Anti-tumor compound and application thereof

Abstract

The invention relates to an anti-tumor compound and application thereof, in particular to a ligand conjugate or a tautomer, a meso-mer, a raceme, an enantiomer, a diastereoisomer of the ligand conjugate, or a mixture form of the ligand conjugate or a pharmaceutically acceptable salt of the ligand conjugate or the tautomer, the meso-mer, the raceme, the enantiomer and the diastereoisomer. The invention also relates to a preparation method and application of the ligand conjugate.

Description

An antitumor compound and its application Technical Field

[0001] The present application relates to the field of biomedicine, and specifically to an anti-tumor compound and its application. Background Art

[0002] Antibody-drug conjugates (ADCs) link monoclonal antibodies or antibody fragments to biologically active cytotoxins via stable chemical linker compounds. These ADCs leverage the specificity of antibodies for binding to surface antigens on both normal and tumor cells and the high efficiency of cytotoxic substances, resulting in anti-tumor effects. While the camptothecin derivative exatecan has been reported in the literature, further development of ADCs with improved efficacy and safety is still needed.

[0003] Summary of the Invention

[0004] In one aspect, the present application provides a ligand conjugate or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate comprises a structure represented by formula (I):

[0005]

[0006] In one embodiment, the structure represented by formula (I) comprises the structure represented by (Ia):

[0007]

[0008] In one embodiment, the structure represented by formula (I) comprises the structure represented by formula (Ib):

[0009]

[0010] wherein R1 and R2 are each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0011] Alternatively, R1 and R2 together with the carbon atom to which they are attached form a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0012] L is an optionally substituted linker,

[0013] Ab is a ligand, a is a number greater than 0, and a is a decimal or an integer.

[0014] In the structure represented by formula (I), L is a linker -L1-L2-L3-L4-L5-.

[0015] In the structure shown in formula (I), the L1 is optionally substituted The L1 is directly connected to the Ab.

[0016] In the structure shown in formula (I), L2 is a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-,

[0017] X1 is selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic and optionally substituted alicyclic,

[0018] wherein m1, m2 and n are each independently selected from an integer of at least 0, and p is selected from an integer of 2 to 8.

[0019] In the structure shown in formula (I), L2 is optionally substituted -(CH2CH2O) n -C(O)-.

[0020] In the structure represented by formula (I), n is 2.

[0021] In the structure shown in formula (I), L2 is optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-.

[0022] In the structure represented by formula (I), X1 is selected from the group consisting of -O- and optionally substituted -C(O)-NH-.

[0023] In the structure represented by formula (I), m1 is 2.

[0024] In the structure represented by formula (I), m2 is 2.

[0025] In the structure represented by formula (I), X1 is a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group.

[0026] In the structure represented by formula (I), X1 is an optionally substituted phenyl group.

[0027] In the structure represented by formula (I), X1 is an optionally substituted pyridyl group.

[0028] In the structure represented by formula (I), m1 is 0.

[0029] In the structure represented by formula (I), m2 is 1.

[0030] In the structure shown in formula (I), X1 is optionally substituted

[0031] In the structure represented by formula (I), X1 is an optionally substituted cyclohexyl group.

[0032] In the structure represented by formula (I), m1 is 1.

[0033] In the structure represented by formula (I), m2 is 0.

[0034] In the structure shown in formula (I), L2 is optionally substituted -(CH2) p -C(O)-.

[0035] In the structure represented by formula (I), p is 5.

[0036] In the structure shown in formula (I), the L2 is selected from the following groups: Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0037] In the structure represented by formula (I), L3 is a peptide residue.

[0038] In the structure represented by formula (I), L3 is a peptide residue composed of amino acids selected from the following group: phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid and glycine.

[0039] In the structure represented by formula (I), L3 is a peptide residue consisting of amino acids selected from the group consisting of glycine, phenylalanine, valine and citrulline.

[0040] In the structure represented by formula (I), L3 is a peptide residue selected from the following group: -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-) and -valine-citrulline-(-Val-Cit-).

[0041] In the structure shown in formula (I), the L3 is selected from the following groups:

[0042]

[0043] In the structure shown in formula (I), L4 is an optionally substituted -L 4a -NR4-CH2-L 4b -,

[0044] L 4a Does not exist or L 4a is optionally substituted

[0045] L 4b Does not exist or L 4b is optionally substituted

[0046] R4 and R5 are each independently selected from the group consisting of hydrogen and optionally substituted alkyl.

[0047] In the structure shown in formula (I), the L4 is optionally substituted

[0048] In the structure shown in formula (I), the L4 is optionally substituted

[0049] In the structure shown in formula (I), the L4 is optionally substituted

[0050] In the structure shown in formula (I), the L4 is optionally substituted

[0051] In the structure represented by formula (I), R4 is selected from the following group: hydrogen and optionally substituted methyl.

[0052] In the structure represented by formula (I), R5 is selected from the following group: hydrogen and optionally substituted methyl.

[0053] In the structure shown in formula (I), the L4 is selected from the following groups: Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0054] In the structure shown in formula (I), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0055]

[0056] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0057] Here, v is selected from a number that is at least 0.

[0058] In the structure shown in formula (I), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0059]

[0060] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0061] Here, v is selected from a number that is at least 0.

[0062] In the structure shown in formula (I), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0063]

[0064] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0065] Here, v is selected from a number that is at least 0.

[0066] In the structure represented by formula (I), R6 is hydrogen.

[0067] In the structure represented by formula (I), R6 is an optionally substituted methyl group.

[0068] In the structure represented by formula (I), R6 is a methyl group substituted with fluorine.

[0069] In the structure represented by formula (I), R6 is a trifluoromethyl group.

[0070] In the structure represented by formula (I), R6 is an optionally substituted cycloalkyl group.

[0071] In the structure represented by formula (I), R6 is an optionally substituted cyclopropyl group.

[0072] In the structure represented by formula (I), R7 is hydrogen.

[0073] In the structure represented by formula (I), R6 and R7 together with the atoms to which they are attached form an optionally substituted cyclopropyl group.

[0074] In the structure represented by formula (I), R6 and R7 together with the atoms to which they are attached form an optionally substituted cyclobutyl group.

[0075] In the structure represented by formula (I), v is 0.

[0076] In the structure represented by formula (I), v is 1.

[0077] In the structure shown in formula (I), the L5 is selected from the following groups: Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0078] In the ligand conjugate of the present application, the Ab is an antibody or an antigen-binding fragment thereof.

[0079] In the ligand conjugate of the present application, the antibody is selected from the following group: murine antibody, chimeric antibody, humanized antibody and fully human antibody.

[0080] In the ligand conjugate of the present application, the antibody is a monoclonal antibody.

[0081] In the ligand conjugate of the present application, the antigen-binding fragment is selected from the following groups: Fab, Fab′, Fv fragment, F(ab′) 2 , F(ab) 2 , scFv, di-scFv, VHH and dAb.

[0082] In the ligand conjugate of the present application, the Ab comprises a HER2 antibody and / or a TROP2 antibody.

[0083] In the ligand conjugate of the present application, wherein the Ab comprises HCDR1, HCDR2 and HCDR3 of the heavy chain variable region, the amino acid sequence of the HCDR1 is shown in SEQ ID NO: 1, the amino acid sequence of the HCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of the HCDR3 is shown in SEQ ID NO: 3.

[0084] In the ligand conjugate of the present application, wherein the Ab comprises LCDR1, LCDR2 and LCDR3 of the light chain variable region, the amino acid sequence of the LCDR1 is shown in SEQ ID NO: 4, the amino acid sequence of the LCDR2 is shown in SEQ ID NO: 5, and the amino acid sequence of the LCDR3 is shown in SEQ ID NO: 6.

[0085] In the ligand conjugate of the present application, the Ab comprises a heavy chain variable region, and the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 7.

[0086] In the ligand conjugate of the present application, the Ab comprises a light chain variable region, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 8.

[0087] In the ligand conjugate of the present application, the Ab comprises a heavy chain, and the amino acid sequence of the heavy chain is shown in SEQ ID NO:9.

[0088] In the ligand conjugate of the present application, the Ab comprises a light chain, and the amino acid sequence of the light chain is shown in SEQ ID NO: 10.

[0089] In the ligand conjugate of the present application, wherein the Ab comprises HCDR1, HCDR2 and HCDR3 of the heavy chain variable region, the amino acid sequence of the HCDR1 is shown in SEQ ID NO: 11, the amino acid sequence of the HCDR2 is shown in SEQ ID NO: 12, and the amino acid sequence of the HCDR3 is shown in SEQ ID NO: 13.

[0090] In the ligand conjugate of the present application, wherein the Ab comprises LCDR1, LCDR2 and LCDR3 of the light chain variable region, the amino acid sequence of the LCDR1 is shown in SEQ ID NO: 14, the amino acid sequence of the LCDR2 is shown in SEQ ID NO: 15, and the amino acid sequence of the LCDR3 is shown in SEQ ID NO: 16.

[0091] In the ligand conjugate of the present application, the Ab comprises a heavy chain variable region, and the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 17.

[0092] In the ligand conjugate of the present application, the Ab comprises a light chain variable region, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 18.

[0093] In the ligand conjugate of the present application, the Ab comprises a heavy chain, and the amino acid sequence of the heavy chain is shown in SEQ ID NO: 19.

[0094] In the ligand conjugate of the present application, the Ab comprises a light chain, and the amino acid sequence of the light chain is shown in SEQ ID NO: 20.

[0095] On the other hand, the present application also provides a ligand conjugate or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate is selected from the following groups of structures:

[0096]

[0097]

[0098]

[0099]

[0100]

[0101] Wherein Ab is a ligand, a is a number greater than 0, and a is a decimal or an integer.

[0102] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate comprises a structure represented by formula (II):

[0103]

[0104] in,

[0105] R1 and R2 are each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0106] Alternatively, R1 and R2 together with the carbon atom to which they are attached form a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0107] Lx is a connecting group, wherein Lx is L1x -L2-L3-L4-L5-, the L 1x Can be linked directly or indirectly to a ligand.

[0108] In one embodiment, the structure represented by formula (II) comprises the structure represented by formula (II-a):

[0109]

[0110] In one embodiment, the structure represented by formula (II) comprises the structure represented by formula (II-b):

[0111]

[0112] In the structure shown in formula (II), the L 1x It can be directly or indirectly linked to the sulfhydryl group of the ligand.

[0113] In the structure shown in formula (II), the L 1x is optionally substituted

[0114] In the structure represented by formula (II), the L2 comprises a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-,

[0115] X1 is selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic and optionally substituted alicyclic,

[0116] wherein m1, m2 and n are each independently selected from an integer of at least 0, and p is selected from an integer of 2 to 8.

[0117] In the structure represented by formula (II), the L2 comprises an optionally substituted -(CH2CH2O) n -C(O)-.

[0118] In the structure represented by formula (II), n is 2.

[0119] In the structure shown in formula (II), L2 is optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-.

[0120] In the structure represented by formula (II), X1 is selected from the group consisting of -O- and optionally substituted -C(O)-NH-.

[0121] In the structure represented by formula (II), m1 is 2.

[0122] In the structure represented by formula (II), m2 is 2.

[0123] In the structure represented by formula (II), X1 is a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group.

[0124] In the structure represented by formula (II), X1 is an optionally substituted phenyl group.

[0125] In the structure represented by formula (II), X1 is an optionally substituted pyridyl group.

[0126] In the structure represented by formula (II), m1 is 0.

[0127] In the structure represented by formula (II), m2 is 1.

[0128] In the structure shown in formula (II), X1 is optionally substituted

[0129] In the structure represented by formula (II), X1 is an optionally substituted cyclohexyl group.

[0130] In the structure represented by formula (II), m1 is 1.

[0131] In the structure represented by formula (II), m2 is 0.

[0132] In the structure shown in formula (II), L2 is optionally substituted -(CH2) p -C(O)-.

[0133] In the structure represented by formula (II), p is 5.

[0134] In the structure shown in formula (II), the L2 is selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0135] In the structure represented by formula (II), L3 is a peptide residue.

[0136] In the structure represented by formula (II), L3 is a peptide residue composed of amino acids selected from the following group: phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid and glycine.

[0137] In the structure represented by formula (II), L3 is a peptide residue consisting of amino acids selected from the group consisting of glycine, phenylalanine, valine and citrulline.

[0138] In the structure represented by formula (II), L3 is a peptide residue selected from the following group: -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-) and -valine-citrulline-(-Val-Cit-).

[0139] In the structure represented by formula (II), the L3 comprises a structure selected from the following group:

[0140]

[0141] In the structure shown in formula (II), the L4 is an optionally substituted -L 4a -NR4-CH2-L 4b -,

[0142] L 4a Does not exist or L 4a is optionally substituted

[0143] L 4b Does not exist or L 4b is optionally substituted

[0144] R4 and R5 are each independently selected from the group consisting of hydrogen and optionally substituted alkyl.

[0145] In the structure shown in formula (II), the L4 is optionally substituted

[0146] In the structure shown in formula (II), the L4 is optionally substituted

[0147] In the structure shown in formula (II), the L4 is optionally substituted

[0148] In the structure shown in formula (II), the L4 is optionally substituted

[0149] In the structure represented by formula (II), R4 is selected from the following group: hydrogen and optionally substituted methyl.

[0150] In the structure represented by formula (II), R5 is selected from the following group: hydrogen and optionally substituted methyl.

[0151] In the structure shown in formula (II), the L4 is selected from the following groups: Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0152] In the structure shown in formula (II), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0153]

[0154] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0155] Here, v is selected from a number that is at least 0.

[0156] In the structure shown in formula (II), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0157]

[0158] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0159] Here, v is selected from a number that is at least 0.

[0160] In the structure shown in formula (II), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0161]

[0162] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0163] Here, v is selected from a number that is at least 0.

[0164] In the structure represented by formula (II), R6 is hydrogen.

[0165] In the structure represented by formula (II), R6 is an optionally substituted methyl group.

[0166] In the structure represented by formula (II), R6 is a methyl group substituted with fluorine.

[0167] In the structure represented by formula (II), R6 is a trifluoromethyl group.

[0168] In the structure represented by formula (II), R6 is an optionally substituted cycloalkyl group.

[0169] In the structure represented by formula (II), R6 is an optionally substituted cyclopropyl group.

[0170] In the structure represented by formula (II), R7 is hydrogen.

[0171] In the structure represented by formula (II), R6 and R7 together with the atoms to which they are attached form an optionally substituted cyclopropyl group.

[0172] In the structure represented by formula (II), R6 and R7 together with the atoms to which they are attached form an optionally substituted cyclobutyl group.

[0173] In the structure represented by formula (II), v is 0.

[0174] In the structure represented by formula (II), v is 1.

[0175] In the structure shown in formula (II), the L5 is selected from the following groups: Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0176] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate is selected from the following groups of structures:

[0177]

[0178]

[0179]

[0180]

[0181] On the other hand, the present application also provides a linker as shown in formula (L-1), which is used to obtain a ligand-drug conjugate formed by connecting a drug unit to a ligand via the linker:

[0182] -L1-L2-L3-L4-L5-(L-1),

[0183] Wherein, L1 is optionally substituted

[0184] The L2 is selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)- and optionally substituted -(CH2CH2O) n -C(O)-,

[0185] X1 is selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic and optionally substituted alicyclic,

[0186] wherein m1, m2 and n are each independently selected from an integer of at least 0,

[0187] In the structure represented by formula (L-1), n ​​is 2.

[0188] In the structure represented by formula (L-1), X1 is selected from the group consisting of -O- and optionally substituted -C(O)-NH-.

[0189] In the structure represented by formula (L-1), m1 is 2.

[0190] In the structure represented by formula (L-1), m2 is 2.

[0191] In the structure represented by formula (L-1), X1 is a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group.

[0192] In the structure represented by formula (L-1), X1 is an optionally substituted phenyl group.

[0193] In the structure represented by formula (L-1), X1 is an optionally substituted pyridyl group.

[0194] In the structure represented by formula (L-1), m1 is 0.

[0195] In the structure represented by formula (L-1), m2 is 1.

[0196] In the structure represented by formula (L-1), X1 is optionally substituted

[0197] In the structure represented by formula (L-1), X1 is an optionally substituted cyclohexyl group.

[0198] In the structure represented by formula (L-1), m1 is 1.

[0199] In the structure represented by formula (L-1), m2 is 0.

[0200] In the structure shown in formula (L-1), the L2 is selected from the following groups: Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0201] In the structure represented by formula (L-1), L3 is a peptide residue selected from the following group: -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-) and -valine-citrulline-(-Val-Cit-).

[0202] In the structure represented by formula (L-1), L3 is a structure selected from the following group:

[0203]

[0204] In the structure represented by formula (L-1), L4 is an optionally substituted -L 4a -NR4-CH2-L 4b -,

[0205] L 4a Does not exist or L 4a is optionally substituted

[0206] L 4b Does not exist or L 4b is optionally substituted

[0207] R4 and R5 are each independently selected from the group consisting of hydrogen and optionally substituted alkyl.

[0208] In the structure shown in formula (L-1), the L4 is optionally substituted

[0209] In the structure shown in formula (L-1), the L4 is selected from the following groups: Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0210] In the structure shown in formula (L-1), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0211]

[0212] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0213] Here, v is selected from a number that is at least 0.

[0214] In the structure shown in formula (L-1), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0215]

[0216] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0217] Here, v is selected from a number that is at least 0.

[0218] In the structure shown in formula (L-1), the L5 is optionally substituted The L5 is directly connected to the following structure:

[0219]

[0220] R6 and R7 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 together with the atoms to which they are attached form an optionally substituted cycloalkyl,

[0221] Here, v is selected from a number that is at least 0.

[0222] In the structure represented by formula (L-1), R6 is hydrogen.

[0223] In the structure represented by formula (L-1), R6 is an optionally substituted methyl group.

[0224] In the structure represented by formula (L-1), R6 is a methyl group substituted with fluorine.

[0225] In the structure represented by formula (L-1), R6 is a trifluoromethyl group.

[0226] In the structure represented by formula (L-1), R6 is an optionally substituted cycloalkyl group.

[0227] In the structure represented by formula (L-1), R7 is hydrogen.

[0228] In the structure represented by formula (L-1), R6 and R7 together with the atoms to which they are attached form an optionally substituted cyclopropyl group.

[0229] In the structure represented by formula (L-1), R6 and R7 together with the atoms to which they are attached form an optionally substituted cyclobutyl group.

[0230] In the structure represented by formula (L-1), v is 0.

[0231] In the structure represented by formula (L-1), v is 1.

[0232] In the structure shown in formula (L-1), the L5 is selected from the following groups: Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0233] On the other hand, the present application also provides a linker or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the linker comprises a structure selected from the following group:

[0234]

[0235]

[0236] On the other hand, the present application also provides a linker as shown in formula (L-2), which is used to obtain a ligand-drug conjugate formed by connecting the drug unit to the ligand via the linker:

[0237] -L1-L2-L3-L4-L5-(L-2),

[0238] L1 is optionally substituted

[0239] L2 is a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0240] L3 is a structure selected from the following group:

[0241] L4 is optionally substituted -L 4a -NR4-CH2-L 4b -,

[0242] L 4a Does not exist or L 4a is optionally substituted

[0243] L 4b Does not exist or L 4b is optionally substituted L 4a With L 4b Not existing at the same time,

[0244] R4 and R5 are each independently selected from the group consisting of hydrogen and optionally substituted alkyl,

[0245] The L5 is a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0246] In the structure shown in formula (L-2), the L4 is optionally substituted

[0247] In the structure shown in formula (L-2), the L4 is optionally substituted

[0248] In the structure shown in formula (L-2), the L4 is optionally substituted

[0249] In the structure shown in formula (L-2), the L4 is selected from the following groups: Optionally substituted Optionally substituted and optionally substituted

[0250] On the other hand, the present application also provides a linker or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the linker comprises a structure selected from the following group:

[0251]

[0252] On the other hand, the present application also provides a pharmaceutical composition containing the ligand conjugate of the present application, or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically acceptable salt, prodrug or solvate, and / or the compound of the present application, and optionally a pharmaceutically acceptable carrier.

[0253] On the other hand, the present application also provides the use of the ligand conjugate of the present application, or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically acceptable salt, prodrug or solvate, the compound of the present application, and / or the pharmaceutical composition of the present application in the preparation of a medicament for treating and / or preventing tumors.

[0254] In one embodiment, the tumor is selected from the group consisting of tumors associated with expression of the following targets: HER2 and TROP2.

[0255] In one embodiment, the tumor associated with the target expression includes a tumor with high expression of the target and / or a tumor positive for the target.

[0256] In one embodiment, the tumor comprises a solid tumor and / or a hematological tumor.

[0257] In one embodiment, the tumor is selected from the group consisting of breast cancer, gastric cancer, ovarian cancer, bladder cancer, colorectal cancer, endometrial cancer, kidney cancer, lung cancer, pancreatic cancer, prostate cancer, and thyroid cancer.

[0258] In one embodiment, the tumor is selected from the group consisting of breast cancer, ovarian cancer, cervical cancer, endometrial cancer, urothelial cancer, lung cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, bladder cancer, kidney cancer, pancreatic cancer, thyroid cancer, and head and neck cancer.

[0259] Those skilled in the art can easily discern other aspects and advantages of the present application from the detailed description below. In the detailed description below, only exemplary embodiments of the present application are shown and described. As will be appreciated by those skilled in the art, the content of the present application enables those skilled in the art to modify the disclosed specific embodiments without departing from the spirit and scope of the invention to which the present application relates. Accordingly, the description in the specification of the present application is merely exemplary and not restrictive. DETAILED DESCRIPTION

[0260] The following describes the implementation of the present invention through specific embodiments. People familiar with this technology can easily understand other advantages and effects of the present invention from the contents disclosed in this specification.

[0261] Definition of terms

[0262] In this application, the term "ligand" generally refers to a macromolecular compound that can recognize and bind to an antigen or receptor associated with a target cell. The function of the ligand can be to present the drug to the target cell population bound to the ligand. These ligands include but are not limited to protein hormones, lectins, growth factors, antibodies or other molecules that can bind to cells, receptors and / or antigens. In this application, the ligand can be represented by Ab, and the ligand antigen forms a connection bond with the linker through a heteroatom on the ligand. It can be an antibody or an antigen-binding fragment thereof. The antibody can be selected from a chimeric antibody, a humanized antibody, a fully human antibody or a murine antibody; the antibody can be a monoclonal antibody. For example, the antibody can be an antibody or an antigen-binding fragment thereof that targets a target selected from the following groups: HER2 and TROP2.

[0263] In this application, the terms "Trop2" and "TROP2" generally refer to a single-pass transmembrane type I cell membrane protein. In this application, the term "Trop2" may also encompass homologs, variants, and isoforms of Trop 2, including spliced ​​isoforms. The term "Trop" also includes proteins having one or more sequences of Trop 2 homologs, variants, and isoforms, as well as fragments of the sequences, as long as they are variant proteins (including isoforms). Trop2 may be human Trop2. For example, Uniprot Accession No. P09758 provides a description of Trop2 and its sequence.

[0264] In this application, the term "HER2" generally refers to human epidermal growth factor receptor 2 (HER2). For example, the term "HER2" refers to any natural HER2 from any human source. The term also encompasses "full-length" and unprocessed HER2 and any form of HER2 (e.g., mature protein) processed in the cell. The term also encompasses naturally occurring variants and isoforms of HER2, such as splice variants or allelic variants. For example, Uniprot accession number P04626 provides a description of HER2 and sequences.

[0265] In this application, the term "trastuzumab" generally refers to an antibody that targets HER2. For example, trastuzumab can be described in US20060275305A1. In this application, trastuzumab can refer to an antibody or antigen-binding fragment comprising the heavy chain variable region CDR1-3 and light chain variable region CDR1-3 of trastuzumab. In this application, trastuzumab can refer to an antibody or antigen-binding fragment comprising the heavy chain variable region and light chain variable region of trastuzumab.

[0266] In this application, the term "peptide residue" generally refers to a residue comprising one or more amino acid residues linked together. For example, one or more amino acids in a polypeptide residue may be optionally substituted. For example, a polypeptide residue herein may comprise glycine-glycine-phenylalanine-glycine (Gly-Gly-Phe-Gly).

[0267] In this application, the term "Drug unit" generally refers to a chemical moiety that is directly or indirectly conjugated to an antibody or antigen-binding fragment to form an immunoconjugate. For example, a "Drug unit" includes, but is not limited to, a compound with anti-tumor activity as described herein. For example, a Drug unit includes a topoisomerase inhibitor.

[0268] As used herein, the term "compound with anti-tumor activity" generally refers to a compound that has the ability to reduce the proliferation rate, viability, or metastatic activity of tumor cells. For example, anti-tumor activity can be demonstrated by a decrease in the growth rate of abnormal cells or a stabilization or reduction in tumor size during treatment, or by a prolonged survival period resulting from treatment compared to a control without treatment. Anti-tumor activity can be assessed using recognized in vitro or in vivo tumor models, such as xenograft models.

[0269] In this application, the term "topoisomerase inhibitor" generally refers to compounds including topoisomerase I inhibitors and topoisomerase II inhibitors or their derivatives. Examples of topoisomerase I inhibitors include, but are not limited to, camptothecin and its analogs. For example, topoisomerase can refer to an enzyme that corrects the number of DNA strands by cutting the phosphodiester bonds in one or both strands of DNA and then rewinding and sealing them.

[0270] In this application, the term "camptothecin analogue" generally refers to a compound that is structurally similar to or derived from camptothecin. For example, the structure of camptothecin can be recorded in CAS accession number 7689-03-4. For example, a camptothecin analogue can refer to isatecan (CAS accession number 171335-80-1).

[0271] In this application, the term "tumor" generally refers to any new, pathological tissue growth. For the purposes of this application, angiogenesis is part of the characteristics of tumors. Tumors can be benign or malignant. The term "tumor" is generally used to refer to benign or malignant tumors, while the term "cancer" is generally used to refer to malignant tumors, which can be metastatic or non-metastatic. For research purposes, these tumor tissues can be isolated from readily available sources using methods well known to those skilled in the art.

[0272] In the present application, the term "alkyl" generally refers to a residue derived from an alkane by removing a hydrogen atom. An alkyl group can be substituted or non-substituted, substituted or non-substituted. The term "alkyl" generally refers to a saturated straight or branched aliphatic hydrocarbon group having a residue derived from the same carbon atom or two different carbon atoms of the parent alkane by removing a hydrogen atom, and can be a straight or branched group containing 1 to 20 carbon atoms, for example, a chain alkyl group containing 1 to 12 carbon atoms, for example, 1 to 6 carbon atoms. Non-limiting examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, propyl, butyl, etc. The alkyl group may be substituted or unsubstituted, substituted or unsubstituted, for example, when substituted, the substituent may be substituted at any available point of attachment, and the substituent may be independently selected from one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio and oxo, for example, hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H or C 1-6 Aliphatic group.

[0273] In this application, the term "alkylene" generally refers to a saturated straight-chain or branched aliphatic hydrocarbon group having two residues derived from the same carbon atom or two different carbon atoms of an alkane group, and can be a straight-chain or branched group containing 1 to 20 carbon atoms. For example, the term "methylene" can refer to a residue derived from a group containing 1 carbon atom by removing two hydrogen atoms. The methylene group can be substituted or unsubstituted, substituted or unsubstituted; for example, an alkylene group containing 1 to 12 carbon atoms, for example, an alkylene group containing 1 to 6 carbon atoms. Non-limiting examples of alkylene groups include, but are not limited to, methylene (-CH2-), 1,1-ethylene (-CH(CH3)-), 1,2-ethylene (-CH2CH2)-, 1,1-propylene (-CH(CH2CH3)-), 1,2-propylene (-CH2CH(CH3)-), 1,3-propylene (-CH2CH2CH2-), 1,4-butylene (-CH2CH2CH2CH2-), and 1,5-butylene (-CH2CH2CH2CH2CH2-), and the like. Alkylene may be substituted or unsubstituted, substituted or unsubstituted, for example, when substituted, the substituent may be substituted at any available point of attachment, and the substituent may be independently selected from one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio and oxo, for example, hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H or C 1-6 Aliphatic groups. Methylene or alkylene groups may be substituted or unsubstituted.

[0274] In this application, the term "alkenyl" generally refers to a straight or branched hydrocarbon group containing one or more double bonds. Illustrative examples of alkenyl include allyl, homoallyl, vinyl, crotyl, butenyl, pentenyl, and hexenyl. C 2-6 Illustrative examples of alkenyl groups include butadienyl, pentadienyl, hexadienyl and hexatrienyl and their branched forms. The position of the unsaturated bond (double bond) can be at any position of the carbon chain. The alkenyl group can be substituted or unsubstituted.

[0275] In this application, the term "alkenylene" generally refers to a residue derived from an alkene carbon atom by removing two hydrogen atoms. For example, it can be allylene, vinylene, butenylene, pentenylene and hexenylene. Alkenylene can be substituted or unsubstituted.

[0276] In the present application, the term "alkynyl" generally refers to an unsaturated straight-chain or branched alkynyl group, such as ethynyl, 1-propynyl, propargyl, butynyl, etc. Alkynyl groups can be substituted or unsubstituted.

[0277] In this application, the term "alkynylene" generally refers to a residue derived from a carbon atom of an alkyne by removing two hydrogen atoms. For example, it may be ethynylene, propynylene, propargylene, butynylene, etc. Alkynylenes may be substituted or unsubstituted.

[0278] In this application, the term "aryl" generally refers to a residue derived from an aromatic ring by removing a hydrogen atom. The term "aromatic ring" can refer to a 6- to 14-membered all-carbon monocyclic ring or a fused polycyclic ring (i.e., a ring sharing adjacent pairs of carbon atoms) with a conjugated π electron system, which can be 6- to 10-membered, such as benzene and naphthalene. The aromatic ring can be fused to a heteroaryl, heterocyclyl, or cycloalkyl ring, wherein the ring connected to the parent structure is the aryl ring. Aryl groups can be substituted or unsubstituted. When substituted, the substituents can be one or more of the following groups independently selected from the following groups: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, and heterocycloalkylthio. Aryl groups can be substituted or unsubstituted.

[0279] In this application, the term "arylene" generally refers to a residue derived from a carbon atom in an aromatic ring by removing two hydrogen atoms. Examples include phenylene and naphthylene. Arylene can be substituted or unsubstituted.

[0280] As used herein, the term "heteroaryl" generally refers to a residue derived from a carbon atom in a heteroaromatic ring by removing a hydrogen atom. The term "heteroaromatic ring" refers to a heteroaromatic system containing 1 to 4 heteroatoms and 5 to 14 ring atoms, wherein the heteroatoms may be selected from the group consisting of oxygen, sulfur, and nitrogen. Heteroaryl groups may be 5 to 10-membered, and may be 5- or 6-membered, such as furanyl, thienyl, pyridyl, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, imidazolyl, tetrazolyl, and the like. The heteroaryl ring may be fused to an aryl, heterocyclyl, or cycloalkyl ring, wherein the ring attached to the parent structure is the heteroaryl ring. Heteroaryl can be optionally substituted or unsubstituted. When substituted, the substituent can be one or more of the following groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, and heterocycloalkylthio. Heteroaryl can be substituted or unsubstituted.

[0281] In this application, the term "heteroarylene" generally refers to a residue derived from a carbon atom of a heteroaromatic ring by removing two hydrogen atoms. For example, it may be furanylene, thienylene, pyridylene, pyrrolylene, pyrimidylene, pyrazinylene, imidazolylene, tetrazolylene, etc. The heteroarylene group may be substituted or unsubstituted.

[0282] As used herein, the term "alicyclic group" generally refers to a residue derived by removing a hydrogen atom from the same carbon atom or multiple different carbon atoms of an aliphatic ring. The term "cycloalkane" generally refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon, wherein the carbocyclic ring contains 3 to 20 carbon atoms, may contain 3 to 12 carbon atoms, may contain 3 to 10 carbon atoms, or may contain 3 to 8 carbon atoms. Non-limiting examples of alicyclic groups include cyclopropane, cyclobutane, cyclopentane, cyclopentenyl, cyclohexane, cyclohexenyl, cyclohexadienyl, cycloheptane, cycloheptatrienyl, cyclooctanyl, and the like; polycyclic carbocyclic rings may include spiro, fused, and bridged carbocyclic rings. Alicyclic groups may be substituted or unsubstituted. As used herein, the term "carbocyclic group" generally refers to a residue derived by removing a hydrogen atom from a carbon atom of a carbocyclic ring. The term "carbocycle" generally refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon ring, wherein the carbocycle contains 3 to 20 carbon atoms, may contain 3 to 12 carbon atoms, may contain 3 to 10 carbon atoms, and may contain 3 to 8 carbon atoms. Non-limiting examples of monocyclic carbocycles include cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclohexadiene, cycloheptane, cycloheptatriene, cyclooctane, and the like; polycyclic carbocycles may include spirocyclic, fused, and bridged carbocycles. Carbocyclyl groups may be substituted or unsubstituted. In some cases, alicyclic and carbocyclic rings may be used interchangeably.

[0283] As used herein, the term "partially unsaturated" generally refers to a cyclic structure containing at least one double or triple bond between the ring molecules. The term "partially unsaturated" encompasses cyclic structures with multiple unsaturations, but is not intended to include aromatic or heteroaromatic rings as defined herein. The term "unsaturated" refers to a moiety having one or more degrees of unsaturation.

[0284] In this application, the term "alicyclic group" generally refers to a residue derived from a carbon atom of an alicyclic ring by removing two hydrogen atoms. Examples include cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cyclohexadienylene, cycloheptanylene, cycloheptatrienylene, and cyclooctanylene. Polycyclic carbocycles may include spiro, fused, and bridged carbocycles. Alicyclic groups may be substituted or unsubstituted.

[0285] In this application, the term "alicyclic group" generally refers to a stable, non-aromatic, 3- to 7-membered monocyclic carbocyclic ring structure, a fused 7- to 10-membered bicyclic heterocyclic ring structure, or a bridged 6- to 10-membered bicyclic heterocyclic ring structure. These ring structures may be saturated or partially saturated and, in addition to carbon atoms, may contain one or more heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen. For example, these ring structures may contain 1 to 4 heteroatoms as defined above. When used to refer to atoms in an alicyclic heterocyclic ring structure, the term "nitrogen" may include substituted nitrogen. For example, an alicyclic heterocyclic group may include a "heterocycloalkyl" group, which may refer to a stable, non-aromatic, 3- to 7-membered monocyclic carbocyclic ring structure, a fused 7- to 10-membered bicyclic heterocyclic ring structure, or a bridged 6- to 10-membered bicyclic heterocyclic ring structure. In addition to carbon atoms, these ring structures may contain one or more heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen. For example, these ring structures may contain 1 to 4 heteroatoms as defined above. Heterocycloalkyl groups may be substituted or unsubstituted. Alicyclic heterocyclic groups may be substituted or unsubstituted.

[0286] In the present application, the term "aliphatic heterocyclic group" generally refers to a residue derived from a carbon atom of an aliphatic heterocyclic ring by removing two hydrogen atoms. The aliphatic heterocyclic group may be substituted or unsubstituted.

[0287] In this application, the term "optional" or "optionally" generally means that the subsequently described event or circumstance can but need not occur, and the description includes instances where the event or circumstance occurs or does not occur. For example, "a heterocyclic group optionally substituted with an alkyl group" means that the alkyl group can but need not be present, and the description includes instances where the heterocyclic group is substituted with an alkyl group and instances where the heterocyclic group is not substituted with an alkyl group.

[0288] In this application, the term "substituted" generally refers to one or more hydrogen atoms in a group, for example up to 5, for example 1 to 3 hydrogen atoms, which are independently replaced by a corresponding number of substituents. The substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) whether substitution is possible or not without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (e.g., olefinic) bond. For example, the optionally substituted substituents are optionally selected from hydrogen, protium, deuterium, tritium, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, and oxo, and can be, for example, hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic group.

[0289] In this application, as known to those skilled in the art, terms such as "alkyl", "alkenyl", "cycloalkyl", etc. may be preceded by an identifier to indicate the number of atoms present in the group in a particular case, for example, C1-C4 alkyl, C3-C7 cycloalkyloxy, C1-C4 alkylcarbonylamino, etc., and the subscript number after "C" indicates the number of carbon atoms present in the group. For example, C3 alkyl refers to an alkyl group with three carbon atoms (e.g., n-propyl, isopropyl); C 1-10 In the examples, the members of the group may have any number of carbon atoms falling within the range of 1-10.

[0290] One or more hydrogen atoms, for example up to 5, for example 1 to 3, in a group are independently replaced by a corresponding number of substituents. The substituents are only in their possible chemical positions, and a person skilled in the art can determine (by experiment or theory) which substitutions are possible or impossible without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (e.g., olefinic) bond.

[0291] In this application, the term "compound" generally refers to a substance having two or more different elements. For example, the compound of the present application may be an organic compound, for example, the compound of the present application may be a compound with a molecular weight of less than 500, a compound with a molecular weight of less than 1000, a compound with a molecular weight of more than 1000, or a compound with a molecular weight of more than 1000 or more than 10000. In this application, a compound may also refer to a compound connected by chemical bonds, for example, a compound in which one or more molecules with a molecular weight of less than 1000 are connected to a biomacromolecule by a chemical bond, and the biomacromolecule may be a polysaccharide, protein, nucleic acid, polypeptide, etc. For example, the compound of the present application may include a compound in which a protein is connected to one or more molecules with a molecular weight of less than 1000, a compound in which a protein is connected to one or more molecules with a molecular weight of less than 10000, or a compound in which a protein is connected to one or more molecules with a molecular weight of less than 10000.

[0292] In this application, the term "comprising" generally refers to including the features specified but not excluding other elements. The terms "above" and "below" generally refer to including the number.

[0293] In this application, the term "about" generally refers to a variation within a range of 0.5%-10% above or below the specified value, for example, a variation within a range of 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% above or below the specified value.

[0294] In the present application, the compound of the present application includes its tautomer, mesomorph, racemate, enantiomer and / or diastereomer of compound.In the present application, the term "diastereomer" generally refers to a stereoisomer with two or more chiral centers and whose molecules are not mirror images of each other. Diastereomers can have different physical properties, for example, melting point, boiling point, spectral properties and reactivity. In the present application, the term "tautomer" or "tautomeric form" is used interchangeably, generally referring to structural isomers of different energies that can be converted to each other by low energy barriers (low energy barrier). For example, proton tautomers (protontautomers) (also referred to as prototropic tautomers (prototropic tautomers)) include the mutual conversions carried out by proton migration, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers (valence tautomers) include the mutual conversions carried out by the reorganization of some bonding electrons. As used herein, the term "meso" generally refers to a molecule containing asymmetric atoms but possessing symmetry such that the total optical rotation is zero. The term "racemate" or "racemic mixture" refers to a composition composed of equimolar amounts of two enantiomeric species.

[0295] In the present application, some atoms of the compounds of the present application may appear in more than one isotopic form. For example, hydrogen may appear in the form of protium ( 1 H), deuterium ( 2 H) and tritium ( 3 H), carbon can exist in three different isotopes ( 12 C. 13 C and 14 C) naturally occurring. Examples of isotopes that can be incorporated into the compounds of the present application also include, but are not limited to 15 N. 18 O. 17 O. 18 F. 32 P. 33 P. 129 I. 131 I. 123 I. 124 I. 125 I, or similar isotopes. Therefore, the compounds of the present application may be enriched in one or more of these isotopes relative to the natural abundance of these isotopes. As known to those skilled in the art, such isotopically enriched compounds can be used for a variety of purposes. For example, using heavy isotopes such as deuterium ( 2 Deuterium (H) substitution may offer certain therapeutic advantages, possibly due to greater metabolic stability. 2The natural abundance of deuterium (H) is about 0.015%. Therefore, there is one deuterium atom for approximately every 6500 hydrogen atoms in nature. Therefore, the deuterium-containing compounds of the present application have a deuterium abundance greater than 0.015% at one or more positions (as the case may be). Unless otherwise indicated, the structures described herein may also include compounds that differ only in the presence or absence of one or more isotopically enriched atoms. For example, compounds whose remaining portions are consistent with the present structure except that hydrogen atoms are replaced by deuterium or tritium, or carbon atoms are replaced by carbon 13 or carbon 14, are within the scope of the present application.

[0296] As used herein, the term "pharmaceutical composition" generally refers to a mixture containing one or more compounds described herein, or their physiologically / pharmaceutically acceptable salts or prodrugs, and other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. Pharmaceutical compositions can facilitate administration to an organism, facilitating absorption of the active ingredient and thereby exerting its biological activity. Conventional pharmaceutical compositions can be prepared using techniques commonly used in the art.

[0297] In this application, the term "pharmaceutically acceptable salt" or "pharmaceutically usable salt" generally refers to a salt of the compound or ligand-drug conjugate of the present application, or a salt of the compound described in the present application. Such salts may be safe and / or effective when used in mammals and may have the desired biological activity. The antibody-antibody drug conjugate compound of the present application may form a salt with an acid. Non-limiting examples of pharmaceutically acceptable salts include: hydrochloride, hydrobromide, hydroiodide, sulfate, bisulfate, citrate, acetate, succinate, ascorbate, oxalate, nitrate, sorbate, hydrogen phosphate, dihydrogen phosphate, salicylate, hydrogen citrate, tartrate, maleate, fumarate, formate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, or p-toluenesulfonate.

[0298] In the present application, the term "conjugate" generally refers to a compound prepared by one or more chemical reactions of the compounds of the present application, or connected to each other through one or more connecting structures such as a bridge, a spacer, or a connecting part.

[0299] In this application, the term "pharmaceutically acceptable carrier" generally refers to a carrier for administering therapeutic agents, such as antibodies or polypeptides, genes and other therapeutic agents. The term refers to any pharmaceutical carrier that does not itself induce the production of antibodies harmful to the individual receiving the composition and can be administered without excessive toxicity. For example, a pharmaceutically acceptable carrier can be distinguished from a nucleic acid vector used to contain a target gene in genetic engineering. Suitable carriers can be large, slowly metabolized macromolecules, such as proteins, polysaccharides, polylactic acid, polyglycolic acid, polyamino acids, amino acid copolymers, lipid aggregates and inactivated viral particles. These carriers are well known to those skilled in the art. Pharmaceutically acceptable carriers in therapeutic compositions may include liquids, such as water, saline, glycerol and ethanol. Auxiliary substances, such as wetting agents or emulsifiers, pH buffer substances, etc., may also be present in these carriers.

[0300] In this application, "antibody" can generally cover monoclonal antibodies, polyclonal antibodies, dimers, multimers, multispecific antibodies (such as bispecific antibodies) and antibody fragments, as long as they show the desired biological activity. Antibodies can be mouse, human, humanized, chimeric antibodies or derived from other species. Antibodies are proteins produced by the immune system that can recognize and bind to specific antigens. Target antigens generally have a large number of binding sites, also known as epitopes, that are recognized by the CDRs of multiple antibodies. Each antibody that specifically binds to different epitopes has a different structure. Therefore, an antigen can have more than one corresponding antibody. Antibodies include full-length immunoglobulin molecules or immunologically active portions of full-length immunoglobulin molecules, i.e., molecules containing antigens or portions thereof that specifically bind to targets of interest, such targets including, but not limited to, cancer cells or cells that produce autoimmune antibodies associated with autoimmune diseases. The immunoglobulins described herein can be of any type (e.g., IgG, IgE, IgM, IgD, and IgA), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass of immunoglobulin molecules. Immunoglobulins can be derived from any species. However, in one aspect, the immunoglobulins are derived from humans, mice, or rabbits. "Antibody fragments" can comprise a portion of a full-length antibody, generally its antigen-binding region or variable region. Examples of antibody fragments include: Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; minibodies; fragments prepared from Fab expression libraries; anti-idiotypic (anti-Id) antibodies; CDRs (complementarity determining regions); and any of the above epitope-binding fragments that immunospecifically bind to cancer cell antigens, viral antigens, or microbial antigens; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. The antibodies that constitute the antibody-drug conjugates herein can retain their original antigen-binding ability in the wild-type state. Therefore, the antibodies in the present application can, for example, specifically bind to antigens. The antigens involved include, for example, tumor-associated antigens (TAAs), cell surface receptor proteins and other cell surface molecules, cell survival regulators, cell proliferation regulators, molecules related to tissue growth and differentiation (such as known or predicted functional), lymphokines, cytokines, molecules involved in cell cycle regulation, molecules involved in angiogenesis, and molecules related to angiogenesis (such as known antibodies). The antigens bound by antibodies can be one or a subset of the above categories, while other subsets contain other molecules / antigens with special properties (compared to the target antigen). Antibodies used in antibody drug conjugates include, but are not limited to, antibodies against cell surface receptors and tumor-associated antigens. Such tumor-associated antigens are well known in the industry and can be prepared by antibody preparation methods and information well known in the industry.These targets can be specifically expressed on the surface of one or more cancer cells, while being little or not expressed on the surface of one or more non-cancerous cells. Generally, such tumor-associated polypeptides can be more overexpressed on the surface of cancer cells than on the surface of non-cancerous cells.

[0301] In this application, the term "chimeric antibody" generally refers to an antibody formed by fusing the variable region of a murine antibody with the constant region of a human antibody, which can reduce the immune response induced by the murine antibody. To create a chimeric antibody, a hybridoma that secretes a murine-specific monoclonal antibody can be established. The variable region genes can then be cloned from the murine hybridoma cells. The constant region genes of a human antibody can then be cloned as needed. The murine variable region genes and the human constant region genes can then be linked to form a chimeric gene, which is then inserted into an expression vector. The chimeric antibody molecule can then be expressed in either eukaryotic or prokaryotic systems.

[0302] In this application, the term "humanized antibody", also known as CDR-grafted antibody, generally refers to antibodies produced by transplanting mouse CDR sequences into human antibody variable region frameworks, i.e., different types of human germline antibody framework sequences. This can overcome the heterologous reactions induced by chimeric antibodies due to the large amount of mouse protein components they carry. Such framework sequences can be obtained from public DNA databases or published references that include germline antibody gene sequences. For example, the germline DNA sequences of human heavy and light chain variable region genes can be found in the "VBase" human germline sequence database.

[0303] In this application, the terms "fully human antibody", "fully human antibody" or "completely human antibody" are also called "fully human monoclonal antibody", and the variable region and constant region of the antibody can be both human, eliminating immunogenicity and toxic side effects. The development of monoclonal antibodies has gone through four stages, namely: murine monoclonal antibodies, chimeric monoclonal antibodies, humanized monoclonal antibodies and fully human monoclonal antibodies. The antibody or ligand described in this application can be a fully human monoclonal antibody. Related technologies for the preparation of fully human antibodies can be: human hybridoma technology, EBV-transformed B lymphocyte technology, phage display technology (phage display), transgenic mouse antibody preparation technology (transgenic mouse) and single B cell antibody preparation technology, etc.

[0304] In the present application, term " CDR " generally refers to one of 6 hypervariable regions that mainly contribute to antigen combination in the variable domains of antibody.One of the most frequently used definitions of described 6 CDRs is provided by Kabat EA et al., Chothia et al. and MacCallum et al. As used in the present application, the Kabat definition of CDR can be applied to CDR1, CDR2 and CDR3 (CDR L1, CDR L2, CDR L3 or L1, L2, L3) of light chain variable domain, and CDR1, CDR2 and CDR3 (CDR H1, CDR H2, CDR H3 or H1, H2, H3) of heavy chain variable domain.

[0305] In the present application, the term "group capable of coupling with a thiol group" generally means that compound A has a thiol group, and compound B has a group capable of coupling with a thiol group, and compound B reacts with the thiol group of compound A through the group capable of coupling with a thiol group, thereby achieving the connection between compound A and compound B.

[0306] In the present application, the term "linker" generally refers to a chemical structure fragment or bond that is connected to one group at one end and to another group at the other end, and can also be connected to other linkers before being connected to the drug and / or ligand. The directly or indirectly connected ligand can refer to the group being directly connected to the ligand through a covalent bond, or it can be connected to the ligand through a linker. For example, the linker can be the structure shown in the linker described in the present application. For example, a chemical structure fragment or bond containing an acid-labile linker structure (such as a hydrazone), a protease-sensitive (such as a peptidase-sensitive) linker structure, a photolabile linker structure, a dimethyl linker structure, or a disulfide-containing linker structure can be used as a linker.

[0307] In this application, the term "linking group" generally refers to a group capable of connecting to another group. For example, a compound having a linking group can be connected to another group through a coupling reaction between the linking group and the other group. For example, a maleimide group can serve as a linking group.

[0308] In this application, the term "disease associated with the expression of a target" generally means that the occurrence and / or progression of the disease is associated with the expression level of the target. For example, the expression level of a target in cells from a disease area, such as a specific tissue or organ of a patient, is increased relative to the expression level of normal cells from the tissue or organ, i.e., highly expressed. Or, for example, the expression level of a target in cells from a disease area, such as a specific tissue or organ of a patient, is decreased relative to the expression level of normal cells from the tissue or organ, i.e., low expressed. Or, for example, cells from a disease area, such as a specific tissue or organ of a patient, express a target, i.e., are positive. Or, for example, cells from a disease area, such as a specific tissue or organ of a patient, do not express a target, i.e., are negative. For example, the characteristics of target expression can be determined by standard assays known in the art.

[0309] As used herein, the term "effective amount" generally refers to an amount of a therapeutic agent that treats, alleviates, or prevents a target disease or condition, or an amount that exhibits a detectable therapeutic or preventive effect. The precise effective amount for a given subject depends on the subject's size and health, the nature and extent of the condition, and the therapeutic agent and / or combination of therapeutic agents selected for administration. Therefore, it is not useful to specify an exact effective amount in advance. However, for a given condition, the effective amount can be determined by routine experimentation, which is within the judgment of the clinician.

[0310] Unless otherwise specified, all compounds mentioned in this application are intended to include all possible optical isomers, such as single chiral compounds, or mixtures of various chiral compounds (i.e., racemates). In all compounds of this application, each chiral carbon atom may optionally be in the R configuration or the S configuration, or a mixture of the R and S configurations.

[0311] In the present application, the term "compound of the present application" generally refers to the compound of the present application. The term also includes various crystal forms, pharmaceutically acceptable salts, hydrates or solvates of the compound of the present application.

[0312] When a trade name is used herein, the trade name is intended to include the trade name product formulation, its corresponding generic drug, and the active pharmaceutical ingredient of the trade name product.

[0313] Detailed Description of the Invention

[0314] In one aspect, the present application provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (I):

[0315] For example it could be

[0316]

[0317]

[0318] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0319] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0320] L may be an optionally substituted linker,

[0321] Ab may be a ligand, and a may be a number at least 0.

[0322] For example, in the structure shown in formula (I), the L may include a linker L1, which may be directly or indirectly connected to the ligand. For example, L1 in the structure represented by formula (I) may exist in an open ring form represented by the following formula.

[0323]

[0324] For example, in the structure shown in formula (I), the L may further comprise a linker L2. For example, the L2 may be directly or indirectly connected to the L1. For example, the L2 may comprise a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-, X1 can be selected from the following group: -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic group and optionally substituted alicyclic group, wherein m1, m2 and n can each independently be selected from a number of at least 0.

[0325] For example, in the structure shown in formula (I), the L2 may comprise an optionally substituted -(CH2CH2O) n -C(O)-. For example, wherein n can be 2.

[0326] For example, in the structure shown in formula (I), the L2 may comprise an optionally substituted -(CH2) m1 -X1-(CH2) m2-C(O)-. For example, X1 can be selected from the group consisting of -O- and optionally substituted -C(O)-NH-. For example, m1 can be 2. For example, m2 can be 2.

[0327] For example, in the structure represented by formula (I), X1 can include a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group. For example, X1 can include an optionally substituted phenyl group. For example, X1 can include an optionally substituted pyridyl group. For example, m1 can be 0. For example, m2 can be 1.

[0328] For example, in the structure shown in formula (I), X1 may include an optionally substituted heteroalicyclic group containing two oxygen atoms. For example, X1 may comprise an optionally substituted cyclohexyl group. For example, m1 may be 1. For example, m2 may be 0.

[0329] For example, in the structure shown in formula (I), the L2 may comprise an optionally substituted -(CH2) p -C(O)-. For example, p may be 5.

[0330] For example, in the structure shown in formula (I), the L2 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0331] For example, in the structure shown in formula (I), the L may further comprise a linker L3. For example, the L3 may be directly or indirectly connected to the L2. For example, the L3 may comprise a peptide residue.

[0332] For example, the L3 may comprise a peptide residue consisting of an amino acid selected from the group consisting of phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid, and glycine. For example, the L3 may comprise a peptide residue consisting of an amino acid selected from the group consisting of glycine, phenylalanine, valine, and citrulline. For example, the L3 may comprise a peptide residue selected from the group consisting of -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-), and -valine-citrulline-(-Val-Cit-).

[0333] For example, in the structure represented by formula (I), the L3 may comprise a structure selected from the following group:

[0334]

[0335] For example, in the structure represented by formula (I), the L may further comprise a linker L4. For example, the L4 may be directly or indirectly connected to the L3.

[0336] For example, in the structure shown in formula (I), the L4 may include an optionally substituted -L 4a -NR4-CH2-L 4b -, L 4a Can be absent or L 4a May contain optionally substituted L 4b Can be absent or L 4b May contain optionally substituted R4 and R5 may each independently be selected from the group consisting of hydrogen and optionally substituted alkyl.

[0337] For example, in the structure shown in formula (I), the L4 may include an optionally substituted For example, the L4 may comprise an optionally substituted For example, the L4 may comprise an optionally substituted For example, the L4 may comprise an optionally substituted For example, the R4 can be selected from the following group: hydrogen and an optionally substituted methyl group. For example, the R5 can be selected from the following group: hydrogen and an optionally substituted methyl group.

[0338] For example, in the structure shown in formula (I), the L4 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0339] For example, in the structure represented by formula (I), the L may further include a linker L5. For example, the L5 may be directly or indirectly connected to the L4.

[0340] For example, in the structure shown in formula (I), the L5 may include an optionally substituted R6 and R7 can each be independently selected from the following group: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cycloalkyl, wherein v can be selected from a number that is at least 0.

[0341] For example, in the structure shown in formula (I), R6 can be hydrogen. For example, R6 can be an optionally substituted methyl group. For example, R6 can be an optionally substituted halomethyl group. For example, R6 can be a methyl group substituted with fluorine. For example, R6 can be a trifluoromethyl group. For example, R6 can be an optionally substituted cycloalkyl group. For example, R6 can be an optionally substituted cyclopropyl group. For example, in the structure shown in formula (I), R7 can be hydrogen.

[0342] For example, in the structure shown in formula (I), R6 and R7 can form an optionally substituted cyclopropyl group together with the atom to which they are connected. For example, R6 and R7 can form an optionally substituted cyclobutyl group together with the atom to which they are connected. For example, v can be 0. For example, v can be 1.

[0343] For example, in the structure shown in formula (I), the L5 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0344] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (I):

[0345]

[0346] For example it could be

[0347]

[0348] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0349] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0350] L may be an optionally substituted linker, wherein L may comprise -L1-L2-L3-L4-L5-,

[0351] Ab may be a ligand, and a may be a number at least 0.

[0352] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (I):

[0353]

[0354] For example it could be

[0355]

[0356] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0357] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0358] L may be an optionally substituted linker, wherein L may comprise -L1-L2-L3-L4-L5-,

[0359] Ab can be a ligand, a can be a number at least 0,

[0360] Wherein, the L1 may comprise a linker connected to a thiol group,

[0361] The L2 may comprise a group selected from the following group: optionally substituted -(CH2) m1-X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-, X1 may be selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted phenyl, optionally substituted pyridyl, optionally substituted heteroalicyclic group containing two oxygen atoms and four carbon atoms, and optionally substituted cyclohexyl, wherein m1, m2, and n may each be independently selected from a number that is at least 0;

[0362] Said L3 may comprise a peptide residue;

[0363] The L4 may contain optionally substituted Optionally substituted Optionally substituted or optionally substituted For example, the R4 can be selected from the following groups: hydrogen and optionally substituted C1-C6 alkyl. For example, the R5 can be selected from the following groups: hydrogen and optionally substituted C1-C6 alkyl;

[0364] The L5 may contain optionally substituted R6 and R7 can each be independently selected from the following group: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 can form an optionally substituted cycloalkyl together with the atoms to which they are attached, wherein v can be selected from a number that is at least 0. For example, cycloalkylalkyl in the present application can refer to an alkyl substituted by a cycloalkyl, wherein the cycloalkylalkyl can be further optionally substituted by another group.

[0365] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (I):

[0366]

[0367] For example it could be

[0368]

[0369] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0370] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0371] L may be an optionally substituted linker, wherein L may comprise -L1-L2-L3-L4-L5-,

[0372] Ab can be a ligand, a can be a number at least 0,

[0373] Wherein, the L1 may contain optionally substituted

[0374] The L2 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0375] The L3 may comprise a structure selected from the following group:

[0376] The L4 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0377] The L5 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0378] For example, the Ab of the present application may comprise an antibody or an antigen-binding fragment thereof.

[0379] For example, the antibody may be selected from the group consisting of a murine antibody, a chimeric antibody, a humanized antibody, and a fully human antibody. For example, the antibody may comprise a monoclonal antibody. For example, the antibody may comprise a bispecific antibody. For example, the antigen-binding fragment may be selected from the group consisting of a Fab, a Fab′, an Fv fragment, a F(ab′)2, a F(ab)2, a scFv, a di-scFv, a VHH, and a dAb.

[0380] For example, wherein the Ab can be selected from the following group: HER2 antibody and TROP2 antibody.

[0381] The ligands described herein may comprise at least one CDR in the variable region VH of an antibody heavy chain. The CDRs may be defined according to Kabat.

[0382] In the present application, the ligand may comprise HCDR1, and the HCDR1 may comprise the amino acid sequence shown in any one of SEQ ID NOs: 1 and 11. The CDRs may be defined according to Kabat.

[0383] In the present application, the ligand may comprise HCDR2, and the HCDR2 may comprise the amino acid sequence shown in any one of SEQ ID NOs: 2 and 12. The CDR may be defined according to Kabat.

[0384] In the present application, the ligand may comprise HCDR3, and the HCDR3 may comprise the amino acid sequence shown in any one of SEQ ID NOs: 3 and 13. The CDR may be defined according to Kabat.

[0385] In the present application, the isolated ligand may comprise HCDR1-3, wherein the HCDR1 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1 and 11; the HCDR2 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 2 and 12; and the HCDR3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 3 and 13. The CDRs may be defined according to Kabat.

[0386] For example, the ligands described herein may comprise HCDRs 1-3, wherein HCDR 1 may comprise the amino acid sequence set forth in SEQ ID NO: 1; HCDR 2 may comprise the amino acid sequence set forth in SEQ ID NO: 2; and HCDR 3 may comprise the amino acid sequence set forth in SEQ ID NO: 3. For example, the ligands described herein may have HER2 binding ability. The CDRs may be defined according to Kabat.

[0387] For example, the ligands described herein may comprise HCDRs 1-3, wherein HCDR 1 may comprise the amino acid sequence set forth in SEQ ID NO: 11; HCDR 2 may comprise the amino acid sequence set forth in SEQ ID NO: 12; and HCDR 3 may comprise the amino acid sequence set forth in SEQ ID NO: 13. For example, the ligands described herein may have TROP2 binding ability. The CDRs may be defined according to Kabat.

[0388] In the present application, the ligand may comprise at least one CDR in the antibody light chain variable region VL. The CDRs described in the present application may be defined according to Kabat or Chothia, and CDR sequences defined in various ways are all within the scope of protection of the present application.

[0389] In the present application, the ligand may comprise LCDR1, and the LCDR1 may comprise the amino acid sequence shown in any one of SEQ ID NOs: 4 and 14. The CDRs may be defined according to Kabat.

[0390] In the present application, the ligand may comprise LCDR2, and the LCDR2 may comprise the amino acid sequence shown in any one of SEQ ID NOs: 5 and 15. The CDRs may be defined according to Kabat.

[0391] In the present application, the ligand may comprise LCDR3, and the LCDR3 may comprise the amino acid sequence shown in any one of SEQ ID NOs: 6 and 16. The CDRs may be defined according to Kabat.

[0392] In the present application, the isolated ligand may comprise LCDR1-3, wherein the LCDR1 comprises the amino acid sequence shown in any one of SEQ ID NOs: 4 and 14; the LCDR2 comprises the amino acid sequence shown in any one of SEQ ID NOs: 5 and 15; and the LCDR3 comprises the amino acid sequence shown in any one of SEQ ID NOs: 6 and 16. The CDRs may be defined according to Kabat.

[0393] For example, the ligand described herein may comprise LCDRs 1-3, wherein LCDR 1 may comprise the amino acid sequence set forth in SEQ ID NO: 4; LCDR 2 may comprise the amino acid sequence set forth in SEQ ID NO: 5; and LCDR 3 may comprise the amino acid sequence set forth in SEQ ID NO: 6. For example, the ligand described herein may have HER2 binding ability. The CDRs may be defined according to Kabat.

[0394] For example, the ligand described herein may comprise LCDR1-3, wherein LCDR1 may comprise the amino acid sequence set forth in SEQ ID NO: 14; LCDR2 may comprise the amino acid sequence set forth in SEQ ID NO: 15; and LCDR3 may comprise the amino acid sequence set forth in SEQ ID NO: 16. For example, the ligand described herein may have TROP2 binding ability. The CDRs may be defined according to Kabat.

[0395] In the present application, the ligand may comprise LCDR1-3 and HCDR1-3. The HCDR1 comprises the amino acid sequence shown in any one of SEQ ID NOs: 1 and 11; the HCDR2 comprises the amino acid sequence shown in any one of SEQ ID NOs: 2 and 12; and the HCDR3 comprises the amino acid sequence shown in any one of SEQ ID NOs: 3 and 13. The LCDR1 comprises the amino acid sequence shown in any one of SEQ ID NOs: 4 and 14; the LCDR2 comprises the amino acid sequence shown in any one of SEQ ID NOs: 5 and 15; and the LCDR3 comprises the amino acid sequence shown in any one of SEQ ID NOs: 6 and 16. The CDRs may be defined according to Kabat.

[0396] For example, the ligand described herein may comprise LCDRs 1-3 and HCDRs 1-3, wherein the HCDR 1 comprises the amino acid sequence set forth in SEQ ID NO: 1; the HCDR 2 comprises the amino acid sequence set forth in SEQ ID NO: 2; and the HCDR 3 comprises the amino acid sequence set forth in SEQ ID NO: 3, the LCDR 1 comprises the amino acid sequence set forth in SEQ ID NO: 4; the LCDR 2 comprises the amino acid sequence set forth in SEQ ID NO: 5; and the LCDR 3 comprises the amino acid sequence set forth in SEQ ID NO: 6. The CDRs may be defined according to Kabat.

[0397] For example, the ligand described herein may comprise LCDR1-3 and HCDR1-3, wherein the HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 11; the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 12; and the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 14; the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 15; and the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 16. The CDRs may be defined according to Kabat.

[0398] In the present application, the ligand may comprise a heavy chain variable region VH, and the VH may comprise the amino acid sequence shown in any one of SEQ ID NOs: 7 and 17.

[0399] In the present application, the ligand may comprise a light chain variable region VL, and the VL may comprise the amino acid sequence shown in any one of SEQ ID NOs: 8 and 18.

[0400] In the present application, the ligand may comprise a light chain variable region VL and a heavy chain variable region VH, wherein the VH may comprise the amino acid sequence shown in any one of SEQ ID NOs: 7 and 17, and the VL may comprise the amino acid sequence shown in any one of SEQ ID NOs: 8 and 18.

[0401] For example, the ligand described herein may comprise a light chain variable region VL and a heavy chain variable region VH, wherein the VH may comprise the amino acid sequence set forth in SEQ ID NO: 7, and the VL may comprise the amino acid sequence set forth in SEQ ID NO: 8. For example, the ligand described herein may have HER2 binding ability.

[0402] For example, the ligand described herein may comprise a light chain variable region VL and a heavy chain variable region VH, wherein the VH may comprise the amino acid sequence set forth in SEQ ID NO: 17, and the VL may comprise the amino acid sequence set forth in SEQ ID NO: 18. For example, the ligand described herein may have TROP2 binding ability.

[0403] In the present application, the ligand may comprise HCDR1-3 in the heavy chain variable region VH, and the VH may comprise the amino acid sequence shown in any one of SEQ ID NOs: 7 and 17.

[0404] In the present application, the ligand may comprise LCDR1-3 in the light chain variable region VL, and the VL may comprise the amino acid sequence shown in any one of SEQ ID NOs: 8 and 18.

[0405] In the present application, the ligand may comprise LCDR1-3 in the light chain variable region VL and HCDR1-3 in the heavy chain variable region VH, wherein the VH may comprise the amino acid sequence shown in any one of SEQ ID NOs: 7 and 17, and the VL may comprise the amino acid sequence shown in any one of SEQ ID NOs: 8 and 18.

[0406] For example, the ligand described herein may comprise LCDR1-3 in the light chain variable region VL and HCDR1-3 in the heavy chain variable region VH, wherein the VH may comprise the amino acid sequence set forth in SEQ ID NO: 7, and the VL may comprise the amino acid sequence set forth in SEQ ID NO: 8. For example, the ligand described herein may have HER2 binding ability.

[0407] For example, the ligand described herein may comprise LCDR1-3 in the light chain variable region VL and HCDR1-3 in the heavy chain variable region VH, wherein the VH may comprise the amino acid sequence set forth in SEQ ID NO: 17, and the VL may comprise the amino acid sequence set forth in SEQ ID NO: 18. For example, the ligand described herein may have TROP2 binding ability.

[0408] In the present application, the ligand may comprise a heavy chain, and the heavy chain may comprise the amino acid sequence shown in any one of SEQ ID NOs: 9 and 19.

[0409] In the present application, the ligand may comprise a light chain, and the light chain may comprise the amino acid sequence shown in any one of SEQ ID NOs: 10 and 20.

[0410] In the present application, the ligand may comprise an antibody light chain and an antibody heavy chain, wherein the heavy chain may comprise the amino acid sequence shown in any one of SEQ ID NOs: 9 and 19, and the light chain may comprise the amino acid sequence shown in any one of SEQ ID NOs: 10 and 20.

[0411] In the present application, the ligand may comprise an antibody light chain and an antibody heavy chain, wherein the heavy chain may comprise the amino acid sequence shown in SEQ ID NO: 9, and the light chain may comprise the amino acid sequence shown in SEQ ID NO: 10.

[0412] In the present application, the ligand may comprise an antibody light chain and an antibody heavy chain, wherein the heavy chain may comprise the amino acid sequence shown in SEQ ID NO: 19, and the light chain may comprise the amino acid sequence shown in SEQ ID NO: 20.

[0413] The antibodies of the present application can be prepared using techniques well known in the art, such as the hybridoma method, recombinant DNA technology, phage display technology, synthetic technology, or a combination of such technologies, or other techniques known in the art. Variants can refer to amino acid sequence mutants of the antibody, as well as covalent derivatives of the native polypeptide, provided that the biological activity equivalent to that of the native polypeptide is retained. Amino acid sequence mutants generally differ from the native amino acid sequence in that one or more amino acids in the native amino acid sequence are substituted, or one or more amino acids are deleted and / or inserted into the polypeptide sequence. Deletion mutants include fragments of the native polypeptide and N-terminal and / or C-terminal truncation mutants. Typically, amino acid sequence mutants have at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% homology to the native sequence.

[0414] For example, a can be the average molar ratio of drug molecules to antibody molecules in the antibody-drug conjugate obtained after coupling a single antibody molecule to a drug molecule, and a can be an integer or decimal from 1 to 8, for example, a can be about 1 to about 2, about 1 to about 3, about 1 to about 4, about 1 to about 5, about 1 to about 6, about 1 to about 7, or about 1 to about 8; for example, m can be about 2 to about 8, about 3 to about 8, about 4 to about 8, about 5 to about 8, about 6 to about 8, about 7 to about 8, or about 1, about 2, about 3, about 4, about 5, about 6, about 7, or about 8. For example, a can be determined by a method selected from the group consisting of hydrophobic chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and liquid chromatography-mass spectrometry.

[0415] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure selected from the following group:

[0416]

[0417]

[0418]

[0419]

[0420]

[0421]

[0422]

[0423]

[0424]

[0425] Wherein Ab is a ligand, a is a number greater than 0, and a is a decimal or an integer.

[0426] In one aspect, the present application provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (II):

[0427] For example it could be

[0428]

[0429] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0430] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0431] Lx may be a linking group.

[0432] For example, in the structure shown in formula (II), the Lx may include a linking group L 1x , the L 1x Can be directly or indirectly connected to the ligand. 1x Can be directly or indirectly connected to the sulfhydryl group of the ligand. 1x May contain optionally substituted For example, in the structure shown in formula (II), L 1x It can exist in an open ring form as shown below.

[0433]

[0434] For example, in the structure shown in formula (II), the Lx may further include a linker L2. For example, the L2 may be connected to the L 1x For example, the L2 may comprise a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p-C(O)-, X1 can be selected from the following group: -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic group and optionally substituted alicyclic group, wherein m1, m2 and n can each independently be selected from a number of at least 0.

[0435] For example, in the structure shown in formula (II), the L2 may comprise an optionally substituted -(CH2CH2O) n -C(O)-. For example, wherein n can be 2.

[0436] For example, in the structure shown in formula (II), the L2 may comprise an optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-. For example, X1 can be selected from the group consisting of -O- and optionally substituted -C(O)-NH-. For example, m1 can be 2. For example, m2 can be 2.

[0437] For example, in the structure represented by formula (II), X1 can include a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group. For example, X1 can include an optionally substituted phenyl group. For example, X1 can include an optionally substituted pyridyl group. For example, m1 can be 0. For example, m2 can be 1.

[0438] For example, in the structure shown in formula (II), X1 may include an optionally substituted heteroalicyclic group containing two oxygen atoms. For example, X1 may comprise an optionally substituted cyclohexyl group. For example, m1 may be 1. For example, m2 may be 0.

[0439] For example, in the structure shown in formula (II), the L2 may comprise an optionally substituted -(CH2) p -C(O)-. For example, p may be 5.

[0440] For example, in the structure shown in formula (II), the L2 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0441] For example, in the structure shown in formula (II), the Lx may further comprise a linker L3. For example, the L3 may be directly or indirectly connected to the L2. For example, the L3 may comprise a peptide residue.

[0442] For example, the L3 may comprise a peptide residue consisting of an amino acid selected from the group consisting of phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid, and glycine. For example, the L3 may comprise a peptide residue consisting of an amino acid selected from the group consisting of glycine, phenylalanine, valine, and citrulline. For example, the L3 may comprise a peptide residue selected from the group consisting of -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-), and -valine-citrulline-(-Val-Cit-).

[0443] For example, in the structure represented by formula (II), the L3 may comprise a structure selected from the following group:

[0444]

[0445] For example, in the structure represented by formula (II), the Lx may further comprise a linker L4. For example, the L4 may be directly or indirectly connected to the L3.

[0446] For example, in the structure shown in formula (II), the L4 may include an optionally substituted -L 4a -NR4-CH2-L 4b -, L 4a Can be absent or L 4a May contain optionally substituted L 4b Can be absent or L 4b May contain optionally substituted R4 and R5 may each independently be selected from the group consisting of hydrogen and optionally substituted alkyl.

[0447] For example, in the structure shown in formula (II), the L4 may include an optionally substituted For example, the L4 may comprise an optionally substituted For example, the L4 may comprise an optionally substituted For example, the L4 may comprise an optionally substituted For example, the R4 can be selected from the following group: hydrogen and an optionally substituted methyl group. For example, the R5 can be selected from the following group: hydrogen and an optionally substituted methyl group.

[0448] For example, in the structure shown in formula (II), the L4 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0449] For example, in the structure represented by formula (II), the Lx may further include a linker L5. For example, the L5 may be directly or indirectly connected to the L4.

[0450] For example, in the structure shown in formula (II), the L5 may include an optionally substituted R6 and R7 can each be independently selected from the following group: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cycloalkyl, wherein v can be selected from a number that is at least 0.

[0451] For example, in the structure shown in formula (II), R6 can be hydrogen. For example, R6 can be an optionally substituted methyl group. For example, R6 can be an optionally substituted halomethyl group. For example, R6 can be a methyl group substituted with fluorine. For example, R6 can be a trifluoromethyl group. For example, R6 can be an optionally substituted cycloalkyl group. For example, R6 can be an optionally substituted cyclopropyl group. For example, in the structure shown in formula (I), R7 can be hydrogen.

[0452] For example, in the structure shown in formula (II), R6 and R7 can form an optionally substituted cyclopropyl group together with the atom to which they are connected. For example, R6 and R7 can form an optionally substituted cyclobutyl group together with the atom to which they are connected. For example, v can be 0. For example, v can be 1.

[0453] For example, in the structure shown in formula (II), the L5 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0454] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (II):

[0455] For example it could be

[0456]

[0457] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0458] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0459] Lx may be an optionally substituted linking group, wherein Lx may comprise L 1x -L2-L3-L4-L5-.

[0460] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (II):

[0461] For example it could be

[0462]

[0463] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0464] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0465] Lx may be an optionally substituted linker, said Lx may comprise L 1x -L2-L3-L4-L5-,

[0466] Among them, the L 1xmay contain a linking group that can be linked to a thiol group,

[0467] The L2 may comprise a group selected from the following group: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-, X1 may be selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted phenyl, optionally substituted pyridyl, optionally substituted heteroalicyclic group containing two oxygen atoms and four carbon atoms, and optionally substituted cyclohexyl, wherein m1, m2, and n may each be independently selected from a number that is at least 0;

[0468] Said L3 may comprise a peptide residue;

[0469] The L4 may contain optionally substituted Optionally substituted Optionally substituted or optionally substituted For example, the R4 can be selected from the following groups: hydrogen and optionally substituted C1-C6 alkyl. For example, the R5 can be selected from the following groups: hydrogen and optionally substituted C1-C6 alkyl;

[0470] The L5 may comprise an optionally substituted R6 and R7 can each be independently selected from the following group: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 can form an optionally substituted cycloalkyl together with the atoms to which they are attached, wherein v can be selected from a number that is at least 0. For example, cycloalkylalkyl in the present application can refer to an alkyl substituted by a cycloalkyl, wherein the cycloalkylalkyl can be further optionally substituted by another group.

[0471] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (II):

[0472] For example it could be

[0473]

[0474] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0475] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0476] Lx may be an optionally substituted linking group, wherein Lx may comprise L 1x -L2-L3-L4-L5-,

[0477] Among them, the L 1x May contain optionally substituted

[0478] The L2 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0479] The L3 may comprise a structure selected from the following group:

[0480] The L4 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0481] The L5 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0482] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure selected from the following group:

[0483]

[0484]

[0485]

[0486]

[0487]

[0488]

[0489]

[0490]

[0491] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (III):

[0492] For example it could be

[0493]

[0494] in,

[0495] R1 and R2 may each be independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0496] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group;

[0497] L can be an optionally substituted linker.

[0498] For example, in the structure represented by formula (III), the L may include a linker L1, and the L1 may be directly or indirectly connected to the ligand.

[0499] For example, in the structure shown in formula (III), the L1 may contain an optionally substituted For example, in the structure represented by formula (III), L1 may exist in an open ring form represented by the following formula.

[0500]

[0501] For example, in the structure represented by formula (III), the L may further include a linker L2.

[0502] For example, in the structure represented by formula (III), the L2 can be directly or indirectly connected to the L1.

[0503] For example, in the structure shown in formula (III), the L2 may comprise a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-,

[0504] X1 may be selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic and optionally substituted alicyclic,

[0505] Wherein, m1, m2 and n can be each independently selected from a number of at least 0.

[0506] For example, in the structure shown in formula (III), the L2 may comprise an optionally substituted -(CH2CH2O) n -C(O)-.

[0507] For example, in the structure represented by formula (III), n can be 2.

[0508] For example, in the structure shown in formula (III), the L2 may comprise an optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-.

[0509] For example, in the structure represented by formula (III), X1 can be selected from the group consisting of -O- and optionally substituted -C(O)-NH-.

[0510] For example, in the structure represented by formula (III), m1 can be 2.

[0511] For example, in the structure represented by formula (III), m2 can be 2.

[0512] For example, in the structure represented by formula (III), X1 may include a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group.

[0513] For example, in the structure represented by formula (III), X1 may comprise an optionally substituted phenyl group.

[0514] For example, in the structure represented by formula (III), X1 may comprise an optionally substituted pyridyl group.

[0515] For example, in the structure represented by formula (III), m1 can be 0.

[0516] For example, in the structure represented by formula (III), m2 can be 1.

[0517] For example, in the structure represented by formula (III), X1 may comprise an optionally substituted heteroalicyclic group comprising two oxygen atoms.

[0518] For example, in the structure shown in formula (III), X1 may include an optionally substituted

[0519] For example, in the structure represented by formula (III), X1 may comprise an optionally substituted cyclohexyl group.

[0520] For example, in the structure represented by formula (III), m1 can be 1.

[0521] For example, in the structure represented by formula (III), m2 can be 0.

[0522] For example, in the structure shown in formula (III), the L2 may comprise an optionally substituted -(CH2) p -C(O)-.

[0523] For example, in the structure represented by formula (III), p can be 5.

[0524] For example, in the structure shown in formula (III), the L2 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0525] For example, in the structure represented by formula (III), the L may further include a linker L3.

[0526] For example, in the structure represented by formula (III), the L3 can be directly or indirectly connected to the L2.

[0527] For example, in the structure represented by formula (III), the L3 may comprise a peptide residue.

[0528] For example, in the structure represented by formula (III), L3 may comprise a peptide residue consisting of amino acids selected from the group consisting of phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid and glycine.

[0529] For example, in the structure represented by formula (III), the L3 may comprise a peptide residue consisting of an amino acid selected from the group consisting of glycine, phenylalanine, valine, and citrulline.

[0530] For example, in the structure represented by formula (III), L3 may comprise a peptide residue selected from the following group: -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-) and -valine-citrulline-(-Val-Cit-).

[0531] For example, in the structure represented by formula (III), the L3 may comprise a structure selected from the following group:

[0532]

[0533] For example, in the structure represented by formula (III), the L may further include a linker L4.

[0534] For example, in the structure represented by formula (III), the L4 can be directly or indirectly connected to the L3.

[0535] For example, in the structure shown in formula (III), the L4 may include an optionally substituted -L 4a -NR4-CH2-L 4b -,

[0536] L 4a Can be absent or L 4a May contain optionally substituted

[0537] L 4b Can be absent or L 4b May contain optionally substituted

[0538] R4 and R5 may each independently be selected from the group consisting of hydrogen and optionally substituted alkyl.

[0539] For example, in the structure shown in formula (III), the L4 may include an optionally substituted

[0540] For example, in the structure shown in formula (III), the L4 may include an optionally substituted

[0541] For example, in the structure shown in formula (III), the L4 may include an optionally substituted

[0542] For example, in the structure shown in formula (III), the L4 may include an optionally substituted

[0543] For example, in the structure represented by formula (III), the R4 can be selected from the following group: hydrogen and optionally substituted methyl.

[0544] For example, in the structure represented by formula (III), the R5 can be selected from the following group: hydrogen and optionally substituted methyl.

[0545] For example, in the structure shown in formula (III), the L4 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0546] For example, in the structure represented by formula (III), the L may further include a linker L5.

[0547] For example, in the structure represented by formula (III), the L5 can be directly or indirectly connected to the L4.

[0548] For example, in the structure shown in formula (III), the L5 may include an optionally substituted

[0549] R6 and R7 may each be independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 may be taken together with the atoms to which they are attached to form an optionally substituted cycloalkyl,

[0550] Here, v can be selected from a number that is at least 0.

[0551] For example, in the structure represented by formula (III), R6 may be hydrogen.

[0552] For example, in the structure represented by formula (III), R6 may be an optionally substituted methyl group.

[0553] For example, in the structure represented by formula (III), R6 may be an optionally substituted halomethyl group.

[0554] For example, in the structure represented by formula (III), R6 may be a methyl group substituted with fluorine.

[0555] For example, in the structure represented by formula (III), R6 may be a trifluoromethyl group.

[0556] For example, in the structure represented by formula (III), R6 may be an optionally substituted cycloalkyl group.

[0557] For example, in the structure represented by formula (III), R6 may be an optionally substituted cyclopropyl group.

[0558] For example, in the structure represented by formula (III), R7 may be hydrogen.

[0559] For example, in the structure represented by formula (III), R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cyclopropyl group.

[0560] For example, in the structure shown in formula (III), R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cyclobutyl group.

[0561] For example, in the structure represented by formula (III), v can be 0.

[0562] For example, in the structure represented by formula (III), v can be 1.

[0563] For example, in the structure shown in formula (III), the L5 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0564] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure selected from the following group:

[0565]

[0566]

[0567]

[0568]

[0569]

[0570]

[0571]

[0572]

[0573]

[0574] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (L-1):

[0575] -L1-L2-L3-L4-L5-(L-1),

[0576] in,

[0577] L1, L2, L3, L4 and L5 can each independently be a linker,

[0578] Wherein, the L2 may comprise a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)- and optionally substituted -(CH2CH2O) n -C(O)-,

[0579] X1 may be selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic and optionally substituted alicyclic,

[0580] wherein m1, m2 and n can each be independently selected from a number that is at least 0.

[0581] For example, in the structure represented by formula (L-1), the L2 may comprise an optionally substituted -(CH2CH2O) n -C(O)-. For example, wherein n can be 2.

[0582] For example, in the structure represented by formula (L-1), the L2 may comprise an optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-. For example, X1 can be selected from the group consisting of -O- and optionally substituted -C(O)-NH-. For example, m1 can be 2. For example, m2 can be 2.

[0583] For example, in the structure represented by formula (L-1), X1 may include a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group. For example, X1 may include an optionally substituted phenyl group. For example, X1 may include an optionally substituted pyridyl group. For example, m1 may be 0. For example, m2 may be 1.

[0584] For example, in the structure represented by formula (L-1), X1 may include an optionally substituted heteroalicyclic group containing two oxygen atoms. For example, X1 may comprise an optionally substituted cyclohexyl group. For example, m1 may be 1. For example, m2 may be 0.

[0585] For example, in the structure shown in formula (L-1), the L2 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted

[0586] For example, in the structure represented by formula (L-1), the L1 may contain an optionally substituted For example, L1 in the structure represented by formula (L-1) may exist in an open ring form represented by the following formula.

[0587]

[0588] For example, in the structure represented by formula (L-1), L3 may comprise a peptide residue. For example, L3 may comprise a peptide residue composed of amino acids selected from the following group: phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid, and glycine. For example, L3 may comprise a peptide residue composed of amino acids selected from the following group: glycine, phenylalanine, valine, and citrulline. For example, L3 may comprise a peptide residue selected from the following group: -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-), and -valine-citrulline-(-Val-Cit-).

[0589] For example, in the structure represented by formula (L-1), the L3 may include a structure selected from the following group:

[0590]

[0591] For example, in the structure represented by formula (L-1), the L4 may include an optionally substituted -L 4a -NR4-CH2-L 4b -, L 4a Can be absent or L 4a May contain optionally substituted L 4b Can be absent or L 4b May contain optionally substituted R4 and R5 may each independently be selected from the group consisting of hydrogen and optionally substituted alkyl.

[0592] For example, in the structure shown in formula (L-1), the L4 may contain an optionally substituted Optionally substituted Optionally substituted or optionally substituted For example, the R4 can be selected from the following group: hydrogen and an optionally substituted methyl group. For example, the R5 can be selected from the following group: hydrogen and an optionally substituted methyl group.

[0593] For example, in the structure shown in formula (L-1), the L4 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0594] For example, in the structure shown in formula (L-1), the L5 may include an optionally substituted The L5 can be directly connected to the following structure: For example, wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0595] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group,

[0596] R6 and R7 can each be independently selected from the following group: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cycloalkyl, wherein v can be selected from a number that is at least 0.

[0597] For example, in the structure shown in formula (L-1), the R6 can be hydrogen. For example, the R6 can be an optionally substituted methyl group. For example, the R6 can be an optionally substituted halomethyl group. For example, the R6 can be a methyl group substituted with fluorine. For example, the R6 can be a trifluoromethyl group. For example, the R6 can be an optionally substituted cycloalkyl group. For example, the R6 can be an optionally substituted cyclopropyl group. For example, the R7 can be hydrogen. For example, R6 and R7 can form an optionally substituted cyclopropyl group together with the atoms to which they are attached. For example, R6 and R7 can form an optionally substituted cyclobutyl group together with the atoms to which they are attached. For example, v can be 0. For example, v can be 1.

[0598] For example, in the structure shown in formula (L-1), the L5 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0599] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (L-1):

[0600] -L1-L2-L3-L4-L5-(L-1),

[0601] in,

[0602] Wherein, the L1 may comprise a linker connected to a thiol group,

[0603] The L2 may comprise a group selected from the following group: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)- and optionally substituted -(CH2CH2O) n -C(O)-, X1 may be selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted phenyl, optionally substituted pyridyl, optionally substituted heteroalicyclic group containing two oxygen atoms and four carbon atoms, and optionally substituted cyclohexyl, wherein m1, m2, and n may each be independently selected from a number that is at least 0;

[0604] Said L3 may comprise a peptide residue;

[0605] The L4 may contain optionally substituted Optionally substituted Optionally substituted or optionally substituted For example, the R4 can be selected from the following groups: hydrogen and optionally substituted C1-C6 alkyl. For example, the R5 can be selected from the following groups: hydrogen and optionally substituted C1-C6 alkyl;

[0606] The L5 may contain optionally substituted The L5 can be directly connected to the following structure: For example,

[0607] wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0608] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group,

[0609] R6 and R7 can each be independently selected from the following group: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 can form an optionally substituted cycloalkyl together with the atoms to which they are attached, wherein v can be selected from a number that is at least 0. For example, cycloalkylalkyl in the present application can refer to an alkyl substituted by a cycloalkyl, wherein the cycloalkylalkyl can be further optionally substituted by another group.

[0610] In another aspect, the present application further provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (L-1):

[0611] -L1-L2-L3-L4-L5-(L-1),

[0612] Wherein, the L1 may contain optionally substituted

[0613] The L2 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0614] The L3 may comprise a structure selected from the following group:

[0615] The L4 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0616] The L5 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted The L5 can be directly connected to the following structure: For example, wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0617] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group.

[0618] In another aspect, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure selected from the following groups:

[0619]

[0620]

[0621]

[0622] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (L-2):

[0623] -L1-L2-L3-L4-L5-(L-2),

[0624] Wherein, L1, L2, L3, L4 and L5 can each independently be a linker,

[0625] L4 may contain an optionally substituted -L 4a -NR4-CH2-L 4b -,

[0626] L 4a Can be absent or L 4a May contain optionally substituted

[0627] L 4b Can be absent or L 4b May contain optionally substituted L 4a With L 4b Can not exist at the same time,

[0628] R4 and R5 may each independently be selected from the group consisting of hydrogen and optionally substituted alkyl.

[0629] For example, in the structure shown in formula (L-2), the L4 comprises an optionally substituted Optionally substituted or optionally substituted For example, the R4 can be selected from the following group: hydrogen and an optionally substituted methyl group. For example, the R5 can be selected from the following group: hydrogen and an optionally substituted methyl group.

[0630] For example, in the structure shown in formula (L-2), the L4 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0631] For example, in the structure shown in formula (L-2), the L1 may contain an optionally substituted For example, in the structure represented by formula (L-2), L1 may exist in an open ring form represented by the following formula.

[0632]

[0633] For example, in the structure represented by formula (L-2), the L2 may comprise a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-, X1 is selected from the following group: -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic group and optionally substituted alicyclic group, wherein m1, m2 and n can each independently be selected from a number of at least 0.

[0634] For example, in the structure represented by formula (L-2), the L2 may comprise an optionally substituted -(CH2CH2O) n -C(O)-. For example, n may be 2.

[0635] For example, in the structure represented by formula (L-2), the L2 may contain an optionally substituted -(CH2) m1 -X1-(CH2) m2-C(O)-. For example, X1 can be selected from the following group: -O- and optionally substituted -C(O)-NH-. For example, m1 can be 2. For example, m2 can be 2. For example, X1 can include a group selected from the following group: an optionally substituted aryl group and an optionally substituted heteroaryl group. For example, X1 can include an optionally substituted phenyl group. For example, X1 can include an optionally substituted pyridyl group. For example, m1 can be 0. For example, m2 can be 1. For example, X1 can include an optionally substituted heteroalicyclic group containing two oxygen atoms. For example, X1 can include an optionally substituted For example, X1 may include an optionally substituted cyclohexyl group. For example, m1 may be 1. For example, m2 may be 0. For example, the L2 may include an optionally substituted -(CH2) p -C(O)-. For example, p may be 5.

[0636] For example, in the structure shown in formula (L-2), the L2 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0637] For example, in the structure represented by formula (L-2), L3 may comprise a peptide residue. For example, L3 may comprise a peptide residue composed of amino acids selected from the following group: phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid, and glycine. For example, L3 may comprise a peptide residue composed of amino acids selected from the following group: glycine, phenylalanine, valine, and citrulline. For example, L3 may comprise a peptide residue selected from the following group: -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-), and -valine-citrulline-(-Val-Cit-).

[0638] For example, in the structure represented by formula (L-2), the L3 may include a structure selected from the following group:

[0639]

[0640] For example, in the structure shown in formula (L-2), the L5 may include an optionally substituted The L5 can be directly connected to the following structure: For example, wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0641] Alternatively, R1 and R2 can form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group, and R6 and R7 can each be independently selected from the group consisting of hydrogen, deuterium, an optionally substituted alkyl group, an optionally substituted haloalkyl group, an optionally substituted cycloalkyl group, and an optionally substituted cycloalkylalkyl group, or R6 and R7 can form together with the atom to which they are attached an optionally substituted cycloalkyl group, wherein v can be selected from a number that is at least 0.

[0642] For example, in the structure shown in formula (L-2), the R6 can be hydrogen. For example, the R6 can be an optionally substituted methyl group. For example, the R6 can be an optionally substituted halomethyl group. For example, the R6 can be a methyl group substituted with fluorine. For example, the R6 can be a trifluoromethyl group. For example, the R6 can be an optionally substituted cycloalkyl group. For example, the R6 can be an optionally substituted cyclopropyl group. For example, the R7 can be hydrogen. For example, R6 and R7 can form an optionally substituted cyclopropyl group together with the atoms to which they are attached. For example, R6 and R7 can form an optionally substituted cyclobutyl group together with the atoms to which they are attached. For example, v can be 0. For example, v can be 1.

[0643] For example, in the structure shown in formula (L-2), the L5 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0644] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (L-2):

[0645] -L1-L2-L3-L4-L5-(L-2),

[0646] Wherein, the L1 may comprise a linker connected to a thiol group,

[0647] The L2 may comprise a group selected from the following group: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-, X1 may be selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted phenyl, optionally substituted pyridyl, optionally substituted heteroalicyclic group containing two oxygen atoms and four carbon atoms, and optionally substituted cyclohexyl, wherein m1, m2, and n may each be independently selected from a number that is at least 0;

[0648] Said L3 may comprise a peptide residue;

[0649] The L4 may contain optionally substituted Optionally substituted Optionally substituted For example, the R4 can be selected from the following groups: hydrogen and optionally substituted C1-C6 alkyl. For example, the R5 can be selected from the following groups: hydrogen and optionally substituted C1-C6 alkyl;

[0650] The L5 may contain optionally substituted The L5 can be directly connected to the following structure: For example, wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0651] Alternatively, R1 and R2 can form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group, and R6 and R7 can each be independently selected from the group consisting of hydrogen, deuterium, an optionally substituted alkyl group, an optionally substituted haloalkyl group, an optionally substituted cycloalkyl group, and an optionally substituted cycloalkylalkyl group, or R6 and R7 can form together with the atom to which they are attached an optionally substituted cycloalkyl group, wherein v can be selected from a number that is at least 0. For example, cycloalkylalkyl in the present application can refer to an alkyl group substituted by a cycloalkyl group, wherein the cycloalkylalkyl group can further be optionally substituted by another group.

[0652] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (L-2):

[0653] -L1-L2-L3-L4-L5-(L-2),

[0654] Wherein, the L1 may contain optionally substituted

[0655] The L2 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0656] The L3 may comprise a structure selected from the following group:

[0657] The L4 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0658] The L5 may comprise a structure selected from the following group: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted The L5 can be directly connected to the following structure: For example, wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0659] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group.

[0660] In another aspect, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure selected from the following groups:

[0661]

[0662] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (Lx-1):

[0663] L 1x -L2-L3-L4-L5-(Lx-1),

[0664] in,

[0665] L 1x It may contain a linking group, L2, L3, L4 and L5 may each independently be a linker,

[0666] Wherein, the L2 may comprise a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)- and optionally substituted -(CH2CH2O) n -C(O)-,

[0667] X1 may be selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic and optionally substituted alicyclic,

[0668] wherein m1, m2 and n can each be independently selected from a number that is at least 0.

[0669] For example, in the structure represented by formula (Lx-1), the L2 may comprise an optionally substituted -(CH2CH2O) n -C(O)-.

[0670] For example, in the structure represented by formula (Lx-1), n ​​may be 2.

[0671] For example, in the structure represented by formula (Lx-1), the L2 may comprise an optionally substituted -(CH2) m1-X1-(CH2) m2 -C(O)-.

[0672] For example, in the structure represented by formula (Lx-1), X1 can be selected from the group consisting of -O- and optionally substituted -C(O)-NH-.

[0673] For example, in the structure represented by formula (Lx-1), m1 may be 2.

[0674] For example, in the structure represented by formula (Lx-1), m2 can be 2.

[0675] For example, in the structure represented by formula (Lx-1), X1 may include a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group.

[0676] For example, in the structure represented by formula (Lx-1), X1 may include an optionally substituted phenyl group.

[0677] For example, in the structure represented by formula (Lx-1), X1 may include an optionally substituted pyridyl group.

[0678] For example, in the structure represented by formula (Lx-1), m1 may be 0.

[0679] For example, in the structure represented by formula (Lx-1), m2 can be 1.

[0680] For example, in the structure represented by formula (Lx-1), X1 may include an optionally substituted heteroalicyclic group containing two oxygen atoms.

[0681] For example, in the structure represented by formula (Lx-1), X1 may include an optionally substituted

[0682] For example, in the structure represented by formula (Lx-1), X1 may include an optionally substituted cyclohexyl group.

[0683] For example, in the structure represented by formula (Lx-1), m1 may be 1.

[0684] For example, in the structure represented by formula (Lx-1), m2 can be 0.

[0685] For example, in the structure shown in formula (Lx-1), the L2 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted

[0686] For example, in the structure shown in formula (Lx-1), the L 1x May contain optionally substituted For example, in the structure represented by formula (Lx-1), L 1x It can exist in an open ring form as shown below.

[0687]

[0688] For example, in the structure represented by formula (Lx-1), the L3 may comprise a peptide residue.

[0689] For example, in the structure represented by formula (Lx-1), the L3 may comprise a peptide residue consisting of amino acids selected from the following group: phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid and glycine.

[0690] For example, in the structure represented by formula (Lx-1), the L3 may include a peptide residue consisting of an amino acid selected from the group consisting of glycine, phenylalanine, valine, and citrulline.

[0691] For example, in the structure represented by formula (Lx-1), the L3 may comprise a peptide residue selected from the following group: -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-) and -valine-citrulline-(-Val-Cit-).

[0692] For example, in the structure represented by formula (Lx-1), the L3 may include a structure selected from the following group:

[0693]

[0694] For example, in the structure represented by formula (Lx-1), the L4 may include an optionally substituted -L 4a -NR4-CH2-L 4b -,

[0695] L 4a Can be absent or L 4a May contain optionally substituted

[0696] L 4b Can be absent or L 4b May contain optionally substituted

[0697] R4 and R5 may each independently be selected from the group consisting of hydrogen and optionally substituted alkyl.

[0698] For example, in the structure shown in formula (Lx-1), the L4 may contain an optionally substituted

[0699] For example, in the structure shown in formula (Lx-1), the L4 may contain an optionally substituted

[0700] For example, in the structure shown in formula (Lx-1), the L4 may contain an optionally substituted

[0701] For example, in the structure shown in formula (Lx-1), the L4 may contain an optionally substituted

[0702] For example, in the structure represented by formula (Lx-1), the R4 can be selected from the following group: hydrogen and optionally substituted methyl.

[0703] For example, in the structure represented by formula (Lx-1), the R5 can be selected from the following group: hydrogen and optionally substituted methyl.

[0704] For example, in the structure shown in formula (Lx-1), the L4 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0705] For example, in the structure shown in formula (Lx-1), the L5 may include an optionally substituted The L5 can be directly connected to the following structure: For example, wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0706] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group,

[0707] R6 and R7 may each be independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 may be taken together with the atoms to which they are attached to form an optionally substituted cycloalkyl,

[0708] Here, v can be selected from a number that is at least 0.

[0709] For example, in the structure represented by formula (Lx-1), R6 may be hydrogen.

[0710] For example, in the structure represented by formula (Lx-1), R6 may be an optionally substituted methyl group.

[0711] For example, in the structure represented by formula (Lx-1), R6 may be an optionally substituted halogenated methyl group.

[0712] For example, in the structure represented by formula (Lx-1), R6 may be a methyl group substituted with fluorine.

[0713] For example, in the structure represented by formula (Lx-1), R6 may be a trifluoromethyl group.

[0714] For example, in the structure represented by formula (Lx-1), R6 may be an optionally substituted cycloalkyl group.

[0715] For example, in the structure represented by formula (Lx-1), R6 may be an optionally substituted cyclopropyl group.

[0716] For example, in the structure represented by formula (Lx-1), R7 may be hydrogen.

[0717] For example, in the structure represented by formula (Lx-1), R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cyclopropyl group.

[0718] For example, in the structure represented by formula (Lx-1), R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cyclobutyl group.

[0719] For example, in the structure represented by formula (Lx-1), v can be 0.

[0720] For example, in the structure represented by formula (Lx-1), v may be 1.

[0721] For example, in the structure shown in formula (Lx-1), the L5 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0722] In another aspect, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure selected from the following groups:

[0723]

[0724]

[0725]

[0726] On the other hand, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound may comprise a structure represented by formula (Lx-2):

[0727] L 1x -L2-L3-L4-L5-(Lx-2),

[0728] Among them, L 1x It may contain a linking group, L2, L3, L4 and L5 may each independently be a linker,

[0729] L4 may contain an optionally substituted -L 4a -NR4-CH2-L 4b -,

[0730] L 4a Can be absent or L 4a May contain optionally substituted

[0731] L 4b Can be absent or L 4b May contain optionally substituted L 4a With L 4b Can not exist at the same time,

[0732] R4 and R5 may each independently be selected from the group consisting of hydrogen and optionally substituted alkyl.

[0733] For example, in the structure shown in formula (Lx-2), the L4 comprises an optionally substituted

[0734] For example, in the structure shown in formula (Lx-2), the L4 comprises an optionally substituted

[0735] For example, in the structure shown in formula (Lx-2), the L4 may contain an optionally substituted

[0736] For example, in the structure represented by formula (Lx-2), the R4 can be selected from the following group: hydrogen and optionally substituted methyl.

[0737] For example, in the structure represented by formula (Lx-2), the R5 can be selected from the following group: hydrogen and optionally substituted methyl.

[0738] For example, in the structure shown in formula (Lx-2), the L4 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0739] For example, in the structure shown in formula (Lx-2), the L 1x May contain optionally substituted For example, in the structure shown in formula (Lx-2), L 1x It can exist in an open ring form as shown below.

[0740]

[0741] For example, in the structure represented by formula (Lx-2), the L2 may comprise a group selected from the following groups: optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-, optionally substituted -(CH2CH2O) n -C(O)- and optionally substituted -(CH2) p -C(O)-,

[0742] X1 is selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic and optionally substituted alicyclic,

[0743] wherein m1, m2 and n can each be independently selected from a number that is at least 0.

[0744] For example, in the structure represented by formula (Lx-2), the L2 may comprise an optionally substituted -(CH2CH2O) n -C(O)-.

[0745] For example, in the structure represented by formula (Lx-2), n can be 2.

[0746] For example, in the structure represented by formula (Lx-2), the L2 may comprise an optionally substituted -(CH2) m1 -X1-(CH2) m2 -C(O)-.

[0747] For example, in the structure represented by formula (Lx-2), X1 can be selected from the following group: -O- and optionally substituted -C(O)-NH-.

[0748] For example, in the structure represented by formula (Lx-2), m1 may be 2.

[0749] For example, in the structure represented by formula (Lx-2), m2 can be 2.

[0750] For example, in the structure represented by formula (Lx-2), X1 may include a group selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group.

[0751] For example, in the structure represented by formula (Lx-2), X1 may include an optionally substituted phenyl group.

[0752] For example, in the structure represented by formula (Lx-2), X1 may include an optionally substituted pyridyl group.

[0753] For example, in the structure represented by formula (Lx-2), m1 may be 0.

[0754] For example, in the structure represented by formula (Lx-2), m2 can be 1.

[0755] For example, in the structure represented by formula (Lx-2), X1 may include an optionally substituted heteroalicyclic group containing two oxygen atoms.

[0756] For example, in the structure represented by formula (Lx-2), X1 may include an optionally substituted

[0757] For example, in the structure represented by formula (Lx-2), X1 may include an optionally substituted cyclohexyl group.

[0758] For example, in the structure represented by formula (Lx-2), m1 may be 1.

[0759] For example, in the structure represented by formula (Lx-2), m2 can be 0.

[0760] For example, in the structure represented by formula (Lx-2), the L2 may comprise an optionally substituted -(CH2) p -C(O)-.

[0761] For example, in the structure represented by formula (Lx-2), p can be 5.

[0762] For example, in the structure shown in formula (Lx-2), the L2 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0763] For example, in the structure represented by formula (Lx-2), the L3 may comprise a peptide residue.

[0764] For example, in the structure represented by formula (Lx-2), the L3 may comprise a peptide residue consisting of amino acids selected from the following group: phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid and glycine.

[0765] For example, in the structure represented by formula (Lx-2), the L3 may include a peptide residue consisting of an amino acid selected from the group consisting of glycine, phenylalanine, valine, and citrulline.

[0766] For example, in the structure represented by formula (Lx-2), the L3 may comprise a peptide residue selected from the following group: -glycine-phenylalanine-glycine-(-Gly-Phe-Gly-), -glycine-glycine-phenylalanine-glycine-(-Gly-Gly-Phe-Gly-) and -valine-citrulline-(-Val-Cit-).

[0767] For example, in the structure represented by formula (Lx-2), the L3 may include a structure selected from the following group:

[0768]

[0769] For example, in the structure shown in formula (Lx-2), the L5 may include an optionally substituted The L5 can be directly connected to the following structure: For example, wherein R1 and R2 may be each independently selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C1-C8 alkyl group, an optionally substituted C1-C8 haloalkyl group, and an optionally substituted C1-C8 deuterated alkyl group;

[0770] Alternatively, R1 and R2 may form together with the carbon atom to which they are attached a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted alicyclic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group,

[0771] R6 and R7 may each be independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R6 and R7 may be taken together with the atoms to which they are attached to form an optionally substituted cycloalkyl,

[0772] Here, v can be selected from a number that is at least 0.

[0773] For example, in the structure represented by formula (Lx-2), R6 may be hydrogen.

[0774] For example, in the structure represented by formula (Lx-2), the R6 may be an optionally substituted methyl group.

[0775] For example, in the structure represented by formula (Lx-2), R6 may be an optionally substituted halogenated methyl group.

[0776] For example, in the structure represented by formula (Lx-2), R6 may be a methyl group substituted with fluorine.

[0777] For example, in the structure represented by formula (Lx-2), R6 may be a trifluoromethyl group.

[0778] For example, in the structure represented by formula (Lx-2), the R6 may be an optionally substituted cycloalkyl group.

[0779] For example, in the structure represented by formula (Lx-2), R6 may be an optionally substituted cyclopropyl group.

[0780] For example, in the structure represented by formula (Lx-2), R7 may be hydrogen.

[0781] For example, in the structure represented by formula (Lx-2), R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cyclopropyl group.

[0782] For example, in the structure represented by formula (Lx-2), R6 and R7 can be taken together with the atoms to which they are attached to form an optionally substituted cyclobutyl group.

[0783] For example, in the structure represented by formula (Lx-2), v can be 0.

[0784] For example, in the structure represented by formula (Lx-2), v may be 1.

[0785] For example, in the structure shown in formula (Lx-2), the L5 may comprise a structure selected from the following groups: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted

[0786] In another aspect, the present application also provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound comprises a structure selected from the following group:

[0787]

[0788]

[0789] Pharmaceutical composition

[0790] The pharmaceutical compositions described herein may contain, in addition to the active compound, one or more excipients, which may be selected from the following groups: fillers (diluents), binders, wetting agents, disintegrants, and excipients. Depending on the method of administration, the composition may contain 0.1 to 99% by weight of the active compound.

[0791] The pharmaceutical composition containing the active ingredient may be in a form suitable for oral administration, such as a tablet, troche, lozenge, aqueous or oily suspension, dispersible powder or granules, emulsion, hard or soft capsule, or syrup. Oral compositions may be prepared according to any method known in the art for preparing pharmaceutical compositions, and may contain a binder, a filler, a lubricant, a disintegrant, or a pharmaceutically acceptable wetting agent. The composition may also contain one or more ingredients selected from the group consisting of a sweetener, a flavoring agent, a coloring agent, and a preservative.

[0792] Aqueous suspensions may contain the active ingredient and excipients suitable for preparing aqueous suspensions for mixing. Aqueous suspensions may also contain one or more preservatives, such as one or more colorants, one or more flavorings, and one or more sweeteners. Oil suspensions may be prepared by suspending the active ingredient in a vegetable oil. Oil suspensions may contain a thickening agent. The sweeteners and flavorings mentioned above may also be added.

[0793] Pharmaceutical compositions can also be prepared as dispersible powders and granules for preparing aqueous suspensions, providing the active ingredient, which is mixed with water to form one or more of a dispersant, wetting agent, suspending agent, or preservative. Other excipients such as sweeteners, flavoring agents, and coloring agents may also be added. These compositions can be preserved by the addition of antioxidants such as ascorbic acid. The pharmaceutical compositions of the present application can also be in the form of oil-in-water emulsions.

[0794] The pharmaceutical composition may be in the form of a sterile injectable aqueous solution. Acceptable solvents or solvents that may be used include water, Ringer's solution, and isotonic sodium chloride solution. The sterile injectable formulation may be a sterile injectable oil-in-water microemulsion in which the active ingredient is dissolved in an oil phase. For example, the active ingredient may be dissolved in a mixture of soybean oil and lecithin. The oil solution may then be added to a mixture of water and glycerol to form a microemulsion. The injection or microemulsion may be injected into the patient's bloodstream via local, bolus injection. Alternatively, the solution or microemulsion may be administered in a manner that maintains a constant circulating concentration of the compound of the present invention. To maintain this constant concentration, a continuous intravenous drug delivery device may be used. For example, the device may be an intravenous pump.

[0795] The pharmaceutical composition may be in the form of a sterile injectable aqueous or oily suspension for intramuscular and subcutaneous administration. Such suspensions may be prepared according to known techniques using suitable dispersants or wetting agents and suspending agents as described herein. Sterile injectable formulations may also be sterile injectable solutions or suspensions prepared in a parenterally acceptable nontoxic diluent or solvent. Alternatively, a sterile fixed oil may conveniently be used as a solvent or suspending medium.

[0796] The compounds of the present invention may be administered in the form of suppositories for rectal administration. These pharmaceutical compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid in the rectum, thereby dissolving and releasing the drug in the rectum. Such substances include cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol.

[0797] As is well known to those skilled in the art, the dosage of a drug depends on a variety of factors, including but not limited to the following: the activity of the specific compound used, the age of the patient, the weight of the patient, the health status of the patient, the behavior of the patient, the diet of the patient, the time of administration, the route of administration, the rate of excretion, the combination of drugs, etc.; in addition, the optimal treatment mode, such as the mode of treatment, the daily dosage of the compound described in the present application or its tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt thereof, and / or the compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt thereof, or the type of pharmaceutically acceptable salt thereof can be verified according to traditional treatment regimens.

[0798] Methods of prevention and / or treatment

[0799] The present application provides a compound of the present application or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically acceptable salt and / or the use of the pharmaceutical composition of the present application in the preparation of a medicament, and the medicament of the present application can be used to treat and / or prevent tumors. For example, the tumor described in the present application can be selected from tumors associated with the expression of the following groups of targets: HER2 and TROP2. For example, the tumor associated with the expression of the target described in the present application can include tumors with high expression of the target and / or tumors that are positive for the target. For example, the tumor described in the present application can include solid tumors and / or blood tumors. For example, the tumor described in the present application can be selected from the following groups: breast cancer, gastric cancer, ovarian cancer, bladder cancer, colorectal cancer, endometrial cancer, kidney cancer, lung cancer, pancreatic cancer, prostate cancer and thyroid cancer. For example, the tumor described herein can be selected from the following group: breast cancer, ovarian cancer, cervical cancer, endometrial cancer, urothelial cancer, lung cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, bladder cancer, kidney cancer, pancreatic cancer, thyroid cancer and head and neck cancer.

[0800] The present application provides a compound of the present application or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically acceptable salt and / or pharmaceutical composition of the present application, which can be used to treat and / or prevent tumors. For example, the tumor described in the present application can be selected from tumors associated with the expression of the following groups of targets: HER2 and TROP2. For example, the tumor associated with the expression of the target described in the present application can include tumors with high expression of the target and / or tumors that are positive for the target. For example, the tumor described in the present application can include solid tumors and / or blood tumors. For example, the tumor described in the present application can be selected from the following groups: breast cancer, gastric cancer, ovarian cancer, bladder cancer, colorectal cancer, endometrial cancer, kidney cancer, lung cancer, pancreatic cancer, prostate cancer and thyroid cancer. For example, the tumor described herein can be selected from the following group: breast cancer, ovarian cancer, cervical cancer, endometrial cancer, urothelial cancer, lung cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, bladder cancer, kidney cancer, pancreatic cancer, thyroid cancer and head and neck cancer.

[0801] The present application provides a method for treating and / or preventing tumors, which may comprise administering to a subject in need thereof a compound of the present application or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof and / or a pharmaceutical composition of the present application. For example, the tumor described in the present application may be selected from tumors associated with the expression of the following groups of targets: HER2 and TROP2. For example, the tumor associated with the expression of the target described in the present application may include tumors with high expression of the target and / or tumors that are positive for the target. For example, the tumor described in the present application may include solid tumors and / or blood tumors. For example, the tumor described in the present application may be selected from the following groups: breast cancer, gastric cancer, ovarian cancer, bladder cancer, colorectal cancer, endometrial cancer, kidney cancer, lung cancer, pancreatic cancer, prostate cancer and thyroid cancer. For example, the tumor described herein can be selected from the following group: breast cancer, ovarian cancer, cervical cancer, endometrial cancer, urothelial cancer, lung cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, bladder cancer, kidney cancer, pancreatic cancer, thyroid cancer and head and neck cancer.

[0802] Without intending to be bound by any theory, the following examples are merely intended to illustrate the compounds, preparation methods, and uses of the present application, and are not intended to limit the scope of the present invention.

[0803] Example

[0804] Example 1

[0805] Example 1.1

[0806]

[0807]

[0808]

[0809]

[0810] first step

[0811] Compound 1a (50.00 g, 135.90 mmol) and 2-hydroxybenzyl acetate (45.00 g, 271.70 mmol) were added sequentially to a 1 L three-necked flask. After nitrogen displacement, anhydrous tetrahydrofuran (500 mL) was added. The reaction system was placed in an ice bath, and anhydrous p-toluenesulfonic acid (2.30 g, 13.40 mmol) was added. The reaction was stirred and continued for 2 hours under ice bath. Water (1 L) and ethyl acetate (1 L) were added to the reaction solution, and the layers were separated. The organic phase was washed sequentially with aqueous sodium bicarbonate solution, water, and aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue. The residue was purified by silica gel column chromatography (methanol:dichloromethane = 0-100%) to obtain compound 1b (27.00 g) in a yield of 42%.

[0812] MS-ESI calculated value [M+Na] + 497, measured value: 497.

[0813] Step 2

[0814] Compound 1b (17.00 g, 35.86 mmol) was dissolved in N,N-dimethylacetamide (170 mL), and 1,8-diazobisspiro[5.4.0]undec-7-ene (2.78 g, 18.29 mmol) was added. The mixture was reacted at room temperature under nitrogen for 1 hour. Pyridinium p-toluenesulfonate (4.59 g, 18.29 mmol), 1-hydroxybenzotriazole (4.59 g, 34.00 mmol), 1c (16.66 g, 33.18 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.37 g, 33.18 mmol) were then added to the reaction mixture. The mixture was stirred at room temperature for 2.5 hours. 2-Methyltetrahydrofuran (175 mL) and saturated aqueous sodium chloride solution (260 mL) were added to the reaction solution, and the organic phase was extracted and separated. The aqueous phase was further extracted with 2-methyltetrahydrofuran (100 mL×2). The organic phases were combined and washed once with 10% citric acid (90 mL), three times with saturated sodium bicarbonate (175 mL×3), and once with saturated brine (100 mL). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to about 50 mL. Isopropanol (120 mL) was added, and the mixture was further concentrated to about 50 mL. Isopropanol (300 mL) was added, and the temperature was raised to 60°C and stirred for 1 hour. The solution was then cooled to 0-5°C and stirred for 2 hours. The solid was collected by filtration and rinsed with 5°C isopropanol to obtain compound 1d (19.00 g). Yield: 78%.

[0815] Step 3

[0816] Compound 1d (11.50 g, 15.65 mmol) was dissolved in a mixture of tetrahydrofuran (230 mL) and water (115 mL). 1,8-diazabicyclo[5.4.0]undec-7-ene (10.70 g, 70.39 mmol) was added, and the mixture was stirred at room temperature under a nitrogen atmosphere for 4 hours. The reaction system was extracted five times with methyl tert-butyl ether (100 mL x 5). The aqueous phase was concentrated to obtain a yellow oil, which was dissolved in isopropanol (70 mL). This solution was then added dropwise to methyl tert-ether (700 mL). A white solid precipitated and was collected by filtration. The solid was dissolved in ethanol and concentrated under reduced pressure to obtain compound 1e (9.50 g) as a white foamy solid in a 93% yield.

[0817] Step 4

[0818] Compound 1e (1.00 g, 1.53 mmol) was dissolved in a mixture of acetonitrile (10 mL) and water (20 mL), and 1f (0.54 g, 1.75 mmol) was added. The mixture was stirred at room temperature under nitrogen for 5 hours. Water (20 mL) was added to the reaction system, and the pH was adjusted to 3-4 with 0.5N aqueous hydrochloric acid. The mixture was extracted four times with a mixed solvent of isopropanol / dichloromethane (v:v = 4:1, 50 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford a yellow oil. The oil was dissolved in a mixed solvent of dichloromethane / methanol (v:v = 4:1, 5 mL). The solution was added dropwise to methyl tert-butyl ether (100 mL), resulting in the precipitation of a white solid, which was collected by filtration to afford compound 1g (850 mg), in a 90% yield.

[0819] MS-ESI calculated value [M+Na] + 639, measured value: 639.

[0820] Step 5

[0821] Compound 1h (12.20 g, 46.39 mmol) was weighed into a three-necked flask (500 mL). After nitrogen replacement, the reaction flask was placed in an ice bath and anhydrous N,N-dimethylformamide (120 mL) was added. Imidazole (15.77 g, 232.00 mmol) and triethylsilyl chloride (27.97 g, 185.56 mmol) were added to the reaction system in sequence. After stirring for ten minutes, 4-dimethylaminopyridine (5.66 g, 46.39 mmol) was added and the reaction was continued at 0°C with stirring for 3 hours. The reaction system was diluted with methyl tert-butyl ether (1.20 L), and then water (1.2 L) was added for separation. The aqueous phase was extracted with methyl tert-butyl ether (1.2 L), and the organic phases were combined. The organic phase was washed once more with water (1.20 L), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue, which was purified by silica gel column chromatography (ethyl acetate:petroleum ether = 0-100%) to obtain crude product 1i (16.00 g).

[0822] Step 6

[0823] Crude product 1i (16.00 g, 32.59 mmol) and Lawesson's reagent (13.18 g, 32.59 mmol) were weighed into a 1 L three-necked flask. Anhydrous toluene (600 mL) was added. After nitrogen displacement, the reaction system was heated to 125°C and refluxed for 5 hours. The reaction solution was concentrated to obtain a residue, which was purified by silica gel column chromatography (ethyl acetate:petroleum ether = 0-100%) to obtain crude product 1j (16.00 g).

[0824] Step 7

[0825] Crude product 1j (16 g) was dissolved in anhydrous tetrahydrofuran (640 mL). Triethylamine trihydrofluoride (11.93 g, 74.00 mmol) was added dropwise under ice-cooling. After complete addition, the mixture was slowly returned to room temperature with stirring. After reacting overnight at room temperature, the reaction system was diluted with ethyl acetate (1 L). The layers were separated, and the organic phase was washed with saturated brine (500 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue. The residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether = 0-100%) to provide compound 1k (6.38 g), with a three-step yield of 49%.

[0826] Step 8

[0827] Compound 1l (3.00 g, 12.00 mmol), 1k (4.33 g, 15.52 mmol), pyridinium p-toluenesulfonate (3.90 g, 15.50 mmol), and o-methylphenol (15 mL) were placed in a 500 mL three-necked flask. Anhydrous toluene (300 mL) was added. After nitrogen displacement, the reaction system was heated to 120°C in an oil bath for 32 hours. The reaction system was cooled to room temperature and the insoluble solid was collected by filtration. The crude product was slurried with methyl tert-butyl ether (60 mL) for 1 hour, filtered, and dried to obtain compound 1m (3.0 g) in a yield of 51%.

[0828] Step 9

[0829] Compound 1m (2.30 g, 4.67 mmol) was weighed into a 500 mL single-necked bottle, and 6N aqueous hydrochloric acid (230 mL) was added. The reaction system was heated to 110°C and refluxed for 12 hours. The reaction system was hot filtered to remove insoluble matter, and the filtrate was concentrated under reduced pressure to obtain the crude product 1n (a set of diastereomers). Preparative HPLC purification afforded compounds 1n-P1 (412 mg, the less polar isomer by TLC) and 1n-P2 (495 mg, the more polar isomer by TLC) in a yield of 34%.

[0830] Step 10

[0831] Compound 1n-P1 (50 mg, 0.09 mmol), 1g (76 mg, 0.12 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (31 mg, 0.16 mmol) and N,N-dimethylformamide (2 mL) were added to a 10 mL single-necked bottle in sequence. 2,4,6-trimethylpyridine (60 mg, 0.49 mmol) was then added dropwise to the mixture. After the addition was complete, the mixture was stirred at room temperature for 3 hours. The reaction solution was added dropwise to methyl tert-butyl ether (60 mL). Solids precipitated and were collected by filtration. The solids were dissolved in a mixed solvent of dichloromethane / methanol (V:V=6:1, 30 mL) and concentrated to obtain a crude product. The crude product was purified by liquid phase preparative separation to obtain compound II-12-a (33 mg) in a yield of 35%.

[0832] MS-ESI calculated value [M+H] + 1050, measured value: 1050.

[0833] 1H NMR (400MHz, DMSO-d6) δ8.65(t,J=6.4Hz,1H),8.60(d,J=8.8Hz,1H),8.28(t,J=5.6Hz,1H) ,8.10(d,J=8.0Hz,1H),8.06(t,J=6.0Hz,1H),7.99(t,J=5.6Hz,1H),7.79(d,J=10.8Hz,1H ),7.78(s,1H),7.28-7.14(m,5H),6.97(s,1H),5.90(d,J=16.4Hz,1H),5.70-5,60(m,1H), 5.51(s,1H),5.46(d,J=2.8Hz,1H),5.30(d,J=19.6Hz,1H),4.67(d,J=6.4Hz,1H),4.51-4.4 1(m,1H),4.18-4.04(m,2H),3.77-3.73(m,1H),3.73-3.68(m,2H),3.68-3.62(m,2H),3.62 -3.58(m,1H),3.58-3.54(m,1H),3.38-3.31(m,2H),3.30-3.20(m,1H),3.20-3.08(m,1H),3 .01(dd,J=14.0,4.8Hz,1H),2.80-2.71(m,1H),2.37(s,3H),2.26-2.15(m,2H),2.08(t,J= 7.6Hz,2H),1.94-1.82(m,2H),1.54-1.37(m,4H),1.25-1.10(m,2H),0.85(t,J=7.6Hz,3H).

[0834] Example 1.2

[0835]

[0836]

[0837] first step

[0838] Compound 2a (1.00 g, 7.52 mmol) was dissolved in N,N-dimethylformamide (10 mL), and maleic anhydride (0.74 g, 7.52 mmol) was added. The mixture was stirred at room temperature under nitrogen atmosphere for 16 hours. This was designated as solution A and set aside.

[0839] Take a 50mL three-necked flask, add N-hydroxysuccinimide (3.46g, 30.08mmol) and N,N-dimethylformamide (10mL), cool to 0℃, add trifluoroacetic anhydride (6.31g, 30.08mmol) dropwise, stir for 0.5 hours, then add 2,4,6-trimethylpyridine (5.46g, 45.10mmol), continue stirring for 0.5 hours after the addition is complete, and add the reaction solution dropwise to the above solution A. After the addition is complete, stir at room temperature for 16 hours. The reaction system is added with 1N hydrochloric acid to adjust the pH to 2-3, extracted with dichloromethane (50mL), and the organic phase is washed three times with water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue. The residue is purified by silica gel column chromatography (ethyl acetate: petroleum ether = 0-100%) to obtain compound 2b (1.20g), yield: 51%.

[0840] Step 2

[0841] Compound 2b (0.40 g, 1.29 mmol) was dissolved in a mixed solvent of acetonitrile (8 mL) and water (16 mL), and compound 1e (0.54 g, 0.80 mmol) was added. The mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. The reaction solution was concentrated under reduced pressure and directly purified by preparative HPLC to give compound 2c (0.30 g) in a yield of 61%.

[0842] Step 3

[0843] Compound 1n (50 mg, 0.09 mmol), 2c (76 mg, 0.12 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (31 mg, 0.16 mmol), and N,N-dimethylformamide (2 mL) were added sequentially to a 10 mL single-necked flask. 2,4,6-Trimethylpyridine (60 mg, 0.49 mmol) was then added dropwise to the mixture. After the addition was complete, the mixture was stirred at room temperature for 3 hours. The reaction solution was added dropwise to methyl tert-butyl ether (60 mL). A solid precipitated and was collected by filtration. The solid was dissolved in a dichloromethane / methanol mixture (V:V = 6:1, 30 mL) and concentrated to give a crude product. The crude product was purified by liquid phase preparative HPLC to give compound II-1-a (16 mg) in a yield of 17%.

[0844] MS-ESI calculated value [M+H] + 1052, measured value: 1052.

[0845] 1H NMR (400MHz, DMSO-d6) δ8.65(t,J=6.8Hz,1H),8.61(d,J=9.2Hz,1H),8.28(t,J=4. 4Hz,1H),8.14-8.06(m,2H),8.06(t,J=5.6Hz,1H),7.82(d,J=11.2Hz,1H),7.79(s ,1H),7.28-7.13(m,5H),6.99(s,2H),5.92(d,J=16.8Hz,1H),5.70-5,60(m,1H),5 .53(d,J=8.0Hz,1H),5.48(d,J=4.8Hz,1H),5.37(d,J=19.6Hz,1H),4.68(d,J=6.4 Hz,1H),4.51-4.41(m,1H),4.17-4.04(m,2H),3.72-3.68(m,2H),3.68-3.63(m,2H ),3.62-3.58(m,1H),3.58-3.54(m,3H),3.54-3.39(m,3H),3.48-3.43(m,2H),3.1 9-3.08(m,1H),3.06-2.97(m,1H),2.80-2.70(m,1H),2.70-2.65(m,1H),2.39(s,3 H),2.35-2.28(m,3H),2.27-2.18(m,2H),1.94-1.82(m,2H),0.85(t,J=7.2Hz,3H).

[0846] Example 1.3

[0847]

[0848] first step

[0849] Compound 3a (10.00 g, 95.11 mmol) was dissolved in N,N-dimethylformamide (100 mL), and maleic anhydride (9.32 g, 95.11 mmol) was added. The mixture was stirred at room temperature under nitrogen for 16 hours. Water (250 mL) was added to the reaction solution, and the aqueous phase was extracted with dichloromethane / isopropanol (v:v = 4:1, 200 mL x 3). The organic phases were combined and concentrated under reduced pressure to obtain crude product 3b (12.00 g).

[0850] Step 2

[0851] Crude product 3b (4.00 g, 31.70 mmol) was dissolved in N,N-dimethylformamide (60 mL), and di(p-nitrobenzene) carbonate (16.40 g, 53.95 mmol) was added. The temperature was raised to 30°C, and N,N-diisopropylethylamine (4.18 g, 32.40 mmol) was added. The reaction mixture was stirred for 2 hours. The reaction solution was cooled to room temperature, and water (600 mL) was added. The aqueous phase was extracted with dichloromethane (300 mL x 2). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a residue. The residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether = 0-100%) to obtain compound 3c (2.40 g), with a two-step yield of 13%.

[0852] Step 3

[0853] Compound 3c (400 mg, 1.14 mmol) was dissolved in a mixture of acetonitrile (8 mL) and water (16 mL). Compound 1e (760 mg, 1.13 mmol) was added and stirred at room temperature under nitrogen for 16 hours. The reaction solution was directly purified by preparative HPLC to afford compound 3d (109 mg) in a 15% yield.

[0854] Step 4

[0855] To a single-necked flask (10 mL) were added compound 1n-P1 (69 mg, 0.12 mmol), 3d (110 mg, 0.17 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (44 mg, 0.23 mmol) and N,N-dimethylformamide (2.5 mL) in sequence, and then 2,4,6-trimethylpyridine (84 mg, 0.69 mmol) was added dropwise to the mixture. The reaction was stirred at room temperature for 3 hours. The reaction solution was added dropwise to methyl tert-butyl ether (75 mL), and a solid precipitated. The solid was collected by filtration and dissolved in a dichloromethane / methanol mixed solvent (V:V=6:1, 30 mL). The residue was concentrated under reduced pressure to obtain a residue, which was purified by preparative HPLC to obtain compound II-3-a (45 mg) in a yield of 35%.

[0856] MS-ESI calculated value [M+H] + 1068.4, measured value: 1068.9.

[0857] 1H NMR (400MHz, DMSO-d6) δ8.68(t,J=6.8Hz,1H),8.62(d,J=9.2Hz,1H),8.31(t,J=5.6Hz,1H),8.12(d,J=8.0Hz,1H),7.99(t,J=5.6Hz,1H),7.78(s,1H ),7.77(d,J=10.8Hz,1H),7.38(t,J=6.0Hz,1H),7.27-7.13(m,5H),6.99( s,2H),5.90(d,J=16.4Hz,1H),5.70-5,61(m,1H),5.51(s,1H),5.46(d,J= 4.4Hz,1H),5.29(d,J=19.6Hz,1H),4.67(d,J=6.4Hz,1H),4.51-4.41(m,1 H),4.17-4.04(m,2H),4.02-3.94(m,2H),3.79-3.67(m,3H),3.35-3.20(m ,1H),3.20-3.07(m,1H),3.00(dd,J=14.0,4.4Hz,1H),2.78-2.65(m,1H), 2.37(s,3H),2.25-2.15(m,2H),1.92-1.82(m,2H),0.85(t,J=7.2Hz,3H).

[0858] Example 1.4

[0859]

[0860] first step

[0861] Compound 4a (2.00 g, 7.52 mmol) and β-alanine (0.67 g, 7.52 mmol) were dissolved in acetonitrile (20 mL). The mixture was cooled to 0°C and N,N-diisopropylethylamine (1.94 g, 15.03 mmol) was added. After the addition, the mixture was returned to room temperature and stirred for 16 hours. Water (100 mL) was added to the reaction solution, which was then extracted with dichloromethane / isopropanol (v:v = 4:1, 250 mL x 10). The organic phases were combined and concentrated to obtain a residue, which was then purified by silica gel column chromatography (methanol:dichloromethane = 0-100%) to obtain compound 4b (2.00 g).

[0862] Step 2

[0863] Compound 4b (1.80 g, 7.50 mmol) was dissolved in N,N-diisopropylethylamine (8 mL), and dicyclohexylcarbodiimide (1.85 g, 9.00 mmol) was added. The mixture was stirred for 30 minutes after addition. N-hydroxysuccinimide (0.95 g, 8.25 mmol) was then added, and the mixture was stirred at room temperature for 16 hours. The reaction solution was filtered and directly purified by preparative HPLC to obtain compound 4c (530 mg) in a yield of 21%.

[0864] Step 3

[0865] Compound 4c (0.50 g, 1.48 mmol) was dissolved in a mixture of acetonitrile (8 mL) and water (16 mL), and 1e (0.98 g, 1.50 mmol) was added. The mixture was stirred at room temperature under nitrogen for 16 hours. The reaction solution was directly subjected to liquid-phase preparative separation and purification to afford compound 4d (42 mg) in a 4% yield.

[0866] Step 4

[0867] To a single-necked flask (10 mL) were added compound 1n-P1 (26 mg, 0.046 mmol), 4d (42 mg, 0.065 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (16 mg, 0.083 mmol), and N,N-dimethylformamide (1 mL) in sequence. 2,4,6-trimethylpyridine (32 mg, 0.26 mmol) was then added dropwise to the mixture. The reaction was allowed to react at room temperature for 3 hours. The reaction solution was added dropwise to methyl tert-butyl ether (30 mL). A solid precipitated and was collected by filtration. The solid was dissolved in a dichloromethane / methanol mixed solvent (V:V = 6:1, 30 mL) and concentrated under reduced pressure to obtain a residue. The residue was purified by preparative HPLC to obtain compound II-2-a (13 mg) in a yield of 26%.

[0868] MS-ESI calculated value [M+H] + 1079.4, measured value: 1079.9.

[0869] 1H NMR (400MHz, DMSO-d6) δ8.68(t,J=6.8Hz,1H),8.63(d,J=8.8Hz,1H),8.31(t,J=6.0Hz,1H),8.18(t,J=7.2Hz,1H),8.10(d,J=7.2Hz,1H),8.03(t,J=5 .6Hz,1H),7.98(t,J=5.6Hz,1H),7.82(d,J=10.8Hz,1H),7.79(s,1H),7.28 -7.13(m,5H),6.98(s,2H),6.70(s,1H),5.90(d,J=16.8Hz,1H),5.70-5,60 (m,1H),5.56-5.45(m,2H),5.36(d,J=19.6Hz,1H),4.68(d,J=6.8Hz,1H),4 .53-4.42(m,1H),4.18-4.04(m,2H),3.78-3.64(m,5H),3.62-3.52(m,4H), 3.22-3.14(m,1H),3.06-2.97(m,1H),2.80-2.70(m,1H),2.68-2.65(m,1H) ,2.39(s,3H),2.34-2.16(m,6H),1.92-1.82(m,2H),0.85(t,J=7.2Hz,3H).

[0870] Example 1.5

[0871]

[0872]

[0873] first step

[0874] Under nitrogen protection and at 0°C, 1n (24.00 mg, 0.053 mmol) and 1g (32.78 mg, 0.053 mmol) were dissolved in N,N-dimethylformamide (1.5 mL). A solution of N,N-diisopropylethylamine (17.10 mg, 0.0133 mmol) in N,N-dimethylformamide (0.4 mL) was added dropwise, followed by a solution of 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (24.20 mg, 0.064 mmol) in N,N-dimethylformamide (0.6 mL). After the addition was complete, the mixture was kept at 0°C for 1 hour. The reaction solution was sent for preparative purification to obtain compounds II-12-a (16 mg) and II-12-b (19 mg), with a combined yield of 64%.

[0875] II-12-b:

[0876] MS-ESI calculated value [M+H] + 1050.4, measured value: 1050.3.

[0877] 1 H NMR (400MHz, DMSO-d6) δ8.71-8.61(m,2H),8.31(t,J=4.8Hz,1H),8.12(d,J=7.2Hz,1H),8.07(t,J=6.0Hz,1H ),8.00(t,J=5.2Hz,1H),7.82(dd,J=10.8,2.0Hz,1H),7.80(s,1H),7.28-7.13(m,6H),6.99(s,2H),6.70(br s,1H),5.92(d,J=16.8Hz,1H),5.70-5,61(m,1H),5.52(d,J=17.2Hz,2H),5.37(d,J=19.6Hz,1H) ,4.68(d,J=6.8Hz,2H),4.51-4.41(m,1H),4.18-4.04(m,2H),3.77-3.50(m,7H),3.32-3.20(m,1H) ),3.20-3.08(m,1H),3.07-2.96(m,1H),2.82-2.71(m,1H),2.39(s,3H),2.26-2.15(m,2H),2.09 (t,J=7.6Hz,2H),1.96-1.82(m,2H),1.52-1.39(m,4H),1.25-1.10(m,2H),0.85(t,J=7.6Hz,3H).

[0878] Example 1.6

[0879]

[0880] first step

[0881] To a single-necked flask (25 mL) were added 1n (20 mg, 0.04 mmol) and a 1.2 mg / mL solution of glycolic acid in N,N-dimethylformamide (2.00 mL, 0.032 mmol) in sequence. The reaction system was cooled to 0 ° C. N,N-diisopropylethylamine (11 mg, 0.08 mmol), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphorus were added in sequence. To the mixture was added 1.2 mg / mL of glycolic acid in N,N-dimethylformamide (0.20 mL, 0.003 mmol) and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1 mg). The reaction was continued for 1 hour, and the reaction system was diluted with ethyl acetate (80 mL). The organic phase was washed with 0.5N dilute hydrochloric acid (5 mL x 1), saturated sodium bicarbonate solution (10 mL x 2) and saturated brine (10 mL x 5), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue. The residue was purified by preparative thin-layer chromatography (methanol:dichloromethane) to give compounds X (2 mg) and Y (5 mg). The total yield was 34%.

[0882] X:

[0883] MS-ESI calculated value [M+H] + 510, the actual measured value is 510.

[0884] 1 H NMR (400MHz, DMSO-d6) δ8.54(d,J=8.8Hz,1H),7.82(d,J=10.8Hz,1H),7.80(s,1H) ,5.92(d,J=16.8Hz,1H),5.69–5.60(m,1H),5.53(d,J=20.4Hz,1H),5.52(d,J=16. 4Hz,1H),5.35(d,J=20.0Hz,1H),4.15–3.98(m,2H),3.30–3.22(m,1H),3.19–3.09 (m,1H),2.40(s,3H),2.26–2.14(m,2H),1.96–1.84(m,2H),0.86(t,J=7.2Hz,3H).

[0885] Y:

[0886] MS-ESI calculated value [M+H] + 510, the actual measured value is 510.

[0887] 1H NMR (400MHz, DMSO-d6) δ8.54(d,J=9.2Hz,1H),7.81(d,J=11.2Hz,1H),7.80(s,1H) ,6.69(s,1H),5.92(d,J=16.8Hz,1H),5.69–5.62(m,1H),5.62–5.56(m,1H),5.55–5 .47(m,2H),5.33(d,J=20.0Hz,1H),4.16–3.98(m,2H),3.30–3.20(m,1H),3.16–3.0 7(m,1H),2.39(s,3H),2.26–2.15(m,2H),1.95–1.85(m,2H),0.86(t,J=7.2Hz,3H).

[0888] Example 2

[0889] Method for preparing antibody-drug conjugates

[0890] The antibody was dialyzed into 50mM PB (pH 7.4 ± 0.1) buffer to obtain an antibody intermediate. To 20mg of the antibody intermediate, 0.2mL of 10mM diethylenetriaminepentaacetic acid (DTPA) stock solution was added to a final DTPA concentration of 1mM. A 10mM tris(2-carboxyethyl)phosphine hydrochloride (TCEP) stock solution was added, with a molar ratio of reducing agent TCEP to antibody of (2.4-2.6):1.0. 50mM PB (pH 7.4 ± 0.1) buffer was added to the reaction system to make up 2mL. After thorough mixing, the mixture was placed in a thermomixer at 25 ± 2°C, 400 rpm, and the reduction reaction lasted for 120-150 minutes. After the reduction was complete, an appropriate amount of 5mM linker-drug stock solution was added to each reaction system in an ice-water bath, with a molar ratio of linker-drug to antibody of (8.0-10.0):1.0. After thorough mixing, place in a thermomixer and allow the coupling reaction to proceed at 25 ± 2°C, 400 rpm, for 60-90 minutes. After the coupling is complete, dialyze the ADC sample into a dialysis solution (20 mM His / His-HCl, pH 6.0 ± 0.1) using an ultrafiltration centrifuge tube to obtain the ADC stock solution, which is then aliquoted and stored at -80°C.

[0891] Linker-payload Compound Antibody Antibody-Drug Conjugate ADC II-1-a (Example 1.2) Trazutumab Trazutumab ADC I-1-a II-2-a (Example 1.4) Trazutumab Trazutumab ADC I-2-a II-3-a (Example 1.3) Trazutumab Trazutumab ADC I-3-a II-12-a (Example 1.1) Trazutumab Trazutumab ADC I-12-a II-12-b (Example 1.5) Trazutumab Trazutumab ADC I-12-b II-1-a (Example 1.2) TROP2 Antibody TROP2 Antibody ADC IIa

[0892] An exemplary TROP2 antibody sequence may comprise LCDR1-3 in the light chain variable region VL and HCDR1-3 in the heavy chain variable region VH, wherein the VH may comprise the amino acid sequence shown in SEQ ID NO: 17, and the VL may comprise the amino acid sequence shown in SEQ ID NO: 18.

[0893] Example 3

[0894] In vitro proliferation inhibition assay of human tumor cells

[0895] Human breast cancer cells SK-BR-3 or gastric cancer cells NCI-N87 in the logarithmic growth phase were resuspended in complete culture medium and adjusted to the appropriate concentration. The cells were then added to a 96-well cell culture plate at a rate of 100 μL per well. The plates were incubated overnight in a 37°C, 5% CO2 incubator. The cell suspension was added to one of the 96 wells of the plate. Before addition, the cell suspension was detected using the CTG assay (CellTiter Glo assay kit, Promega, G7558) to determine the G0 value.

[0896] The linker-drug of the present application is obtained by referring to the method of Example 1 of the present application, and the antibody-drug conjugate (ADC) of the present application is obtained by referring to the method of Example 2 of the present application. For example, the linker-payload compound II-1 can be obtained by referring to the method of Example 1, and then coupled with any antibody (e.g., a HER2 antibody) by referring to the method of Example 2 of the present application to obtain ADC I-1. The sample of the control group can be prepared by referring to Example 2 of the present application and coupled with any antibody (e.g., a HER2 antibody).

[0897] The obtained ADC working solution was added to the cell culture plate using HP D300 in duplicate, with a starting ADC concentration of 1 μM and a 4-fold serial dilution for a total of 9 concentrations. The cell culture plate was placed in a 37°C, 5% CO2 incubator for 120 hours, then the cell plate was removed and equilibrated to room temperature. The luminescence reading was measured using the CellTiter Glo assay kit (Promega, G7558) and a multifunctional microplate reader (PerkinElmer, EnVision). The drug efficacy inhibition rate curve was plotted using XLFit and the IC was calculated. 50 and GI 50 value.

[0898] Table 1 In vitro proliferation inhibition assay activity of human tumor cells

[0899]

[0900]

[0901] Table 2 In vitro tumor cell proliferation inhibition assay activity

[0902]

[0903] As shown in Table 1 and Table 2, according to the activity test results, the ADCs prepared from the compounds of the present application all exhibited certain anti-tumor activity and were superior to the control group ADC1. The structure of the control group ADC1 can be shown as follows:

[0904]

[0905] In vitro proliferation inhibition assay of human tumor cells

[0906] Human tumor cells in the logarithmic growth phase were harvested, digested, resuspended in fresh complete culture medium, and adjusted to the appropriate concentration. The cells were then added to a 96-well cell culture plate at 150 μL / well. The cell culture plate was placed in a 37°C, 5% CO2 incubator and cultured overnight. The next day, different concentrations of the ADC sample to be tested (maximum final concentration 1 μM, 4-fold serial dilution) or buffer control were added to the corresponding wells of the cell culture plate. After further incubation in a carbon dioxide incubator for 120 hours, the test plate was equilibrated to room temperature and the luminescence readings were detected using the CellTiter Glo assay kit (Promega, G7558) and a multi-function microplate reader (Enspire 2300, PerkinElmer). The cell inhibition rate was calculated according to the following formula: Inhibition rate (%) = (1 – (RLU) ADC –RLU 空 白 ) / (RLU缓冲液 –RLU 空白 ))×100%. XLFit was used to draw the efficacy inhibition rate curve and calculate the IC 50 The experimental results showed that the inhibitory activity of the TROP2 antibody ADC IIa against multiple tumor cell lines with different target expression levels was significantly better than that of the control group ADC2 (see Table 3).

[0907] Table 3. Inhibitory activity against human tumor cell proliferation

[0908]

[0909] As shown in Table 3, according to the activity test results, the ADC prepared from the compound of the present application exhibited excellent anti-tumor activity and was superior to the control group ADC2. The structure of the control group ADC2 can be shown as follows:

[0910]

[0911] Example 4

[0912] In vivo antitumor efficacy assay

[0913] Gastric cancer cells NCI-N87 with high target expression were harvested during the logarithmic growth phase, counted, and adjusted to the appropriate concentration. The cells were then resuspended on ice in a 1:1 mixture of serum-free medium and Matrigel (Corning 356234) and inoculated subcutaneously on the right back of BALB / c nude mice, with 200 μL per mouse. After the tumors grew to a measurable size, the long and short diameters of each tumor were measured using a vernier caliper, and the tumor volume was calculated using the following formula: V = (a × b 2 ) / 2, where a represents the long diameter of the tumor and b represents the short diameter of the tumor.

[0914] When the average tumor volume grows to 100-200 mm 3 The animals were randomly divided into groups according to the tumor volume. Tumor-bearing nude mice were injected with solvent control (normal saline) or different doses of ADC (3 mg / kg or 10 mg / kg) through the tail vein for a total of one dose. The long and short diameters of the tumors were measured twice a week, and the animal body weight was recorded. The tumor volume of each group was counted, and the tumor growth inhibition rate (TGI) was calculated according to the following formula: TGI = 100% × [1-(TVt T -TV0 T ) / (TVt C -TV0 C )]. Where (TVt T represents the tumor volume of the drug-treated group on the day of measurement, TV0 T TVt represents the tumor volume of the drug-treated group at the time of grouping; Crepresents the tumor volume of the solvent control group on the day of measurement, TV0 C It represents the tumor volume of the solvent control group at the time of grouping (see Table 4).

[0915] Table 4. Growth inhibition rate of NCI-N87 nude mouse subcutaneous transplanted tumor

[0916] Compound dose inhibition rate TGI (%) Control group ADC 13 mg / kg 56% Control group ADC 110 mg / kg 108% Trazutumab ADC I-1-a 3 mg / kg 71% Trazutumab ADC I-1-a 10 mg / kg 111% Trazutumab ADC I-3-a 3 mg / kg 67% Trazutumab ADC I-2-a 3 mg / kg 80%

[0917] Activity test results show that the ADCs prepared from the compounds of this application all exhibited certain in vivo anti-tumor activity, showing significantly stronger anti-tumor activity than the control ADC1. Tumor-bearing mice tolerated all of the above drugs well, without experiencing symptoms such as weight loss.

[0918] In vivo antitumor efficacy assay

[0919] Calu-6 human lung cancer cells with low target expression in the logarithmic growth phase were collected, counted, and resuspended in EMEM culture medium. The cell concentration was adjusted to 5×10 7 Cells / mL were placed on ice until ready for use. Cells were injected subcutaneously into female BALB / c nude mice using a syringe. Each animal was inoculated with 100 μL (5×10 6 The Calu-6 nude mouse xenograft tumor model was established. After the tumor grew to a measurable range, the long and short diameters of each tumor were measured with a vernier caliper, and the tumor volume was calculated according to the following formula: V = (a × b 2 ) / 2, where a represents the long diameter of the tumor and b represents the short diameter of the tumor.

[0920] When the tumor volume reaches an average of 150 mm 3 The mice were randomly divided into groups according to the tumor volume and weight. Tumor-bearing nude mice were injected with solvent control (normal saline) or different doses of ADC (3 mg / kg or 10 mg / kg) through the tail vein once a week for a total of 3 times. The long and short diameters of the tumors were measured twice a week, and the weight of the animals was recorded. The tumor volume of each group was counted, and the tumor growth inhibition rate TGI was calculated according to the following formula: TGI = 100% × [1-(TVt T -TV0 T ) / (TVt C -TV0 C )]. Where (TVt Trepresents the tumor volume of the drug-treated group on the day of measurement, TV0 T TVt represents the tumor volume of the drug-treated group at the time of grouping; C represents the tumor volume of the solvent control group on the day of measurement, TV0 C The tumor volume of the solvent control group at the time of grouping is shown in Table 5.

[0921] The experimental results showed that TROP2 antibody ADC IIa had an inhibitory effect on the growth of Calu-6 subcutaneous transplanted tumors at doses of 3 mg / kg and 10 mg / kg, and the inhibitory effect was better than that of the control group ADC2 at a dose of 10 mg / kg.

[0922] Table 5. Calu-6 nude mouse subcutaneous transplant tumor growth inhibition rate

[0923]

[0924] Example 5

[0925] Cell proliferation inhibition assay

[0926] KPL-4 tumor cells in the logarithmic growth phase were taken and resuspended in fresh RPMI1640 culture medium. The cells were counted and the cell suspension was adjusted to 2×10 4 Cells / mL. The cell suspension was inoculated into a 96-well cell culture plate at 100 μL / well and cultured overnight in a carbon dioxide incubator (37°C, 5% CO2). The next day, one of the 96-well plates seeded with cells was removed and equilibrated to room temperature. 100 μL of CellTiter-Glo reagent (Promega, USA), which had been pre-equilibrated to room temperature and mixed thoroughly, was added to each well of the test plate. After incubation in the dark for 30 minutes, the luminescence value was read on a microplate reader (recorded as the G0 value). Another parallel plate was taken and different concentrations of the test compound or DMSO (final concentration 0.5%) were added to the corresponding wells of the test plate. After incubation in a carbon dioxide incubator for 72 hours, the test plate was equilibrated to room temperature and the cell activity was detected using the CellTiter-Glo reagent, which was recorded as the G3 value.

[0927] The cell proliferation rate was calculated according to the following formula: Cell proliferation rate (%) = (average value of G3 in the test compound wells - average value of G0) / (average value of G3 in the DMSO control wells - average value of G0) * 100. Graphpad Prism software was used to fit the inhibition curve and calculate the GI 50 Values ​​(see table below).

[0928] Compound GI 50 (nM)X(Example 1.6)13.9Y(Example 1.6)10.3DXd72

[0929] Corresponding compound X (Example 1.6); Corresponding compound Y (Example 1.6);

[0930] The foregoing detailed description is provided by way of explanation and example and is not intended to limit the scope of the appended claims. Various changes to the embodiments listed in the present application are obvious to those skilled in the art and are intended to be within the scope of the appended claims and their equivalents.

Claims

1. A ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate comprises the structure shown in formula (I): Wherein, R 1 and R 2 each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C 1 -C 8 alkyl group, an optionally substituted C 1 -C 8 haloalkyl group and an optionally substituted C 1 -C 8 deuterated alkyl group; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of: an optionally substituted alicyclic group, an optionally substituted aliphatic heterocyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group; L is an optionally substituted linker, Ab is a ligand, a is a number greater than 0, and a is a decimal or an integer.

2. A ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate comprises the structure shown in formula (I-a): Wherein, R 1 and R 2 each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl and an optionally substituted C 1 -C 8 deuterated alkyl; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted heteroalicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group; L is an optionally substituted linker, Ab is a ligand, a is a number greater than 0, and a is a decimal or an integer.

3. A ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate comprises the structure shown in formula (I-b): Wherein, R 1 and R 2 each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl and an optionally substituted C 1 -C 8 deuterated alkyl; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of: an optionally substituted alicyclic group, an optionally substituted heteroalicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group; L is an optionally substituted linker, Ab is a ligand, a is a number greater than 0, and a is a decimal or an integer.

4. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof according to any one of claims 1-3, The said L is the connector - L 1 -L 2 -L 3 -L 4 -L 5 -.

5. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof according to claim 4, The said L 1 is optionally substituted The said L 1 is directly connected to the said Ab.

6. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof according to any one of claims 4-5, The L 2 is a group selected from the group consisting of: optionally substituted -(CH 2 ) m1 -X 1 -(CH 2 ) m2 -C(O)-, optionally substituted -(CH 2 CH 2 O) n -C(O)- and optionally substituted -(CH 2 ) p -C(O)-, X 1 selected from the group consisting of: -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroalicyclic group, and optionally substituted alicyclic group Wherein, m1, m2 and n are each independently selected from integers of at least 0, and p is selected from integers from 2 to 8.

7. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof according to claim 6, The L 2 is optionally substituted -(CH 2 CH 2 O) n -C(O)-.

8. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof according to any one of claims 6-7, Wherein, n is 2.

9. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof according to claim 6, The L 2 is optionally substituted -(CH 2 ) m1 -X 1 -(CH 2 ) m2 -C(O)-.

10. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof according to claim 9, X 1 selected from the group consisting of -O- and optionally substituted -C(O)-NH-.

11. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof according to any one of claims 9-10, Wherein, m1 is 2.

12. The ligand conjugate according to any one of claims 9-11, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 2.

13. The ligand conjugate according to claim 9, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is a group selected from the group consisting of: optionally substituted aryl and optionally substituted heteroaryl.

14. The ligand conjugate according to claim 13, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted phenyl group.

15. The ligand conjugate according to claim 13, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted pyridyl group.

16. The ligand conjugate according to any one of claims 13-15, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m1 is 0.

17. The ligand conjugate according to any one of claims 13-16, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 1.

18. The ligand conjugate according to claim 9, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is optionally substituted 19. The ligand conjugate according to claim 9, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted cyclohexyl group.

20. The ligand conjugate according to any one of claims 18-19, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m1 is 1.

21. The ligand conjugate according to any one of claims 18-20, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 0.

22. The ligand conjugate according to claim 6, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 2 is optionally substituted -(CH 2 ) p -C(O)-.

23. The ligand conjugate according to claim 22, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, p is 5.

24. The ligand conjugate according to any one of claims 4-23, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said L 2 is a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 25. The ligand conjugate according to any one of claims 4-24, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 3 is a peptide residue.

26. The ligand conjugate according to any one of claims 4-25, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a peptide residue composed of amino acids selected from the following group: phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid, and glycine.

27. The ligand conjugate according to any one of claims 4-26, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a peptide residue composed of amino acids selected from the following group: glycine, phenylalanine, valine, and citrulline.

28. The ligand conjugate according to any one of claims 4-27, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a peptide residue selected from the group consisting of -Gly-Phe-Gly-, -Gly-Gly-Phe-Gly-, and -Val-Cit-.

29. The ligand conjugate according to any one of claims 4-28, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a structure selected from the following group:

30. The ligand conjugate according to any one of claims 4-29, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said L 4 is optionally substituted -L 4a -NR 4 -CH 2 -L 4b -, L 4a absent or L 4a is optionally substituted L 4b is absent or L 4b is optionally substituted R 4 and R 5 are each independently selected from the group consisting of hydrogen and optionally substituted alkyl groups.

31. The ligand conjugate according to claim 30, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted 32. The ligand conjugate according to claim 30, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted 33. The ligand conjugate according to claim 30, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted 34. The ligand conjugate according to claim 30, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted 35. The ligand conjugate according to any one of claims 30-34, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said R 4 is selected from the group consisting of hydrogen and optionally substituted methyl.

36. The ligand conjugate according to any one of claims 30-35, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said R 5 is selected from the group consisting of: hydrogen and optionally substituted methyl.

37. The ligand conjugate according to any one of claims 4-36, or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said L 4 is a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 38. A ligand conjugate as described in any one of claims 4 - 37, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 5 is optionally substituted The said L 5 is directly connected to the following structural formula: R 6 and R 7 each independently selected from the group consisting of: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached form an optionally substituted cycloalkyl wherein, v is selected from numbers of at least 0.

39. A ligand conjugate as described in any one of claims 4 - 38, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 5 is optionally substituted The said L 5 is directly connected to the following formula structure: R 6 and R 7 each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached form an optionally substituted cycloalkyl wherein, v is selected from numbers of at least 0.

40. A ligand conjugate as described in any one of claims 4 - 39, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 5 is optionally substituted The said L 5 is directly connected to the following structural formula: R 6 and R 7 each independently is selected from the following groups: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached forms an optionally substituted cycloalkyl wherein, v is selected from numbers of at least 0.

41. A ligand conjugate as described in any one of claims 38 - 40, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said R 6 is hydrogen.

42. A ligand conjugate as described in any one of claims 38 - 40, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said R 6 is an optionally substituted methyl group.

43. A ligand conjugate as described in claim 42, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The R 6 is a fluorine-substituted methyl group.

44. A ligand conjugate as described in any one of claims 42 - 43, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The R 6 is trifluoromethyl.

45. A ligand conjugate as described in any one of claims 38 - 40, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The R 6 is an optionally substituted cycloalkyl group.

46. A ligand conjugate as described in claim 45, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The R 6 is an optionally substituted cyclopropyl group.

47. A ligand conjugate as described in any one of claims 38 - 46, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said R 7 is hydrogen.

48. A ligand conjugate as described in any one of claims 38 - 40, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, R 6 and R 7 together with the atoms to which it is attached form an optionally substituted cyclopropyl group.

49. A ligand conjugate as described in claim 48, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, R 6 and R 7 together with the atoms to which it is attached form an optionally substituted cyclobutyl group.

50. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 38 - 49, wherein, v is 0.

51. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 38 - 49, wherein, v is 1.

52. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 4 - 51, The L 5 is a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 53. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 1 - 52, wherein said Ab is an antibody or an antigen - binding fragment thereof.

54. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in claim 53, wherein said antibody is selected from the group consisting of murine antibodies, chimeric antibodies, humanized antibodies, and fully human antibodies.

55. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 53 - 54, wherein said antibody is a monoclonal antibody.

56. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in claim 53, Wherein the antigen-binding fragment is selected from the group consisting of: Fab, Fab′, Fv fragment, F(ab') 2 , F(ab) 2 , scFv, di-scFv, VHH and dAb.

57. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 1 - 56, wherein said Ab comprises a HER2 antibody and / or a TROP2 antibody.

58. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 1 - 57, wherein said Ab comprises HCDR1, HCDR2, and HCDR3 of the heavy - chain variable region, the amino acid sequence of HCDR1 is as shown in SEQ ID NO: 1, the amino acid sequence of HCDR2 is as shown in SEQ ID NO: 2, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO:

3.

59. A ligand conjugate or a tautomer, meso form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 1 - 58, Wherein the Ab comprises LCDR1, LCDR2 and LCDR3 of the light chain variable region, the amino acid sequence of the LCDR1 is as shown in SEQ ID NO: 4, the amino acid sequence of the LCDR2 is as shown in SEQ ID NO: 5, and the amino acid sequence of the LCDR3 is as shown in SEQ ID NO:

6.

60. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, according to any one of claims 1-59, wherein the Ab comprises a heavy chain variable region, and the amino acid sequence of the heavy chain variable region is as shown in SEQ ID NO:

7.

61. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, according to any one of claims 1-60, wherein the Ab comprises a light chain variable region, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO:

8.

62. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, according to any one of claims 1-61, wherein the Ab comprises a heavy chain, and the amino acid sequence of the heavy chain is as shown in SEQ ID NO:

9.

63. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, according to any one of claims 1-62, wherein the Ab comprises a light chain, and the amino acid sequence of the light chain is as shown in SEQ ID NO:

10.

64. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, according to any one of claims 1-57, wherein the Ab comprises HCDR1, HCDR2 and HCDR3 of the heavy chain variable region, the amino acid sequence of the HCDR1 is as shown in SEQ ID NO: 11, the amino acid sequence of the HCDR2 is as shown in SEQ ID NO: 12, and the amino acid sequence of the HCDR3 is as shown in SEQ ID NO:

13.

65. The ligand conjugate or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, according to claim 64, wherein the Ab comprises LCDR1, LCDR2 and LCDR3 of the light chain variable region, the amino acid sequence of the LCDR1 is as shown in SEQ ID NO: 14, the amino acid sequence of the LCDR2 is as shown in SEQ ID NO: 15, and the amino acid sequence of the LCDR3 is as shown in SEQ ID NO:

16.

66. The ligand conjugate according to any one of claims 64 - 65, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the Ab comprises a heavy chain variable region, and the amino acid sequence of the heavy chain variable region is as shown in SEQ ID NO:

17.

67. The ligand conjugate according to any one of claims 64 - 66, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the Ab comprises a light chain variable region, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO:

18.

68. The ligand conjugate according to any one of claims 64 - 67, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the Ab comprises a heavy chain, and the amino acid sequence of the heavy chain is as shown in SEQ ID NO:

19.

69. The ligand conjugate according to any one of claims 64 - 68, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the Ab comprises a light chain, and the amino acid sequence of the light chain is as shown in SEQ ID NO:

20.

70. A ligand conjugate or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate is a structure selected from the following group: where Ab is a ligand, and a is a number greater than 0, and a is a decimal or an integer.

71. A compound or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate comprises the structure shown in formula (II): wherein, R 1 and R 2 each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl, and an optionally substituted C 1 -C 8 deuterated alkyl; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of: an optionally substituted alicyclic group, an optionally substituted heteroalicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group; Lx is a linking group, and the Lx is L 1x -L 2 -L 3 -L 4 -L 5 -, and the L 1x can be directly linked to the ligand.

72. A compound or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate comprises the structure shown in formula (II - a): wherein, R 1 and R 2 each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl and an optionally substituted C 1 -C 8 deuterated alkyl; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted heteroalicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group; Lx is a linking group, and the Lx is L 1x -L 2 -L 3 -L 4 -L 5 -, and the L 1x is capable of being directly linked to a ligand.

73. A compound or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the ligand conjugate comprises the structure shown in formula (II - b): wherein, R 1 and R 2 each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl and an optionally substituted C 1 -C 8 deuterated alkyl; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of: an optionally substituted alicyclic group, an optionally substituted heteroalicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group; Lx is a linking group, and the Lx is L 1x -L 2 -L 3 -L 4 -L 5 -, and the L 1x can be directly linked to the ligand.

74. The compound according to any one of claims 71 - 73, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 1x can be directly connected to the sulfhydryl group of the ligand.

75. The compound according to any one of claims 71 - 74, or a tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 1x is optionally substituted 76. A compound as claimed in any one of claims 71 - 75, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 2 comprises a group selected from the group consisting of: optionally substituted -(CH 2 ) m1 -X 1 -(CH 2 ) m2 -C(O)-, optionally substituted -(CH 2 CH 2 O) n -C(O)- and optionally substituted -(CH 2 ) p -C(O)-, X 1 selected from the group consisting of: -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl and optionally substituted cycloalkyl, wherein, m1, m2 and n are each independently selected from integers of at least 0, and p is selected from integers from 2 to 8.

77. A compound as claimed in claim 76, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 2 is optionally substituted -(CH 2 CH 2 O) n -C(O)-.

78. A compound as claimed in claim 77, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, n is 2.

79. A compound as claimed in claim 76, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 2 comprises optionally substituted -(CH 2 ) m1 -X 1 -(CH 2 ) m2 -C(O)-.

80. A compound as claimed in any one of claim 79, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 selected from the group consisting of -O- and optionally substituted -C(O)-NH-.

81. A compound as claimed in any one of claims 79 - 80, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m1 is 2.

82. A compound as claimed in any one of claims 79 - 81, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 2.

83. A compound as claimed in claim 79, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is a group selected from the group consisting of: optionally substituted aryl and optionally substituted heteroaryl.

84. A compound as claimed in claim 83, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted phenyl group.

85. A compound as claimed in claim 83, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted pyridyl group.

86. A compound as claimed in any one of claims 83 - 85, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m1 is 0.

87. A compound as claimed in any one of claims 83 - 86, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 1.

88. A compound as claimed in claim 79, or a tautomer, meso - form, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is optionally substituted 89. The compound according to claim 79, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted cyclohexyl group.

90. The compound according to any one of claims 88 - 89, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m1 is 1.

91. The compound according to any one of claims 88 - 90, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 0.

92. The compound according to claim 76, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said L 2 is optionally substituted -(CH 2 ) p -C(O)-.

93. The compound according to claim 92, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, p is 5.

94. The compound according to any one of claims 71 - 93, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 2 a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 95. The compound according to any one of claims 71 - 94, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 3 is a peptide residue.

96. The compound according to any one of claims 71 - 95, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a peptide residue composed of amino acids selected from the following group: phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid, and glycine.

97. The compound according to any one of claims 71 - 96, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a peptide residue composed of amino acids selected from the group consisting of glycine, phenylalanine, valine, and citrulline.

98. The compound according to any one of claims 71 - 97, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a peptide residue selected from the group consisting of: -Gly-Phe-Gly-, -Gly-Gly-Phe-Gly- and -Val-Cit-.

99. The compound according to any one of claims 71 - 98, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 structures selected from the following group:

100. The compound according to any one of claims 71 - 99, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted -L 4a -NR 4 -CH 2 -L 4b - L 4a is absent or L 4a is optionally substituted L 4b absent or L 4b is optionally substituted R 4 and R 5 are each independently selected from the group consisting of: hydrogen and optionally substituted alkyl.

101. The compound according to claim 100, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted 102. The compound according to claim 100, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted 103. The compound according to claim 100, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted 104. The compound according to claim 100, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said L 4 is optionally substituted 105. The compound according to any one of claims 100-104, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said R 4 is selected from the group consisting of: hydrogen and optionally substituted methyl.

106. The compound according to any one of claims 100-105, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said R 5 is selected from the group consisting of hydrogen and optionally substituted methyl.

107. The compound according to any one of claims 71-106, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 4 structures selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 108. The compound according to any one of claims 71-107, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 5 is optionally substituted The said L 5 is directly connected to the following structural formula: R 6 and R 7 each independently selected from the group consisting of: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached form an optionally substituted cycloalkyl wherein, v is selected from numbers of at least 0.

109. The compound according to any one of claims 71-108, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 5 is optionally substituted The said L 5 is directly connected to the following structural formula: R 6 and R 7 each independently selected from the group consisting of: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached form an optionally substituted cycloalkyl wherein, v is selected from numbers of at least 0.

110. The compound according to any one of claims 71-109, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 5 is optionally substituted The said L 5 is directly connected to the following structural formula: R 6 and R 7 each independently selected from the group consisting of hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached form an optionally substituted cycloalkyl wherein, v is selected from numbers of at least 0.

111. The compound according to any one of claims 108-110, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said R 6 is hydrogen.

112. The compound according to any one of claims 108-110, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The R 6 is an optionally substituted methyl group.

113. The compound according to claim 112, or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The R 6 is a fluorine-substituted methyl group.

114. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 112 - 113, The R 6 is trifluoromethyl.

115. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 108 - 110, The R 6 is an optionally substituted cycloalkyl group.

116. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in claim 115, The said R 6 is an optionally substituted cyclopropyl group.

117. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 108 - 116, The said R 7 is hydrogen.

118. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 108 - 110, R 6 and R 7 together with the atom(s) to which it is attached form an optionally substituted cyclopropyl group.

119. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in claim 118, R 6 and R 7 together with the atom(s) to which it is attached form an optionally substituted cyclobutyl group.

120. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 108 - 119, wherein, v is 0.

121. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 108 - 119, wherein, v is 1.

122. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in any one of claims 71 - 121, Said L 5 is a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 123. A compound or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound is selected from the structures of the following group:

124. A linker as shown in formula (L - 1), which is used to obtain a ligand - drug conjugate formed by connecting a drug unit and a ligand via the linker: -L 1 -L 2 -L 3 -L 4 -L 5 -(L - 1), wherein, L 1 is optionally substituted The L 2 A group selected from the group consisting of: optionally substituted -(CH 2 ) m1 -X 1 -(CH 2 ) m2 -C(O)- and optionally substituted -(CH 2 CH 2 O) n -C(O)-, X 1 selected from the group consisting of -O-, optionally substituted -C(O)-NH-, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl and optionally substituted cycloalkyl, wherein, m1, m2 and n are each independently selected from integers of at least 0.

125. The linker as described in claim 124 or a tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, n is 2.

126. The linker according to any one of claims 124-125, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 selected from the group consisting of -O- and optionally substituted -C(O)-NH-.

127. The linker according to any one of claims 124-126, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m1 is 2.

128. The linker according to any one of claims 124-127, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 2.

129. The linker according to any one of claims 124-125, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is a group selected from the group consisting of: optionally substituted aryl and optionally substituted heteroaryl.

130. The linker according to claim 129, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted phenyl group.

131. The linker according to claim 129, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted pyridyl group.

132. The linker according to any one of claims 129-131, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m1 is 0.

133. The linker according to any one of claims 129-132, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 1.

134. The linker according to any one of claims 124-125, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 optionally substituted 135. The linker according to any one of claims 124-125, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, X 1 is an optionally substituted cyclohexyl group.

136. The linker according to any one of claims 134-135, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m1 is 1.

137. The linker according to any one of claims 134-136, or a tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein, m2 is 0.

138. The linker as described in any one of claims 124 - 137, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 2 is a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 139. The linker as described in any one of claims 124 - 138, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a peptide residue selected from the group consisting of -Gly-Phe-Gly-, -Gly-Gly-Phe-Gly-, and -Val-Cit-.

140. The linker as described in any one of claims 124 - 139, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 3 is a structure selected from the following group:

141. The linker as described in any one of claims 124 - 140, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted -L 4a -NR 4 -CH 2 -L 4b - L 4a absent or L 4a is optionally substituted L 4b absent or L 4b is optionally substituted R 4 and R 5 are each independently selected from the group consisting of: hydrogen and optionally substituted alkyl groups.

142. The linker as described in claim 141, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 4 is optionally substituted 143. The linker as described in claim 141, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The L 4 a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 144. The linker as described in any one of claims 124 - 143, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 5 is optionally substituted The said L 5 is directly connected to the following structural formula: R 6 and R 7 are each independently selected from the group consisting of: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached form an optionally substituted cycloalkyl, R 1 and R 2 are each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, optionally substituted C 1 -C 8 alkyl, optionally substituted C 1 -C 8 haloalkyl, and optionally substituted C 1 -C 8 deuterated alkyl; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted heteroalicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group. wherein, v is selected from numbers of at least 0.

145. The linker as described in any one of claims 124 - 144, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said L 5 is optionally substituted The said L 5 is directly connected to the following structural formula: R 6 and R 7 are each independently selected from the group consisting of: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached form an optionally substituted cycloalkyl, R 1 and R 2 are each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl, and an optionally substituted C 1 -C 8 deuterated alkyl; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of an optionally substituted alicyclic group, an optionally substituted heteroalicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group. wherein, v is selected from numbers of at least 0.

146. The linker as described in any one of claims 124 - 145, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, Said L 5 is optionally substituted The said L 5 is directly connected to the following structural formula: R 6 and R 7 are each independently selected from the group consisting of: hydrogen, deuterium, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, and optionally substituted cycloalkylalkyl, or R 6 and R 7 together with the atom to which it is attached form an optionally substituted cycloalkyl, R 1 and R 2 are each independently selected from the group consisting of: a hydrogen atom, a deuterium atom, a halogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl, and an optionally substituted C 1 -C 8 deuterated alkyl; Alternatively, R 1 and R 2 together with the carbon atom to which it is attached form a structure selected from the group consisting of: an optionally substituted alicyclic group, an optionally substituted heteroalicyclic group, an optionally substituted aryl group, and an optionally substituted heteroaryl group, wherein, v is selected from numbers of at least 0.

147. The linker as described in any one of claims 144 - 146, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The said R 6 is hydrogen.

148. The linker as described in any one of claims 144 - 146, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The R 6 is an optionally substituted methyl group.

149. The linker as described in claim 148, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, The R 6 is a fluorine-substituted methyl group.

150. The linker as described in any one of claims 148 - 149, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, The R 6 is trifluoromethyl.

151. The linker as described in any one of claims 144 - 146, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, The R 6 is an optionally substituted cycloalkyl group.

152. The linker as described in any one of claims 144 - 151, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, The said R 7 is hydrogen.

153. The linker as described in any one of claims 144 - 146, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, R 6 and R 7 together with the atoms to which it is attached form an optionally substituted cyclopropyl group.

154. The linker as described in claim 153, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, R 6 and R 7 together with the atoms to which it is attached form an optionally substituted cyclobutyl group.

155. The linker as described in any one of claims 144 - 154, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, wherein, v is 0.

156. The linker as described in any one of claims 144 - 154, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, wherein, v is 1.

157. The linker as described in any one of claims 124 - 156, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, Said L 5 Structures selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 158. A linker or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, wherein the linker comprises a structure selected from the following group:

159. A linker as shown in formula (L - 2), which is used to obtain a ligand - drug conjugate formed by connecting a drug unit and a ligand via the linker: -L 1 -L 2 -L 3 -L 4 -L 5 -(L - 2), L 1 is optionally substituted L 2 is a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted L 3 is a structure selected from the following group: L 4 is optionally substituted -L 4a -NR 4 -CH 2 -L 4b -, L 4a is absent or L 4a is optionally substituted L 4b absent or L 4b is optionally substituted L 4a and L 4b do not both fail to exist R 4 and R 5 each independently selected from the group consisting of hydrogen and optionally substituted alkyl, The L 5 is a structure selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted Optionally substituted and optionally substituted 160. The linker as described in claim 159, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, The said L 4 is optionally substituted 161. The linker as described in claim 159, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, The said L 4 is optionally substituted 162. The linker as described in claim 159, or its tautomer, meso form, racemic form, enantiomer, diastereoisomer, or a mixture thereof, or its pharmaceutically acceptable salt or hydrate, The said L 4 is optionally substituted 163. The linker or its tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, as described in claim 159 The L 4 structures selected from the group consisting of: optionally substituted Optionally substituted Optionally substituted and optionally substituted 164. A linker or its tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, wherein the linker comprises a structure selected from the following group:

165. A pharmaceutical composition comprising the ligand conjugate according to any one of claims 1 - 70, or its tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt, prodrug or solvate thereof, and / or the compound according to any one of claims 71 - 123, and optionally a pharmaceutically acceptable carrier.

166. Use of the ligand conjugate according to any one of claims 1 - 70, or its tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt, prodrug or solvate thereof, the compound according to any one of claims 71 - 123, or its tautomer, meso form, racemic form, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt or hydrate thereof, and / or the pharmaceutical composition according to claim 165 in the preparation of a drug for treating and / or preventing tumors.

167. The use according to claim 166, wherein the tumors are selected from tumors associated with the expression of the following group of targets: HER2 and TROP2.

168. The use according to claim 167, wherein the tumors associated with the expression of the target comprise tumors with high expression of the target and / or tumors positive for the target.

169. The use according to any one of claims 166 - 168, wherein the tumors comprise solid tumors and / or hematological tumors.

170. The use according to any one of claims 166 - 169, wherein the tumors are selected from the following group: breast cancer, ovarian cancer, cervical cancer, endometrial cancer, urothelial cancer, lung cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, bladder cancer, kidney cancer, pancreatic cancer, thyroid cancer, and head and neck cancer.