 1 , AA, n, L 2 , and R 6 are independently as defined herein. In some embodiments, L 1 is C 1-20 alkylene or C 2-20 heteroalkylene; n is 0, 1, 2, 3, 4, 5, or 6; each AA is independently an amino acid; and L 2 is C 1-40 alkylene or C 2-40 heteroalkylene, wherein the C 1-40 alkylene or C 2-40 heteroalkylene optionally includes a phenylene within the C 1-40 alkylene or C 2-40 heteroalkylene chain, and the C 1-40 alkylene or C 2-40 heteroalkylene is optionally substituted with one or more (e.g., one or two) oxo groups. In some embodiments, L 1 is C 1-20 alkylene or C2-20 Heteroalkylene; n is 0, 1, 2, 3, 4, 5 or 6; Each AA is independently an amino acid; and L 2 is C 1-40 alkylene or C 2-40 heteroalkylene, wherein the C 1-40 alkylene or C 2-40 heteroalkylene is optionally substituted with one or more (e.g., one or two) oxo groups. In some embodiments, n is 0. In some embodiments, n is 1, 2, 3, 4, 5, 6 or 7. In some embodiments, n is 2, 3, 4, 5, 6 or 7. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, L 1 is C 1-20 alkylene. In some embodiments, L 1 is C 1-10 alkylene. In some embodiments, L 1 is C 2-6 alkylene. In some embodiments, L 1 is C 2-20 heteroalkylene. In some embodiments, L 1 is C 2-10 heteroalkylene. In some embodiments, L 1 is C 2-6 heteroalkylene. In some embodiments, L 1 is -(CH2) p -X 1 -(CH2) q -X 2 -* or -X 1 -(CH2) p -phenylene-(CH2) q -X 2 -*, wherein the * bond is attached to -(AA) n -L 2 -R 6 ; and X 1 is a bond, -O-, -S-, or -NH-; X 2 is a bond, -O-, -S-, or -NH-; p is 1, 2, 3, or 4; and q is 1, 2, 3, or 4. In some embodiments, L 1 is -X 1 -(CH2) p -phenylene-(CH2) q -X 2 -*, where the * bond is attached to -(AA) n -L 2 -R 6 ; and X 1 is a bond, -O-, -S-, or -NH-; X 2 is a bond, -O-, -S-, or -NH-; p is 1, 2, 3, or 4; and q is 1, 2, 3, or 4. In some embodiments, L 1 is -(CH2) p -X 1 -(CH2) q -X 2 -*, where the * bond is attached to -(AA) n -L 2 -R 6 ; and X 1 is a bond, -O-, -S-, or -NH-; X 2 is a bond, -O-, -S-, or -NH-; p is 1, 2, 3, or 4; and q is 1, 2, 3, or 4. In some embodiments, L 1 is -CH2-X 1 -CH2-X 2 -*. In some embodiments, L 1 is -(CH2)2-X 1 -CH2-X 2 -*. In some embodiments, L 1 is -(CH2)3-X 1 -CH2-X 2 -*. In some embodiments, L 1 is -(CH2)4-X 1 -CH2-X 2 -*. In some embodiments, L 1 is -CH2-X 1 -(CH2)2-X2 -*. In some embodiments, L 1 is -(CH2)2-X 1 -(CH2)2-X 2 -*. In some embodiments, L 1 is -(CH2)3-X 1 -(CH2)2-X 2 -*. In some embodiments, L 1 is -(CH2)4-X 1 -(CH2)2-X 2 -*. In some embodiments, L 1 is -CH2-X 1 -(CH2)3-X 2 -*. In some embodiments, L 1 is -(CH2)2-X 1 -(CH2)3-X 2 -*. In some embodiments, L 1 is -(CH2)3-X 1 -(CH2)3-X 2 -*. In some embodiments, L 1 is -(CH2)4-X 1 -(CH2)3-X 2 -*. In some embodiments, L 1 is -CH2-X 1 -(CH2)4-X 2 -*. In some embodiments, L 1 is -(CH2)2-X 1 -(CH2)4-X 2 -*. In some embodiments, L 1 is -(CH2)3-X 1 -(CH2)4-X 2 -*. In some embodiments, L 1 is -(CH2)4-X 1 -(CH2)4-X 2 -*. In some embodiments, X 1 is a bond. In some embodiments, X 1 is -O-. In some embodiments, X 1 is -S-. In some embodiments, X 1 is -NH-. In some embodiments, X 2 is a bond. In some embodiments, X 2is -O-. In some embodiments, X 2 is -S-. In some embodiments, X 2 is -NH-. In some embodiments, L 1 is -CH2-X 1 -CH2-NH-*. In some embodiments, L 1 is -(CH2)2-X 1 -CH2-NH-*. In some embodiments, L 1 is -(CH2)3-X 1 -CH2-NH-*. In some embodiments, L 1 is -(CH2)4-X 1 -CH2-NH-*. In some embodiments, L 1 is -CH2-X 1 -(CH2)2-NH-*. In some embodiments, L 1 is -(CH2)2-X 1 -(CH2)2-NH-*. In some embodiments, L 1 is -(CH2)3-X 1 -(CH2)2-NH-*. In some embodiments, L 1 is -(CH2)4-X 1 -(CH2)2-NH-*. In some embodiments, L 1 is -CH2-X 1 -(CH2)3-NH-*. In some embodiments, L 1 is -(CH2)2-X 1 -(CH2)3-NH-*. In some embodiments, L 1 is -(CH2)3-X 1 -(CH2)3-NH-*. In some embodiments, L 1 is -(CH2)4-X 1 -(CH2)3-NH-*. In some embodiments, L 1 is -CH2-X 1 -(CH2)4-NH-*. In some embodiments, L 1 is -(CH2)2-X 1 -(CH2)4-NH-*. In some embodiments, L 1 is -(CH2)3-X 1 -(CH2)4-NH-*. In some embodiments, L 1is -(CH2)4-X 1 -(CH2)4-NH-*. In some embodiments, L 1 is -CH2-O-CH2-X 2 -*. In some embodiments, L 1 is -(CH2)2-O-CH2-X 2 -*. In some embodiments, L 1 is -(CH2)3-O-CH2-X 2 -*. In some embodiments, L 1 is -(CH2)4-O-CH2-X 2 -*. In some embodiments, L 1 is -CH2-O-(CH2)2-X 2 -*. In some embodiments, L 1 is -(CH2)2-O-(CH2)2-X 2 -*. In some embodiments, L 1 is -(CH2)3-O-(CH2)2-X 2 -*. In some embodiments, L 1 is -(CH2)4-O-(CH2)2-X 2 -*. In some embodiments, L 1 is -CH2-O-(CH2)3-X 2 -*. In some embodiments, L 1 is -(CH2)2-O-(CH2)3-X 2 -*. In some embodiments, L 1 is -(CH2)3-O-(CH2)3-X 2 -*. In some embodiments, L 1 is -(CH2)4-O-(CH2)3-X 2 -*. In some embodiments, L 1 is -CH2-O-(CH2)4-X 2 -*. In some embodiments, L 1 is -(CH2)2-O-(CH2)4-X 2 -*. In some embodiments, L 1 is -(CH2)3-O-(CH2)4-X 2 -*. In some embodiments, L 1 is -(CH2)4-O-(CH2)4-X 2 -*. In some embodiments, L 1 is wherein the *-key is attached to -(AA) n -L 2 -R 6 . In some embodiments, L 1 is -(CH2) p -O-(CH2) q -NH-*. In some embodiments, L 1 is -CH2-O-CH2-NH-*. In some embodiments, L 1 is -(CH2)2-O-CH2-NH-*. In some embodiments, L 1 is -(CH2)3-O-CH2-NH-*. In some embodiments, L 1 is -(CH2)4-O-CH2-NH-*. In some embodiments, L 1 is -CH2-O-(CH2)2-NH-*. In some embodiments, L 1 is -(CH2)2-O-(CH2)2-NH-*. In some embodiments, L 1 is -(CH2)3-O-(CH2)2-NH-*. In some embodiments, L 1 is -(CH2)4-O-(CH2)2-NH-*. In some embodiments, L 1 is -CH2-O-(CH2)3-NH-*. In some embodiments, L 1 is -(CH2)2-O-(CH2)3-NH-*. In some embodiments, L 1 is -(CH2)3-O-(CH2)3-NH-*. In some embodiments, L 1 is -(CH2)4-O-(CH2)3-NH-*. In some embodiments, L 1 is -CH2-O-(CH2)4-NH-*. In some embodiments, L 1 is -(CH2)2-O-(CH2)4-NH-*. In some embodiments, L 1 is -(CH2)3-O-(CH2)4-NH-*. In some embodiments, L 1 is -(CH2)4-O-(CH2)4-NH-*. In certain embodiments, L comprises more than one consecutive amino acid to form a moiety having the formula -(AA)n - peptide unit. In certain embodiments, having the formula -(AA) n - peptide unit consists of 2 to 7 amino acids, wherein these amino acids are linked by peptide (i.e., amide) bonds. In certain embodiments, for the formula -(AA) n - peptide unit, linker L 1 binds to AA at its C-terminus and to L 2 -R 6 portion binds. Peptide unit -(AA) n - The amino acid sequence is not particularly limited, but examples include L- or D-amino acids and may include amino acids having the following structures, such as β-alanine, ε-aminohexanoic acid, γ-aminobutyric acid, α-amino acids, or non-natural types of amino acids such as N-methylated amino acids. Specific examples include phenylalanine (Phe; F), tyrosine (Tyr; Y), leucine (Leu; L), glycine (Gly; G), alanine (Ala; A), valine (Val; V), lysine (Lys; K), citrulline (Cit), serine (Ser; S), glutamic acid (Glu; E), and aspartic acid (Asp; D). In certain embodiments, the peptide unit -(AA) n - contains one or more (e.g., 2 to 7, or 2 to 5, or 3 to 5, or 4) amino acid residues independently selected from phenylalanine, glycine, valine, lysine, citrulline, serine, glutamic acid, and aspartic acid. In certain embodiments, -(AA) n - is selected from -FGG-, -FGGD-, -FGG-(D-)D-, -FGGE-, -GFGG-, -FGGS-, -FGGK-, -GFGGD-, -GGFGG-, -GFGGDD-, -GFGGDK-, -FGGGFGG-, wherein (D-)D refers to D-aspartic acid. In some embodiments, n is 2, 3, 4, 5, 6 or 7, and each AA is independently selected from Gly and Phe. In some embodiments, -(AA) n is -Gly-Phe-Gly-Gly- (-GFGG-). In some embodiments, -(AA) n is wherein the bond aa is attached to L 2 . In some embodiments, -(AA) n is wherein the bond aa is attached to L 2。 In some embodiments, -(AA) n is wherein the bond aa is attached to L 2 。 In some embodiments, L 2 is an optionally oxygen-substituted C 1-40 alkylene. In some embodiments, L 2 is an optionally oxygen-substituted C 1-30 alkylene. In some embodiments, L 2 is an optionally oxygen-substituted C 1-20 alkylene. In some embodiments, L 2 is an optionally oxygen-substituted C 1-10 alkylene. In some embodiments, L 2 is an optionally oxygen-substituted C 5-40 alkylene. In some embodiments, L 2 is an optionally oxygen-substituted C 5-30 alkylene. In some embodiments, L 2 is an optionally oxygen-substituted C 5-20 alkylene. In some embodiments, L 2 is an optionally oxygen-substituted C 5-10 alkylene. In some embodiments, L 2 is -C(O)-C 0-39 alkylene. In some embodiments, L 2 is -C(O)-C 1-15 alkylene. In some embodiments, L 2 is -C(O)-C 1-10 alkylene. In some embodiments, L 2 is -C(O)-C 5-10 alkylene. In some embodiments, L 2 is an optionally oxygen-substituted C 2-40 heteroalkylene. In some embodiments, L 2 is -C(O)-C 1-39 heteroalkylene. In some embodiments, L 2 is -C(O)-(CH2CH2O) 1-10 -CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O) 1-8-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O) 1-5 -CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O) 2-10 -CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O) 2-8 -CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O) 2-5 -CH2CH2-. In some embodiments, L 2 is -C(O)-CH2CH2O-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O)2-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O)3-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O)4-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O)5-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O)6-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O)7-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O)8-CH2CH2-. In some embodiments, L 2 is --C(O)-(CH2CH2O)9-CH2CH2-. In some embodiments, L 2 is -C(O)-(CH2CH2O) 10 -CH2CH2-. In some embodiments, L 2 is wherein the bond ab is attached to R 6 . In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-(AA) n -C(O)-C 1-10 alkylene-R 6 In some embodiments, R 5is -(CH2) p -O-(CH2) q -NH-(AA) n -C(O)-(CH2) 1-10 -CH2CH2-R 6 。 In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-GFGG-C(O)-C 1-10 alkylene-R 6 。In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-GFGG-C(O)-(CH2) 1-10 -CH2CH2-R 6 。 In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-(AA) n -C(O)-C 1-30 heteroalkylene-R 6 。In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-(AA) n -C(O)-(CH2CH2O) 1-10 -CH2CH2-R 6 。 In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-GFGG-C(O)-C 1-35 heteroalkylene-R 6 。In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-GFGG-C(O)-C 1-30 heteroalkylene-R 6 。In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-GFGG-C(O)-(CH2CH2O) 1-10 -CH2CH2-R 6 。 In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-GFGG-C(O)-C 1-35 heteroalkylene-R 6 。In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-GFGG-C(O)-C 1-30 heteroalkylene-R 6 。In some embodiments, R 5 is -(CH2) p -O-(CH2) q -NH-GFGG-C(O)-(CH2CH2O) 1-10 -CH2CH2-R 6 。 In some embodiments, R 5 is wherein, R 6 is a heterocyclic group, and the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, R 5 is wherein, R 6 is a heterocyclic group, and the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, R 5 is wherein, R 6 is a heterocyclic group, and the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, q is 1. In some embodiments, q is 2. In some embodiments, q is 3. In some embodiments, q is 4. In some embodiments, p is 1 and q is 1. In some embodiments, p is 2 and q is 1. In some embodiments, p is 3 and q is 1. In some embodiments, p is 4 and q is 1. In some embodiments, p is 1 and q is 2. In some embodiments, p is 2 and q is 2. In some embodiments, p is 3 and q is 2. In some embodiments, p is 4 and q is 2. In some embodiments, p is 1 and q is 3. In some embodiments, p is 2 and q is 3. In some embodiments, p is 3 and q is 3. In some embodiments, p is 4 and q is 3. In some embodiments, p is 1 and q is 4. In some embodiments, p is 2 and q is 4. In some embodiments, p is 3 and q is 4. In some embodiments, p is 4 and q is 4. In some embodiments, R 6 is hydrogen. In some embodiments, R 6 is a heterocyclic group, and the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In certain embodiments, R 6 is a heterocyclic group. In some embodiments, A 3 is -NH-C(O)R 5 , and both A 1 and A 2 are hydrogen. In some embodiments, A 3 is -NH-C(O)-L 1 -(AA) n -L 2 -R 6 , and both A 1 and A 2 are hydrogen. In some embodiments, A 3 is -NH-C(O)-L 1 -(AA) n -L 2 -R 6 , and both A 1 and A 2 are hydrogen; L 1 is -(CH2) p -X 1 -(CH2) q -X 2 -* or -X 1 -(CH2) p -phenylene-(CH2) q -X 2 -*, wherein * is the bond attached to -(AA) n -L 2 -R6 ; n is 0, 1, 2, 3, 4, 5 or 6; Each AA is independently an amino acid; and L 2 is C 1-40 alkylene or C 2-40 heteroalkylene, wherein C 1-40 alkylene or C 2-40 heteroalkylene optionally contains a phenylene group within C 1-40 alkylene or C 2-40 heteroalkylene, and C 1-40 alkylene or C 2-40 heteroalkylene is optionally substituted by one or more (e.g., one or two) oxo groups. In some embodiments, R 1 , R 2 or R 3 is: wherein R 6 is a heterocyclic group, and the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, R 1 , R 2 or R 3 is: wherein R 6 is a heterocyclic group, and the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, R 1 , R 2 or R 3 is: wherein R 6 is a heterocyclic group, and the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, R 1 , R 2 or R 3 is: wherein R 6 is a heterocyclic group, and the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, R 1 , R 2 or R 3 is: Wherein, R 6 is a heterocyclic group, and said heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment. In some embodiments, R 6 is a heterocyclic group that is covalently linked to an antibody or antigen-binding fragment. In some embodiments, R 6 is a heterocyclic group, wherein said heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment via a cysteine or lysine residue on the antibody or antigen-binding fragment. In some embodiments, R 6 is In some embodiments, R 6 is wherein Ab is an antibody or antigen-binding fragment. In some embodiments, R 1 , R 2 or R 3 is: In some embodiments, R 1 , R 2 or R 3 is: In some embodiments, R 1 , R 2 or R 3 is: In some embodiments, R 1 , R 2 or R 3 is: In some embodiments, R 1 , R 2 or R 3 is: In some embodiments, a compound is provided, the compound being selected from: and In some embodiments, R6 is wherein Ab is an antibody or antigen-binding fragment. In some embodiments, the antibody or antigen-binding fragment can include more than one payload moiety (e.g., a Compound of Formula I). Accordingly, there is also provided a Compound of Formula V: wherein A 1 , A 2 , A 3 and R 4 are each independently as defined herein, one dashed line represents a bond to Ab and the other two dashed lines are absent, and x is from 1 to 20, or from 1 to 15, or from 1 to 10, or from 1 to 5, or from 2 to 8, or from 3 to 8, or from 4 to 8. In some embodiments, x is 4. In some embodiments, x is 5. In some embodiments, x is 6. In some embodiments, x is 7. In some embodiments, x is 8. In some embodiments, x is 4, 6 or 8. In some embodiments, x is from 4 to 8. In some embodiments, there is provided a compound selected from: and wherein Ab is an antibody or antigen-binding fragment. Examples of antibodies include, but are not limited to, 3F8 (anti-GD2), Abagovumab (anti-CA-125), Abciximab (anti-CD41 (integrin α-IIb)), adalimumab (anti-TNF-α), Adecatumumab (anti-EpCAM, CD326), afelimomab (anti-TNF-α), afuzumab (anti-CD20), alacizumab (anti-VEGFR2), ALD518 (anti-IL-6), alemtuzumab (Campath, MabCampath, anti-CD52), arcitumomab (anti-CEA), anatumomab (anti-TAG-72), anrukinzumab (IMA-638, anti-IL-13), apolizumab (anti-HLA-DR), asimab (anti-CEA), asizumab (anti-L-selectin (CD62L)), Atizumab (tocilizumab, Actemra, RoActemra, anti-IL-6 receptor), atorolimumab (anti-Rhesus factor), bapineuzumab (anti-β-amyloid), basiliximab (Simulect, anti-CD25 (α-chain of the IL-2 receptor)), bevacizumab (anti-phosphatidylserine), betumomab (LymphoScan, anti-CD22), belimumab (Benlysta, LymphoStat-B, anti-BAFF), benralizumab (anti-CD125), betilimumab (anti-CCL11 (eotaxin-1)), besilesomab (Scintimmun, anti-CEA-related antigen), bevacizumab (Avastin, anti-VEGF-A), Biciromab (FibriScint, anti-fibrin II β-chain), Bivatuzumab (anti-CD44 v6), Bliantomomab (BiTE, anti-CD19), Brentuximab (cAC10, anti-CD30 TNFRSF8), briakinumab (anti-IL-12, IL-23), canakinumab (Ilaris, anti-IL-1), cantuzumab (C242, anti-CanAg), Capromab, catumaxomab (Removab, anti-EpCAM, anti-CD3), CC49 (anti-TAG-72), cedelizumab (anti-CD4), certolizumab (Cimzia anti-TNF-α), cetuximab (Erbitux, IMC-C225, anti-EGFR), Citatuzumab bogatox (anti-EpCAM), cixutumumab (anti-IGF-1), clenoliximab (anti-CD4), clivatuzumab (anti-MUC1),Conatumumab (anti-TRAIL-R2), CR6261 (anti-influenza A hemagglutinin), Dacetuzumab (anti-CD40), Daclizumab (Zenapax, anti-CD25 (alpha chain of the IL-2 receptor)), Daratumumab (anti-CD38 (circular ADP-ribose hydrolase)), Denosumab (Prolia, anti-RANKL), Detumomab (anti-B lymphoma cells), Dorlimomab, Dorlixizumab, Ecromemiximab (anti-GD3 ganglioside), Eculizumab (Soliris, anti-C5), Edobacomab (anti-endotoxin), Edrecolomab (Panorex, MAb17-1A, anti-EpCAM), Efalizumab (Raptiva, anti-LFA-1 (CD11a)), Efungumab (Mycograb, anti-Hsp90), Eltuzumab (anti-SLAMF7), Elsilimomab (anti-IL-6), Enlimomab pegol (anti-ICAM-1 (CD54)), Epitumumab (anti-episialin), Ipatumumab (anti-CD22), Erizumab (anti-ITGB2 (CD18)), Ertumaxomab (Rexomun, anti-HER2 / neu, CD3), Etrolizumab (Abegrin, anti-integrin alpha v beta 3), Exbivirumab (anti-hepatitis B surface antigen), Fanolesomab (NeutroSpec, anti-CD15), Farlimomab (anti-interferon receptor), Farletuzumab (anti-folate receptor 1), Felvizumab (anti-respiratory syncytial virus), Fezaumumab (anti-IL-22), Figitumumab (anti-IGF-1 receptor), Fontolizumab (anti-IFN-gamma), Foravilumab (anti-rabies virus glycoprotein), Fresolimumab (anti-TGF-beta), Galiximab (anti-CD80), Gantenlumab (anti-beta amyloid), Gaviliumab (anti-CD147 (basilgin)), Gemtuzumab (anti-CD33), Gemtuzumab ozogamicin (anti-carbonic anhydrase 9), Glenabumab (CR011, anti-GPNMB), Golimumab (Simponi, anti-TNF-alpha), Gomiliximab (anti-CD23 (IgE receptor)), Anti-HLA-DR antibody, Ibalizumab (anti-CD4), Ipilimumab (anti-CD20),Igovomab (Indimacis-125, anti-CA-125), Imciromab (Myoscint, anti-cardiac myosin), Infliximab (Remicade, anti-TNF-α), Enteromab (anti-CD51), Inolimomab (anti-CD25 (α-chain of the IL-2 receptor)), Inotuzumab (anti-CD22), Ipilimumab (anti-CD152), Iratumumab (anti-CD30 (TNFRSF8)), Keliximab (anti-CD4), Labetuzumab (CEA-Cide, anti-CEA), Lebrikizumab (anti-IL-13), Lemalesomab (anti-NCA-90 (granulocyte antigen)), Lerdelimumab (anti-TGF beta2), Lexatumumab (anti-TRAIL-R2), Libivirumab (anti-hepatitis B surface antigen), Lintuzumab (anti-CD33), Lucatumumab (anti-CD40), Lulliximab (anti-CD23 (IgE receptor)), Mapatumumab (anti-TRAIL-R1), Maslimomab (anti-T-cell receptor), Matuzumab (anti-EGFR), Mepolizumab (Bosaria, anti-IL-5), Metelimumab (anti-TGF beta 1), Milatuzumab (anti-CD74), Minrewamomab (anti-TAG-72), Mituummab (BEC-2, anti-GD3 ganglioside), Muromonab (anti-rhesus factor), Moxetumomab (Numax, anti-respiratory syncytial virus), Muromonab-CD3 (Orthoclone OKT3, anti-CD3), Nacolomab (anti-C242), Natumomab (anti-5T4), Natalizumab (Tysabri, anti-integrin α4), Naxibumab (anti-endotoxin), Necitumumab (anti-EGFR), Nerelimomab (anti-TNF-α), Nimotuzumab (Theracim, Theraloc, anti-EGFR), Nofetuumomab, Ofatumumab (Arzerra, anti-CD20), Odulimumab (Afolimomab, anti-LFA-1 (CD11a)), Ofatumumab (Arzerra, anti-CD20), Olaratumab (anti-PDGF-Rα), Omalizumab (Xolair, anti-IgE Fc region), Oportuzumab (anti-EpCAM), Oregovumab (OvaRex, anti-CA-125),Otelixizumab (anti-CD3), Pagibaximab (anti-lipoteichoic acid), Palivizumab (Synagis, Abbosynagis, anti-respiratory syncytial virus), Panitumumab (Vectibix, ABX-EGF, anti-EGFR), Panobacumab (anti-Pseudomonas aeruginosa), Pasculizumab (anti-IL-4), Pemtumomab (Theragyn, anti-MUC1), Pertuzumab (Omnitarg, 2C4, anti-HER2 / neu), Pexelizumab (anti-C5), Pintumomab (anti-adenocarcinoma antigen), Priliximab (anti-CD4), Pritumumab (anti-vimentin), PRO 140 (anti-CCR5), Racotumomab (1E10, anti-(N-glycolylneuraminic acid (NeuGc, NGNA)-ganglioside GM3)), Rafivirumab (anti-rabies virus glycoprotein), Ramucirumab (anti-VEGFR2), Ranibizumab (Lucentis, anti-VEGF-A), Raxibaucumab (anti-anthrax toxin, protective antigen), Regavirumab (anti-cytomegalovirus glycoprotein B), Reslizumab (anti-IL-5), Rilotumumab (anti-HGF), Rituximab (MabThera, Rituximab, anti-CD20), Robatumumab (anti-IGF-1 receptor), Rontalizumab (anti-IFN-α), Rovizumab (LeukArrest, anti-CD11, CD18), Ruplizumab (Antova, anti-CD154 (CD40L)), Satuumab (anti-TAG-72), Sevizumab (anti-cytomegalovirus), Sibrotuzumab (anti-FAP), Sifalimumab (anti-IFN-α), Siltuximab (anti-IL-6), Siplizumab (anti-CD2), (Smart)MI95 (anti-CD33), Solanezumab (anti-β-amyloid), Sonepcizumab (anti-sphingosine-1-phosphate), Sontuzumab (anti-episialin), Stamulumab (anti-myostatin), Sulesomab (LeukoScan, (anti-NCA-90 (granulocyte antigen)), Tacatuzumab (anti-α-fetoprotein), Tadozumab (anti-integrin αIIbβ3), Talizumab (anti-IgE),Tanezumab (anti-NGF), Tapiliumumab (anti-CD19), Tefibazumab (Aurexis, (anti-aggregation factor A)), Telimomab, Tenatumomab (anti-tenascin C), Teneliximab (anti-CD40), Teplizumab (anti-CD3), TGN1412 (anti-CD28), Ticilimumab (tremelimumab, (anti-CTLA-4)), Tigatuzumab (anti-TRAIL-R2), TNX-650 (anti-IL-13), Tocilizumab (Atizumab, Actemra, RoActemra, (anti-IL-6 receptor)), Toralizumab (anti-CD154 (CD40L)), Tositumomab (anti-CD20), Trastuzumab (Herceptin, (anti-HER2 / neu)), Tremelimumab (anti-CTLA-4), Tucotuzumab celmoleukin (anti-EpCAM), Tuvirumab (anti-hepatitis B virus), Urtoxazumab (anti-Escherichia coli), Ustekinumab (Stelara, anti-IL-12, IL-23), Vapaliximab (anti-AOC3 (VAP-1)), Vedolizumab, (anti-integrin α4β7), Veltuzumab (anti-CD20), Vepalimomab (anti-AOC3 (VAP-1)), Visilizumab (Nuvion, anti-CD3), Vitaxin (anti-vascular integrin avb3), Volociximab (anti-integrin α5β1), Votumumab (HumaSPECT, anti-tumor antigen CTAA16.88), Zalutumumab (HuMax-EGFr, (anti-EGFR)), Zanolimumab (HuMax-CD4, anti-CD4), Ziaralmumab (anti-CD147 (basigin)), Zolimomab (anti-CD5), Etanercept, Alefacept, Abatacept, Rilonacept (Arcalyst), 14F7 (anti-IRP-2 (iron regulatory protein 2)), 14G2a (anti-GD2 ganglioside, from Nat. Cancer Inst. for melanoma and solid tumors), J591 (anti-PSMA, Weill Cornell Medical School for prostate cancers),225.28S (anti-HMW-MAA (High Molecular Weight - Melanoma Associated Antigen), Sorin Radiofavaci S.R.L. (Milan, Italy) for melanoma), COL-1 (anti-CEACAM3, CGM1, from Nat. Cancer Inst. USA for colorectal and gastric cancer), CYT-356 (for prostate cancer), HNK20 (OraVax Inc.). For respiratory syncytial virus), ImmuRAIT (from Immunomedics for NHL), Lym-1 (anti-HLA-DR10, Peregrine Pharm. for cancer), MAK-195F (anti-TNF (Tumor Necrosis Factor; TNFA, TNF-α; TNFSF2), from Abbott / Knoll, for septic shock), MEDI-500, T10B9, anti-CD3, TRαβ (T Cell Receptor α / β) complex, from MedImmune Inc, for graft-versus-host disease), RING SCAN (anti-TAG 72 (Tumor Associated Glycoprotein 72), from Neoprobe Corp., for breast, colon and rectal cancer), avidin (anti-EPCAM (Epithelial Cell Adhesion Molecule), anti-TACSTD1 (Tumor Associated Calcium Signal Transducer 1), anti-GA733-2 (Gastrointestinal Tumor Associated Protein 2), anti-EGP-2 (Epithelial Glycoprotein 2), anti-KSA; KS1 / 4 antigen; M4S; Tumor Antigen 17-1A; CD326, from NeoRx Corp. for colon, ovarian, prostate cancer and NHL), anti-Trop-2-humanized antibody hRS7, LymphoCide (Immunomedics, NJ), Smart ID10 (Protein Design Labs), Oncolym (Techniclone Inc, CA), Allomune (BioTransplant, CA), anti-VEGF (Genentech, CA), CEAcide (Immunomedics, NJ), IMC-1C11 (ImClone Systems) and cetuximab (ImClone)., In some embodiments, the antibody or antigen-binding fragment targets one or more of the following antigens: aminopeptidase N (CD13), annexin A1, B7-H3 (CD276, various cancers), CA125 (ovary), CA15-3 (cancer), CA19-9 (cancer), L6 (cancer), Lewis Y (cancer), Lewis X (cancer), alpha-fetoprotein (cancer), CA242 (colorectal cancer), placental alkaline phosphatase (cancer), prostate-specific antigen (prostate), prostate acid phosphatase (prostate), epidermal growth factor (cancer), CD2 (Hodgkin disease, NHL lymphoma, multiple myeloma), CD3ε (T cell lymphoma, lung cancer, breast cancer, gastric cancer, ovarian cancer, autoimmune diseases, malignant ascites), CD19 (B cell malignancies), CD20 (non-Hodgkin lymphoma), CD22 (leukemia, lymphoma, multiple myeloma, SLE), CD30 (Hodgkin lymphoma), CD33 (leukemia, autoimmune diseases), CD38 (multiple myeloma), CD40 (lymphoma, multiple myeloma, leukemia (CLL)), CD51 (metastatic melanoma, sarcoma), CD52 (leukemia), CD56 (small cell lung cancer, ovarian cancer, Merkel cell carcinoma, and liquid tumors, multiple myeloma), CD66e (cancer), CD70 (metastatic renal cell carcinoma and non-Hodgkin lymphoma), CD74 (multiple myeloma), CD80 (lymphoma), CD98 (cancer), mucin (cancer), CD221 (solid tumors), CD227 (breast cancer, ovarian cancer), CD262 (NSCLC and other cancers), CD309 (ovarian cancer), CD326 (solid tumors), CEACAM3 (colorectal cancer, gastric cancer), CEACAM5 (carcinoembryonic antigen; CEA, CD66e) (breast cancer, colorectal cancer, and lung cancer), DLL4 (Delta-like-4), EGFR (epidermal growth factor receptor, various cancers), CTLA4 (melanoma), CXCR4 (CD184, Heme-oncology, solid tumors), endoglin (CD105, solid tumors), EPCAM (epithelial cell adhesion molecule, bladder cancer, head cancer, cervical cancer, colon cancer, NHL prostate cancer, and ovarian cancer), ERBB2 (epidermal growth factor receptor 2;Lung cancer, breast cancer, prostate cancer), FCGR1 (autoimmune diseases), FOLR (folate receptor, ovarian cancer), GD2 ganglioside (cancer), G-28 (cell surface antigen glycolipid, melanoma), GD3 idiotype (cancer), heat shock protein (cancer), HER1 (lung cancer, gastric cancer), HER2 (breast cancer, lung cancer and ovarian cancer), HLA-DR10 (NHL), HLA-DRB (NHL, B-cell leukemia), human chorionic gonadotropin (cancer), IGF1R (insulin-like growth factor 1 receptor, solid tumors, blood cancers), IL-2 receptor (interleukin 2 receptor, T-cell leukemia and lymphoma), IL-6R (interleukin 6 receptor, multiple myeloma, RA, Castleman disease, IL6-dependent tumors), integrins (αvβ3, α5β1, α6β4, α11β3, α5β5, αvβ5, for different cancers), MAGE-1 (cancer), MAGE-2 (cancer), MAGE-3 (cancer), MAGE4 (cancer), anti-transferrin receptor (cancer), p97 (melanoma), MS4A1 (transmembrane 4 superfamily member A member 1, non-Hodgkin B-cell lymphoma, leukemia), MUC1 or MUC1-KLH (breast cancer, ovarian cancer, cervical cancer, bronchial cancer and gastrointestinal cancer), MUC16 (CA125) (ovarian cancer), CEA (colorectal), gp100 (melanoma), MART1 (melanoma), MPG (melanoma), MS4A1 (transmembrane 4 superfamily A, small cell lung cancer, NHL), Nucleolin, Neu oncogene product (cancer), P21 (cancer), anti-(by-product of N-glycolylneuraminic acid, breast cancer, melanoma cancer), PLAP-like testicular alkaline phosphatase (ovarian cancer, testicular cancer), PSMA (prostate tumor), PSA (prostate), ROBO4, TAG72 (tumor-associated glycoprotein 72, AML, gastric cancer, colorectal cancer, ovarian cancer), T-cell transmembrane protein (cancer), Tie (CD202b), TNFRSF10B (tumor necrosis factor receptor superfamily member 10B, cancer), TNFRSF13B (tumor necrosis factor receptor superfamily member 13B, multiple myeloma, NHL, other cancers, RA and SLE), TPBG (trophoblast glycoprotein, renal cell carcinoma), TRAIL-R1 (tumor necrosis cell apoptosis-inducing ligand receptor 1, lymphoma, NHL, colorectal cancer, lung cancer), VCAM-1 (CD106, melanoma), VEGF, VEGF-A or VEGF-2 (CD309) (multiple cancers).; In some embodiments, the antibody or antigen-binding fragment targets one or more of the following antigens: different clusters of differentiation (CD4, CD5, CD6, CD7, CD8, CD9, CD10, CD11a, CD11b, CD11c, CD12w, CD14, CD15, CD16, CDw17, CD18, CD21, CD23, CD24, CD25, CD26, CD27, CD28, CD29, CD31, CD32, CD34, CD35, CD36, CD37, CD41, CD42, CD43, CD44, CD45, CD46, CD47, CD48, CD49b, CD49c, CD53, CD54, CD55, CD58, CD59, CD61, CD62E, CD62L, CD62P, CD63, CD68, CD69, CD71, CD72, CD79, CD81, CD82, CD83, CD86, CD87, CD88, CD89, CD90, CD91, CD95, CD96, CD100, CD103, CD105, CD106, CD109, CD117, CD120, CD127, CD133, CD134, CD135, CD138, CD141, CD142, CD143, CD144, CD147, CD151, CD152, CD154, CD156, CD158, CD163, CD166, CD168, CD184, CDw186, CD195, CD202(a, b), CD209, CD235a, CD271, CD303, CD304), Annexin A1, Nucleolin, Endoglin (CD105), ROBO4, Aminopeptidase N, Delta-like 4 (DLL4), VEGFR-2 (CD309), CXCR49CD184), Tie2, B7-H3, WT1, MUC1, LMP2, HPVE6 E7, EGFRvIII, HER-2 / neu, Idiotype, MAGE A3, p53 non-mutant, NY-ESO-1, GD2, CEA, MelanA / MART1, Ras mutant, gp100, p53 mutant, Proteinase 3 (PR1), bcr-abl, Tyrosinase, Survivin, hTERT, Sarcoma translocation breakpoint, EphA2, PAP, ML-IAP, AFP, EpCAM, ERG (TMPRSS2ETS fusion gene), NA17, PAX3, ALK, androgen receptor, cyclin B1, polysialic acid, MYCN, RhoC, TRP-2, GD3, fucosyl GM1, mesothelin, PSCA, MAGEA1, sLe(a), CYP1B1, PLAC1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, carbonic anhydrase IX, PAX5, OY-TES1, sperm protein 17, LCK, HMWMAA, AKAP-4, SSX2, XAGE 1, B7H3, Legumain, Tie 2, Page4, VEGFR2, MAD-CT-1, FAP, PDGFR-β, MAD-CT-2, Fos-related antigen 1. In some embodiments, the Ab targets HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70, or EGFR. In some embodiments, a compound is provided selected from: and wherein, the Ab is an antibody or antigen-binding fragment that targets HER2, and x is from 4 to 8. In some embodiments, a compound is provided selected from: and wherein, the Ab is trastuzumab, and x is from 4 to 8. In some embodiments, a compound is provided selected from Table 1A or its stereoisomers or pharmaceutically acceptable salts: Table 1A The compounds of formula I provided herein encompass the stereochemical forms of these compounds, such as optical isomers, for example enantiomers, diastereomers, and mixtures thereof, such as mixtures of enantiomers and / or diastereomers, including racemic mixtures, and equal or unequal mixtures of individual enantiomers and / or diastereomers. All stereochemical forms are contemplated in the present disclosure. Unless otherwise specified, when the disclosed compounds are named or depicted by structure without indicating stereochemistry and have one or more chiral centers, it should be understood to represent all possible stereoisomers of the compound. Representative stereochemical forms are provided throughout the specification, including but not limited to those depicted in Table 1B, Table 1C, and Table 1D. In some embodiments, there is provided a compound selected from Table 1B or a pharmaceutically acceptable salt or solvate thereof: Table 1B In some embodiments, there is provided a compound selected from Table 1C or a pharmaceutically acceptable salt or solvate thereof: Table 1C In some embodiments, there is provided a compound selected from Table 1D or a pharmaceutically acceptable salt or solvate thereof: Table 1D The compounds of formula I include their pharmaceutically acceptable salts. Additionally, the compounds of formula I also include other salts of such compounds, which are not necessarily pharmaceutically acceptable salts and can be used as intermediates for the preparation and / or purification of the compounds of formula I and / or for the separation of the enantiomers of the compounds of formula I. Pharmaceutical Compositions, Routes of Administration, and Methods of Use The compounds provided herein are generally administered in the form of pharmaceutical compositions. In addition to the active compound, the pharmaceutical compositions described in this application may contain one or more excipients, and the excipients may be selected from the components of the following groups: fillers (diluents), binders, wetting agents, disintegrants, solvents, and excipients, etc. Depending on the route of administration, the composition may contain from 0.1% to 99% by weight of the active compound. The pharmaceutical composition can be in the form of a sterile injectable aqueous solution. Acceptable carriers or solvents that can be used are water, Ringer's solution, and isotonic sodium chloride solution. The sterile injectable preparation can be a sterile injectable oil-in-water microemulsion, wherein the active ingredient is dissolved in the oil phase. For example, the active ingredient is dissolved in a mixture of soybean oil and lecithin. The oil solution can then be treated by adding it to a mixture of water and glycerol to form a microemulsion. The injectable or microemulsion can be injected into the bloodstream of a patient by local bolus injection. Alternatively, the solution and microemulsion can be administered in a manner that maintains a constant circulating concentration of the compounds of the present application. To maintain such a constant concentration, a continuous intravenous drug delivery device can be used. For example, the device can be a Deltec CADD-PLUS.TM. 5400 IV pump. The pharmaceutical composition can be in the form of a sterile injectable aqueous or oily suspension for intramuscular and subcutaneous administration. Such suspensions can be formulated according to known techniques by using those suitable dispersing or wetting agents and suspending agents mentioned above herein. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent. Alternatively, a sterile fixed oil is conveniently used as a solvent or suspending medium. The compounds as described herein can have an in vivo tumor-suppressing effect. Tumor cells with high expression of a specific target can include but are not limited to solid tumor cells. For example, tumor cells with high expression of a specific target include but are not limited to gastric cancer cells or breast cancer cells such as those with high expression of a specific target. The compounds described herein can have in vivo tumor targeting ability. The in vivo targeting ability can refer to administering a compound labeled with a signal substance to an animal, and compared with other tissues and organs, the distribution of the labeled compound in the tumor tissue of the animal can increase by more than 1%, or 2% or more, 4% or more, 5% or more, 8% or more, 10% or more, 15% or more, 18% or more, 20% or more, 25% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 95% or more, or can be a distribution increase of more than 1.1-fold, more than 1.3-fold, more than 1.5-fold, more than two-fold, more than three-fold, more than five-fold, more than ten-fold, more than two-fold, more than ten-fold, more than twenty-two-fold, more than thirty-fold, more than fifty-fold, more than one hundred-fold, more than five hundred-fold, more than one thousand-fold or more than one thousand five hundred-fold. The signal substance can be a radioactive substance, for example, the signal substance includes but is not limited to 125I. The animal can include but is not limited to mammals, for example, the animal can include but is not limited to cats, dogs, horses, pigs, cows, sheep, rabbits, mice, rats, monkeys or humans. Administration can include but is not limited to oral, intravenous, intravenous drip, intraperitoneal or topical administration. The tissue or organ can include but is not limited to the heart, liver, spleen, lung, kidney, brain or bone marrow. The compounds disclosed herein, including antibody-drug conjugates, are designed to exhibit cytotoxic activity against cancer cells, and thus the compounds can be used to treat cancer. Accordingly, provided herein is a method for treating cancer in a patient in need thereof, the method comprising administering to the patient a therapeutically acceptable amount of a compound as described herein, or a stereoisomer or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound. In the context of treating a disease, disorder or condition, the terms “treat”, “treating” and “method of treatment” are intended to include: alleviating or eliminating the disorder, disease or condition, or one or more symptoms associated with the disorder, disease or condition; or slowing the progression, spread or worsening of the disease, disorder or condition or one or more of its symptoms. The term “prevent” as used herein is to prevent, in whole or in part, the onset, recurrence or spread of a disease or disorder or its symptoms as described herein. The terms “subject”, “patient” or “individual” as used herein are used interchangeably and refer to any animal, said any animal including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses, primates and humans. In some embodiments, the term refers to a subject, particularly a mammalian subject, in need of diagnosis, prognosis or treatment. In some embodiments, the subject is a human. In some embodiments, the subject has experienced and / or exhibits at least one symptom of a disease, disorder or condition to be treated and / or prevented. Exemplary cancers include, but are not limited to, lung cancer, renal cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer, and esophageal cancer. Also provided herein are methods of treating, preventing, or inhibiting tumor growth in a patient in need thereof, the method comprising administering to the patient a therapeutically acceptable amount of a compound as described herein, or a stereoisomer or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound. The compound as described herein, or a stereoisomer or pharmaceutically acceptable salt thereof, can be administered as a pharmaceutical composition comprising at least one pharmaceutically suitable ingredient. For example, the above pharmaceutical composition can contain at least one pharmaceutical carrier (such as a sterile liquid), such as water and oils (oils of petroleum and animal origin, plant origin, or synthetic origin (the oil can be, for example, peanut oil, soybean oil, mineral oil, sesame oil, etc.)). When the above pharmaceutical composition is administered intravenously, water is a more typical carrier. Saline solution, aqueous glucose solution, and aqueous glycerol solution can also be used as liquid carriers, for example, for injection solutions. Suitable pharmaceutical carriers are known in the art. If desired, the composition can also contain trace amounts of humectants, emulsifiers, or pH buffering agents. Examples of suitable pharmaceutical carriers are disclosed in Remington's Pharmaceutical Sciences by E.W. Martin. The formulation corresponds to the mode of administration. Various delivery systems are known, and various delivery systems can be used to administer the compound as described herein, or a stereoisomer or pharmaceutically acceptable salt thereof. Examples of routes of administration include intradermal, intramuscular, intraperitoneal, intravenous, and subcutaneous routes, but are not limited thereto. For example, administration can be by injection or bolus injection. In certain embodiments, administration is by injection, such as parenteral administration. In some embodiments, the pharmaceutical composition is formulated as a pharmaceutical composition suitable for intravenous administration to humans according to conventional methods. Compositions for intravenous administration are generally solutions in sterile and isotonic aqueous buffer solutions. If desired, the pharmaceutical composition can contain solubilizing agents and local anesthetics to relieve pain at the injection site (such as lidocaine). Generally, the above ingredients are provided separately either as a lyophilized powder or an anhydrous concentrate, which is contained in a container and obtained by sealing in an ampoule or sachet with a certain amount of the active agent or obtained as a mixture of unit dosages. When the pharmaceutical composition is to be administered by injection, the pharmaceutical composition can be administered by injection from an injection vial containing sterile pharmaceutical-grade water or saline. When the pharmaceutical composition is to be administered by injection, an ampoule of sterile water or saline for injection can be provided to mix the above ingredients with each other before administration. In some embodiments, the pharmaceutical composition may be a pharmaceutical composition containing only the compound as described herein or its stereoisomers or pharmaceutically acceptable salts, or a pharmaceutical composition containing the compound as described herein or its stereoisomers or pharmaceutically acceptable salts and a combination containing at least one cancer therapeutic agent other than the conjugate. Thus, in some embodiments, the compound as described herein or its stereoisomers or pharmaceutically acceptable salts can be administered together with other cancer therapeutic agents. Thus, the anti-cancer effect can be enhanced. Another anti-cancer agent for this purpose can be administered to the individual simultaneously with, separately from, or subsequent to the compound, and can be administered with a change in the dosing interval of each agent. Examples of cancer therapeutic agents include albumin-bound paclitaxel, carboplatin, cisplatin, gemcitabine, irinotecan (CPT-11), paclitaxel, pemetrexed, sorafenib, vinorelbine, LH-RH analogs (leuprolide, goserelin, etc.), estramustine phosphate, estrogen antagonists (tamoxifen, raloxifene, etc.), and aromatase inhibitors (anastrozole, letrozole, exemestane, etc.), but are not limited thereto, as long as the cancer therapeutic agent is a drug having anti-tumor activity. The pharmaceutical composition can be formulated into a lyophilized preparation or a liquid preparation to make it a preparation with the desired composition and desired purity. When formulated into a lyophilized preparation, the pharmaceutical composition can be a preparation containing suitable formulation additives used in the art. Similarly for liquid preparations, the pharmaceutical composition can be formulated into a liquid preparation containing various formulation additives used in the art. The composition and concentration of the pharmaceutical composition can vary depending on the administration method. However, when the compound has a high affinity for the antigen, i.e., a high affinity (=low Kd value) in terms of the dissociation constant of the antigen (i.e., Kd value), the compound contained in the pharmaceutical composition can exhibit a drug effect even at a small dose. Therefore, in order to determine the dose of the compound, the dose can be determined according to the circumstances related to the affinity between the compound and the antigen. When the compound is administered to a human, for example, about 0.001 mg / kg to 100 mg / kg can be administered once or several times at intervals of once for 1 day to 180 days. On the other hand, the present application provides a compound as described herein, or a tautomer, mesomer, racemate, enantiomer, diastereomer or a mixture thereof, or a mixture thereof, and provides the use of a compound or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof in the preparation of a drug for treating and / or preventing tumors. The tumors can be selected from tumors associated with the expression of HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 or EGFR. The tumors can be selected from lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer and esophageal cancer. The tumors can be selected from tumors associated with the expression of HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 or EGFR. The tumors can be selected from lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer and esophageal cancer. In certain embodiments, there is provided a compound or a stereoisomer or a pharmaceutically acceptable salt thereof as described herein for treating and / or preventing tumors. In some embodiments, the tumors can be selected from tumors associated with the expression of HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 or EGFR. The tumors can be selected from the group consisting of lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer and esophageal cancer. In some embodiments, the compound comprises an antibody or an antigen-binding fragment that targets tumor cells. In some embodiments, the compound comprises an antibody or antigen-binding fragment, which is an anti-A33 antibody or antigen-binding fragment, an anti-B7-H3 antibody or antigen-binding fragment, an anti-CNAG antibody or antigen-binding fragment, an anti-CD20 antibody or antigen-binding fragment, an anti-CD22 antibody or antigen-binding fragment, an anti-CD30 antibody or antigen-binding fragment, an anti-CD33 antibody or antigen-binding fragment, an anti-CD56 antibody or antigen-binding fragment, an anti-CD70 antibody or antigen-binding fragment, an anti-CEA antibody or antigen-binding fragment, an anti-Cripto antibody or antigen-binding fragment, an anti-EphA2 antibody or antigen-binding fragment, an anti-G250 antibody or antigen-binding fragment, an anti-MUC1 antibody or antigen-binding fragment, an anti-GPNMB antibody or antigen-binding fragment, an anti-integrin antibody or antigen-binding fragment, an anti-PSMA antibody or antigen-binding fragment, an anti-tenascin C antibody or antigen-binding fragment, an anti-SLC44A4 antibody or antigen-binding fragment, or an anti-mesothelin antibody or antigen-binding fragment. In some embodiments, the compound comprises an antibody or antigen-binding fragment, which is an anti-B7-H3 antibody or antigen-binding fragment, an anti-CD30 antibody or antigen-binding fragment, an anti-CD33 antibody or antigen-binding fragment, or an anti-CD70 antibody or antigen-binding fragment. In some embodiments, the compound comprises an antibody or antigen-binding fragment, which is an anti-B7-H3 antibody or antigen-binding fragment. As used herein, the term "antibody" or "antigen-binding fragment" refers to an immunoglobulin and is a molecule containing an antigen-binding site that immunospecifically binds to an antigen. The class of the antibody or antigen-binding fragment can be any one of IgG, IgE, IgM, IgD, IgA, and IgY, and preferably is IgG. The subclass of the antibody or antigen-binding fragment can be any one of IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2, and preferably is IgG1 or IgG2. The antibody or antigen-binding fragment can be derived from any species, including human, rat, mouse, or rabbit. In the case where the antibody or antigen-binding fragment is derived from a species other than human, well-known techniques can be used to chimerize or humanize it. The antibody or antigen-binding fragment can be a polyclonal antibody or a monoclonal antibody. In some embodiments, the antibody or antigen-binding fragment is a monoclonal antibody. The antibody or antigen-binding fragment is capable of targeting tumor cells. Since the antibody or antigen-binding fragment is conjugated to a drug or payload having antitumor activity through a linker, the antibody can possess one or more of the properties of recognizing tumor cells, binding to tumor cells, internalizing into tumor cells, or killing tumor cells. The binding activity of an antibody or antigen-binding fragment to tumor cells can be confirmed using flow cytometry. Internalization of an antibody or antigen-binding fragment into tumor cells can be confirmed using the following: (1) an assay that visualizes the antibody or antigen-binding fragment incorporated into cells under a fluorescence microscope using a secondary antibody (fluorescently labeled) that binds to the therapeutic antibody (Cell Death and Differentiation (2008) 15, 751-761), (2) an assay that measures the amount of fluorescence incorporated into cells using a secondary antibody (fluorescently labeled) that binds to the antibody or antigen-binding fragment (Molecular Biology of the Cell, Volume 15, 5268-5282, December 2004). Or (3) the mAb-ZAP assay, which uses an immunotoxin that binds to the antibody or antigen-binding fragment, where the toxin is released after incorporation into cells to inhibit cell growth (BioTechniques 28: 162-165, 2000, January). For example, the tumor can be selected from tumors associated with the following set of expressions: 5T4, AGS-16, ANGPTL4, ApoE, CD19, CTGF, CXCR5, FGF2, MCPT8, MFI2, MS4A7, NCA, Sema5b, SLITRK6, STC2, TGF,0772P, 5T4, ACTA2, ADGRE1, AG-7, AIF1, AKR1C1, AKR1C2, ASLG659, Axl, B7H3, BAFF-R, BCMA, BMPR1B, BNIP3, C1QA, C1QB, CA6, CADM1, CCD79b, CCL5, CCR5, CCR7, CD1lc, CD123, CD138, CD142, CD147, CD166, CD19, CD19, CD22, CD21, CD20, CD205, CD22, CD223, CD228, CD25, CD30, CD33, CD37, CD38, CD40, CD45, CD45(PTPRC), CD46, CD47, CD49D(ITGA4), CD56, CD66e, CD70, CD71, CD72, CD74, CD79a, CD79b, CD80, CDCP1, CDH11, CD11b, CEA, CEACAM5, c-Met, COL6A3, FLT3, FOLR-α, GD2, GEDA, GPC-1, GPNMB, GPR20, GZMB, HER2, HER3, HLA-DOB, HMOX1, IFI6, IFNG, IGF-1R, IGFBP3, IL10RA1, IL-13R, IL-2, IL20Ra, IL-3, IL-4, IL-6, IRTA2, KISS1R, KRT33A, LIV-1, LOX, LRP-1, LRRC15, LUM, LY64, LY6E, Ly86, LYPD3, MDP, MMP10, MMP14, MMP16, MPF, MSG783, MSLN, MUC-1, NaPi2b, Napi3b, Nectin-4, Nectin-4, NOG, P2X5, pCAD, P-Cadherin, PDGFRA, PDK1, PD-L1, PFKFB3, PGF, PGK1, PIK3AP1, PIK3CD, PLOD2, PSCA, PSCAhlg, PSMA, PSMA, PTK7, P-Cadherin, RNF43, NaPi2b, ROR1, ROR2, SERPINE1, SLC39A6, SLTRK6, STAT1, STEAP1, STEAP2, TCF4, TENB2, TGFB1, TGFB2, TGFBR1, TNFRSF21, TNFSF9,Trop-2, TrpM4, Tyro7, UPK1B, VEGFA, WNT5A, epidermal growth factor, glycan, mesothelin, sodium phosphate cotransporter 2B, occludin-18.2, endothelin receptor, mucins (such as mucin 1 and mucin 16), guanylate cyclase C, integrin α4β7, integrin α5β6, trophoblast glycoprotein, and tissue factor. Dosage The specific dosage level of the compounds in this application for any particular individual will depend on a variety of factors, including the activity of the specific compound used, the age, body weight, general health status, gender, diet, time of administration, route of administration, excretion rate, drug combination, and the severity of the specific disease suffered by the individual being treated. For example, the dosage can be expressed as milligrams per kilogram of the individual's body weight (mg / kg) of the compounds described herein. A dosage between about 0.1 mg / kg and 150 mg / kg may be appropriate. In some embodiments, about 0.1 mg / kg to 100 mg / kg may be appropriate. In other embodiments, a dosage between 0.5 mg / kg and 60 mg / kg may be appropriate. In some embodiments, a dosage of about 0.0001 mg to about 100 mg per kilogram of body weight per day, about 0.001 mg to about 50 mg of the compound per kilogram of body weight, or about 0.01 mg to about 10 mg of the compound per kilogram of body weight may be appropriate. When adjusting the dosage between individuals with very different body sizes, standardizing the dosage based on the body weight of the individual is particularly useful, such as when using the drug in children and adults or when converting the effective dosage in non-human individuals (such as dogs) to a dosage suitable for human individuals. Synthesis of Compounds The compounds can be prepared using the methods disclosed herein and their conventional modifications, which will be apparent in view of the disclosure herein and methods well known in the art. In addition to the teachings herein, conventional and well-known synthetic methods can be used. The synthesis of the typical compounds described herein can be accomplished as described in the following examples. If available, these reagents can be purchased from commercial sources, such as from Sigma Aldrich or other chemical reagent suppliers. General Synthetic Method These compounds can be prepared using the methods disclosed herein and conventional improvements to these methods, which are apparent in view of the disclosure herein and methods well known in the art. In addition to the teachings herein, conventional and well-known synthetic methods can also be used. The synthesis of the typical compounds described herein can be accomplished in the manner described in the following examples. If available, the reagents and starting materials can be purchased from commercial sources, such as from Sigma Aldrich or other chemical reagent suppliers. It will be appreciated that, when typical or preferred process conditions are given (i.e., reaction temperature, time, molar ratio of reactants, solvent, pressure, etc.), other process conditions may also be used unless otherwise stated. The optimal reaction conditions may vary depending on the specific reactants or solvents used, but those skilled in the art can determine these conditions through routine optimization procedures. Additionally, to prevent undesired reactions of certain functional groups, it may be necessary to use conventional protecting groups. Suitable protecting groups for various functional groups, as well as suitable conditions for protecting and deprotecting specific functional groups, are well known in the art. For example, many protecting groups are described in Wuts, P.G.M., Greene, T.W., & Greene, T.W. (2006). Greene’s protective groups in organic synthesis. Hoboken, N.J., Wiley-Interscience and the references cited therein. Furthermore, the compounds of the present disclosure may contain one or more chiral centers. Thus, if desired, these compounds can be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers, diastereomers, or as mixtures enriched in stereoisomers. Unless otherwise stated, all such stereoisomers (and mixtures enriched in stereoisomers) are included within the scope of the present disclosure. Pure stereoisomers (or mixtures enriched in stereoisomers) can be prepared using, for example, optically active starting materials or stereoselective reagents well known in the art. Alternatively, methods such as chiral column chromatography, chiral resolving agents, etc. can also be used to separate the racemic mixtures of these compounds. The starting materials for the following reactions are generally known compounds or can be prepared by known procedures or obvious modifications thereof. For example, many starting materials are available from commercial suppliers such as Aldrich Chemical Co. (Milwaukee, Wisconsin, USA), Bachem (Torrance, California, USA), Emka-Chemce or Sigma (St. Louis, Missouri, USA). Other reagents can be prepared by the procedures described in standard reference works or obvious modifications thereof, such as Fieser and Fieser’s Reagents for Organic Synthesis, Volumes 1-15 (John Wiley, and Sons, 1991), Rodd’s Chemistry of Carbon Compounds, Volumes 1-5, and Supplements (Elsevier Science Publishers, 1989), Organic Reactions, Volumes 1-40 (John Wiley, and Sons, 1991), March’s Advanced Organic Chemistry, (John Wiley, and Sons, 5th Edition, 2001), and Larock’s Comprehensive Organic Transformations (VCH Publishers Inc., 1989). The compounds described herein can be prepared according to the following schemes. Scheme I illustrates the preparation of the compound of formula I, wherein, R 1 、R 2 or R 3 is hydrogen. In Scheme I, R 4 is as defined herein, and PG is a protecting group (e.g., Ac). Scheme I In Scheme I, the compound I-1 is protected by using a suitable amine protecting group (such as acetyl halide) to obtain the compound of formula II-2. The compound I-2 is oxidized and then selectively deprotected to obtain the compound I-3. The compound I-3 is contacted with the compound I-4 and then deprotected to obtain the compound of formula I-5 (i.e., the compound of formula I, wherein, R 1 、R 2 or R 3is hydrogen) Scheme II illustrates the preparation of additional compounds of Formula I. In Scheme II, x, R 4 and R 5 As defined herein, Ab is an antibody or antigen-binding fragment, and LG is a leaving group (such as -OH, -alkoxy, halogen, etc.). Scheme II In Scheme II, a compound of Formula II-2 is provided by contacting Compound I-5 with Compound II-1 under standard amide bond-forming reaction conditions. Under conditions known in the art, an antibody-drug conjugate of Formula II-3 can be provided from the compound of Formula II-2, wherein R 5 comprises a suitable functional group that binds to the amino acid side chain of the antibody or antigen-binding fragment (for example, wherein R 6 is a compound of pyrrole-2,5-dione-1-yl). Contacting Compound I-5 with a suitable arylating reagent (such as tris(3-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)bismuthane) and then performing a deprotection and amination reaction can give a compound of Formula II-4 (such as R 1 is -C6 aryl-C 1-6 alkyl-NH2 of Formula I). Acylation of Compound II-4 with Compound II-1 under standard amide bond-forming reaction conditions gives Compound II-5. Under conditions known in the art, an antibody-drug conjugate of Formula II-6 can be provided from the compound of Formula II-5, wherein R 5 comprises a suitable functional group that binds to the amino acid side chain of the antibody or antigen-binding fragment (for example, R 6 is a compound of pyrrole-2,5-dione-1-yl). Suitable starting materials and reagents can be purchased or prepared by methods known to those skilled in the art. After each reaction is completed, each intermediate compound or final compound can be recovered by conventional techniques such as neutralization, extraction, precipitation, chromatography, filtration, etc. and selectively purified. Examples The following examples are used to illustrate specific embodiments of the present disclosure. Those skilled in the art should understand that the techniques disclosed in the following examples represent techniques that can function well in the practice of the present disclosure, and thus can be considered to constitute specific modes of practicing the present disclosure. However, according to the present disclosure, those skilled in the art should understand that many changes can be made to the disclosed specific embodiments without departing from the spirit and scope of the present disclosure and still obtain the same or similar results. Example 1: Synthesis of Compound C-1a and Compound C-1b Preparation of Compound 1-2 To a solution of Compound 1-1 (3 g, 13.5 mmol) in THF (15 mL) and MeOH (15 mL) was added NH4HCO2 (5.09 g, 80.7 mmol) and NaBH4 (2.55 g, 67.4 mmol), and the reaction solution was reacted at room temperature for 2 h. The reaction was monitored by LCMS. When the raw materials disappeared, the reaction was completed. After the reaction was completed, a white solid was precipitated and filtered out from the reaction solution to obtain 2.9 g of Compound 1-2. LCMS (m / z) [M+H] + = 208.0 Preparation of Compound 1-3 Compound 1-2 (3.0 g, 13.3 mmol) was placed in a reaction flask and dissolved in DCM (30 mL), cooled with ice ethanol, TEA (6.75 g, 66.7 mmol) was added and stirred for 10 min, then MsCl (4.12 g, 36.0 mmol) was slowly added dropwise and stirred for half an hour. The completion of the reaction was monitored by LCMS. The reaction solution was extracted with water (50 mL) and DCM (3×50 mL). The organic phase was collected, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated at low temperature to obtain 2.91 g of Compound 1-3. LCMS (m / z) [M-95] + = 208.0 Preparation of Compound 1-4 Compound 1-3 (2.91 g, 9.6 mmol) and NaN3 (1.24 g, 19.2 mmol) were placed in a reaction flask and then DMF (30 mL) was added. The reaction solution was heated to 60 °C and reacted for 2 h. The completion of the reaction was monitored by LCMS. Water (100 mL) was added to the reaction solution and extracted with EA (3×60 mL). The organic phase was collected, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain Compound 1-4. The yield was not calculated. LCMS (m / z) [M-42] + = 208.0, RT: 1.33 min Preparation of Compound 1-5 Compound 1-4 (crude) and THF (40 mL) were placed in a reaction flask, Pd / C (200 mg) was added, and the mixture was stirred overnight under H2. The completion of the reaction was monitored by LCMS. The reaction solution was filtered and concentrated to obtain 1.4 g of compound 1-5. The yield was not calculated. LCMS (m / z) [[M-16]] + = 178.2, RT: 0.513 min. Preparation of Compound 1-6 Compound 1-5 (1.4 g, 7.21 mmol) was placed in a reaction flask, dissolved in DCM (14 mL) under nitrogen protection, DIPEA (2.8 g, 21.6 mmol) was added, and then CH3COCl (1.41 g, 18.0 mmol) was slowly added dropwise in an ice-water bath. The reaction solution was allowed to warm to room temperature and react for 0.5 h. The completion of the reaction was monitored by LCMS. The reaction solution was added with water (50 mL) and extracted with dichloromethane (3 × 50 mL). The organic phase was collected, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain 1.6 g of compound 1-6. The four-step yield was 43%. Preparation of Compound 1-7 Compound 1-6 (1.46 g, 5.76 mmol) was placed in a reaction flask, acetone (16 ml) and an aqueous solution of 15% MgSO4 (16 ml) were added to dissolve it, and then KMnO4 (1.86 g, 11.8 mmol) was added portionwise under nitrogen protection in an ice-water bath at 0 °C. The reaction solution was stirred in the ice-water bath for 1 h and then stirred at room temperature for another 1 h. The completion of the reaction was monitored by LCMS. The reaction solution was filtered and washed with ethyl acetate. The filtrate was extracted with water, the organic phase was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, purified by a reverse-phase column (acetonitrile: water 30%), collected, and lyophilized to obtain 800 mg of compound 1-7. The yield was 48%. Preparation of Compound 1-8 Compound 1-7 (800 mg, 2.74 mmol) was dissolved in a mixture of DCM / MeOH (16 ml / 8 ml, 20V / 10V), concentrated hydrochloric acid (4.8 ml, 6V) was added dropwise, and the reaction was carried out at 25 °C to 30 °C for 17 h. The reaction was monitored by TLC. The completion of the reaction was monitored by TLC. The reaction solution was diluted with DCM, and the pH was adjusted to 6 - 7 by slowly adding aqueous sodium hydroxide solution (0.5 M). After separation of the reaction solution, the aqueous phase was extracted with DCM, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and slurried with methyl tert-butyl ether to obtain 553 mg of compound 1-8. The yield was 80%. Preparation of Compound 1-10 Compound 1-8 (230 mg, 0.92 mmol) and compound 1-9 (220 mg, 0.836 mmol) were placed in a reaction flask, dissolved in toluene (5 ml), then PPTS (150 mg, 0.6 mmol) was added under nitrogen protection, and the mixture was heated to 120 °C and refluxed for 18 h. A black solid was precipitated from the reaction solution. The completion of the reaction was monitored by LCMS. The reaction solution was concentrated and rotary dried, the obtained solid was dissolved in DMF, purified by a reverse-phase column (acetonitrile: water 20%), recovered, and freeze-dried to obtain 245 mg of compound 1-10. The yield was 56%. Preparation of Compounds C-1a and C-1b Compound 1-10 (245 mg, 0.51 mmol) was dissolved in aqueous hydrochloric acid (6 mol, 5 ml), heated to 110 °C and refluxed for 8 h. The completion of the reaction was monitored by LCMS. The reaction solution was mixed with water and acetonitrile, and after removing hydrochloric acid, it was freeze-dried. Compounds C-1a (30 mg) and C-1b (58 mg) were obtained. Compound C-1a: LCMS (m / z) [M+H] + = 436.2. 1 H NMR (400 MHz, DMSO): δ 8.32 (brs, 3H), 8.00 (d, J = 10.8 Hz, 1H), 7.33 (s, 1H), 6.54 (s, 1H), 5.49–5.33 (m, 3H), 5.30–5.13 (m, 2H), 3.31–3.27 (m, 2H), 2.56 (s, 3H), 2.20 (d, J = 8.0 Hz, 1H), 1.90 - 1.80 (m, 2H), 0.89 (t, J = 7.2 Hz, 3H). Compound C-1b: LCMS (m / z) [M+H] += 436.2. 1 1H NMR (400 MHz, DMSO) δ 8.34 (brs, 3H), 8.00 (d, J = 10.8 Hz, 1H), 7.34 (s, 1H), 6.53 (s, 1H), 5.51–5.31 (m, 3H), 5.30–5.13 (m, 2H), 3.33 - 3.25 (m, 2H), 2.56 (s, 3H), 2.25–2.14 (m, 1H), 1.98–1.77 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). Example 2: Synthesis of Compound C-2a and Compound C-2b Preparation of Compound 2-3 Dissolve Compound 2-1 (50.0 g, 263 mmol) in dioxane (1.2 L) and H2O (300 mL), add Compound 2-2 (38.8 g, 290 mmol), Cs2CO3 (257 g, 789 mmol) and Pd(PPh3)4 (3.04 g, 2.63 mmol), react at 95 °C for 18 h, monitor the reaction by LCMS and check if the starting materials disappear. After the reaction is completed, add water (500 mL) to the reaction solution and extract with EA (3 × 200 mL). Combine the organic phases, wash with water (3 × 300 mL) and saturated sodium chloride (1 L), dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude product. Mix the crude product with silica gel and purify by column chromatography (PE / EA) to obtain 32 g of Compound 2-3. The yield is 88%. Preparation of Compound 2-4 Dissolve Compound 2-3 (32 g, 233 mmol) by adding MeOH (300 mL), then add 10% Pd / C (3.2 g), react at room temperature (25 °C) for 18 h, monitor the reaction by LCMS and check if the starting materials disappear. Filter the reaction solution through diatomaceous earth and wash with methanol (1 L). Rotavapor the filtrate to obtain 27 g of Compound 2-4. The yield is 84%. Preparation of Compound 2-5 Dissolve compound 2-4 (27 g, 194 mmol) in DCM (300 mL), add Ac2O (23.8 g, 232.8 mmol), and stir at 25 °C for 3 h. TLC (PE / EA = 1 / 1) was used to detect the completion of the reaction. Then, add water (500 mL) to the reaction solution, and extract with DCM (3 × 200 mL). Combine the organic phases, wash with saturated sodium chloride (1 L), dry over anhydrous sodium sulfate, filter, and concentrate to obtain 32 g of compound 2-5. The crude product was directly used in the next reaction. The yield was 91%. Preparation of Compound 2-6 Dissolve compound 2-5 (32 g, 182 mmol) in DMF (320 mL), then add NBS (65 g, 363 mmol), and stir at 25 °C for 18 h. TLC (PE / EA = 1 / 1) was used to detect the completion of the reaction. Add 500 mL of water to the reaction solution, and extract with EA (3 × 200 mL). Combine the organic phases, wash with water (3 × 300 mL), wash with saturated sodium chloride (500 mL), dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude product. The crude product was purified by column chromatography to obtain 38 g of compound 2-6. The yield was 83%. Preparation of Compound 2-7 Under N2 protection, place compound 2-6 (30 g, 119 mmol) in a dry three-necked flask, dissolve it by adding 250 mL of THF, cool to about -90 °C, slowly add 3 M MeLi solution (60 mL, 179 mmol) while maintaining the temperature below -80 °C, and stir at the same temperature for 30 min. Then, slowly add 2.5 M n-BuLi / THF solution (72 mL, 178.8 mmol) and stir at -90 °C for 30 min. Then, slowly add a THF (50 mL) solution of cyclobutanone (10.1 g, 143 mmol) and stir at this temperature for 1 h. LCMS was used to detect whether the reaction occurred, leaving 15% of the starting material, and the main peak was the product. Quench the reaction by adding 200 mL of saturated aqueous ammonium chloride solution to the reaction solution, and then extract with EA (3 × 50 mL). Combine the organic phases, wash with saturated sodium chloride (100 mL), dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude product. The crude product was purified by column chromatography to obtain 27 g of compound 2-7. The yield was not calculated. Preparation of Compound 2-8 Compound 2-7 (27 g, 107 mmol) was added to DCM (540 mL) and H2O (540 mL), followed by the addition of AgNO3 (3.65 g, 21.5 mmol) and K2S2O8 (87.1 g, 322.3 mmol). The mixture was stirred at 25 °C for 18 h. The reaction was monitored by LCMS, and the starting material disappeared, with the main peak corresponding to the product. The reaction was stopped. 1 L of water was added to the reaction solution, and then the mixture was extracted with DCM (3 × 300 mL). The organic phases were combined, washed with saturated sodium chloride (1 L), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was mixed with silica gel and purified by column chromatography to obtain 11 g of compound 2-8. The two-step yield was 38%. Preparation of Compound 2-9 Under N2 protection, potassium tert-butoxide (9.45 g, 84.3 mmol) was added to tert-butanol (30 mL) and THF (60 mL). Then, a solution of compound 2-8 (6 g, 24.1 mmol) in THF (60 mL) was slowly added dropwise at about 0 °C, and the mixture was stirred at 0 °C for 30 min. Then, n-butyl nitrite (9.45 g, 84.3 mmol) was slowly added, and the mixture was stirred at 0 °C for 1 h. TLC (PE / EA = 1 / 1) indicated the completion of the reaction. 300 mL of water was added to the reaction solution, and then 1 M HCl was added to adjust the pH to 2-3. A large amount of solid precipitated, which was filtered and washed with water (500 mL). The filter cake was collected, 50 mL of PE:MTBE = 10:1 was added, and the mixture was stirred at 25 °C for 1 h, filtered, and the filter cake was collected and dried with an oil pump to obtain 6.3 g of compound 2-9. The yield was 94%. Preparation of Compound 2-11 Compound 2-9 (7.3 g, 26.2 mmol) was dissolved in MeOH (220 mL), 4 M HCl / MeOH (13.2 mL, 52.4 mmol) was added, followed by the addition of 10% Pd / C (730 mg), and the mixture was stirred at 28 °C for 18 h. The reaction was monitored by LCMS, and the starting material disappeared. TEA (9.37 g, 91.8 mmol) and Ac2O (6.16 g, 60.3 mmol) were added to the reaction solution, and the mixture was stirred at 28 °C for 1 h. The reaction was monitored by LCMS, and the starting material disappeared. The reaction solution was filtered through diatomaceous earth and washed with methanol (1 L). The filtrate was rotary evaporated to obtain the crude product. The crude product was purified by column chromatography to obtain 2 g of compound 2-11. The two-step yield was 25%. Preparation of Compound 2-12 Compound 2-11 (2 g, 6.53 mmol) was added to DCM (40 mL) and MeOH (20 mL), followed by the addition of concentrated hydrochloric acid (12 mL), and the mixture was stirred at 28 °C for 18 h. The reaction was monitored by LCMS, and the starting material disappeared, with the main peak being the product. The reaction was terminated. 30 mL of water was added to the reaction solution, followed by the addition of saturated aqueous sodium bicarbonate to adjust the pH to 9 - 10, and then the mixture was extracted with DCM (3 × 20 mL). The organic phases were combined, washed with saturated sodium chloride (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. 20 mL of PE:MTBE = 10:1 was added to the filter cake, stirred at 25 °C for 1 h and filtered, and the filter cake was collected to obtain 1.7 g of compound 2-12. The yield was not calculated. Preparation of Compound 2-13 Compound 2-12 (330 mg, 1.25 mmol) was dissolved in toluene (10 mL), HM-582_8 (299 mg, 1.14 mmol) and PPTS (143 mg, 0.57 mmol) were added, and the mixture was stirred at 125 °C for 24 h. The reaction was monitored by LCMS, and 15% of the starting material remained, with the main peak being the product. The reaction was stopped. The reaction solution was rotary evaporated to directly obtain the crude product. The crude product was mixed with silica gel and purified by column chromatography to obtain 350 mg of compound 2-13. The two-step yield was 57%. Preparation of Compounds C-2a and C-2b Compound 2-13 (350 mg, 0.712 mmol) was added to 6 M aqueous HCl (7 mL), and the mixture was refluxed and stirred at 110 °C for 4 h. The reaction was monitored by LCMS, and the starting material disappeared. The reaction was stopped. The reaction solution was directly lyophilized to obtain the crude product. The crude product was directly purified by NP-HPLC to obtain 80 mg of compound C-2a and 75 mg of compound C-2b, both of which were light yellow solids. The two-step yield was 49%. Compound C-2a: LCMS (m / z) [M+H] + = 450.2. 11H NMR (400 MHz, DMSO): δ 8.52–8.38 (m, 3H), 7.89 (d, J = 11.1 Hz, 1H), 7.36 (s, 1H), 6.56 (s, 1H), 5.74–5.69 (m, 2H), 5.55–5.30 (m, 3H), 5.10 (s, 1H), 3.48–3.43 (m, 1H), 3.24–3.10 (m, 1H), 2.94–2.88 (m, 2H), 2.56–2.53 (m, 1H), 2.28–2.13 (m, 1H), 1.99–1.81 (m, 2H), 1.22 (t, J = 7.5 Hz, 3H), 0.89 (t, J = 7.3 Hz, 3H).

[0287] Compound C-2b: LCMS (m / z) [M+H] + = 450.2. 1 1H NMR (400 MHz, DMSO): δ 8.57–8.35 (m, 3H), 7.90 (d, J = 11.1 Hz, 1H), 7.36 (s, 1H), 6.55 (s, 1H), 5.78–5.64 (m, 1H), 5.53–5.36 (m, 3H), 5.11 (s, 1H), 3.44–3.37 (m, 1H), 3.24–3.12 (m, 1H), 2.97–2.85 (m, 2H), 2.56–2.52 (m, 1H), 2.26–2.14 (m, 1H), 1.96–1.81 (m, 2H), 1.22 (t, J = 7.5 Hz, 3H), 0.88 (t, J = 7.3 Hz, 3H). Example 3: Synthesis of Compound C-3a and Compound C-3b Preparation of Compound 3-3 Dissolve Compound 3-1 (33 g, 142 mmol) in dioxane (300 mL) and H2O (150 mL), add boronate 3-2 (28.7 g, 171 mmol), K3PO4 (90.6 g, 427 mmol) and Pd(dppf)Cl2 (10.4 g, 14.2 mmol). React the reaction solution at 115 °C for 48 h. Monitor the reaction by LCMS and check for disappearance of the starting materials. After completion of the reaction, add water (1 L) to the reaction solution, then extract with EA (3 × 300 mL). Combine the organic phases, wash with water (3 × 500 mL) and saturated sodium chloride (1 L), dry over anhydrous sodium sulfate, filter and concentrate to obtain the crude product. The crude product is purified by column chromatography to obtain 24 g of Compound 3-3. The yield is 87%. Preparation of Compound 3-4 Dissolve Compound 3-3 (24 g, 124 mmol) by adding MeOH (300 mL), then add 10% Pd / C (3.0 g), and react at room temperature (28 °C) for 18 h. Check whether the reaction occurs by LCMS, and the raw materials disappear. Filter the reaction solution through diatomaceous earth and wash it with methanol (1 L). Rotate and dry the filtrate to obtain 25 g of Compound 3-4. The yield is not calculated. Preparation of Compound 3-5 Dissolve Compound 3-4 (25 g, 128 mmol) in DMF (300 mL), then add NBS (46 g, 256 mmol), and stir at 25 °C for 18 h. TLC (PE / EA = 1 / 1) shows that the reaction is complete. Add 500 mL of water to the reaction solution, then extract with EA (3 × 200 mL). Combine the organic phases, wash with water (3 × 300 mL), wash with saturated sodium chloride (500 mL), dry over anhydrous sodium sulfate, filter and concentrate to obtain the crude product. Mix the crude product with silica gel and purify it by column chromatography to obtain 28 g of Compound 3-5. The two-step yield is 80%. Preparation of Compound 3-6 Under N2 protection, place Compound 3-5 (10 g, 36.5 mmol) in a dry three-necked flask, dissolve it by adding 100 mL of THF, cool to about -90 °C, slowly dropwise add 1.6 M MeLi solution (46 mmol, 73.0 mmol) while maintaining the temperature below -80 °C, and stir at the same temperature for 30 min. Subsequently, slowly dropwise add 2.5 M n-BuLi / THF solution (29.1 mmol, 73.0 mmol) and stir at -90 °C for 30 min. Then, slowly dropwise add a solution of cyclobutanone (3.07 g, 143 mmol) in THF (50 mL) and stir at this temperature for 1 h. Check whether the reaction occurs by LCMS, and 15% of the raw materials remain, where the main peak is the product. Quench the reaction by adding 200 mL of saturated ammonium chloride aqueous solution to the reaction solution, then add 200 mL of water, and extract with EA (3 × 100 mL). Combine the organic phases, wash with saturated sodium chloride (100 mL), dry over anhydrous sodium sulfate, filter and concentrate to obtain the crude product. Mix the crude product with silica gel and purify it by column chromatography to obtain 7.9 g of Compound 3-6. The yield is not calculated. Preparation of Compound 3-7 Compound 3-6 (7.9 g, 29.8 mmol) was added to DCM (160 mL) and H2O (160 mL), then AgNO3 (1.01 g, 5.96 mmol) and K2S2O8 (24.2 g, 89.3 mmol) were added, and the mixture was stirred at 28 °C for 18 h. The reaction was monitored by LCMS, and the starting material disappeared, with the main peak being the product. The reaction was stopped. 1 L of water was added to the reaction solution, and then it was extracted with DCM (3 × 100 mL). The organic phases were combined, washed with saturated sodium chloride (500 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was mixed with silica gel and purified by column chromatography to obtain 1.45 g of compound 3-7. The two-step yield was 16%. Preparation of Compound 3-8 Under N2 protection, potassium tert-butoxide (2.16 g, 19.3 mmol) was added to tert-butanol (8 mL) and THF (8 mL), then a solution of compound 3-7 (1.45 g, 5.51 mmol) in THF (13 mL) was slowly added dropwise at about 0 °C, and the mixture was stirred at 0 °C for 30 min. Then n-butyl nitrite (1.14 g, 11.1 mmol) was slowly added and the mixture was stirred at 0 °C for 1 h. TLC (PE / EA = 1 / 1) showed that the reaction was complete. 50 mL of water was added to the reaction solution, then 1 M HCl was added to adjust the pH to 2-3, and it was extracted with EA (3 × 20 mL). The organic phases were combined, washed with saturated sodium chloride (500 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. 20 mL of PE:MTBE = 10:1 was added to the crude product, stirred at 25 °C for 1 h, and filtered. The filter cake was collected and dried with an oil pump to obtain 1.55 g of compound 3-8. The yield was not calculated. Preparation of Compound 3-10 Compound 3-8 (1.55 g, 5.30 mmol) was dissolved in MeOH (47 mL), 4 M HCl / MeOH (2.65 mL, 52.4 mmol) was added, then 10% Pd / C (300 mg) was added, and the mixture was stirred at 28 °C for 3 h. The reaction was monitored by LCMS, and the starting material disappeared. TEA (1.89 g, 18.6 mmol) and Ac2O (1.25 g, 12.2 mmol) were added to the reaction solution, and the mixture was stirred at 28 °C for 1 h. The reaction was monitored by LCMS, and the starting material disappeared. The reaction solution was filtered through diatomaceous earth and washed with methanol (300 mL). The filtrate was rotary evaporated to obtain the crude product. The crude product was purified by column chromatography to obtain 500 mg of compound 3-10. The three-step yield was 37%. Preparation of Compound 3-11 Compound 3-10 (500 mg, 1.56 mmol) was added to DCM (10 mL) and MeOH (5 mL), then concentrated hydrochloric acid (3 mL) was added, and the mixture was stirred at 28 °C for 18 h. The reaction was monitored by LCMS, and the raw material disappeared, with the main peak being the product. The reaction was stopped. 30 mL of water was added to the reaction solution, then saturated sodium bicarbonate aqueous solution was added to adjust the pH to 9 - 10, and the mixture was extracted with DCM (3 × 10 mL). The organic phases were combined, washed with saturated sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated to obtain the crude product. 15 mL of PE:MTBE = 10:1 was added to the filter cake, and the mixture was stirred at 25 °C for 1 h and then filtered. The filter cake was collected to obtain 320 mg of Compound 3-11. The yield was not calculated. Preparation of Compound 3-12 Compound 3-11 (320 mg, 1.15 mmol) was dissolved in toluene (8 mL), HM-582_8 (275 mg, 1.05 mmol) and PPTS (132 mg, 0.52 mmol) were added, and the mixture was stirred at 125 °C for 24 h. The reaction was monitored by LCMS, and 15% of the raw material remained, with the main peak being the product. The reaction was stopped. The reaction solution was directly rotary evaporated to obtain the crude product. The crude product was mixed with silica gel and purified by column chromatography to obtain 400 mg of Compound 3-12. The two-step yield was 69%. 1.2.10 Preparation of Compound C-3a and Compound C-3b Compound 3-12 (400 mg) was added to 6M HCl aqueous solution (5 mL), and the mixture was refluxed and stirred at 110 °C for 4 h. The reaction was monitored by LCMS, and the raw material disappeared. The reaction was stopped. The reaction solution was directly lyophilized to obtain the crude product. The crude product was directly purified by NP-HPLC to obtain 55 mg of Compound C-3a and 90 mg of Compound C-3b. The yield was 40%. Compound C-3a: LCMS (m / z) [M+H] + = 464.2. 11H NMR (400 MHz, DMSO) δ 8.51 (brs, 3H), 7.89 (d, J = 10.2 Hz, 1H), 7.37 (s, 1H), 6.57 (s, 1H), 5.74–5.69 (m, 1H), 5.56–5.36 (m, 3H), 5.11 (s, 1H), 3.66–3.54 (m, 1H), 3.49–3.40 (m, 1H), 3.26–3.13 (m, 1H), 2.59–2.54 (m, 1H), 2.26–2.15 (m, 1H), 1.97–1.82 (m, 2H), 1.45 - 1.35 (m, 6H), 0.91 (t, J = 7.6 Hz, 3H). Compound C-3b: LCMS (m / z) [[M+H]] + = 464.2. 1 1H NMR (400 MHz, DMSO) δ 8.50 (brs, 3H), 7.89 (d, J = 10.2 Hz, 1H), 7.37 (s, 1H), 6.57 (s, 1H), 5.79–5.64 (m, 1H), 5.55–5.38 (m, 3H), 5.12 (s, 1H), 3.63 - 3.57 (m, 1H), 3.48–3.41 (m, 1H), 3.26–3.13 (m, 1H), 2.58–2.54 (m, 1H), 2.27–2.13 (m, 1H), 1.97–1.83 (m, 2H), 1.46–1.34 (m, 6H), 0.90 (t, J = 7.6 Hz, 2H). Example 4: Synthesis of Compound C-4a Preparation of Compound 4-2 Compound 4-1 (10 g, 53.5 mmol) and imidazole (10.9 g, 160 mmol) were dissolved in THF (100 mL), and TBSCl (12.1 g, 80.1 mmol) dissolved in 30 mL of ultradry THF was added using a pressure-equalized dropping funnel. The system was purged with N2, and the reaction solution was stirred at room temperature for 17 h. TLC (PE:EA = 10) showed completion of the reaction. The reaction solution was added to water (100 mL), extracted with ethyl acetate (150 mL), and washed three times with water (50 mL). The organic phase was dried over anhydrous sodium sulfate, concentrated, and further purified by column chromatography to give 15 g of Compound 4-2. The yield was 94%. Preparation of Compound 4-3 At -70 °C, n-butyllithium (24.45 mL, 61 mmol, 2.5 M) was added to a solution of compound 4-2 (15.0 g, 49.7 mmol) in THF (150 mL), and the mixture was stirred at -70 °C for 1 h. Then, bismuth tribromide (8.19 g, 19.9 mmol) dissolved in ultra-dry THF (20 mL) was added, and the mixture was stirred at -70 °C for 0.5 h. The mixture was gradually warmed to room temperature and stirred for 2 h. TLC (PE:EA = 10:1) showed that the reaction was complete. The reaction solution was poured into water (100 mL), extracted with DCM (100 mL), washed with water (50 mL), dried over anhydrous sodium sulfate, rotary evaporated, and further purified by column chromatography to obtain 5 g of compound 4-3. The yield was 12%. Preparation of Compound 4-4 To a solution of compound 4-3 (4.0 g, 4.5 mmol), irinotecan (400 mg, 0.919 mmol, prepared according to Example 5), and cupric acetate anhydrous (33.8 mg, 1.83 mmol) in 1,2-dichloroethane (40 mL) was added TEA (279 mg, 2.7 mmol), and the reaction was carried out at 50 °C for 2 h. LCMS showed that the reaction was complete. Water (50 mL) was added to the reaction solution, and the mixture was extracted with DCM (100 mL), dried over anhydrous sodium sulfate, rotary evaporated, and purified by column to obtain 110 mg of compound 4-4. The yield was 17%. Preparation of Compound 4-5 Compound 4-4 (100 mg, 0.153 mmol) was added to a 50 mL reaction flask, then THF (1 mL) and aqueous HCl solution (2 M, 1 mL) were added, and the reaction was carried out at 0 °C for 1 h. LCMS showed that the starting material had completely reacted. 1 mL of acetonitrile was added to the reaction solution, and it was directly lyophilized to obtain 90 mg of compound 4-5. The yield was not calculated. Preparation of Compound 4-6 At 0 °C, MsCl (29 mg, 0.26 mmol) was added to a solution of compound 4-5 (70 mg, 0.129 mmol) and TEA (39 mg, 0.387 mmol) in DCM (1 mL), and the reaction was carried out for 1 h. After monitoring the completion of the reaction by LCMS, hexamine (90 mg, 0.65 mmol) was added to the reaction flask and the reaction was carried out at room temperature for 2 h. LCMS showed that the reaction was complete. The reaction solution was added to water and extracted with DCM. Then, the organic phase and the aqueous phase were sent for analysis, and the product was in the aqueous phase. 55 mg of compound 4-6 was obtained by lyophilizing the aqueous phase. The yield was not calculated. Preparation of Compound C-4a Compound 4-6 (50 mg, mmol) was added to a reaction flask, then 1 mL of THF and 1 mL of aqueous hydrochloric acid solution (6 M) were added, and the reaction was carried out at 0 °C for 2 h. LCMS showed that the reaction was completed. The reaction solution was directly sent for preparation to obtain 1.3 mg of the product. The yield was not calculated. LCMS (m / z) + = 541.3. Example 5: Synthesis of Compound C-5a and Compound C-5b Preparation of Compound 5-2 In an N2 atmosphere, a solution of Compound 5-1 (48.0 g, 287 mmol) and NaOAc (28.3 g, 345 mmol) in AcOH (165 mL) was warmed to 60 °C, and Br2 (55.0 g, 345 mmol in AcOH) was added dropwise. Then the reaction solution was warmed to 80 °C and stirred for 3 h. After monitoring the completion of the reaction by LCMS, the reaction solution was cooled to room temperature, then poured into ice water (2.5 L) and stirred for 30 min. The yellow solid was filtered out, dried at 50 °C, and further purified by silica gel column chromatography to obtain 62 g of Compound 5-2. The yield was 90%. LCMS (m / z) = 246.0. Preparation of Compound 5-4 In an N2 atmosphere, a solution of Compound 5-2 (5.0 g, 20.3 mmol) in THF (50 mL) was cooled to -78 °C, MeLi (8.13 mL, 24.4 mmol) was added dropwise and stirred for 1 h, then n-BuLi (9.76 mL, 24.4 mmol) was added and stirred for 1.5 h. After that, a solution of Compound 5-3 (4.52 g, 24.4 mmol) in THF (10 mL) was added dropwise to the reaction solution and stirred at -78 °C for 1.5 h. After monitoring the completion of the reaction by LCMS, saturated aqueous NH4Cl solution (200 mL) was added to the reaction solution and extracted with EA (150 mL * 3). The organic layer was washed with saturated NaCl (200 mL * 3), dried and concentrated to obtain a yellow crude product, which was further purified by column chromatography to obtain 2.0 g of Compound 5-4. The yield was 28%. Preparation of Compound 5-5 In an N2 atmosphere, AgNO3 (169 mg, 1.0 mmol) and K2S2O8 (8.42 g, 31.2 mmol) were added to a solution of compound 5-4 (3.67 g, 10.4 mmol) in DCM (70 mL) / water (70 mL) at 0 °C. The reaction solution was stirred overnight at 0 °C to room temperature. After monitoring the completion of the reaction by TLC, the reaction solution was separated and extracted with DCM (50 mL × 3). The organic layer was washed with saturated Na2SO3 (100 mL × 3), dried and concentrated to obtain the crude product, which was further purified by column chromatography to obtain 1.77 g of compound 5-5. The yield was 47%. Preparation of Compound 5-6 In an N2 atmosphere, concentrated HCl (5.0 mL) was added dropwise to a solution of compound 5-5 (1.77 g, 5.1 mmol) in a mixture of DCM (40 mL) and MeOH (20 mL) at 0 °C. The reaction solution was stirred overnight at room temperature. After monitoring the completion of the reaction by TLC, the reaction solution was concentrated to obtain 1.05 g of compound 5-6, which was directly used in the next reaction step. Preparation of Compound 5-7 In an N2 atmosphere, a solution of compound 5-6 (1.05 g, 4.3 mmol) and K2CO3 (1.3 g, 9.4 mmol) in THF (18 mL) / water (27 mL) was added dropwise to a solution of FmocCl (1.16 g, 4.5 mmol) in THF (2 mL) at 0 °C. The reaction solution was stirred at the same temperature for 3 h. After monitoring the completion of the reaction by TLC, the reaction solution was separated by adding 2-Me-THF (100 mL). The organic layer was washed with water (70 mL × 3), dried and concentrated, and further purified by column chromatography to obtain 927 mg of compound 5-7. The yield was 48%. Preparation of Compound 5-8 In an N2 atmosphere, a solution of compound 5-7 (368 mg, 0.86 mmol), compound 1-9 (202 mg, 0.86 mmol) and PPTS (43 mg, 0.17 mmol) in toluene (9.0 mL) was heated to 125 °C (external temperature) and stirred under reflux overnight. After completion of the reaction, the reaction solution was cooled to room temperature and concentrated to dryness to obtain a reddish-brown solid, which was further separated by preparative high performance liquid chromatography and freeze-dried to obtain 52 mg of compound 5-8. The yield was 14%. Preparation of Compound C-5 (Compound C-5a and Compound C-5b) At 0 °C, diethylamine (1.0 mL) was added to a solution of compound 5-8 (52 mg, 0.08 mmol) in DCM (2.0 mL). After completion of the reaction was monitored by TLC, the reaction solution was directly concentrated to dryness and further separated by preparative liquid chromatography to give 4 mg of compound C-5 as a mixture of compound C-5a and compound C-5b. The yield was not calculated. LCMS (m / z) = 436.1. 1 HNMR (400 MHz, DMSO): δ 7.86 (d, J = 10.8 Hz, 1H), 7.35 (s, 1H), 6.56 (s, 1H), 5.46 (s, 2H), 5.30 (s, 2H), 3.89 - 3.85 (m, 1H), 3.52 - 3.50 (m, 2H), 3.27–3.20 (m, 1H), 3.12 - 3.09 (m, 1H), 2.46 (s, 1H), 2.41 (s, 2H), 1.96–1.81 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H). Example 6: Synthesis of compound C-6a and compound C-6b Preparation of compound 6-2 In an N2 atmosphere, Ra-Ni (4.0 g) was added to a solution of compound 6-1 (9.0 g, 27.1 mmol) in MeOH (450 mL). The system was replaced with H2 three times, warmed to 50 °C and stirred for 16 h. After completion of the reaction was monitored by LCMS, the reaction solution was cooled to room temperature, filtered, concentrated and further purified by column chromatography to give 6.7 g of compound 6-2. The yield was 85%. Preparation of compound 6-3 In an N2 atmosphere, CHP (cumene hydroperoxide, 2.1 g, 13.8 mmol, 2.0 eq) was added dropwise to a solution of compound 6-2 (2.0 g, 6.9 mmol), HM-582B_24 (93 mg, 1.3 mmol), and K2CO3 (2.39 g, 17.3 mmol) in toluene (120 mL), and the reaction solution was stirred at 50 °C for 24 h. CHP (cumene hydroperoxide, 2.1 g, 13.8 mmol, 2.0 eq) was added, and the reaction solution was continuously stirred at 50 °C for 24 h. CHP (cumene hydroperoxide, 2.1 g, 13.8 mmol, 2.0 eq) was added, and the reaction solution was continuously stirred at 50 °C for 24 h. After the reaction was monitored by LCMS and completed, the reaction solution was cooled to room temperature, diluted with water (200 mL), and extracted with EA (150 mL * 3). The organic layer was washed with saturated Na2SO3 (200 mL * 3), dried, and concentrated to obtain a reddish-brown mixture, which was further separated by silica gel column chromatography (eluted with DCM / MeOH = 50 / 1 - 10 / 1) to obtain the crude product of compound 6-3 (354 mg, Y 17%). Preparation of Compound 6-4 In an N2 atmosphere, TFA (2.5 mL) was added dropwise to a solution of compound 6-3 (354 mg, 1.16 mmol, 1.0 eq) in DCM (5 mL) at 0 °C. The reaction solution was stirred at the same temperature for 3 h. After the reaction was monitored by LCMS and completed, the reaction solution was concentrated, and the resulting reddish-brown mixture was lyophilized at 0 °C to obtain compound 6-4 (332 mg), which could be directly used in the next reaction step. Preparation of Compound 6-6 In an N2 atmosphere, a solution of compound 6-4 (332 mg, 1.27 mmol), compound 6-5 (317 mg, 1.27 mmol), and PPTS (64 mg, 0.25 mmol) in toluene (9.0 mL) was heated to 125 °C (external temperature) and stirred under reflux overnight. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated to dryness to obtain a reddish-brown solid, which was further purified by column chromatography to obtain 122 mg of compound 6-6 (yield 26%), which was directly used in the next reaction step. Preparation of Compound 6-7, Compound C-6a, and Compound C-6b A solution of compound 6-6 (122 mg, 256 mmol) in dilute hydrochloric acid solution (6 M aqueous solution, 5 mL) was heated under reflux for 3 h. The completion of the reaction was monitored by LCMS. The reaction solution was directly concentrated to dryness, and two main peaks were separated by preparative liquid chromatography. The preparative solution containing the product was lyophilized to obtain P1 (C-6a, 7.2 mg) and P3 (C-6b, 8.1 mg) respectively. LCMS (m / z) = 435.2. 1 H NMR (400 MHz, MeOD) δ 7.79 (d, J = 10.7 Hz, 1H), 7.68 (s, 1H), 5.50 (dd, J = 41.9, 18.8 Hz, 2H), 5.11 (s, 1H), 4.59 (d, J = 18.6 Hz, 1H), 4.31 (d, J = 18.6 Hz, 1H), 3.42 (d, J = 18.1 Hz, 1H), 3.18 (s, 1H), 2.62 (d, J = 12.7 Hz, 1H), 2.49 (s, 3H), 2.41 (s, 1H), 2.00–1.85 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H). LCMS (m / z) = 435.2. 1 H NMR (400 MHz, MeOD) δ 7.79 (d, J = 10.7 Hz, 1H), 7.67 (s, 1H), 5.51 (q, J = 18.8 Hz, 2H), 4.58 (d, J = 18.4 Hz, 1H), 4.31 (d, J = 18.6 Hz, 1H), 3.41 (s, 1H), 3.18 (s, 1H), 2.60 (s, 1H), 2.50 (s, 3H), 2.41 (s, 1H), 1.99–1.85 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). Example 7: Synthesis of Compound D-2 Reaction subject: Preparation of 7-3: Compound 7-2 (7 g, 10.16 mmol) and compound 7-1 (3.41 g, 10.16 mmol) were dissolved in DMF (70 mL), and DIPEA (3.93 g, 30.5 mmol) was added thereto. The reaction was carried out at room temperature for 1 h to obtain a clear, transparent and viscous product (5 g, yield: 54). LCMS: Mobile phase: A: water (0.01% TFA) B: ACN (0.01% TFA); Gradient: 5% to 95% B in 0.6 min; Flow rate: 0.8 mL / min; Column: Poroshell 120 EC-C18, 2.1 * 50 mm, 1.9 μm A = RP = 517; Oven temperature: 45 °C. MS(+) = 117; RT = 0.91 min. Preparation of compound D-2: Dissolve compound C1-B (2.6 g, 5.5 mmol) and compound 7-3 (5 g, 5.5 mmol) in DMF (50 mL). Then add DIC (1.4 g, 11 mmol), HOBt (1.5 g, 11 mmol) and DIPEA (709 mg, 5.5 mmol) to the reaction, and stir it at room temperature for 1 hour to obtain white product D-2 (2.1 g, yield: 28%). LCMS: Mobile phase: A: water (0.01% TFA) B: ACN (0.01% TFA); Gradient: 5% to 95% B in 0.6 min; Flow rate: 0.8 ml / min; Column: Poroshell 120 EC-C18, 2.1 * 50 mm, 1.9 μm A = RP = 517; Oven temperature: 45 °C. MS(+) = 117; Rt = 1.06 min . Example 8: Synthesis of compound D-3 Reaction topic: Dissolve 10 g of compound 7-5 in 100 ml of DCM / TFA (1:1), stir it at room temperature for 1 hour, and rotary dry to obtain white product 7-1 (11.5 g, yield: 100%). LCMS: Mobile phase: A: water (0.01% FA) B: ACN (0.01% FA); Gradient: 5% to 95% B in 0.8 min; Flow rate: 0.8 mL / min; Column: Poroshell 120 EC-C18, 2.1 * 50 mm, 1.9 μm; Oven temperature: 45 °C. MS(+) = 337; RT = 0.42 min. Preparation of 7-4: Dissolve compound 7-1 (11.5 g, 34 mmol) and FmocoSu (17.3, 51 mmol) in THF / H2O (120 mL, 1:1), and add NaHCO3 (5.75 g, 68 mmol) thereto. Stir the reaction at room temperature for 16 h, and adjust the pH to <5 with HCl. A white solid precipitates, which is filtered and dried to obtain the white final product (16.9 g, yield: 88%). LCMS: Mobile phase: A: water (0.01% FA) B: ACN (0.01% FA); Gradient: 5% to 95% B in 0.8 min; Flow rate: 0.8 mL / min; Column: Poroshell 120 EC-C18, 2.1*50 mm, 1.9 μm; Oven temperature: 45 °C. MS(+) = 559; RT = 1.00 min. Preparation of 8-5: Dissolve compound 7-4 (16.8 g, 30 mmol) and S1 (4-aminobenzyl alcohol, 4.07 g, 33 mmol) in DMF (180 mL), and add HATU (14.9 g, 39 mmol) and DIPEA (9.7 g, 75 mmol) thereto. Carry out the reaction at room temperature for 2 h. LCMS: Mobile phase: A: water (0.01% TFA) B: ACN (0.01% TFA); Gradient: 5% to 95% B in 1.3 min; Flow rate: 0.8 mL / min; Column: Poroshell 120 EC-C18, 2.1*50 mm, 1.9 μm; Oven temperature: 45 °C. MS(+) = 646; RT = 1.04 min. Preparation of 8-6: Dissolve compound 8-5 (6 g, 9 mmol) and S1 (bis(4-nitrophenyl) carbonate, 4.13 g, 13.5 mmol) in DMF (60 mL), and add DIPEA (3.5 g, 27 mmol) thereto. Carry out the reaction at room temperature for 2 h, and obtain the white final product (4.16 g, yield: 55%) by reverse-phase purification. LCMS: Mobile phase: A: water (0.01% TFA) B: ACN (0.01% TFA); Gradient: 5% to 95% B in 1.3 min; Flow rate: 0.8 mL / min; Column: Poroshell 120 EC-C18, 2.1*50 mm, 1.9 μm; Oven temperature: 45 °C. RT = 1.23 min. Preparation of 8-7: Compound 8-6 (7 g, 8.45 mmol) and compound C-1b (3.58 g, 7.6 mmol) were dissolved in DMF (70 mL), and HOBT (2.28 g, 16.9 mmol) and DIPEA (3.27 g, 25.3 mmol) were added thereto. The reaction was carried out at room temperature for 1 hour, and then added to methyl tert-butyl ether to precipitate a white solid, which was dried to obtain a light brown crude product (7 g, yield: 73%). LCMS: Mobile phase: A: water (0.01% TFA) B: ACN (0.01% TFA); Gradient: 5% to 95% B in 2.0 min; Flow rate: 1.2 mL / min; Column: Shim-pack Scepter C18-120, 3.0 * 33 mm, 3 μm; Oven temperature: 45 °C. RT = 1.57 min. Preparation of 8-6: Compound 8-7 was dissolved in DMF (70 mL), and triethylenediamine (1.4 g, 12.45 mmol) was added. The reaction was carried out at room temperature for 2 hours, and a white final product (3.65 g, yield: 65%) was obtained by reverse-phase purification. LCMS: Mobile phase: A: water (0.01% TFA) B: ACN (0.01% TFA); Gradient: 5% to 95% B in 1.3 min; Flow rate: 0.8 mL / min; Column: Poroshell 120EC-C18, 2.1 * 50 mm, 1.9 μm; Oven temperature: 45 °C. RT = 0.93 min. Preparation of D-3: Compound 8-8 (3.65 g, 4 mmol) and 7-2 (3.07 g, 4.45 mmol) were dissolved in DMF (40 mL), and DIPEA (522 mg, 4 mmol) was added thereto. The reaction was carried out at room temperature for 0.5 hour, and a white final product (3.1 g, yield: 52%) was obtained by reverse-phase purification. LCMS: Mobile phase: A: water (0.01% TFA) B: ACN (0.01% TFA); Gradient: 5% to 95% B in 1.3 min; Flow rate: 0.8 mL / min; Column: Poroshell 120EC-C18, 2.1 * 50 mm, 1.9 μm; Oven temperature: 45 °C. MS(+) = 84; RT = 1.01 min. Biological assay Example 1: Cytotoxicity test of the compound This example tested the ability of four compounds to induce cytotoxicity. The molecules were compound C-2a, compound C-2b, compound C-6a, and compound C-6b. MMAE and DXD (irinotecan derivative of ADC) were used as benchmark references. HT-29 (colorectal cancer) and MDA-MB-468 (TNBC) cells were harvested and seeded into 96-well cell culture plates at 3000 cells per well. Then they were incubated overnight at 37 °C and 5% CO2. Each compound was diluted 3-fold from 500 nM and added to each well respectively. After 5 days, 30 μL of Cell Titer-Glo luminescent buffer was added to each well, and the plate was incubated at room temperature for 20 min. The luminescence signal was detected by an Envison microplate reader. The results are shown in Table 1. As shown, MMAE, DXD, C-2a, and C-2b inhibited cell proliferation in a concentration-dependent manner. Table 1. Results of cytotoxicity test In the second round of testing, C-2a and C-2b, along with six other compounds (C-1a, C-1b, C-3a, C-3b, C-5a, and C-4a), were tested using the same cell lines plus A549 (NSCLC cell line). The results are shown in Table 2. Table 2. Results of the second round of cytotoxicity test All tested compounds inhibited cell proliferation in a concentration-dependent manner. Example 2: Binding of HER2 ADC to human HER2-positive and -negative cells Flow cytometry was used to evaluate the cell-based binding of antibody-drug conjugates (trastuzumab-DXd, ADC-1, ADC-2, ADC-3, ADC-4, and ADC-5) to tumor cells (all ADC-1 to ADC-5 included trastuzumab as an antioxidant). Briefly, NCI-N87, SK-BR-3, BT-474, JIMT-1, and MDA-MB-468 cells were incubated with titrated antibody-drug conjugates (from 100 nM, 5-fold dilution, 8 points) at 4 °C for 60 min. Then the cells were washed twice with FACS buffer and stained with a fluorescent-conjugated secondary antibody (Alexa 647 Goat Anti-Human IgG, Jackson, 109-605-098) at 4 °C for 60 min. After that, the cells were washed twice and analyzed by flow cytometry. As shown in Figures 1A to 1E, all antibody-drug conjugates (trastuzumab-DXd, ADC-1, ADC-2, ADC-3, ADC-4, and ADC-5) can effectively bind to human HER2-expressing tumor cells in a dose-dependent manner. Example 3: Binding of ADC-3 to human HER2-positive and -negative cells at drug-to-antibody ratios of 4 (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) Flow cytometry was used to evaluate the cell-based binding of antibody-drug conjugates (trastuzumab-DXd, ADC-2, ADC-3-4 (DAR4), ADC-3-6 (DAR6), and ADC-3-8 (DAR8)) to tumor cells. Briefly, NCI-N87, SK-BR-3, BT-474, JIMT-1, MDA-MB-231, and MDA-MB-468 cells were incubated with titrated antibody-drug conjugates (from 100 nM, 5-fold dilutions, 8 points) at 4 °C for 60 minutes. The cells were then washed twice with FACS buffer and stained with a fluorescent-conjugated secondary antibody (Alexa 647 Goat Anti-Human IgG, Jackson, 109-605-098) at 4 °C for 60 minutes. After that, the cells were washed twice and analyzed by flow cytometry. As shown in Figures 2A to 2F, all antibody-drug conjugates (trastuzumab-DXd, ADC-2, ADC-3-4 (DAR4), ADC-3-6 (DAR6), and ADC-3-8 (DAR8)) can effectively bind to human HER2-expressing tumor cells in a dose-dependent manner. Example 4: Cytotoxicity of HER2 ADCs against human HER2-positive and -negative cells The cytotoxicity of antibody-drug conjugates (trastuzumab-DXd, ADC-1, ADC-2, ADC-3, ADC-4, and ADC-5) against tumor cells expressing human HER2 was evaluated using the CellTiter-Glo luminescent cell viability assay (Promega, G7573). Briefly, NCI-N87, SK-BR-3, BT-474, JIMT-1, and MDA-MB-468 cells were incubated with titrated antibody-drug conjugates (from 100 nM, 5-fold dilution, 9 points) in a 96-well plate in a 37 °C cell culture incubator for 6 days. Cell viability was evaluated using the CellTiter-Glo kit (Promega, G7573) according to the manufacturer's instructions. As shown in FIGS. 3A to 3E, SK-BR-3 cells were more sensitive to all antibody-drug conjugates (trastuzumab-DXd, ADC-1, ADC-2, ADC-3, ADC-4, and ADC-5) than other tumor cells, and ADC-1 showed the highest in vitro anti-tumor ability. In NCI-N87, SK-BR-3, and BT-474 cells, the anti-tumor activity of ADC-1 was approximately 3-fold higher than that of trastuzumab-DXd. Example 5: Cytotoxicity of ADC-3 with drug-to-antibody ratios (ADC-3-4), 6 (ADC-3-6), and 8 (ADC-3-8) against human HER2-positive and -negative cells The cytotoxicity of antibody-drug conjugates (trastuzumab-DXd, ADC-2, ADC-3-4 (DAR4), ADC-3-6 (DAR6), and ADC-3-8 (DAR8)) against tumor cells expressing human HER2 was evaluated using the CellTiter-Glo luminescent cell viability assay (Promega, G7573). Briefly, NCI-N87, SK-BR-3, BT-474, JIMT-1, MDA-MB-231, and MDA-MB-468 cells were incubated with titrated antibody-drug conjugates (from 100 nM, 5-fold dilution, 9 points) in a 96-well plate in a 37 °C cell culture incubator for 6 days. Cell viability was evaluated using the CellTiter-Glo kit (Promega, G7573) according to the manufacturer's instructions. As shown in FIGS. 4A to 4F, SK-BR-3 cells were more sensitive to all antibody-drug conjugates (trastuzumab-DXd, ADC-1, ADC-2, ADC-3-4, ADC-3-6, ADC-3-8, ADC-4, and ADC-5) than other tumor cells, and ADC-2 showed excellent in vitro anti-tumor ability. Example 6: Bystander killing effect of HER2 ADC on human HER2-negative MDA-MB-468 cells The bystander killing effect of antibody-drug conjugates (trastuzumab-DXd, ADC-1, ADC-2, and ADC-3) on human HER2-negative tumor cells (MDA-MB-468) was evaluated using the CellTiter-Glo luminescent cell viability assay (Promega, G7573). Briefly, SK-BR-3 cells (5000 cells / well) were incubated with titrated antibody-drug conjugates (from 100 nM, 5-fold dilution, 9 points) in a 96-well plate in a 37 °C cell culture incubator for 6 days. Then the cell culture supernatant was transferred to the MDA-MB-468 cell culture (2000 cells / well) and incubated for another 6 days. Cell viability was evaluated using the CellTiter-Glo kit (Promega, G7573) according to the manufacturer's instructions. As shown in Figures 5A and 5B, ADC-1 and ADC-2 had stronger cytotoxicity against the target SK-BR-3 cells than trastuzumab-DXd (T-DXd), and all of ADC-1, ADC-2, and ADC-3 exhibited a smaller bystander effect than trastuzumab-DXd. In particular, ADC-1 had the most prominent performance in both cell lines. Example 7: Bystander effect of ADC-3 with drug-to-antibody ratios of 4, 6, 8 (DAR 4, 6, 8) on human HER2-negative MDA-MB-468 cells The bystander killing effect of antibody-drug conjugates (trastuzumab-DXd, ADC-2, ADC-3 (DAR4), ADC-3 (DAR6), ADC-3 (DAR8)) on human HER2-negative tumor cells (MDA-MB-468) and human HER2-low-expressing tumor cells (MDA-MB-231) was evaluated using the CellTiter-Glo luminescent cell viability assay (Promega, G7573). Briefly, SK-BR-3 cells (5000 cells / well) were incubated with titrated antibody-drug conjugates (from 100 nM, 5-fold dilution, 9 points) in a 96-well plate in a 37 °C cell culture incubator for 6 days. Then the cell culture supernatant was transferred to the MDA-MB-468 cell culture (2000 cells / well) and incubated for another 6 days. Cell viability was evaluated using the CellTiter-Glo kit (Promega, G7573) according to the manufacturer's instructions. As shown in FIGS. 6A and 6B, ADC-2 has stronger targeted cytotoxicity and a milder bystander effect than trastuzumab-DXd, while in both experiments, ADC-3 is as good as trastuzumab-DXd at different DARs. Example 8: Comparison of Payloads in the JIMT-1 CDX Model Conjugated to Trastuzumab Each NOG mouse was inoculated with 8 million JIMT-1 cells. When the tumor size reached approximately 100 mm 3 , trastuzumab-DXd and ADC-2 were intravenously injected once a week for a total of three weeks. The tumor size was measured three times a week. As Figure 7 shown, the ADC molecules tested had similar in vivo anti-tumor effects, even in one test where ADC-2 (6 mpk) was used at a lower dose than trastuzumab-DXd (10 mpk). *** The scope of the present disclosure is not limited by the specific embodiments, which are intended to be illustrative of individual aspects of the present disclosure, and any compositions or methods that are functionally equivalent are within the scope of the present disclosure. It will be apparent to those skilled in the art that various modifications and variations can be made to the methods and compositions of the present disclosure without departing from the spirit or scope of the present disclosure. Accordingly, the present disclosure is intended to cover modifications and variations of the present disclosure provided they fall within the scope of the appended claims and their equivalents. All publications and patent applications mentioned in this specification are incorporated herein by reference to the extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

Claims

1. A compound of formula I: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein, A 1 is -NHR 1 , wherein, R 1 is hydrogen, -C6 aryl-C 1-6 alkyl-NH2, -C(O)R 5 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 2 and A 3 are both hydrogen; or A 2 is -NHR 2 , wherein, R 2 is hydrogen, -C6 aryl-C 1-6 alkyl-NH2, -C(O)R 5 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 1 and A 3 are both hydrogen; or A 3 is -NHR 3 , wherein R 3 is hydrogen, -C6 aryl-C 1-6 alkyl-NH2, -C(O)R 5 or -C6 aryl-C 1-6 alkyl-NHC(O)R 5 ; and A 1 and A 2 are both hydrogen; R 4 is - C 1-6 alkyl; provided that when A 1 is - NHR 1 then R 4 is not methyl; R 5 is - L - R 6 ; L is a linker moiety; and R 6 is hydrogen or a heterocyclic group, wherein the heterocyclic group is optionally covalently linked to an antibody or antigen-binding fragment.

2. The compound according to claim 1, wherein the compound of formula I is represented by formula II: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein, R 4 is - C 2-6 alkyl group.

3. The compound according to claim 1, wherein the compound of formula I is represented by formula III: or a stereoisomer or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1, wherein the compound of formula I is represented by formula IV: or a stereoisomer or a pharmaceutically acceptable salt thereof.

5. The compound according to any one of the preceding claims, wherein, R 5 is - L 1 -(AA) n -L 2 -R 6 ; and L 1 is C 1-20 alkylene or C 2-20 heteroalkylene; n is 0, 1, 2, 3, 4, 5 or 6; each AA is independently an amino acid; and L 2 is C 1-40 alkylene or C 2-40 heteroalkylene, wherein said C 1-40 alkylene or C 2-40 heteroalkylene is optionally substituted with one or more oxo groups.

6. The compound according to any one of claims 1 to 5, wherein L 1 is C 1-20 alkylene.

7. The compound according to any one of claims 1 to 5, wherein L 1 is C 1-20 heteroalkylene.

8. A compound according to any one of claims 1 to 5, wherein L 1 is -(CH2) p -X 1 -(CH2) q -X 2 -* or -X 1 -(CH2) p -phenylene-(CH2) q -X 2 -*; and wherein said * bond is attached to -(AA) n -L 2 -R 6 : X 1 is a bond, -O-, -S-, or -NH-; X 2 is a bond, -O-, -S-, or -NH-; p is 1, 2, 3 or 4; and q is 1, 2, 3, or 4.

9. The compound according to claim 8, wherein, L 1 is -(CH2) p -O-(CH2) q -NH-*.

10. The compound according to claim 8, wherein L 1 is -CH2-O-CH2-NH-*.

11. The compound according to claim 8, wherein, L 1 is -(CH2)2-O-CH2-NH-*.

12. The compound according to any one of claims 1 to 11, wherein, n is 1, 2, 3, 4, 5 or 6.

13. The compound according to any one of claims 1 to 11, wherein n is 4.

14. The compound according to any one of claims 1 to 13, wherein, Each AA is independently selected from Gly and Phe.

15. The compound according to any one of claims 1 to 13, wherein, -(AA) n -is -GFGG- or -FGG-.

16. The compound according to any one of claims 1 to 15, wherein, L 2 is an alkylene group optionally substituted with one or more oxo groups 1-40 and.

17. The compound according to any one of claims 1 to 15, wherein L 2 is -C(O)-C 0-39 alkylene.

18. A compound according to any one of claims 1 to 15, wherein L 2 is a C 2-40 heteroalkylene optionally substituted with one or more oxo groups.

19. The compound according to any one of claims 1 to 15, wherein L 2 is -C(O)-C 1-39 heteroalkylene.

20. The compound according to any one of claims 1 to 15, wherein L 2 is -C(O)-(CH2CH2O) 1-10 -CH2CH2-.

21. The compound according to any one of claims 1 to 20, wherein, R 4 is ethyl.

22. The compound according to any one of claims 1 to 20, wherein R 4 is isopropyl.

23. A compound according to any one of claims 1 to 20, wherein, R 5 is -(CH2) p -O-(CH2) q -NH-(AA) n -C(O)-C 1-10 alkylene-R 6 。 24. A compound according to any one of claims 1 to 20, wherein, R 5 is -(CH2) p -O-(CH2) q -NH-(AA) n -C(O)-C 1-30 heteroalkylene-R 6 。 25. The compound according to any one of claims 1 to 20, wherein, R 5 is -(CH2) p -O-(CH2) q -NH-(AA) n -C(O)-(CH2CH2O) 1-10 -CH2CH2-R 6 。 26. The compound according to any one of claims 1 to 25, wherein, R 6 is 27. The compound according to any one of claims 1 to 25, wherein, R 6 is wherein Ab is an antibody or antigen-binding fragment.

28. A compound selected from: and Among them, Ab is an antibody or antigen-binding fragment targeting HER2; and x is from 4 to 8.

29. The compound according to claim 27, wherein, Ab targets HER2, HER3, B7H3, TROP2, Claudin18.2, CD30, CD33, CD70 or EGFR.

30. A compound selected from: and Among them, Ab is trastuzumab; and x is from 4 to 8.

31. A compound selected from Table 1A, Table 1B, Table 1C or Table 1D, or a stereoisomer or a pharmaceutically acceptable salt thereof.

32. A pharmaceutical composition comprising the compound according to any one of claims 1 to 31, or a stereoisomer or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

33. A method for treating cancer in a patient in need thereof, comprising administering to the patient a therapeutically acceptable amount of the compound according to any one of claims 1 to 31, or a stereoisomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 32.

34. The method according to claim 33, wherein the cancer is lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer, or esophageal cancer.

35. A method for treating, preventing or inhibiting tumor growth in a patient in need thereof, comprising administering to the patient a therapeutically acceptable amount of the compound according to any one of claims 1 to 31, or a stereoisomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 32.

36. The method according to claim 35, wherein the tumor is associated with the expression of HER2, HER3, B7H3, TROP2, Claudin18.2, CD30, CD33, CD70 or EGFR.

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