Antitumor, compound, and preparation method therefor and use thereof

Abstract

The present application relates to an anti-tumor compound and a preparation method and use thereof, and in particular to a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, and a preparation method and use thereof.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedicine, and in particular to an anti-tumor compound and a preparation method and use thereof.BACKGROUND

[0002] Currently, small molecules with cytotoxicity for antibody-drug conjugates (ADCs) can be camptothecin derivatives, which produce an anti-tumor effect by inhibiting topoisomerase I. Camptothecin derivatives can be used in ADCs. There is still a need to develop camptothecin derivatives and ADC drugs with better therapeutic effect and / or safety.SUMMARY

[0003] The present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, which may have one or more effects selected from the group consisting of: (1) having inhibitory activity against in vitro proliferation of tumor cells; (2) having targeting inhibition; (3) having plasma stability; (4) having in vivo tumor inhibiting effect; (5) having bystander effect; (6) having capacity in inhibiting transport via a transporter; (7) having in vivo tumor targeting capability; and (8) having good in vivo safety.

[0004] In one aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure shown as formula (II-A): wherein, X 1< is saturated C, and X 1< is substituted with R n< ; ring A is selected from the group consisting of: 3-10 membered saturated or partially unsaturated heterocyclyl and 3-10 membered saturated or partially unsaturated carbocyclyl, wherein ring A is substituted with 0 or at least 1 substituent R 1a< ; when ring A is 3-10 membered saturated or partially unsaturated carbocyclyl, ring A is substituted with p L 2< , and L 2< is not R n< ; or, when ring A is 3-10 membered saturated or partially unsaturated heterocyclyl, ring A is substituted with p L 2< ; L 2< is -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< is -(C(R 3a< )(R 3b< )) m -, wherein when L 3< comprises a methylene unit, 0 or at least 1 methylene unit of L 3< is independently replaced by -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, - S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 2< is selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein when L 1< comprises a methylene unit, 0 or at least 1 methylene unit of L 1< is independently replaced by -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, - S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1a< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< , each R 6< and each R n< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, - N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), - SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 0, and p is an integer ≥ 1.

[0005] In one aspect, the present application provides a compound of general formula (II-E x ) or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein, X 1< is saturated C, and X 1< is substituted with R n< ; ring A is selected from the group consisting of: 3-10 membered saturated or partially unsaturated heterocyclyl and 3-10 membered saturated or partially unsaturated carbocyclyl, wherein ring A is substituted with 0 or at least 1 substituent R 1a< ; when ring A is 3-10 membered saturated or partially unsaturated carbocyclyl, ring A is substituted with p L 2< , and L 2< is not R n< ; or, when ring A is 3-10 membered saturated or partially unsaturated heterocyclyl, ring A is substituted with p L 2< ; L 2< is -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< is -(C(R 3a< )(R 3b< )) m -, wherein when L 3< comprises a methylene unit, 0 or at least 1 methylene unit of L 3< is independently replaced by -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, - S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 2< is selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein when L 1< comprises a methylene unit, 0 or at least 1 methylene unit of L 1< is independently replaced by -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, - S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1a< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< , each R 6< and each R n< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, - N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), - SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 0, and p is an integer ≥ 1.

[0006] In one aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure shown as formula (II-C x ): wherein, L is -L a -L b -L c -; -L a - is selected from the group consisting of: wherein W is -(C(R wa< )(R wb< )) wn -, Y is -(OCH 2 CH 2 ) yn -O yp -, and Z is -(C(R za< )(R zb< )) zn ; wherein wn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of W is independently replaced by -Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, -N(R wx< )SO 2 -, - SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N2)-; wherein yn is selected from the group consisting of integers ≥ 0, and yp is 0 or 1; wherein zn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of Z is independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )-, - C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, -N(R zx< )SO 2 -, - SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or independently substituted with at least 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , -N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), - SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< , or a C 1-6 aliphatic group optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - is selected from the group consisting of: wherein R L1< and R L2< are each independently selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; wherein, X 1< is saturated C, and X 1< is substituted with R n< ; ring A is selected from the group consisting of: 3-10 membered saturated or partially unsaturated heterocyclyl and 3-10 membered saturated or partially unsaturated carbocyclyl, wherein ring A is substituted with 0 or at least 1 substituent R 1a< ; when ring A is 3-10 membered saturated or partially unsaturated carbocyclyl, ring A is substituted with p L 2< , and L 2< is not R n< ; or, when ring A is 3-10 membered saturated or partially unsaturated heterocyclyl, ring A is substituted with p L 2< ; L 2< is -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< is -(C(R 3a< )(R 3b< )) m -, wherein when L 3< comprises a methylene unit, 0 or at least 1 methylene unit of L 3< is independently replaced by -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, - S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 2< is selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein when L 1< comprises a methylene unit, 0 or at least 1 methylene unit of L 1< is independently replaced by -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, - S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1a< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< , each R 6< and each R n< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, - N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), - SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 0, and p is an integer ≥ 1.

[0007] In one aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure shown as formula (II-Dx): wherein, Ab is a ligand, and an average connection number N a< is an integer or a decimal from 1 to 10; L is -La-Lb-Lc-; -L a - is selected from the group consisting of: wherein W is -(C(R wa< )(R wb< )) wn -, Y is -(OCH 2 CH 2 ) yn -O yp -, and Z is -(C(R za< )(R zb< )) zn ; wherein wn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of W is independently replaced by -Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, -N(R wx< )SO 2 -, - SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N2)-; wherein yn is selected from the group consisting of integers ≥ 0, and yp is 0 or 1; wherein zn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of Z is independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )-, - C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, -N(R zx< )SO 2 -, - SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or independently substituted with at least 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , -N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), - SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< , or a C 1-6 aliphatic group optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - is selected from the group consisting of: wherein R L1< and R L2< are each independently selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; wherein, X 1< is saturated C, and X 1< is substituted with R n< ; ring A is selected from the group consisting of: 3-10 membered saturated or partially unsaturated heterocyclyl and 3-10 membered saturated or partially unsaturated carbocyclyl, wherein ring A is substituted with 0 or at least 1 substituent R 1a< ; when ring A is 3-10 membered saturated or partially unsaturated carbocyclyl, ring A is substituted with p L 2< , and L 2< is not R n< ; or, when ring A is 3-10 membered saturated or partially unsaturated heterocyclyl, ring A is substituted with p L 2< ; L 2< is -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< is -(C(R 3a< )(R 3b< )) m -, wherein when L 3< comprises a methylene unit, 0 or at least 1 methylene unit of L 3< is independently replaced by -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, - S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 2< is selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein when L 1< comprises a methylene unit, 0 or at least 1 methylene unit of L 1< is independently replaced by -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, - S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1a< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< , each R 6< and each R n< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, - N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), - SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 0, and p is an integer ≥ 1.

[0008] In one aspect, the present application provides a compound of general formula (II-F x ) or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein, L x< is L ax -L b -L c -; L ax - is selected from the group consisting of: wherein R hal< is iodine or bromine; wherein W is -(C(R wa< )(R wb< )) wn -, Y is -(OCH 2 CH 2 ) yn -O yp -, and Z is -(C(R za< )(R zb< )) zn ; wherein wn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of W is independently replaced by -Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, -N(R wx< )SO 2 -, - SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn is selected from the group consisting of integers ≥ 0, and yp is 0 or 1; wherein zn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of Z is independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )-, - C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, -N(R zx< )SO 2 -, - SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or independently substituted with at least 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , -N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), - SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< , or a C 1-6 aliphatic group optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - is selected from the group consisting of: wherein R L1< and R L2< are each independently selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; wherein, X 1< is saturated C, and X 1< is substituted with R n< ; ring A is selected from the group consisting of: 3-10 membered saturated or partially unsaturated heterocyclyl and 3-10 membered saturated or partially unsaturated carbocyclyl, wherein ring A is substituted with 0 or at least 1 substituent R 1a< ; when ring A is 3-10 membered saturated or partially unsaturated carbocyclyl, ring A is substituted with p L 2< , and L 2< is not R n< ; or, when ring A is 3-10 membered saturated or partially unsaturated heterocyclyl, ring A is substituted with p L 2< ; L 2< is -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< is -(C(R 3a< )(R 3b< )) m -, wherein when L 3< comprises a methylene unit, 0 or at least 1 methylene unit of L 3< is independently replaced by -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, - S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 2< is selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein when L 1< comprises a methylene unit, 0 or at least 1 methylene unit of L 1< is independently replaced by -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, - S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1a< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< , each R 6< and each R n< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, - N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), - SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 0, and p is an integer ≥ 1.

[0009] In one aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises the following group of structures:

[0010] In one aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure shown as formula (III-A): wherein, R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; X is -L 1< -CH 2 -C(O)-; L 1< is -(C(R 3a< )(R 3b< )) m -, wherein 0 or at least 1 methylene unit of L 1< is independently replaced by - C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; wherein each R 2< , each R 3a< , each R 3b< and each R 4b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m is selected from the group consisting of integers ≥ 0, and n is selected from the group consisting of integers ≥ 1; when R 1< is -O- or -HN-, at least 1 methylene unit of L 1< is independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-, or each R 3a< and each R 3b< are not both hydrogen.

[0011] In one aspect, the present application provides a compound of general formula (III-E) or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; X is -L 1< -CH 2 -C(O)-; L 1< is -(C(R 3a< )(R 3b< )) m -, wherein 0 or at least 1 methylene unit of L 1< is independently replaced by - C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; wherein each R 2< , each R 3a< , each R 3b< and each R 4b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m is selected from the group consisting of integers ≥ 0, and n is selected from the group consisting of integers ≥ 1; when R 1< is -O- or -HN-, at least 1 methylene unit of L 1< is independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-, or each R 3a< and each R 3b< are not both hydrogen.

[0012] In one aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure shown as formula (III-C): wherein, L is -L a -L b -L c -; -L a - is selected from the group consisting of: wherein W is -(C(R wa< )(R wb< )) wn -, Y is -(OCH 2 CH 2 ) yn -O yp , and Z is -(C(R za< )(R zb< )) zn ; wherein wn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of W is independently replaced by -Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, -N(R wx< )SO 2 -, - SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn is selected from the group consisting of integers ≥ 0, and yp is 0 or 1; wherein zn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of Z is independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )-, - C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, -N(R zx< )SO 2 -, - SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or independently substituted with at least 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , -N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), - SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< , or a C 1-6 aliphatic group optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - is selected from the group consisting of: wherein R L1< and R L2< are each independently selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; wherein R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; X is -L 1< -CH 2 -C(O)-; L 1< is -(C(R 3a< )(R 3b< )) m -, wherein 0 or at least 1 methylene unit of L 1< is independently replaced by - C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; wherein each R 2< , each R 3a< , each R 3b< and each R 4b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O)zR, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m is selected from the group consisting of integers ≥ 0, and n is selected from the group consisting of integers ≥ 1; when R 1< is -O- or -HN-, at least 1 methylene unit of L 1< is independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-, or each R 3a< and each R 3b< are not both hydrogen.

[0013] In one aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure shown as formula (III-D): wherein, Ab is a ligand, and an average connection number N a< is an integer or a decimal from 1 to 10; L is -La-Lb-Lc-; -L a - is selected from the group consisting of: wherein W is -(C(R wa< )(R wb< )) wn -, Y is -(OCH 2 CH 2 ) yn -O yp , and Z is -(C(R za< )(R zb< )) zn ; wherein wn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of W is independently replaced by -Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, -N(R wx< )SO 2 -, - SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn is selected from the group consisting of integers ≥ 0, and yp is 0 or 1; wherein zn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of Z is independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )-, - C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, -N(R zx< )SO 2 -, - SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or independently substituted with at least 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , -N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), - SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< , or a C 1-6 aliphatic group optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - is selected from the group consisting of: wherein R L1< and R L2< are each independently selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; wherein R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; X is -L 1< -CH 2 -C(O)-; L 1< is -(C(R 3a< )(R 3b< )) m -, wherein 0 or at least 1 methylene unit of L 1< is independently replaced by - C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; wherein each R 2< , each R 3a< , each R 3b< and each R 4b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m is selected from the group consisting of integers ≥ 0, and n is selected from the group consisting of integers ≥ 1; when R 1< is -O- or -HN-, at least 1 methylene unit of L 1< is independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-, or each R 3a< and each R 3b< are not both hydrogen.

[0014] In one aspect, the present application provides a compound of general formula (III-F) or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein, L x< is L ax -L b -L c -; L ax - is selected from the group consisting of: wherein R hal< is iodine or bromine; wherein W is -(C(R wa< )(R wb< )) wn -, Y is -(OCH 2 CH 2 ) yn -O yp , and Z is -(C(R za< )(R zb< )) zn ; wherein wn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of W is independently replaced by -Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, -N(R wx< )SO 2 -, - SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn is selected from the group consisting of integers ≥ 0, and yp is 0 or 1; wherein zn is selected from the group consisting of integers ≥ 0, and 0 or at least 1 methylene unit of Z is independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )-, - C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, -N(R zx< )SO 2 -, - SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or independently substituted with at least 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , -N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), - SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< , or a C 1-6 aliphatic group optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - is selected from the group consisting of: wherein R L1< and R L2< are each independently selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; wherein R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; X is -L 1< -CH 2 -C(O)-; L 1< is -(C(R 3a< )(R 3b< )) m -, wherein 0 or at least 1 methylene unit of L 1< is independently replaced by - C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; wherein each R 2< , each R 3a< , each R 3b< and each R 4b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O)zR, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O)zH, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m is selected from the group consisting of integers ≥ 0, and n is selected from the group consisting of integers ≥ 1; when R 1< is -O- or -HN-, at least 1 methylene unit of L 1< is independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-, or each R 3a< and each R 3b< are not both hydrogen.

[0015] In one aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the ligand-drug conjugate comprises the following group of structures:

[0016] In one aspect, the present application provides a method for preparing the compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof disclosed herein, which comprises contacting a ligand Ab with the structure shown as formula (II-F x ) disclosed herein.

[0017] In one aspect, the present application provides a method for preparing the compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof disclosed herein, which comprises contacting a ligand Ab with the structure shown as formula (III-F) disclosed herein.

[0018] In one aspect, the present application provides a pharmaceutical composition, which comprises the compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof disclosed herein, and a pharmaceutically acceptable carrier.

[0019] In one aspect, the present application provides use of the compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof disclosed herein, and / or the pharmaceutical composition disclosed herein, in preparing a medicament for treating and / or preventing a tumor.

[0020] Other aspects and advantages of the present application will be readily apparent to those skilled in the art from the following detailed description. Only exemplary embodiments of the present application have been shown and described in the following detailed description. As those skilled in the art will recognize, the content of the present application enables those skilled in the art to make changes to the specific embodiments disclosed without departing from the spirit and scope of the invention to which the present application pertains. Accordingly, descriptions in the drawings and specification are only illustrative rather than restrictive.BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Specific features of the invention to which the present application pertains are set forth in appended claims. Features and advantages of the invention to which the present application pertains will be better understood by reference to the exemplary embodiments and drawings described in detail below. The drawings are briefly described as follows: FIGs. 1-16 are graphs showing in vivo tumor inhibition results of the compounds disclosed herein.DETAILED DESCRIPTION

[0022] The embodiments of the present invention are described below with reference to specific examples, and other advantages and effects of the present invention will be readily apparent to those skilled in the art from the disclosure of the present specification.Definitions of Terms

[0023] In the present application, the term "ligand" generally refers to a macromolecular compound capable of recognizing and binding to an antigen or receptor associated with a target cell. The role of ligands may be to present the drug to a target cell population to which the ligand binds, and the ligands include, but are not limited to, protein hormones, lectin, growth factors, antibodies, or other molecules capable of binding to a cell, a receptor and / or an antigen. In the present application, the ligand may be represented as Ab, the ligand antigen forms a linking bond with the linking unit through a heteroatom on the ligand, and the ligand may be an antibody or an antigen-binding fragment thereof, wherein the antibody may be selected from the group consisting of a chimeric antibody, a humanized antibody, a fully human antibody or a murine antibody, and the antibody may be a monoclonal antibody. For example, the antibody may be an antibody that targets the following target points: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 or EGFR. For example, the antibody may be an antibody that targets the following target points: 5T4, AGS-16, ANGPTL4, ApoE, CD19, CTGF, CXCR5, FGF2, MCPT8, MFI2, MS4A7, NCA, Sema5b, SLITRK6, STC2, TGF, 0772P, 5T4, ACTA2, ADGRE1, AG-7, AIF1, AKR1C1, AKR1C2, ASLG659, Axl, B7H3, BAFF-R, BCMA, BMPR1B, BNIP3, C1QA, C1QB, CA6, CADM1, CCD79b, CCL5, CCR5, CCR7, CD11c, CD123, CD138, CD142, CD147, CD166, CD19, CD19, CD22, CD21, CD20, CD205, CD22, CD223, CD228, CD25, CD30, CD33, CD37, CD38, CD40, CD45, CD45 (PTPRC), CD46, CD47, CD49D (ITGA4), CD56, CD66e, CD70, CD71, CD72, CD74, CD79a, CD79b, CD80, CDCP1, CDH11, CD11b, CEA, CEACAM5, c-Met, COL6A3, COL7A1, CRIPTO, CSF1R, CTSD, CTSS, CXCL11, CXCL10, DDIT4, DLL3, DLL4, DR5, E16, EFNA4, EGFR, EGFRvIII, EGLN, EGLN3, EMR2, ENPP3, EpCAM, EphA2, EphB2R, ETBR, FcRH2, FcRH1, FGFR2, FGFR3, FLT3, FOLR-α, GD2, GEDA, GPC-1, GPNMB, GPR20, GZMB, HER2, HER3, HLA-DOB, HMOX1, IFI6, IFNG, IGF-1R, IGFBP3, IL10RA1, IL-13R, IL-2, IL20Ra, IL-3, IL-4, IL-6, IRTA2, KISS1R, KRT33A, LIV-1, LOX, LRP-1, LRRC15, LUM, LY64, LY6E, Ly86, LYPD3, MDP, MMP10, MMP14, MMP16, MPF, MSG783, MSLN, MUC-1, NaPi2b, Napi3b, Nectin-4, Nectin-4, NOG, P2X5, pCAD, P-Cadherin, PDGFRA, PDK1, PD-L1, PFKFB3, PGF, PGK1, PIK3AP1, PIK3CD, PLOD2, PSCA, PSCAhlg, PSMA, PSMA, PTK7, P-Cadherin, RNF43, NaPi2b, ROR1, ROR2, SERPINE1, SLC39A6, SLTRK6, STAT1, STEAP1, STEAP2, TCF4, TENB2, TGFB1, TGFB2, TGFBR1, TNFRSF21, TNFSF9, Trop-2, TrpM4, Tyro7, UPK1B, VEGFA, WNT5A, epidermal growth factors, brevican, mesothelin, sodium phosphate cotransporter 2B, Claudin 18.2, endothelin receptors, mucins (such as mucin 1 and mucin 16), guanylate cyclase C, integrin a4p7, integrin a5p6, trophoblast glycoprotein, or tissue factors.

[0024] In the present application, the term "cytotoxic drug" generally refers to a toxic drug, and the cytotoxic drug may have a chemical molecule within the tumor cell that is strong enough to disrupt its normal growth. Cytotoxic drugs can kill tumor cells at a sufficiently high concentration. The "cytotoxic drug" may include toxins, such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, radioisotopes (e.g., At 211< , I 131< , I 125< , Y 90< , Re 186< , Re 188< , Sm 153< , Bi 212< , P 32< or radioactive isotopes of Lu), toxic drugs, chemotherapeutic drugs, antibiotics and nucleolytic enzymes; for example, the cytotoxic drug may be toxic drugs, including but not limited to camptothecin derivatives, which, for example, may be the camptothecin derivative exatecan (chemical name: (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]imidazo[1,2-b]quinoline-10,13(9H,15H)-dione).

[0025] In the present application, the term "linker structure" generally refers to a chemical structural fragment or bond, which is linked to a ligand at one end and linked to a cytotoxic drug at the other end, or linked to other linkers and then linked to the cytotoxic drug. The direct or indirect linking of a ligand may mean that the group is directly linked to the ligand via a covalent bond, and may also be linked to the ligand via a linker structure. For example, the linker structure may be a structure shown as -L ax -L b -L c - and / or -L a -L b -L c - described herein. For example, a chemical structure fragment or bond comprising an acid-labile linker structure (e.g., hydrazone), a protease-sensitive (e.g., peptidase-sensitive) linker structure, a photolabile linker structure, a dimethyl linker structure or a disulfide-containing linker structure may be used as a linker structure.

[0026] In the present application, the term a structure being "optionally linked to other molecular moieties" generally means that the structure is not linked to any other chemical structure, or that the structure is linked (e.g., via a chemical bond or a linker structure) to one or more other chemical structures (e.g., ligands described herein) different from the structure.

[0027] In the present application, the term "ligand-drug conjugate" generally means that a ligand is linked to a biologically active cytotoxic drug via a stable linking unit. In the present application, the "ligand-drug conjugate" may be an antibody-drug conjugate (ADC), which may mean that a monoclonal antibody or an antibody fragment is linked to a biologically active cytotoxic drug via a stable linking unit.

[0028] In the present application, the term "antibody or antigen-binding fragment thereof" generally refers to that immunological binding reagents extend to all antibodies from all species, including dimeric, trimeric and multimeric antibodies; bispecific antibodies; chimeric antibodies; fully humanized antibodies; humanized antibodies; recombinant and engineered antibodies and fragments thereof. The term "antibody or fragment thereof" may refer to any antibody-like molecule having an antigen-binding region, and includes small molecule fragments, such as Fab', Fab, F(ab') 2 , single domain antibodies (DABs), Fv, scFv (single chain Fv), linear antibodies, and diabodies. The term "antigen-binding fragment" may refer to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. For example, a fragment of a full-length antibody can be used to perform the antigen-binding function of the antibody. Techniques for preparing and using various antibody-based constructs and fragments are well known in the art. The antibody may include one or more of an anti-HER2(ErbB2) antibody, an anti-EGFR antibody, an anti-B7-H3 antibody, an anti-c-Met antibody, an anti-HER3(ErbB3) antibody, an anti-HER4(ErbB4) antibody, an anti-CD20 antibody, an anti-CD22 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD44 antibody, an anti-CD56 antibody, an anti-CD70 antibody, an anti-CD73 antibody, an anti-CD105 antibody, an anti-CEA antibody, an anti-A33 antibody, an anti-Cripto antibody, an anti-EphA2 antibody, an anti-G250 antibody, an anti-MUCl antibody, an anti-Lewis Y antibody, an anti-TROP2 antibody, an anti-Claudin 18.2 antibody, an anti-VEGFR antibody, an anti-GPNMB antibody, an anti-Integrin antibody, an anti-PSMA antibody, an anti-Tenascin-C antibody, an anti-SLC44A4 antibody and an anti-Mesothelin antibody; for example, it may be trastuzumab or pertuzumab.

[0029] In the present application, the term "chimeric antibody" generally refers to an antibody obtained by fusing a variable region of a murine antibody and a constant region of a human antibody, which can reduce an immune response induced by the murine antibody. For establishment of a chimeric antibody, a hybridoma secreting murine specific monoclonal antibody can be established, and a variable region gene is cloned from the mouse hybridoma cells; then a constant region gene of human antibody can be cloned as required, and the mouse variable region gene and the human constant region gene are connected to form a chimeric gene; then the chimeric gene is inserted into an expression vector, wherein chimeric antibody molecules can be expressed in a eukaryotic system or a prokaryotic system.

[0030] In the present application, the term "humanized antibody", also referred to as CDR-grafted antibody, generally refers to an antibody produced by grafting mouse CDR sequences into a human antibody variable region framework, i.e., an antibody produced in a different type of human germline antibody framework sequence. Therefore, the heterogeneous reaction induced by the presence of a large number of mouse protein components in the chimeric antibody can be overcome. Such framework sequences can be obtained from public DNA databases or disclosed references that include germline antibody gene sequences. For example, germline DNA sequences of human heavy and light chain variable region genes can be obtained from the "VBase" human germline sequence database.

[0031] In the present application, the term "fully humanized antibody", "fully human antibody" or "completely human antibody", also known as "fully humanized monoclonal antibody", may have both humanized variable region and constant region so as to eliminate immunogenicity and toxic side effects. The development of monoclonal antibodies has four stages, namely murine monoclonal antibodies, chimeric monoclonal antibodies, humanized monoclonal antibodies and fully humanized monoclonal antibodies. The antibodies or ligands described herein can be fully humanized monoclonal antibodies. Relevant technologies for the preparation of fully human antibodies may be: human hybridoma technology, EBV-transformed B-lymphocyte technology, phage display technology, transgenic mouse antibody preparation technology, single B-cell antibody preparation technology, and the like.

[0032] In the present application, the term "CDR" generally refers to one of the 6 hypervariable regions within the variable domain of an antibody which contribute primarily to antigen binding. One of the most common definitions of the 6 CDRs is provided by Kabat E.A. et al., (1991) Sequences of proteins of immunological interest. NIH Publication 91-3242; Chothia et al., "Canonical Structures For the Hypervariable Regions of Immunoglobulins", J. Mol. Biol. 196:901 (1987); and MacCallum et al., "Antibody-Antigen Interactions: Contact Analysis and Binding Site Topography", J. Mol. Biol. 262:732 (1996). As used herein, the Kabat definition of CDRs can be applied to CDR1, CDR2 and CDR3 of the light chain variable domain (CDR L1, CDR L2, CDR L3 or L1, L2, L3), and CDR 1, CDR2 and CDR3 of the heavy chain variable domain (CDR H1, CDR H2, CDR H3 or H1, H2, H3). In the present application, the term "methylene" generally refers to a residue derived by removal of two hydrogen atoms from a group having 1 carbon atom. Methylene may be substituted or unsubstituted, or replaced or unreplaced. The term "alkylene" generally refers to a saturated linear or branched aliphatic hydrocarbon group having 2 residues derived from the parent alkane by removal of two hydrogen atoms from the same carbon atom or two different carbon atoms, and it may be a linear or branched group containing 1 to 20 carbon atoms, such as alkylene containing 1 to 12 carbon atoms (e.g., 1 to 6 carbon atoms). Non-limiting examples of alkylene groups include, but are not limited to, methylene(-CH 2 -), 1,1-ethylidene(-CH(CH 3 )-), 1,2-ethylidene(-CH 2 CH 2 )-, 1,1-propylidene(-CH(CH 2 CH 3 )-), 1,2-propylidene(-CH 2 CH(CH 3 )-), 1,3-propylidene(-CH 2 CH 2 CH 2 -), 1,4-butylidene(-CH 2 CH 2 CH 2 CH 2 -), 1,5-butylidene(-CH 2 CH 2 CH 2 CH 2 CH 2 -), and the like. Alkylene groups may be substituted or unsubstituted, replaced or unreplaced. For example, when it is substituted, substitution with a substituent may be performed at any available linking point, and the substituent is preferably independently optionally selected from one or more of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, and oxo, and it may, e.g., be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , - OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0033] In the present application, the term "arylene" generally refers to a group having two residues derived by removal of two hydrogen atoms from the same carbon atom or two different carbon atoms of the aromatic ring. The term "aromatic ring" may refer to a 6-14 membered all-carbon monocyclic ring or fused polycyclic ring (i.e., rings which share adjacent pairs of carbon atoms) having a conjugated π-electron system, and it may be 6-10 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 moiety is the aryl ring. Aryl may be substituted or unsubstituted, and when it is substituted, the substituent is preferably one or more of the following groups independently selected from the group consisting of: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio and heterocycloalkylthio.

[0034] In the present application, the term "heteroarylene" generally refers to a group having two residues derived by removal of two hydrogen atoms from the same carbon atom or two different carbon atoms of the heteroaromatic ring. The term "heteroaromatic ring" refers to a heteroaromatic system comprising 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 may be 5-10 membered and may be 5- or 6-membered, such as furanyl, thienyl, pyridinyl, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, imidazolyl and tetrazolyl. The heteroaromatic ring can be fused to an aryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent moiety is the heteroaromatic ring. Heteroarylene may be optionally substituted or unsubstituted, and when it is substituted, the substituent is preferably one or more of the following groups independently selected from the group consisting of: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio and heterocycloalkylthio.

[0035] In the present application, the term "heterocyclylene" generally refers to a 3-7 membered monocyclic structure, a fused 7-10 membered bicyclic heterocyclic structure or a bridged 6-10 membered bicyclic heterocyclic structure that is stable and non-aromatic. These cyclic structures may be saturated or partially saturated, and contain one or more heteroatoms in addition to carbon atoms, wherein the heteroatoms may be selected from the group consisting of: oxygen, sulfur and nitrogen. For example, they contain 1 to 4 heteroatoms as defined above. When used to refer to atoms on a heterocyclic cyclic structure, the term "nitrogen" may include nitrogen that undergoes a substitution reaction. Heterocyclylene may be substituted or unsubstituted.

[0036] In the present application, the term "carbocyclylene" generally refers to a group having two residues derived by removal of two hydrogen atoms from the same carbon atom or two different carbon atoms of the carbon ring. The term "carbon ring" generally refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon, and it 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 carbon ring include cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclohexadiene, cycloheptane, cycloheptatriene, cyclooctane, and the like; polycyclic carbon ring may include spiro, fused and bridged carbon rings. Carbocyclylene may be substituted or unsubstituted.

[0037] In the present application, the term "partially unsaturated" generally means that the cyclic structure contains at least one double or triple bond between the ring molecules. The term "partially unsaturated" encompasses cyclic structures having multiple sites of unsaturation, but is not intended to include aromatic or heteroaromatic rings defined herein. The term "unsaturated" means that the moiety has one or more degrees of unsaturation.

[0038] In the present application, the term "halogen" generally refers to fluorine, chlorine, bromine or iodine, and it may be, for example, fluorine or chlorine.

[0039] In the present application, the term "aliphatic group" generally refers to a linear hydrocarbon, branched hydrocarbon or cyclic hydrocarbon having 1 to 12 carbon atoms, and the hydrocarbon may be either a fully saturated hydrocarbon or a hydrocarbon with one or more unsaturated units, but the unsaturated units are not aromatic groups. For example, suitable aliphatic groups may include substituted or unsubstituted linear, branched or cyclic alkyl, alkenyl, alkynyl and mixtures thereof, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. For example, aliphatic groups have 1 to 12, 1 to 8, 1 to 6, 1 to 4 or 1 to 3 carbon atoms.

[0040] In the present application, the term "optional" or "optionally" generally means that the event or circumstance subsequently described may, but not necessarily, occur, and that the description includes instances where the event or circumstance occurs or does not occur. For example, "heterocyclyl group optionally substituted with alkyl" means that alkyl may be, but not necessarily, present, and that the description may include instances where the heterocyclyl group is or is not substituted with alkyl.

[0041] In the present application, the term "substituted" generally means that one or more hydrogen atoms in the group, for example, up to 5 (e.g., 1 to 3) hydrogen atoms, are each independently substituted with a corresponding number of substituents. A substituent is only in its possible chemical position, and those skilled in the art will be able to determine (by experiments or theories) possible or impossible substitution without undue efforts. For example, it may be unstable when amino or hydroxy having a free hydrogen is bound to a carbon atom having an unsaturated (such as olefin) bond.

[0042] In the present application, the term "0 or more (e.g., 0 or at least 1, 0 or 1, or 0) methylene units are replaced "generally means that when the structure comprises one or more methylene units, the one or more methylene units may be unsubstituted or replaced by one or more groups that are not methylene (e.g., -NHC(O)-, -C(O)NH-, -C(O)-, -OC(O)-, -C(O)O-, -NH-, -O-, -S-, -SO-, -SO 2 -, -PH-, -P(=O)H-, -NHSO 2 -, -SO 2 NH-, -C(=S)-, -C(=NH)-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-).

[0043] One or more hydrogen atoms in the group, for example, up to 5 (e.g., 1 to 3) hydrogen atoms, are each independently substituted with a corresponding number of substituents. A substituent is only in its possible chemical position, and those skilled in the art will be able to determine (by experiments or theories) possible or impossible substitution without undue efforts. For example, it may be unstable when amino or hydroxy having a free hydrogen is bound to a carbon atom having an unsaturated (such as olefin) bond.

[0044] In the present application, the term "compound" generally refers to a substance having two or more different elements. For example, the compound disclosed herein may be an organic compound. For example, the compound disclosed herein may be a compound having a molecular weight of no more than 500, a compound having a molecular weight of no more than 1000, a compound having a molecular weight of no less than 1000, or a compound having a molecular weight of no less than 10,000 or no less than 100,000. In the present application, the compound may also refer to a compound that involves linking by a chemical bond, for example, a compound where one or more molecules having a molecular weight of no more than 1000 are linked, by a chemical bond, to a biological macromolecule, wherein the biological macromolecule may be polysaccharide, protein, nucleic acid, polypeptide, and the like. For example, the compound disclosed herein may include a compound where a protein is linked to one or more molecules having a molecular weight of no more than 1000, may include a compound where a protein is linked to one or more molecules having a molecular weight of no more than 10,000, and may include a compound where a protein is linked to one or more molecules having a molecular weight of no more than 100,000.

[0045] In some embodiments, the cytotoxic drug of the compound disclosed herein is directly or indirectly linked to a ligand. In some embodiments, the cytotoxic drug of the compound disclosed herein is directly linked to a ligand via a covalent bond. In some embodiments, the cytotoxic drug of the compound disclosed herein is linked to a ligand via a linker structure. In some embodiments, the compound disclosed herein is a ligand-drug conjugate having a ligand linked to a cytotoxic drug via a linker structure, wherein the cytotoxic drug comprises the structural formula II-A, II-A-1, II-A-2, II-A-3, II-A-4, II-A-5, II-A-6, II-A-7, II-A-8, II-A-9, II-A-10, II-A-11 or II-A-12 disclosed herein, wherein ring A, X 1< , L 1< , and R 2< are each defined as in embodiments of the first aspect.

[0046] In some embodiments, the compound disclosed herein is a ligand-drug conjugate or ADC. In some embodiments, a "mixture" of a compound refers to a composition comprising one or more of the compound and the tautomer, the mesomer, the racemate, the enantiomer and the diastereoisomer thereof. In some embodiments, a "mixture" of a compound refers to a composition comprising its heterogeneous DAR distribution. In one embodiment, a mixture of a compound comprises an ADC having a DAR distribution of 1 to 10, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 (a drug loading of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10). In one embodiment, the ADC mixture comprises the following two: an ADC with DAR of 6 or less (a drug loading of 6 or less) and an ADC with DAR of 8 or more (a drug loading of 8 or more).

[0047] 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 having a structure identical to the structure disclosed herein except for the substitution of the hydrogen atom with deuterium or tritium or the substitution of the carbon atom with carbon 13 or carbon 14 are within the scope of the present application.

[0048] In the present application, the term "pharmaceutical composition" generally refers to a mixture containing one or more of the compounds described herein or a physiologically / pharmaceutically acceptable salt or pro-drug thereof, and other chemical components, for example physiologically / pharmaceutically acceptable carriers and excipients. The pharmaceutical composition may promote the administration to an organism, which facilitates the absorption of the active ingredient, thereby exerting biological activities. For preparation of conventional pharmaceutical compositions, reference can be made to Chinese Pharmacopoeia.

[0049] In the present application, the term "pharmaceutically acceptable salt" generally refers to a salt of a compound or ligand-drug conjugate disclosed herein, or a salt of a compound described herein. Such salts may be safe and / or effective when used in a mammals and may possess the required biological activity, and the antibody-antibody drug conjugate compound disclosed herein may form a salt with an acid, and non-limiting examples of pharmaceutically acceptable salts include: hydrochloride, hydrobromide, hydriodate, sulphate, bisulfate, citrate, acetate, succinate, ascorbate, oxalate, nitrate, sorbate, hydrophosphate, dihydrophosphate, salicylate, hydrocitrate, tartrate, maleate, fumarate, formate, benzoate, mesylate, ethanesulfonate, benzenesulphonate andp-toluenesulfonate.

[0050] In the present application, the term "solvate" or "solvent compound" generally refers to a pharmaceutical acceptable solvate formed by a ligand-drug conjugate compound disclosed herein and one or more solvent molecules, and non-limiting examples of solvent molecules include water, ethanol, acetonitrile, isopropanol, DMSO and ethyl acetate.

[0051] The term "drug loading" generally refers to the average amount of cytotoxic drug loaded per ligand and may also be expressed as the ratio of cytotoxic drug to antibody, and the cytotoxic drug loading may range from 0 to 12 (e.g., 1 to 10) cytotoxic drugs per ligand (Ab). In the embodiments of the present application, the drug loading is expressed as N a< , and exemplary values may be an average of 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10. The drug loading per ADC molecule after the coupling reaction can be characterized by conventional methods such as UV / visible spectroscopy, mass spectrometry, ELISA assays and HPLC.

[0052] The pharmaceutical composition may be in the form of a sterile injectable aqueous or oily suspension for intramuscular and subcutaneous administration. The suspension can be prepared according to a known technique using those suitable dispersing agents or wetting agents and suspending agents described above. The sterile injectable formulation may also be a sterile injection or suspension prepared in a parenterally acceptable non-toxic diluent or solvent, such as a solution prepared in 1,3-butanediol. In addition, a sterile fixed oil may be conveniently used as a solvent or a suspending medium. For example, any blend fixed oil including synthetic mono- or di-glycerides can be used. In addition, fatty acids such as oleic acid may also be used in the preparation of injections.

[0053] In the present application, the term "comprise" "comprising", "contain" or "containing" is generally intended to include the explicitly specified features without excluding other elements. The terms "no less than" and "no more than" generally refer to the situations where the number itself is included. In the present application, the term "about" generally means varying by 0.5%-10% above or below the stated value, for example, varying by 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 stated value.DETAILED DESCRIPTION OF THE INVENTION

[0054] In a first aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-A): wherein, R 1< may be selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; L 2< may be -(C(R 3a< )(R 3b< )) m -R, and m may be selected from the group consisting of integers ≥1; wherein 0 or no less than 1 methylene unit of L 2< may be independently replaced by -Cy-, -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, - N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers ≥1; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -Cy-, -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cy- may be selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cy- is unsubstituted or may be independently substituted with no less than 1 substituent R 7< ; wherein each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; or, R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< may each independently optionally form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; wherein each R 2< , each R 7< and each R 8< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0055] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-A): wherein, R 1< may be selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; L 2< may be -(C(R 3a< )(R 3b< )) m -R, and m may be selected from the group consisting of integers ≥1; wherein 0 or no less than 1 methylene unit of L 2< may be independently replaced by -Cy-, -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, - N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers ≥1; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -Cy-, -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cy- may be selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cy- is unsubstituted or may be independently substituted with no less than 1 substituent R 7< ; wherein each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R 2< , each R 7< and each R 8< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0056] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-A): for example, wherein R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< may each independently optionally form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, - CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< may each independently optionally form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; for example, wherein R 3a< and R 5a< may form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; each R 3b< , each R 4< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< may each independently optionally form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; for example, wherein R 4< and R 5a< may form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; each R 3a< , each R 3b< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< may each independently optionally form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; for example, wherein R 3a< and R 6< may form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; each R 3b< , each R 4< , each R 5a< and each R 5b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< may each independently optionally form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; for example, wherein R 4< and R 6< may independently optionally form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ; each R 3a< , each R 3b< , each R 5a< and each R 5b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, - C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< may each independently optionally form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or may be substituted with no less than 1 substituent R 8< ;

[0057] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-A): wherein, R 1< may be-O-; L 2< may be -(C(R 3a< )(R 3b< )) m -R, and m may be selected from the group consisting of integers from 1 to 3; wherein 0 methylene units of L 2< may be replaced; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers from 2 to 4; wherein 0, 1 or 2 methylene units of L 1< may be replaced by -N(R 6< )C(O)-, -C(O)-, -OC(O)-, -NR 6< -, - O- or -C(=S)-; wherein each R 3a< , each R 3b< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; or R 3a< and R 5a< may form a ring B together with an atom therebetween, wherein the ring B may be selected from 5 membered saturated heterocyclylene, and the ring B is unsubstituted; R may be hydrogen or halogen.

[0058] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-A): wherein, R 1< may be-O-; L 2< may be -(C(R 3a< )(R 3b< )) m -R, and m may be selected from the group consisting of integers 1 and 2; wherein 0 methylene units of L 2< may be replaced; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers 2 and 3; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 3a< , each R 3b< , each R 5a< and each R 5b< may each independently be hydrogen; or R 3a< and R 5a< may form a ring B together with an atom therebetween, wherein the ring B may be selected from 5 membered saturated heterocyclylene having 1 nitrogen heteroatom, and the ring B is unsubstituted; R may be hydrogen.

[0059] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-A): wherein, R 1< may be-O-; L 2< may be -(C(R 3a< )(R 3b< )) m -R, and m may be selected from the group consisting of integers 1 and 2; wherein 0 methylene units of L 2< may be replaced; L 1< may be -(C(R 5a< )(R 5b< )) 2 -; wherein 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 3a< , each R 3b< , each R 5a< and each R 5b< may each independently be hydrogen; or R 3a< and R 5a< may form a ring B together with an atom therebetween, wherein the ring B may be selected from 5 membered saturated heterocyclylene having 1 nitrogen heteroatom, and the ring B is unsubstituted; R may be hydrogen.

[0060] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the following group of structures: wherein, R 1< may be selected from the group consisting of: -O-, -HN-, -P(=O)H- and -S-.

[0061] In another embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-A): wherein, X 1< may be selected from the group consisting of: n, P, and saturated or unsaturated C; when X 1< may be saturated C, X 1< may be substituted with R n< ; ring A optionally links the structure shown as formula (II-A) to other molecular moieties; when X 1< may be saturated C, ring A may be selected from the group consisting of: 3-10 membered saturated or partially unsaturated heterocyclyl, and 3-10 membered saturated or partially unsaturated carbocyclyl, wherein ring A may be substituted with 0 or no less than 1 substituent R 1a< ; or, when X 1< may be unsaturated C, ring A may be selected from the group consisting of: 6-10 membered aryl, 5-8 membered heteroaryl, 3-10 membered partially unsaturated heterocyclyl, and 3-10 membered partially unsaturated carbocyclyl, wherein ring A may be substituted with 0 or no less than 1 substituent R 1b< ; or, when X 1< may be N or P, ring A may be selected from the group consisting of: 5-8 membered heteroaryl and 3-10 membered saturated or partially unsaturated heterocyclyl, wherein ring A may be substituted with 0 or no less than 1 substituent R 1c< , when ring A may be selected from the group consisting of: 6-10 membered aryl, 5-8 membered heteroaryl, and 3-10 membered saturated or partially unsaturated carbocyclyl, ring A may be substituted with p L 2< , wherein L 2< cannot be R n< ; or, when ring A may be 3-10 membered saturated or partially unsaturated heterocyclyl, ring A may be substituted with p L 2< , or ring A may comprise q ring-forming heteroatom X 2< , and X 2< is used to link the structure shown as formula (II-A) to other molecular moieties; X 2< may be selected from the group consisting of: N and P; L 2< may be -R 2< -L 3< -, and R 2< is used to link the structure shown as formula (II-A) to other molecular moieties; L 3< may be -(C(R 3a< )(R 3b< )) m -, wherein when L 3< may comprise a methylene unit, 0 or no less than 1 methylene unit of L 3< may be independently replaced by -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, - C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 2< may be selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< may be -(C(R 5a< )(R 5b< )) n -, wherein when L 1< may comprise a methylene unit, 0 or no less than 1 methylene unit of L 1< may be independently replaced by -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, - C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1a< , each R 1b< , each R 1c< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n may each independently be selected from the group consisting of integers ≥ 0, and p and q may each independently be selected from the group consisting of integers ≥ 1.

[0062] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be saturated C, and X 1< may be substituted with R n< ; ring A may be selected from the group consisting of: 3-10 membered saturated or partially unsaturated heterocyclyl and 3-10 membered saturated or partially unsaturated carbocyclyl, wherein ring A may be substituted with 0 or no less than 1 substituent R 1a< ; ring A may be substituted with p L 2< , wherein p may be selected from the group consisting of integers ≥ 1, and L 2< can not be R n< ; L 2< may be -R 2< -L 3< -; L 3< may be -(C(R 3a< )(R 3b< )) m , and m may be selected from the group consisting of integers ≥0; wherein when L 3< may comprise a methylene unit, 0 or no less than 1 methylene unit of L 3< may be independently replaced by -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, - SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, - N=C- or -C(=N 2 )-; R 2< may be selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers ≥0; wherein when L 1< may comprise a methylene unit, 0 or no less than 1 methylene unit of L 1< may be independently replaced by -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, - SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, - N=C- or -C(=N 2 )-; wherein each R 1a< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< , each R 6< and each R n< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, - N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), - SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0063] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ay): wherein, X 1< may be saturated C, and X 1< may be substituted with R n< ; ring A may be 3-10 membered saturated or partially unsaturated heterocyclyl, and ring A can not be substituted or may be substituted with no less than 1 substituent R 1a< ; ring A may comprise q ring-forming heteroatom X 2< , and X 2< is used for direct or indirect linking of a ligand; q may be selected from the group consisting of integers ≥ 1, and X 2< may be selected from the group consisting of: N and P; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1a< , each R 5a< , each R 5b< , each R 6< and each R n< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0064] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be unsaturated C; ring A may be selected from the group consisting of: 6-10 membered aryl, 5-8 membered heteroaryl, 3-10 membered partially unsaturated heterocyclyl, and 3-10 membered partially unsaturated carbocyclyl, and ring A can not be substituted or may be substituted with no less than 1 substituent R 1b< ; ring A may be substituted with p L 2< , wherein p may be selected from the group consisting of integers ≥ 1; L 2< may be -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< may be -(C(R 3a< )(R 3b< )) m , and m may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 3< may be independently replaced by -N(R 4< )C(O)-, - C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, - N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 2< may be selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1b< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0065] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ay): wherein, X 1< may be unsaturated C; ring A may be 3-10 membered partially unsaturated heterocyclyl, and ring A can not be substituted or may be substituted with no less than 1 substituent R 1b< ; ring A may comprise q ring-forming heteroatom X 2< , and X 2< is used for direct or indirect linking of a ligand; q may be selected from the group consisting of integers ≥ 1, and X 2< may be selected from the group consisting of: N and P; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1b< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0066] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be N or P; ring A may be selected from the group consisting of: 5-8 membered heteroaryl and 3-10 membered saturated or partially unsaturated heterocyclyl, and ring A can not be substituted or may be substituted with no less than 1 substituent R 1c< , ring A may be substituted with p L 2< , wherein p may be selected from the group consisting of integers ≥ 1; L 2< may be -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< may be -(C(R 3a< )(R 3b< )) m , and m may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 3< may be independently replaced by -N(R 4< )C(O)-, - C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, - N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 2< may be selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1c< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0067] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ay): wherein, X 1< may be N or P; ring A may be 3-10 membered saturated or partially unsaturated heterocyclyl, and ring A can not be substituted or may be substituted with no less than 1 substituent R 1c< ; ring A may comprise q ring-forming heteroatom X 2< , and X 2< is used for direct or indirect linking of a ligand; q may be selected from the group consisting of integers ≥ 1, and X 2< may be selected from the group consisting of: N and P; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein each R 1c< , each R 5a< , each R 5b< and each R 6< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0068] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be saturated C, and X 1< may be substituted with R n< ; ring A may be selected from the group consisting of: 3-6 membered saturated heterocyclyl and 3-6 membered saturated or partially unsaturated carbocyclyl; p may be 1, and L 2< can not be R n< ; L 2< may be -R 2< -L 3< -; L 3< may be -(C(R 3a< )(R 3b< )) m -, and m may be selected from the group consisting of integers from 0 to 2, wherein when L 3< may comprise a methylene unit, 0 or 1 methylene unit of L 3< may be replaced by - C(O)- or -C(=S)-; R 2< may be selected from -O-; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of 0 and 1; wherein when L 1< may comprise a methylene unit, 0 or 1 methylene unit of L 1< may be replaced by - C(O)- or -C(=S)-; wherein each R 3a< , each R 3b< , each R 5a< , each R 5b< and each R n< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may independently be hydrogen or halogen.

[0069] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be saturated C, and X 1< is linked to R n< , wherein R n< may be H; ring A may be selected from the group consisting of: 5 membered saturated heterocyclyl having 1 nitrogen heteroatom, and 4-6 membered saturated carbocyclyl; P may be 1; L 2< may be -R 2< -L 3< -, and L 3< is directly linked to ring A; L 3< may be -(C(R 3a< )(R 3b< )) m -, and m may be 0 or 2; R 2< may be -O-; L 1< may be -C(O)-; wherein each R 3a< and each R 3b< may each independently be hydrogen.

[0070] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ay): wherein, X 1< may be saturated C, and X 1< may be substituted with R n< ; ring A may be 3-6 membered saturated heterocyclyl; ring A may comprise 1 ring-forming heteroatom N, and N is used for direct or indirect linking of a ligand; L 1< may be -(C(R 5a< )(R 5b< )) n -, and n may be selected from the group consisting of 0 and 1; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)- or -C(=S)-; wherein each R 5a< , each R 5b< and each R n< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may independently be hydrogen or halogen.

[0071] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ay): wherein, X 1< may be saturated C, and X 1< may be substituted with H; ring A may be 5 membered saturated heterocyclyl having 1 heteroatom N; ring A may comprise 1 ring-forming heteroatom N, and N is used for direct or indirect linking of a ligand; L 1< may be -C(O)-.

[0072] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be unsaturated C; ring A may be selected from the group consisting of: 6 membered aryl, 5-8 membered heteroaryl, 3-10 membered partially unsaturated heterocyclyl, and 3-10 membered partially unsaturated carbocyclyl, and ring A can not be substituted or may be independently substituted with 1 substituent R 1b< ; P may be 1; L 2< may be -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< may be -C(R 3a< )(R 3b< )-; R 2< may be selected from the group consisting of: -O-, -(R 2a< )N- and -S-; L 1< may be -C(R 5a< )(R 5b< )-; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)- or -C(=S)-; wherein each R 1b< , each R 2a< , each R 3a< , each R 3b< , each R 5a< and each R 5b< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may independently be hydrogen or halogen.

[0073] For example, the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be unsaturated C; ring A may be selected from the group consisting of: 6 membered aryl and 5-8 membered heteroaryl; P may be 1; L 2< may be -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< may be -C(R 3a< )(R 3b< )-; R 2< may be selected from the group consisting of: -O-, -(R 2a< )N- and -S-; L 1< may be -C(R 5a< )(R 5b< )-; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)- or -C(=S)-; wherein each R 2a< , each R 3a< , each R 3b< , each R 5a< and each R 5b< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may independently be hydrogen or halogen.

[0074] For example, the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be unsaturated C; ring A may be 6 membered aryl; P may be 1; L 2< may be -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< may be -C(R 3a< )(R 3b< )-; R 2< may be -O-; L 1< may be -C(O)-; wherein each R 3a< , each R 3b< , each R 5a< and each R 5b< may each independently be hydrogen or a C 1-6 aliphatic group;

[0075] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ay): wherein, X 1< may be unsaturated C; ring A may be 5 membered partially unsaturated heterocyclyl; ring A may comprise 1 ring-forming heteroatom N, and N is used for direct or indirect linking of a ligand; L 1< may be -C(R 5a< )(R 5b< ), wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)- or -C(=S)-; wherein each R 5a< and each R 5b< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may independently be hydrogen or halogen.

[0076] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ax): wherein, X 1< may be N; ring A may be 6 membered saturated heterocyclyl; P may be 1; L 2< may be -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< may be -(C(R 3a< )(R 3b< )) m -, and m may be 1 or 2, wherein 0 or 1 methylene unit of L 3< may be replaced by -C(O)- or -C(=S)-; R 2< may be selected from the group consisting of: -O-, -(R 2a< )N- and -S-; L 1< may be -C(R 5a< )(R 5b< )-, wherein 1 methylene unit of L 1< may be replaced by -C(O)- or -C(=S)-; wherein each R 2a< , each R 3a< , each R 3b< , each R 5a< and each R 5b< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may independently be hydrogen or halogen.

[0077] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Ay): wherein, X 1< may be N; ring A may be 5 membered partially unsaturated heterocyclyl; ring A may comprise 1 ring-forming heteroatom N, and N is used for direct or indirect linking of a ligand; L 1< may be -C(R 5a< )(R 5b< ), wherein no less than 1 methylene unit of L 1< may be replaced by -C(O)- or -C(=S)-; wherein each R 5a< and each R 5b< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may independently be hydrogen or halogen.

[0078] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the following group of structures: wherein, R 2< may be selected from the group consisting of: -O-, -HN-, -P(=O)H- and -S-.

[0079] In another embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; X may be selected from the group consisting of: -L 1< -C(R 1a< )(R 1b< )-C(O)-, -L 1< -C(R 1a< )(R 1b< )-C(S)-, -L 1< -L 0< - and -L 3< -L 2< -; L 1< may be -(C(R 3a< )(R 3b< )) m -, wherein when L 1< may comprise a methylene unit, 0 or no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; L 0< may be -C(R 2a< )(R 2b< )-, or L 0< may be -C(=S)-, -C(=NR 4a< )- or -C(=N 2 )-; L 2< may be -C(R 5a< )(R 5b< )-, wherein 0 or 1 methylene unit of L 2< may be replaced by -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; L 3< may be -(C(R 7a< )(R 7b< )) n -, wherein no less than 1 methylene unit of L 3< may be independently replaced by -N(R 8< )C(O)-, -C(O)N(R 8< )-, -OC(O)-, -C(O)O-, -NR 8< -, -O-, -S-, -SO-, -SO 2 -, -P(R 8< )-, - P(=O)(R 8< )-, -N(R 8< )SO 2 -, -SO 2 N(R 8< )-, -N=N-, -C=N- or -N=C-, and 0 or no less than 1 methylene unit of L 3< may also independently be replaced by -C(O)-, -C(=S)-, -C(=NR 8< )- or -C(=N 2 )-; wherein each R 1a< , each R 1b< , each R 2< , each R 2a< , each R 2b< , each R 3a< , each R 3b< , each R 4a< , each R 4b< , each R 5a< , each R 5b< , each R 6< , each R 7a< , each R 7b< and each R 8< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m may be selected from the group consisting of integers ≥ 0, and n may be selected from the group consisting of integers ≥ 1; when R 1< may be -O- or-HN-, and X may be-L 1< -CH 2 -C(O)-, and when L 1< may comprise a methylene unit, no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, - C(=NR 4b< )- or -C(=N 2 )-, or R 3a< and R 3b< can not be both hydrogen in each -C(R 3a< )(R 3b< ) -of L 1< ; when R 1< may be -HN-, X may be -L 1< -L 0< -, and L 0< may be -CH 2 -, no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-, or each R 3a< and each R 3b< can not be both hydrogen; when R 1< may be -O-, X may be -L 3< -C(O)-, and 1 methylene unit of L 3< may be replaced by-NR 8< , R 8< can not be -CH 2 -CH 2 -NH 2 ; when R 1< may be -NH-, and X may be -L 3< -C(O)-, no less than 1 methylene unit of L 3< may be replaced by -N(R 8< )C(O)-, -OC(O)-, -C(O)O-, -S-, -SO-, -SO 2 -, -P(R 8< )-, -P(=O)(R 8< )-, -N(R 8< )SO 2 -, -SO 2 N(R 8< )-, -N=N-, -C=N- or -N=C-.

[0080] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be selected from the group consisting of: -O-, -(R 2< )N- and -S-; X may be -L 1< -C(R 1a< )(R 1b< )-C(S)-; L 1< may be -(C(R 3 a< )(R 3b< )) m , and m may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; R 2< may be halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R 1a< , each R 1b< , each R 3a< , each R 3b< and each R 4b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0081] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -S- or- (R 2< )N-; X may be -L 1< -C(R 1a< )(R 1b< )-C(O)-; L 1< may be -(C(R 3 a< )(R 3b< )) m , and m may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; R 2< may be halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R 1a< , each R 1b< , each R 3a< , each R 3b< and each R 4b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0082] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O- or -HN-; X may be -L 1< -CH 2 -C(O)-; L 1< may be -(C(R 3 a< )(R 3b< )) m , and m may be selected from the group consisting of integers ≥1; wherein no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, - C(=NR 4b< )- or -C(=N 2 )-; wherein each R 3a< , each R 3b< and each R 4b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0083] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O- or -HN-; X may be -L 1< -CH 2 -C(O)-; L 1< may be -(C(R 3a< )(R 3b< )) m , and m may be selected from the group consisting of integers ≥0; R 3a< and R 3b< can not be both hydrogen in each -C(R 3a< )(R 3b< )-, or no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; wherein each R 3a< , each R 3b< and each R 4b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0084] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O-, -S- or -(R 2< )N-; X may be -L 1< -L 0< -; L 0< may be -C(R 2a< )(R 2b< )-, or L 0< may be -C(=S)-, -C(=NR 4a< )- or -C(=N 2 )-; L 1< may be -(C(R 3 a< )(R 3b< )) m , and m may be selected from the group consisting of integers ≥0; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; R 2< may be halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R 2a< , each R 2b< , R 3a< , each R 3b< , each R 4a< and each R 4b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0085] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -HN-; X may be -L 1< -L 0< -; L 0< may be -C(R 2a< )(R 2b< )-, or L 0< may be -C(=S)-, -C(=NR 4a< )- or -C(=N 2 )-; L 1< may be -(C(R 3a< )(R 3b< )) m -, m may be selected from the group consisting of integers ≥ 0, and each R 3a< and each R 3b< can not be both hydrogen; wherein 0 or no less than 1 methylene unit of L 1< may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b< )- or -C(=N 2 )-; wherein each R 2a< , each R 2b< , R 3a< , each R 3b< , each R 4a< and each R 4b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0086] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, X may be -L 3< -L 2< -; L 2< may be -C(R 5a< )(R 5b< )-, wherein 0 or 1 methylene unit of L 2< may be replaced by -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; R 1< may be -S- or -(R 2< )N-; or R 1< may be -O- and L 2< can not be -C(O)-; or R 1< may be -NH- and L 2< can not be -C(O)-; L 3< may be -(C(R 7a< )(R 7b< )) n -, and n may be selected from the group consisting of integers ≥1; wherein no less than 1 methylene unit of L 3< may be independently replaced by -N(R 8< )C(O)-, - C(O)N(R 8< )-, -OC(O)-, -C(O)O-, -NR 8< -, -O-, -S-, -SO-, -SO 2 -, -P(R 8< )-, -P(=O)(R 8< )-, -N(R 8< )SO 2 -, - SO 2 N(R 8< )-, -N=N-, -C=N- or -N=C-, and 0 or no less than 1 methylene unit of L 3< may also be independently replaced by -C(O)-, -C(=S)-, -C(=NR 8< )- or -C(=N 2 )-; R 2< may be halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, - C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R 5a< , each R 5b< , each R 6< , each R 7a< , each R 7b< and each R 8< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0087] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be-O-; X may be -L 3< -L 2< -; wherein L 2< may be -C(O)-; L 3< may be -(C(R 7a< )(R 7b< )) n -, and n may be selected from the group consisting of integers ≥0; wherein no less than 1 methylene unit of L 3< may be independently replaced by -N(R 8< )C(O)-, - C(O)N(R 8< )-, -OC(O)-, -C(O)O-, -NR 8< -, -O-, -S-, -SO-, -SO 2 -, -P(R 8< )-, -P(=O)(R 8< )-, -N(R 8< )SO 2 -, - SO 2 N(R 8< )-, -N=N-, -C=N- or -N=C-, and 0 or no less than 1 methylene unit of L 3< may also be independently replaced by -C(O)-, -C(=S)-, -C(=NR 8< )- or -C(=N 2 )-; wherein each R 7a< , each R 7b< and each R 8< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R or a C 1-6 aliphatic group which may be optionally substituted with R; wherein R, R a< and R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, - NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, - C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; when 1 methylene unit of L 3< may be replaced by -NR 8< , R 8< can not be a C 1-6 aliphatic group which may be substituted with -NH 2 .

[0088] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -HN-; X may be -L 3< -L 2< -; wherein L 2< may be -C(O)-; L 3< may be -(C(R 7a< )(R 7b< )) n -, and n may be selected from the group consisting of integers ≥1; no less than 1 methylene unit of L 3< may be replaced by -N(R 8< )C(O)-, -OC(O)-, -C(O)O-, -S-, -SO-, - SO 2 -, -P(R 8< )-, -P(=O)(R 8< )-, -N(R 8< )SO 2 -, -SO 2 N(R 8< )-, -N=N-, -C=N- or -N=C-, and 0 or no less than 1 methylene unit of L 3< may also be independently replaced by -C(O)N(R 8< )-, -NR 8< - or -O-, and 0 or no less than 1 methylene unit of L 3< may also be independently replaced by -C(O)-, -C(=S)-, - C(=NR 8< )- or -C(=N 2 )-; wherein each R 7a< , each R 7b< and each R 8< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R, each R a< and each R b< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0089] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O-, -S- or- (R 2< )N-; X may be -L 1< -C(R 1a< )(R 1b< )-C(S)-; L 1< may be -(C(R 3a< )(R 3b< )) m -, and m may be 0, 1 or 2; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 1a< , each R 1b< , each R 2< , each R 3a< and each R 3b< may each independently be hydrogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may be hydrogen.

[0090] For example, the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O-; X may be -L 1< -C(R 1a< )(R 1b< )-C(S)-; L 1< may be -(CH 2 ) m -, and m may be 1 or 2; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 1a< and each R 1b< may each independently be hydrogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may be hydrogen.

[0091] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -S- or- (R 2< )N-; X may be -L 1< -C(R 1a< )(R 1b< )-C(O)-; L 1< may be -(C(R 3a< )(R 3b< )) m -, and m may be 0, 1 or 2; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; R 2< may be a C 1-6 aliphatic group; wherein each R 1a< , each R 1b< , each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group.

[0092] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -S- or- (R 2< )N-; X may be -L 1< -C(R 1a< )(R 1b< )-C(O)-; L 1< may be -(C(R 3a< )(R 3b< )) m -, and m may be 1 or 2; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; R 2< may be a C 1-6 aliphatic group; wherein each R 1a< , each R 1b< , each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group.

[0093] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, when R 1< may be -S- or -(R 2< )N-, X may be -L 1< -C(R 1a< )(R 1b< )-C(O)-, L 1< may be -(C(R 3a< )(R 3b< )) m -, and m may be 0, 1 or 2, 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; R 2< may be a C 1-6 aliphatic group; wherein each R 1a< , each R 1b< , each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group; or, when R 1< may be -O-, X may be -L 1< -CH 2 -C(O)-, and L 1< may be -(C(R 3a< )(R 3b< )) 2 -, 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group; each R 3a< and each R 3b< can not be both hydrogen, or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group.

[0094] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O-; X may be -L 1< -CH 2 -C(O)-; L 1< may be -(C(R 3a< )(R 3b< )) 2 -; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group; each R 3a< and each R 3b< can not be both hydrogen, or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group.

[0095] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, when R 1< may be -S- or -(R 2< )N-, X may be -L 1< -C(R 1a< )(R 1b< )-C(O)-, L 1< may be -(C(R 3a< )(R 3b< )) m -, and m may be 0, 1 or 2, 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; R 2< may be a C 1-6 aliphatic group; wherein each R 1a< , each R 1b< , each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group; or, when R 1< may be -O-, and X may be -L 1< -CH 2 -C(O)-, L 1< may be -C(R 3a< )(R 3b< )-, and R 3a< and R 3b< can not be both hydrogen in each -C(R 3a< )(R 3b< )-; wherein each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group.

[0096] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O-; X may be -L 1< -CH 2 -C(O)-; L 1< may be -(C(R 3a< )(R 3b< )) 2 -; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group; R 3a< and R 3b< can not be both hydrogen in each -C(R 3a< )(R 3b< ), or 1 methylene unit of L 1< may be replaced by -C(O)-; wherein each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group.

[0097] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O-; X may be -L 1< -CH 2 -C(O)-; L 1< may be -(CH 2 ) 2 -; wherein 1 methylene unit of L 1< may be replaced by -C(O)-.

[0098] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be-O-; X may be -L 1< -CH 2 -C(O)-; L 1< may be -C(R 3a< )(R 3b< )- m -, m may be selected from the group consisting of integers from 1 to 5, and R 3a< and R 3b< can not be both hydrogen in each -C(R 3a< )(R 3b< )-; wherein each R 3a< and each R 3b< may each independently be hydrogen, halogen, or a C 1-6 aliphatic group which may be optionally substituted with R; wherein each R may be hydrogen or halogen.

[0099] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be-O-; X may be -L 1< -CH 2 -C(O)-; L 1< may be -C(R 3a< )(R 3b< )-, and R 3a< and R 3b< can not be both hydrogen; wherein each R 3a< and each R 3b< may each independently be hydrogen or a C 1-6 aliphatic group.

[0100] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O- or -(R 2< )N-; X may be -L 1< -L 0< -; L 0< may be -CH 2 -, or L 0< may be -C(=S)-; L 1< may be -(CH 2 ) m -, and m may be selected from the group consisting of integers from 0 to 2; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)- or -C(=S)-; R 2< may be a C 1-6 aliphatic group.

[0101] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -NH-; X may be -L 1< -L 0< -; L 0< may be -CH 2 -, or L 0< may be -C(=S)-; L 1< may be -(CH 2 ) m -, and m may be selected from the group consisting of integers from 0 to 2; wherein 0 or 1 methylene unit of L 1< may be replaced by -C(O)- or -C(=S)-.

[0102] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -S- or- (R 2< )N-; X may be -L 3< -L 2< -; wherein L 2< may be -C(O)-; L 3< may be -(CH 2 ) n -, and n may be 4 or 5; wherein 1 methylene unit of L 3< may be replaced by -NR 8< -, -O-, -S- or -SO-; R 2< may be a C 1-6 aliphatic group.

[0103] For example, the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -S- or- (R 2< )N-; X may be -L 3< -L 2< -; wherein L 2< may be -C(O)-; L 3< may be -(CH 2 ) n -, and n may be 4 or 5; wherein 1 methylene unit of L 3< may be replaced by -O-; R 2< may be a C 1-6 aliphatic group.

[0104] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be-O-; X may be -L 3< -L 2< -; wherein L 2< may be -C(O)-; L 3< may be -(C(R 7a< )(R 7b< )) n -, and n may be 4 or 5; wherein 1 methylene unit of L 3< may be replaced by -NR 8< - or -O-, and 0 or 1 methylene unit of L 3< may also be independently replaced by -C(O)- or -C(=S)-; wherein each R 7a< , each R 7b< and each R 8< may each independently be hydrogen or a C 1-6 aliphatic group.

[0105] For example, the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -O-; X may be -L 3< -L 2< -; wherein L 2< may be -C(O)-; L 3< may be -(C(R 7a< )(R 7b< )) 4 -; wherein 1 methylene unit of L 3< may be replaced by -NR 8< - or -O-; wherein each R 7a< , each R 7b< and each R 8< may each independently be hydrogen or a C 1-6 aliphatic group.

[0106] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be-O-; X may be -L 3< -L 2< -; wherein L 2< may be -C(O)-; L 3< may be -(C(R 7a< )(R 7b< )) 4 -; wherein 1 methylene unit of L 3< may be replaced by -NR 8< -; wherein each R 7a< , each R 7b< and each R 8< may each independently be hydrogen or a C 1-6 aliphatic group.

[0107] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-A): wherein, R 1< may be -NH-; X may be -L 3< -L 2< -; wherein L 2< may be -C(O)-; L 3< may be -(CH 2 ) n -, and n may be 4 or 5; wherein 1 methylene unit of L 3< may be replaced by -S-.

[0108] In one embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the following group of structures: wherein R 2< may be a C 1-6 aliphatic group which may be optionally replaced by R, wherein R may be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, - C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H, or a C 1-6 aliphatic group, or wherein, R 2< may be halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, - C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0109] For example, R 2< may be methyl which may be optionally substituted with one or more hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or C 1-6 aliphatic groups. For example, R 2< may be ethyl which may be optionally substituted with hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group. For example, R 2< may be propyl which may be optionally substituted with hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0110] In a second aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-B): wherein, X a< may be nitrogen generated by removal of two hydrogen atoms from an amino group of the cytotoxic drug; L may be -La-Lb-Lc-; -L a - may be selected from the group consisting of: wherein W may be -(C(R wa< )(R wb< )) wn -, Y may be -(OCH 2 CH 2 ) yn -O yp -, and Z may be -(C(R za< )(R zb< )) zn ; wherein wn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of W may be independently replaced by -Cyr-, -N(R wx< )C(O)-, - C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, - N(R wx< )SO 2 -, -SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn may be selected from the group consisting of integers ≥ 0, and yp may be 0 or 1; wherein zn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, - C(O)N(R zx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, - N(R zx< )SO 2 -, -SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- may be selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with no less than 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , - N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), -SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< or a C 1-6 aliphatic group which may be optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - may be selected from the group consisting of: wherein R L1< and R L2< may each independently be selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; R 1< , L 1< and L 2< are defined as in any formula (I-A) in embodiments of the first aspect.

[0111] In another embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Bx) or formula (II-By): wherein, X a< may be nitrogen generated by removal of two hydrogen atoms from an amino group of the cytotoxic drug; L may be -L a -L b -L c -; -L a - may be selected from the group consisting of: wherein W may be -(C(R wa< )(R wb< )) wn -, Y may be -(OCH 2 CH 2 ) yn -O yp -, and Z may be -(C(R za< )(R zb< )) zn ; wherein wn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of W may be independently replaced by -Cyr-, -N(R wx< )C(O)-, - C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, - N(R wx< )SO 2 -, -SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn may be selected from the group consisting of integers ≥ 0, and yp may be 0 or 1; wherein zn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, - C(O)N(R zx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, - N(R zx< )SO 2 -, -SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- may be selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with no less than 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , - N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), -SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< or a C 1-6 aliphatic group which may be optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - may be selected from the group consisting of: wherein R L1< and R L2< may each independently be selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; L 2< , p, ring A, X 1< and L 1< are defined as in any formula (II-Ax) in embodiments of the first aspect; or X 2< , q, ring A, X 1< and L 1< are defined as in any formula (II-Ay) in embodiments of the first aspect. In another embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-B): wherein, X a< may be nitrogen generated by removal of two hydrogen atoms from an amino group of the cytotoxic drug; L may be -La-Lb-Lc-; -L a - may be selected from the group consisting of: wherein W may be -(C(R wa< )(R wb< )) wn -, Y may be -(OCH 2 CH 2 ) yn -O yp , and Z may be -(C(R za< )(R zb< )) zn ; wherein wn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of W may be independently replaced by -Cyr-, -N(R wx< )C(O)-, - C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, - N(R wx< )SO 2 -, -SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn may be selected from the group consisting of integers ≥ 0, and yp may be 0 or 1; wherein zn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, - C(O)N(R zx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, - N(R zx< )SO 2 -, -SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- may be selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with no less than 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , - N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), -SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< or a C 1-6 aliphatic group which may be optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; -L b - represents a peptide residue consisting of 2 to 7 amino acids; -L c - may be selected from the group consisting of: wherein R L1< and R L2< may each independently be selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group; wherein R 1< and X are defined as in any formula (III-A) in embodiments of the first aspect.

[0112] In another embodiment, wn may be selected from the group consisting of integers from 2 to 6, and 0 or 1 methylene unit of W may be independently replaced by -Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )-, - C(O)-, -NR wx< - or -O-.

[0113] For example, wn may be 1, 2, 3 or 6, and 1 methylene unit of W may be independently replaced by - Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )- or -C(O)-.

[0114] In another embodiment, yn may be selected from the group consisting of integers from 0 to 12, and yp may be 0 or 1.

[0115] For example, yn may be 0, 4 or 8, and yp may be 0 or 1.

[0116] In another embodiment, zn may be selected from the group consisting of integers from 0 to 10, and 0 or 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )- or - C(O)-.

[0117] For example, zn may be 1, 2 or 3, and 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )- or -C(O)-.

[0118] In another embodiment, -Cyr- may be selected from the group consisting of: 6-10 membered arylene and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with 1 to 3 substituent R cx< .

[0119] For example, -Cyr- may be 3-10 membered saturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with 1 to 3 substituent R cx< .

[0120] In another embodiment, each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , - N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), -SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< , or a C 1-6 aliphatic group which may be optionally substituted with R r< ; each R r< , each R ra< and each R rb< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0121] For example, each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, halogen, -OR r< , or a C 1-6 aliphatic group which may be optionally substituted with R r< ; each R r< may independently be hydrogen, halogen or a C 1-6 aliphatic group.

[0122] In another embodiment, -L b - represents a peptide residue consisting of 2 to 7 amino acids, and the peptide residue of -L b - may be a peptide residue which may be formed of amino acids which may be selected from the group consisting of: phenylalanine, glycine, alanine, valine, citrulline, lysine, serine, glutamic acid and aspartic acid.

[0123] For example, -L b - represents a peptide residue consisting of 2 to 4 amino acids, and the peptide residue of -L b - may be a peptide residue which may be formed of amino acids which may be selected from the group consisting of: phenylalanine, glycine, alanine, valine, citrulline and lysine.

[0124] For example, -L b - may be selected from the group consisting of:

[0125] For example, -L b - may be

[0126] In another embodiment, -L c - may be selected from the group consisting of:

[0127] For example, -L c - may be selected from the group consisting of: -L c - may be

[0128] In another embodiment, R L1< and R L2< may each independently be selected from the group consisting of: hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, - C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H and a C 1-6 aliphatic group.

[0129] For example, R L1< and R L2< may each independently be selected from the group consisting of: hydrogen, halogen, -OH and a C 1-6 aliphatic group.

[0130] In another embodiment, -L a - may be

[0131] In another embodiment, -L b - may be selected from the group consisting of:

[0132] For example, -L b - may be selected from the group consisting of:

[0133] In one embodiment, -L c - may be

[0134] In one embodiment, -L a -L b -L c - may be selected from the group consisting of:

[0135] The cytotoxic drug is shown as formula (EXA):

[0136] In a third aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-C): wherein, L may be -L a -L b -L c -, and L a , L b and L c are defined as in any formula (I-B) in embodiments of the second aspect; R 1< , L 1< and L 2< are defined as in any formula (I-A) in embodiments of the first aspect.

[0137] In another embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Cx) or formula (II-Cy): wherein, L may be -L a -L b -L c -, and L a , L b and L c are defined as in any formula (II-Bx) in embodiments of the second aspect; L 2< , p, ring A, X 1< and L 1< are defined as in any formula (II-Ax) in embodiments of the first aspect; or X 2< , q, ring A, X 1< and L 1< are defined as in any formula (II-Ay) in embodiments of the first aspect.

[0138] In another embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-C): wherein, L may be -L a -L b -L c -, and L a , L b and L c are defined as in any formula (III-B) in embodiments of the second aspect; wherein R 1< and X are defined as in any formula (III-A) in embodiments of the first aspect.

[0139] In a fourth aspect, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (I-D): wherein, Ab may be a ligand, and an average connection number N a< may be an integer or a decimal from 1 to 10; L may be -L a -L b -L c -, and L a , L b and L c are defined as in any formula (I-B) in embodiments of the second aspect; R 1< , L 1< and L 2< are defined as in any formula (I-A) in embodiments of the first aspect.

[0140] In another embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (II-Dx) or formula (II-Dy): wherein, Ab may be a ligand, and an average connection number N a< may be an integer or a decimal from 1 to 10; L may be -L a -L b -L c -, and L a , L b and L c are defined as in any formula (II-Bx) in embodiments of the second aspect; L 2< , ring A, X 1< and L 1< are defined as in any formula (II-Ax) in embodiments of the first aspect; or X 2< , ring A, X 1< and L 1< are defined as in any formula (II-Ay) in embodiments of the first aspect.

[0141] In another embodiment, the present application provides a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure shown as formula (III-D): wherein, Ab may be a ligand, and an average connection number N a< may be an integer or a decimal from 1 to 10; L may be -L a -L b -L c -, and L a , L b and L c are defined as in any formula (III-B) in embodiments of the second aspect; wherein R 1< and X are defined as in any formula (III-A) in embodiments of the first aspect.

[0142] In another embodiment, the ligand Ab may be an antibody or an antigen-binding fragment thereof.

[0143] For example, the ligand Ab may be selected from the group consisting of: a chimeric antibody, a humanized antibody and a fully humanized antibody.

[0144] For example, the ligand Ab targets the following: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 and EGFR.

[0145] For example, the ligand Ab targets the following; for example, the antibody may be an antibody that targets the following target points: 5T4, AGS-16, ANGPTL4, ApoE, CD19, CTGF, CXCR5, FGF2, MCPT8, MFI2, MS4A7, NCA, Sema5b, SLITRK6, STC2, TGF, 0772P, 5T4, ACTA2, ADGRE1, AG-7, AIF1, AKR1C1, AKR1C2, ASLG659, Axl, B7H3, BAFF-R, BCMA, BMPR1B, BNIP3, C1QA, C1QB, CA6, CADM1, CCD79b, CCL5, CCR5, CCR7, CD11c, CD123, CD138, CD142, CD147, CD166, CD19, CD19, CD22, CD21, CD20, CD205, CD22, CD223, CD228, CD25, CD30, CD33, CD37, CD38, CD40, CD45, CD45 (PTPRC), CD46, CD47, CD49D (ITGA4), CD56, CD66e, CD70, CD71, CD72, CD74, CD79a, CD79b, CD80, CDCP1, CDH11, CD11b, CEA, CEACAM5, c-Met, COL6A3, COL7A1, CRIPTO, CSF1R, CTSD, CTSS, CXCL11, CXCL10, DDIT4, DLL3, DLL4, DR5, E16, EFNA4, EGFR, EGFRvIII, EGLN, EGLN3, EMR2, ENPP3, EpCAM, EphA2, EphB2R, ETBR, FcRH2, FcRH1, FGFR2, FGFR3, FLT3, FOLR-α, GD2, GEDA, GPC-1, GPNMB, GPR20, GZMB, HER2, HER3, HLA-DOB, HMOX1, IFI6, IFNG, IGF-1R, IGFBP3, IL10RA1, IL-13R, IL-2, IL20Ra, IL-3, IL-4, IL-6, IRTA2, KISS1R, KRT33A, LIV-1, LOX, LRP-1, LRRC15, LUM, LY64, LY6E, Ly86, LYPD3, MDP, MMP10, MMP14, MMP16, MPF, MSG783, MSLN, MUC-1, NaPi2b, Napi3b, Nectin-4, Nectin-4, NOG, P2X5, pCAD, P-Cadherin, PDGFRA, PDK1, PD-L1, PFKFB3, PGF, PGK1, PIK3AP1, PIK3CD, PLOD2, PSCA, PSCAhlg, PSMA, PSMA, PTK7, P-Cadherin, RNF43, NaPi2b, ROR1, ROR2, SERPINE1, SLC39A6, SLTRK6, STAT1, STEAP1, STEAP2, TCF4, TENB2, TGFB1, TGFB2, TGFBR1, TNFRSF21, TNFSF9, Trop-2, TrpM4, Tyro7, UPK1B, VEGFA, WNT5A, epidermal growth factors, brevican, mesothelin, sodium phosphate cotransporter 2B, Claudin 18.2, endothelin receptors, mucins (such as mucin 1 and mucin 16), guanylate cyclase C, integrin a4p7, integrin a5p6, trophoblast glycoprotein, and tissue factors.

[0146] In another embodiment, the average connection number N a< may be an integer or a decimal from 2 to 8. For example, the average connection number N a< may be an integer or a decimal from 3 to 8. For example, the average connection number N a< may be an integer or a decimal from 1 to 2, 2 to 3, 3 to 4, 4 to 5, 5 to 6, 6 to 7, 7 to 8, 8 to 9, or 9 to 10.

[0147] In a fifth aspect, the present application provides a compound of general formula (I-E) or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 1< , L 1< and L 2< are defined as in any formula (I-A) in embodiments of the first aspect.

[0148] In another embodiment, the present application provides a compound of general formula (II-E x ) or (II-E y ), or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2< , p, ring A, X 1< and L 1< are defined as in any formula (II-Ax) in embodiments of the first aspect; or X 2< , q, ring A, X 1< and L 1< are defined as in any formula (II-Ay) in embodiments of the first aspect.

[0149] In another embodiment, the present application provides a compound of general formula (III-E) or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 1< and X are defined as in any formula (III-A) in embodiments of the first aspect.

[0150] In a sixth aspect, the present application provides a compound of general formula (I-F) or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein, L x< may be -L ax -L b -L c -; -L ax - may be selected from the group consisting of: wherein R hal< may be iodine or bromine; wherein W may be -(C(R wa< )(R wb< )) wn -, Y may be -(OCH 2 CH 2 ) yn -O yp -, and Z may be -(C(R za< )(R zb< )) zn ; wherein wn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of W may be independently replaced by -Cyr-, -N(R wx< )C(O)-, - C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, - N(R wx< )SO 2 -, -SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn may be selected from the group consisting of integers ≥ 0, and yp may be 0 or 1; wherein zn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, - C(O)N(R zx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, - N(R zx< )SO 2 -, -SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- may be selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with no less than 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , - N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), -SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< or a C 1-6 aliphatic group which may be optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; L b< and L c< are defined as in any formula (I-B) in embodiments of the second aspect; R 1< , L 1< and L 2< are defined as in any formula (I-A) in embodiments of the first aspect.

[0151] In another embodiment, the present application provides a compound of general formula (II-F x ) or (II-F y ), or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein, L x< may be -L ax -L b -L c -; -L ax - may be selected from the group consisting of: wherein R hal< may be iodine or bromine; wherein W may be -(C(R wa< )(R wb< )) wn -, Y may be -(OCH 2 CH 2 ) yn -O yp -, and Z may be -(C(R za< )(R zb< )) zn ; wherein wn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of W may be independently replaced by -Cyr-, -N(R wx< )C(O)-, - C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, - N(R wx< )SO 2 -, -SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn may be selected from the group consisting of integers ≥ 0, and yp may be 0 or 1; wherein zn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, - C(O)N(R zx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, - N(R zx< )SO 2 -, -SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- may be selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with no less than 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , - N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), -SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< or a C 1-6 aliphatic group which may be optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; L b< and L c< are defined as in any formula (II-Bx) in embodiments of the second aspect; wherein L 2< , p, ring A, X 1< and L 1< are defined as in any formula (II-Ax) in embodiments of the first aspect; or X 2< , q, ring A, X 1< and L 1< are defined as in any formula (II-Ay) in embodiments of the first aspect.

[0152] In another embodiment, the present application provides a compound of general formula (III-F) or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein, L x< may be -L ax -L b -L c -; -L ax - may be selected from the group consisting of: wherein R hal< may be iodine or bromine; wherein W may be -(C(R wa< )(R wb< )) wn -, Y may be -(OCH 2 CH 2 ) yn -O yp -, and Z may be -(C(R za< )(R zb< )) zn ; wherein wn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of W may be independently replaced by -Cyr-, -N(R wx< )C(O)-, - C(O)N(R wx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx< -, -O-, -S-, -SO-, -SO 2 -, -P(R wx< )-, -P(=O)(R wx< )-, - N(R wx< )SO 2 -, -SO 2 N(R wx< )-, -C(=S)-, -C(=NR wx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; wherein yn may be selected from the group consisting of integers ≥ 0, and yp may be 0 or 1; wherein zn may be selected from the group consisting of integers ≥ 0, and 0 or no less than 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, - C(O)N(R zx< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx< -, -O-, -S-, -SO-, -SO 2 -, -P(R zx< )-, -P(=O)(R zx< )-, - N(R zx< )SO 2 -, -SO 2 N(R zx< )-, -C(=S)-, -C(=NR zx< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cyr- may be selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with no less than 1 substituent R cx< ; wherein each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , - N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), -SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< or a C 1-6 aliphatic group which may be optionally substituted with R r< ; wherein each R r< , each R ra< and each R rb< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, - S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; L b< and L c< are defined as in any formula (III-B) in embodiments of the second aspect; wherein R 1< and X are defined as in any formula (III-A) in embodiments of the first aspect.

[0153] In another embodiment, L ax - may be selected from the group consisting of: wherein R hal< may be iodine or bromine; wherein W may be -(C(R wa< )(R wb< )) wn -, Y may be -(OCH 2 CH 2 ) yn -O yp -, and Z may be -(C(R za< )(R zb< )) zn .

[0154] In another embodiment, wn may be selected from the group consisting of integers from 2 to 6, and 0 or 1 methylene unit of W may be independently replaced by -Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )-, - C(O)-, -NR wx< - or -O-.

[0155] For example, wn may be 1, 2, 3 or 6, and 1 methylene unit of W may be independently replaced by - Cyr-, -N(R wx< )C(O)-, -C(O)N(R wx< )- or -C(O)-.

[0156] In another embodiment, yn may be selected from the group consisting of integers from 0 to 12, and yp may be 0 or 1.

[0157] For example, yn may be 0, 4 or 8, and yp may be 0 or 1.

[0158] In another embodiment, zn may be selected from the group consisting of integers from 0 to 10, and 0 or 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )- or - C(O)-.

[0159] For example, zn may be 1, 2 or 3, and 1 methylene unit of Z may be independently replaced by -Cyr-, -N(R zx< )C(O)-, -C(O)N(R zx< )- or -C(O)-.

[0160] In another embodiment, -Cyr- may be selected from the group consisting of: 6-10 membered arylene and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with 1 to 3 substituent R cx< .

[0161] For example, -Cyr- may be 3-10 membered saturated carbocyclylene, wherein -Cyr- is unsubstituted or may be independently substituted with 1 to 3 substituent R cx< .

[0162] In another embodiment, each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR r< , -SR r< , - N(R ra< )(R rb< ), -C(O)R r< , -CO 2 R r< , -C(O)C(O)R r< , -C(O)CH 2 C(O)R r< , -S(O)R r< , -S(O) 2 R r< , -C(O)N(R ra< )(R rb< ), -SO 2 N(R ra< )(R rb< ), -OC(O)R r< , -N(R)SO 2 R r< , or a C 1-6 aliphatic group which may be optionally substituted with R r< ; each R r< , each R ra< and each R rb< may each independently be hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -COzH, -C(O)C(O)H, - C(O)CH 2 C(O)H, -S(O)H, -S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group.

[0163] For example, each R wa< , each R wb< , each R za< , each R zb< , each R wx< , each R zx< and each R cx< may each independently be hydrogen, halogen, -OR r< , or a C 1-6 aliphatic group which may be optionally substituted with R r< ; each R r< may independently be hydrogen, halogen or a C 1-6 aliphatic group.

[0164] In another embodiment L ax - may be

[0165] In another embodiment, L ax -L b -L c - may be selected from the group consisting of: and Compounds Disclosed Herein

[0166] In one embodiment, the compounds disclosed herein include but are not limited to: No.StructureP-I-1 P-I-2 P-I-3 P-I-4 P-I-5 P-I-6 P-I-7 P-I-8 P-I-9 P-I-10 P-I-11 P-1-12 P-I-13 P-I-14 P-I-15 P-I-16 P-I-17 P-I-18 P-I-19 P-I-20 P-I-21 P-I-22 P-I-23 P-I-24 P-I-25 P-I-26 P-I-27 P-I-28 P-I-29 P-I-30 P-I-31 P-I-32 P-I-33 P-I-34 P-I-35 P-I-36 P-I-37 P-I-38 P-I-39 P-I-40 P-I-41 P-I-42 P-I-43 P-I-44 P-I-45 P-I-46 P-I-47 L-I-1 L-I-2 L-I-3 L-I-4 L-I-5 L-I-6 L-I-7 L-I-8 L-I-9 L-I-10 L-1-11 L-I-12 L-I-13 L-I-14 L-I-15 L-I-16 L-I-17 L-I-18 L-I-19 L-I-20 L-I-21 L-I-22 L-I-23 L-I-24 L-I-25 L-I-26 L-I-27 L-I-28 L-I-29 L-1-30 L-I-31 L-I-32 L-1-33 L-I-34 L-I-3 5 L-1-36 L-1-37 L-I-38 L-I-39 L-I-40 L-I-41 L-I-42 L-I-43 L-I-44 L-I-45 L-I-46 L-I-47 L-I-48 L-I-49 L-I-50 ADC-I-1 ADC-I-2 ADC-I-3 ADC-I-4 ADC-I-5 ADC-I-6 ADC-I-7 ADC-I-8 ADC-I-9 ADC-I-10 ADC-I-11 ADC-I-12 ADC-I-13 ADC-I-14 ADC-I-15 ADC-I-16 ADC-I-17 ADC-I-18 ADC-I-19 ADC-I-20 ADC-I-21 ADC-I-22 ADC-I-23 ADC-I-24 ADC-I-25 ADC-I-26 ADC-I-27 ADC-I-28 ADC-I-29 ADC-1-30

[0167] The average connection number n in the above list may be an integer or a decimal from 1 to 10. The average connection number n in the above list may be an integer or a decimal from 2 to 8. For example, the average connection number n may be an integer or a decimal from 3 to 8. For example, the average connection number n may be an integer or a decimal from 1 to 2, 2 to 3, 3 to 4, 4 to 5, 5 to 6, 6 to 7, 7 to 8, 8 to 9, or 9 to 10.

[0168] In one embodiment, the compounds disclosed herein include, but are not limited to: No.StructureP-II-1 P-II-2 P-II-3 P-II-4 P-II-5 P-II-6 P-II-7 P-II-8 P-II-9 P-II-10 P-II-11 P-II-12 P-II-13 P-II-14 P-II-15 P-II-16 P-II-17 P-II-18 P-II-19 P-II-20 P-II-21 P-II-22 P-II-23 P-II-24 P-II-25 L-II-1 L-II-2 L-II-3 L-II-4 L-II-5 L-II-6 L-II-7 L-II-8 L-II-9 L-II-10 L-II-11 L-II-12 L-II-13 L-II-14 L-II-15 L-II-16 L-II-17 L-II-18 L-II-19 L-II-20 L-II-21 L-II-22 L-II-23 L-II-24 L-II-25 L-II-26 L-II-27 L-II-28 ADC-II-1 ADC-II-2 ADC-II-3 ADC-II-4 ADC-II-5 ADC-II-6 ADC-II-7 ADC-II-8 ADC-II-9 ADC-II-10 ADC-II-11 ADC-II-12 ADC-II-13 ADC-II-14 ADC-II-15 ADC-II-16 ADC-II-17 ADC-II-18 ADC-II-19 ADC-II-20 ADC-II-21 ADC-II-22 ADC-II-23 ADC-11-24 ADC-II-25 ADC-II-26 ADC-II-27 ADC-11-28 ADC-11-29 ADC-II-30 ADC-11-31 ADC-11-32 ADC-II-33 ADC-II-34 ADC-11-35 ADC-II-36 ADC-II-37 ADC-11-38 ADC-II-39 ADC-II-40 ADC-II-41 ADC-II-42 ADC-II-43 ADC-II-44 ADC-II-45 ADC-II-46 ADC-II-47 ADC-II-48 ADC-II-49 ADC-II-50 ADC-II-51 ADC-II-52 ADC-II-53 ADC-II-54 ADC-II-55 ADC-II-56 ADC-II-57 ADC-II-58

[0169] The average connection number n in the above list may be an integer or a decimal from 1 to 10. The average connection number n in the above list may be an integer or a decimal from 2 to 8. For example, the average connection number n may be an integer or a decimal from 3 to 8. For example, the average connection number n may be an integer or a decimal from 1 to 2, 2 to 3, 3 to 4, 4 to 5, 5 to 6, 6 to 7, 7 to 8, 8 to 9, or 9 to 10.

[0170] In one embodiment, the compounds disclosed herein include, but are not limited to: No.StructureP-III-1 P-III-2 P-III-3 P-III-4 P-III-5 P-III-6 P-III-7 P-III-8 P-III-9 P-III-10 P-III-11 P-III-12 P-III-13 P-III-14 P-III-15 P-III-16 P-III-17 P-III-18 P-III-19 P-III-20 P-III-21 P-III-22 P-III-23 P-III-24 P-III-25 P-III-26 P-III-27 P-III-28 P-III-29 P-III-30 P-III-31 L-III-1 L-III-2 L-III-3 L-III-4 L-III-5 L-III-6 L-III-7 L-III-8 L-III-9 L-III-10 L-III-11 L-III-12 L-III-13 L-III-14 L-III-15 L-III-16 L-III-17 L-III-18 L-III-19 L-III-20 L-III-21 L-III-22 L-III-23 L-III-24 L-III-25 L-III-26 L-III-27 L-III-28 L-III-29 L-III-30 L-III-31 ADC-III-1 ADC-III-2 ADC-III-3 ADC-III-4 ADC-III-5 ADC-III-6 ADC-III-7 ADC-III-8 ADC-III-9 ADC-III-10 ADC-III-11 ADC-III-12 ADC-III-13 ADC-III-14 ADC-III-15 ADC-III-16 ADC-III-17 ADC-III-18 ADC-III-19 ADC-III-20 ADC-III-21 ADC-III-22 ADC-III-23 ADC-III-24 ADC-III-25 ADC-III-26 ADC-III-27 ADC-III-28 ADC-III-29 ADC-III-30 ADC-III-31 ADC-III-32 ADC-III-33 ADC-III-34 ADC-III-35

[0171] The average connection number n in the above list may be an integer or a decimal from 1 to 10. The average connection number n in the above list may be an integer or a decimal from 2 to 8. For example, the average connection number n may be an integer or a decimal from 3 to 8. For example, the average connection number n may be an integer or a decimal from 1 to 2, 2 to 3, 3 to 4, 4 to 5, 5 to 6, 6 to 7, 7 to 8, 8 to 9, or 9 to 10.Ligands

[0172] The ligands described herein may be protein hormones, lectin, growth factors, antibodies, or other molecules capable of binding to a cell, a receptor and / or an antigen. For example, the ligand disclosed herein may be an antibody or an antigen-binding fragment thereof.

[0173] In the present application, the ligand may comprise at least one CDR in the light chain variable region VL of an antibody. The CDRs may be defined according to Kabat.

[0174] In the present application, the antigen-binding protein may comprise an LCDR1, and the LCDR1 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 1-4. The CDRs may be defined according to Kabat.

[0175] In the present application, the antigen-binding protein may comprise an LCDR2, and the LCDR2 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 5-8. The CDRs may be defined according to Kabat.

[0176] In the present application, the antigen-binding protein may comprise an LCDR3, and the LCDR3 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 9-12. The CDRs may be defined according to Kabat.

[0177] In the present application, the isolated antigen-binding protein may comprise LCDRs 1-3, wherein the LCDR1 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 1-4, the LCDR2 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 5-8, and the LCDR3 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 9-12. The CDRs may be defined according to Kabat.

[0178] For example, the antigen-binding protein described herein may comprise the same LCDRs 1-3 as trastuzumab, wherein the LCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 1, the LCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 5, and the LCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 9. For example, the antigen-binding protein described herein may comprise the same LCDRs 1-3 as pertuzumab, wherein the LCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 2, the LCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 6, and the LCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 10. The CDRs may be defined according to Kabat.

[0179] For example, the antigen-binding protein described herein may comprise the same LCDRs 1-3 as sacituzumab, wherein the LCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 3, the LCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 7, and the LCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 11. The CDRs may be defined according to Kabat.

[0180] For example, the antigen-binding protein described herein may comprise the same LCDRs 1-3 as zolbetuximab, wherein the LCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 4, the LCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 8, and the LCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 12. The CDRs may be defined according to Kabat.

[0181] The antigen-binding protein described herein may comprise at least one CDR in the heavy chain variable region VH of an antibody. The CDRs may be defined according to Kabat.

[0182] In the present application, the antigen-binding protein may comprise an HCDR1, and the HCDR1 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 13-16. The CDRs may be defined according to Kabat.

[0183] In the present application, the antigen-binding protein may comprise an HCDR2, and the HCDR2 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 17-20. The CDRs may be defined according to Kabat.

[0184] In the present application, the antigen-binding protein may comprise an HCDR3, and the HCDR3 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 21-24. The CDRs may be defined according to Kabat.

[0185] In the present application, the isolated antigen-binding protein may comprise HCDRs 1-3, wherein the HCDR1 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 13-16, the HCDR2 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 17-20, and the HCDR3 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 21-24. The CDRs may be defined according to Kabat.

[0186] For example, the antigen-binding protein described herein may comprise the same HCDRs 1-3 as trastuzumab, wherein the HCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 13, the HCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 17, and the HCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 21. The CDRs may be defined according to Kabat.

[0187] For example, the antigen-binding protein described herein may comprise the same HCDRs 1-3 as pertuzumab, wherein the HCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 14, the HCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 18, and the HCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 22. The CDRs may be defined according to Kabat.

[0188] For example, the antigen-binding protein described herein may comprise the same HCDRs 1-3 as sacituzumab, wherein the HCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 15, the HCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 19, and the HCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 23. The CDRs may be defined according to Kabat.

[0189] For example, the antigen-binding protein described herein may comprise the same HCDRs 1-3 as zolbetuximab, wherein the HCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 16, the HCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 20, and the HCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 24. The CDRs may be defined according to Kabat.

[0190] In the present application, the isolated antigen-binding protein may comprise LCDRs 1-3 and HCDRs 1-3, wherein The LCDR1 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 1-4, the LCDR2 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 5-8, the LCDR3 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 9-12, the HCDR1 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 13-16, the HCDR2 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 17-20, and the HCDR3 may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 21-24. The CDRs may be defined according to Kabat.

[0191] For example, the antigen-binding protein described herein may comprise the same LCDRs 1-3 and HCDRs 1-3 as trastuzumab, wherein the LCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 1, the LCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 5, the LCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 9, the HCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 13, the HCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 17, and the HCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 21. The CDRs may be defined according to Kabat.

[0192] For example, the antigen-binding protein described herein may comprise the same LCDRs 1-3 and HCDRs 1-3 as pertuzumab, wherein the LCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 2, the LCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 6, the LCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 10, the HCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 14, the HCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 18, and the HCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 22. The CDRs may be defined according to Kabat.

[0193] For example, the antigen-binding protein described herein may comprise the same LCDRs 1-3 and HCDRs 1-3 as sacituzumab, wherein the LCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 3, the LCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 7, the LCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 11, the HCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 15, the HCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 19, and the HCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 23. The CDRs may be defined according to Kabat.

[0194] For example, the antigen-binding protein described herein may comprise the same LCDRs 1-3 and HCDRs 1-3 as zolbetuximab, wherein the LCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 4, the LCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 8, the LCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 12, the HCDR1 may comprise an amino acid sequence set forth in SEQ ID NO: 16, the HCDR2 may comprise an amino acid sequence set forth in SEQ ID NO: 20, and the HCDR3 may comprise an amino acid sequence set forth in SEQ ID NO: 24. The CDRs may be defined according to Kabat.

[0195] In the present application, the antigen-binding protein may comprise a light chain variable region VL, and the VL may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 25-28.

[0196] In the present application, the antigen-binding protein may comprise a heavy chain variable region VH, and the VH may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 29-32. In the present application, the antigen-binding protein may comprise a light chain variable region VL and a heavy chain variable region VH, wherein the VL may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 25-28, and the VH may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 29-32.

[0197] For example, the antigen-binding protein described herein may comprise the same light chain variable region VL and heavy chain variable region VH as trastuzumab, wherein the VL may comprise an amino acid sequence set forth in SEQ ID NO: 25, and the VH may comprise an amino acid sequence set forth in SEQ ID NO: 29.

[0198] For example, the antigen-binding protein described herein may comprise the same light chain variable region VL and heavy chain variable region VH as pertuzumab, wherein the VL may comprise an amino acid sequence set forth in SEQ ID NO: 26, and the VH may comprise an amino acid sequence set forth in SEQ ID NO: 30.

[0199] For example, the antigen-binding protein described herein may comprise the same light chain variable region VL and heavy chain variable region VH as sacituzumab, wherein the VL may comprise an amino acid sequence set forth in SEQ ID NO: 27, and the VH may comprise an amino acid sequence set forth in SEQ ID NO: 31.

[0200] For example, the antigen-binding protein described herein may comprise the same light chain variable region VL and heavy chain variable region VH as zolbetuximab, wherein the VL may comprise an amino acid sequence set forth in SEQ ID NO: 28, and the VH may comprise an amino acid sequence set forth in SEQ ID NO: 32.

[0201] In the present application, the antigen-binding protein may comprise a light chain, and the light chain may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 33-36.

[0202] In the present application, the antigen-binding protein may comprise a heavy chain, and the heavy chain may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 37-40.

[0203] In the present application, the antigen-binding protein may comprise an antibody light chain and an antibody heavy chain, wherein the light chain may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 33-36, and the heavy chain may comprise an amino acid sequence set forth in any one of SEQ ID NOs: 37-40.

[0204] For example, the antigen-binding protein described herein may comprise the same antibody light chain and antibody heavy chain as trastuzumab, wherein the light chain may comprise an amino acid sequence set forth in SEQ ID NO: 33, and the heavy chain may comprise an amino acid sequence set forth in SEQ ID NO: 37.

[0205] For example, the antigen-binding protein described herein may comprise the same antibody light chain and antibody heavy chain as pertuzumab, wherein the light chain may comprise an amino acid sequence set forth in SEQ ID NO: 34, and the heavy chain may comprise an amino acid sequence set forth in SEQ ID NO: 38.

[0206] For example, the antigen-binding protein described herein may comprise the same antibody light chain and antibody heavy chain as sacituzumab, wherein the light chain may comprise an amino acid sequence set forth in SEQ ID NO: 35, and the heavy chain may comprise an amino acid sequence set forth in SEQ ID NO: 39.

[0207] For example, the antigen-binding protein described herein may comprise the same antibody light chain and antibody heavy chain as zolbetuximab, wherein the light chain may comprise an amino acid sequence set forth in SEQ ID NO: 36, and the heavy chain may comprise an amino acid sequence set forth in SEQ ID NO: 40.Prevention and / or Prevention of Tumors

[0208] In another aspect, the present application provides use of the compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition thereof described herein, in preparing a medicament for treating and / or preventing a tumor. The tumor may be selected from the group consisting of tumors associated with expression of the following: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 and EGFR. The tumor may be selected from the group consisting of: lung cancer, kidney cancer, urinary tract carcinoma, colorectal cancer, prostatic cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer and esophageal cancer.

[0209] In another aspect, the present application provides a method for treating and / or preventing a tumor, which comprises administering to a subject in need the compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof described herein, and / or the pharmaceutical composition that may comprise the same. The tumor may be selected from the group consisting of tumors associated with expression of the following: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 and EGFR. The tumor may be selected from the group consisting of: lung cancer, kidney cancer, urinary tract carcinoma, colorectal cancer, prostatic cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer and esophageal cancer.

[0210] In another aspect, the present application provides the compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof described herein, and / or the pharmaceutical composition that may comprise the same, for use in treating and / or preventing a tumor. The tumor may be selected from the group consisting of tumors associated with expression of the following: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 and EGFR. The tumor may be selected from the group consisting of: lung cancer, kidney cancer, urinary tract carcinoma, colorectal cancer, prostatic cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer and esophageal cancer.

[0211] For example, the tumor may be selected from the group consisting of tumors associated with expression of the following: 5T4, AGS-16, ANGPTL4, ApoE, CD19, CTGF, CXCR5, FGF2, MCPT8, MFI2, MS4A7, NCA, Sema5b, SLITRK6, STC2, TGF, 0772P, 5T4, ACTA2, ADGRE1, AG-7, AIF1, AKR1C1, AKR1C2, ASLG659, Axl, B7H3, BAFF-R, BCMA, BMPR1B, BNIP3, C1QA, C1QB, CA6, CADM1, CCD79b, CCL5, CCR5, CCR7, CD11c, CD123, CD138, CD142, CD147, CD166, CD19, CD19, CD22, CD21, CD20, CD205, CD22, CD223, CD228, CD25, CD30, CD33, CD37, CD38, CD40, CD45, CD45 (PTPRC), CD46, CD47, CD49D (ITGA4), CD56, CD66e, CD70, CD71, CD72, CD74, CD79a, CD79b, CD80, CDCP1, CDH11, CD11b, CEA, CEACAM5, c-Met, COL6A3, COL7A1, CRIPTO, CSF1R, CTSD, CTSS, CXCL11, CXCL10, DDIT4, DLL3, DLL4, DR5, E16, EFNA4, EGFR, EGFRvIII, EGLN, EGLN3, EMR2, ENPP3, EpCAM, EphA2, EphB2R, ETBR, FcRH2, FcRH1, FGFR2, FGFR3, FLT3, FOLR-α, GD2, GEDA, GPC-1, GPNMB, GPR20, GZMB, HER2, HER3, HLA-DOB, HMOX1, IFI6, IFNG, IGF-1R, IGFBP3, IL10RA1, IL-13R, IL-2, IL20Ra, IL-3, IL-4, IL-6, IRTA2, KISS1R, KRT33A, LIV-1, LOX, LRP-1, LRRC15, LUM, LY64, LY6E, Ly86, LYPD3, MDP, MMP10, MMP14, MMP16, MPF, MSG783, MSLN, MUC-1, NaPi2b, Napi3b, Nectin-4, Nectin-4, NOG, P2X5, pCAD, P-Cadherin, PDGFRA, PDK1, PD-L1, PFKFB3, PGF, PGK1, PIK3AP1, PIK3CD, PLOD2, PSCA, PSCAhlg, PSMA, PSMA, PTK7, P-Cadherin, RNF43, NaPi2b, ROR1, ROR2, SERPINE1, SLC39A6, SLTRK6, STAT1, STEAP1, STEAP2, TCF4, TENB2, TGFB1, TGFB2, TGFBR1, TNFRSF21, TNFSF9, Trop-2, TrpM4, Tyro7, UPK1B, VEGFA, WNT5A, epidermal growth factors, brevican, mesothelin, sodium phosphate cotransporter 2B, Claudin 18.2, endothelin receptors, mucins (such as mucin 1 and mucin 16), guanylate cyclase C, integrin a4p7, integrin a5p6, trophoblast glycoprotein, and tissue factors. The compound described herein may have inhibitory activity against in vitro proliferation of tumor cells. The inhibitory activity may be that: compared with in a culture medium of tumor cells to which a negative control or a control drug is added, the proliferation capacity of the tumor cells is reduced by no less than 1%, no less than 2%, no less than 4%, no less than 5%, no less than 8%, no less than 10%, no less than 15%, no less than 18%, no less than 20%, no less than 25%, no less than 40%, no less than 50%, no less than 60%, no less than 70%, no less than 80%, no less than 90% or no less than 95% in a culture medium to which the compound disclosed herein is added. For example, the inhibitory activity may be an IC 50 value (nM) for tumor cells of no more than 10000, no more than 5000, no more than 4000, no more than 3000, no more than 2000, no more than 1000, no more than 500, no more than 400, no more than 300, no more than 200, no more than 150, no more than 120, no more than 110, no more than 100, no more than 99, no more than 98, no more than 97, no more than 95, no more than 90, no more than 80, no more than 75, no more than 70, no more than 65, no more than 62, no more than 60, no more than 50, no more than 40, no more than 30, no more than 25, no more than 23, no more than 22, no more than 20, no more than 19, no more than 18, no more than 18.5, no more than 17, no more than 15, no more than 12, no more than 10, no more than 9, no more than 8.5, no more than 7, no more than 6.7, no more than 6, no more than 5.9, no more than 5.5, no more than 5.0, no more than 4.8, no more than 4.5, no more than 4.4, no more than 4, no more than 3.5, no more than 3, no more than 2.5, no more than 2, no more than 1.5, no more than 1.0, no more than 0.5, no more than 0.3, no more than 0.29, no more than 0.25, no more than 0.21, no more than 0.20, no more than 0.18, no more than 0.17, no more than 0.15, no more than 0.12, no more than 0.10, no more than 0.09, no more than 0.08, no more than 0.07, no more than 0.06, no more than 0.05, no more than 0.04, no more than 0.03, no more than 0.02 or no more than 0.01. For example, the tumor cells may include, but are not limited to, solid tumor cells; for example, the tumor cells include, but are not limited to, gastric cancer cells, or breast cancer cells; for example, the tumor cells may include, but are not limited to, NCI-N87 cells, JIMT-1 cells or MBA-MB-231 cells.

[0212] The compound described herein may have targeting inhibition. The targeting inhibition may be that: compared with in a culture medium of tumor cells with high expression of a specific target point to which a negative control or a control drug is added, the proliferation capacity of the tumor cells with high expression of a specific target point is reduced by no less than 1%, no less than 2%, no less than 4%, no less than 5%, no less than 8%, no less than 10%, no less than 15%, no less than 18%, no less than 20%, no less than 25%, no less than 40%, no less than 50%, no less than 60%, no less than 70%, no less than 80%, no less than 90% or no less than 95% in a culture medium to which the compound disclosed herein is added. For example, the targeting inhibition may be an IC 50 value (nM), for tumor cells with high expression of a specific target point, of no more than 10000, no more than 5000, no more than 4000, no more than 3000, no more than 2000, no more than 1000, no more than 500, no more than 400, no more than 300, no more than 200, no more than 185, no more than 150, no more than 120, no more than 110, no more than 100, no more than 99, no more than 98, no more than 97, no more than 95, no more than 91, no more than 80, no more than 74, no more than 70, no more than 65, no more than 62, no more than 60, no more than 50, no more than 40, no more than 30, no more than 25, no more than 23, no more than 22, no more than 20, no more than 19, no more than 18, no more than 18.5, no more than 17, no more than 15, no more than 12, no more than 10, no more than 9, no more than 8.5, no more than 7, no more than 6.7, no more than 6, no more than 5.9, no more than 5.5, no more than 5.0, no more than 4.8, no more than 4.5, no more than 4.4, no more than 4, no more than 3.5, no more than 3, no more than 2.5, no more than 2, no more than 1.5, no more than 1.0, no more than 0.5, no more than 0.3, no more than 0.29, no more than 0.25, no more than 0.21, no more than 0.20, no more than 0.18, no more than 0.17, no more than 0.15, no more than 0.12, no more than 0.10, no more than 0.09, no more than 0.08, no more than 0.07, no more than 0.06, no more than 0.05, no more than 0.04, no more than 0.03, no more than 0.02 or no more than 0.01. For example, the tumor cells with high expression of a specific target point may include, but are not limited to, solid tumor cells; for example, the tumor cells with high expression of a specific target point include, but are not limited to, gastric cancer cells, or breast cancer cells; for example, the tumor cells with high expression of a specific target point may include, but are not limited to, NCI-N87 cells or JIMT-1 cells. The specific target point may include, but is not limited to, HER2 or TROP2.

[0213] The compound described herein may have plasma stability. The plasma stability may be that: the compound disclosed herein releases no more than 50%, no more than 40%, no more than 30%, no more than 20%, no more than 10%, no more than 7%, no more than 5%, no more than 4%, no more than 3%, no more than 2%, no more than 1.9%, no more than 1.8%, no more than 1.7%, no more than 1.6%, no more than 1.5%, no more than 1.4%, no more than 1.3%, no more than 1.2%, no more than 1.1%, no more than 1.0%, no more than 0.9%, no more than 0.8%, no more than 0.7%, no more than 0.6%, no more than 0.5%, no more than 0.4%, no more than 0.3%, no more than 0.2% or no more than 0.1% of the cytotoxic drug 1 day, 3 days, 5 days, 7 days, 14 days, 20 days or 30 days after the compound is added to plasma.

[0214] The compound described herein may have in vivo tumor-inhibiting effect. The tumor-inhibiting effect may be that: compared with the case where a negative control or a control drug is administered to an animal, the tumor of the animal is reduced in volume by no less than 1%, no less than 2%, no less than 4%, no less than 5%, no less than 8%, no less than 10%, no less than 15%, no less than 18%, no less than 20%, no less than 25%, no less than 40%, no less than 50%, no less than 55%, no less than 60%, no less than 70%, no less than 73%, no less than 75%, no less than 80%, no less than 90% or no less than 95% 1 day, 3 days, 5 days, 7 days, 14 days, 20 days, 21 days or 30 days after the compound disclosed herein is administered, or the tumor of the animal is reduced in volume by no less than 1.1 fold, no less than 1.3 fold, no less than 1.5 fold, no less than 2 fold, no less than 3 fold, no less than 5 fold, no less than 10 fold, no less than 20 fold, no less than 22 fold, no less than 30 fold, no less than 50 fold, no less than 100 fold, no less than 500 fold, no less than 1000 fold or no less than 1500 fold 1 day, 3 days, 5 days, 7 days, 14 days, 20 days, 21 days or 30 days after the compound disclosed herein is administered. The animal may include, but is not limited to, a mammal. For example, the animal may include, but is not limited to, a cat, a dog, a horse, a pig, a cow, a sheep, a rabbit, a mouse, a rat, a monkey or a human. The administration may include, but is not limited to, oral administration, intravenous injection, intravenous drip, intraperitoneal injection or topical administration.

[0215] The compound described herein may have a bystander effect. The bystander effect may be that: the compound disclosed herein has no obvious inhibiting effect against cell proliferation of the tumor cells with low expression of a specific target point, but in the co-culturing of the tumor cells with low expression of the specific target point and the tumor cells with high expression of the specific target point, the compound disclosed herein can simultaneously inhibit the cell proliferation of the tumor cells with low expression of the specific target point and the tumor cells with high expression of the specific target point. For example, in the co-culturing of the tumor cells with low expression of the specific target point and the tumor cells with high expression of the specific target point, the inhibiting activity may be an IC 50 value (nM), for the tumor cells with low expression of the specific target point, of no more than 10000, no more than 5000, no more than 4000, no more than 3000, no more than 2000, no more than 1000, no more than 500, no more than 400, no more than 300, no more than 200, no more than 185, no more than 150, no more than 120, no more than 110, no more than 100, no more than 99, no more than 98, no more than 97, no more than 95, no more than 91, no more than 80, no more than 74, no more than 70, no more than 65, no more than 62, no more than 60, no more than 50, no more than 40, no more than 30, no more than 25, no more than 23, no more than 22, no more than 20, no more than 19, no more than 18, no more than 18.5, no more than 17, no more than 15, no more than 12, no more than 10, no more than 9, no more than 8.5, no more than 7, no more than 6.7, no more than 6, no more than 5.9, no more than 5.5, no more than 5.0, no more than 4.8, no more than 4.5, no more than 4.4, no more than 4, no more than 3.5, no more than 3, no more than 2.5, no more than 2, no more than 1.5, no more than 1.0, no more than 0.5, no more than 0.3, no more than 0.29, no more than 0.25, no more than 0.21, no more than 0.20, no more than 0.18, no more than 0.17, no more than 0.15, no more than 0.12, no more than 0.10, no more than 0.09, no more than 0.08, no more than 0.07, no more than 0.06, no more than 0.05, no more than 0.04, no more than 0.03, no more than 0.02 or no more than 0.01. Compared with in tumor cells with high expression of the specific target point, the expression of the specific target point in tumor cells with low expression of the specific target point may be reduced by no less than 1%, no less than 2%, no less than 4%, no less than 5%, no less than 8%, no less than 10%, no less than 15%, no less than 18%, no less than 20%, no less than 25%, no less than 40%, no less than 50%, no less than 60%, no less than 70%, no less than 80%, no less than 90% or no less than 95%. For example, the tumor cells with high expression of a specific target point may include, but are not limited to, solid tumor cells; for example, the tumor cells with high expression of a specific target point include, but are not limited to, gastric cancer cells, or breast cancer cells; for example, the tumor cells with high expression of a specific target point may include, but are not limited to, NCI-N87 cells or JIMT-1 cells. For example, the tumor cells with low expression of a specific target point may include, but are not limited to, solid tumor cells; for example, the tumor cells with low expression of a specific target point include, but are not limited to, breast cancer cells; for example, the tumor cells with low expression of a specific target point may include, but are not limited to, HCC1187 cells.

[0216] The compound described herein may have capacity in inhibiting transport via a transporter. The capacity in inhibiting transport may be a reduction in the efflux ratio of the compound described herein by no less than 1%, no less than 2%, no less than 4%, no less than 5%, no less than 8%, no less than 10%, no less than 15%, no less than 18%, no less than 20%, no less than 25%, no less than 40%, no less than 50%, no less than 60%, no less than 70%, no less than 80%, no less than 90% or no less than 95% compared with a standard of a transport substrate. For example, the testing of the efflux ratio may be a method commonly used by those skilled in the art, or may be described in the examples of the present application.

[0217] The compound described herein may have in vivo tumor targeting capability. The in vivo targeting ability may be that: when the compound labeled with a signal substance is administered to an animal, compared with in other tissues and organs of the animal, the distribution of the labeled compound in a tumor tissue may be increased by no less than 1%, no less than 2%, no less than 4%, no less than 5%, no less than 8%, no less than 10%, no less than 15%, no less than 18%, no less than 20%, no less than 25%, no less than 40%, no less than 50%, no less than 60%, no less than 70%, no less than 80%, no less than 90% or no less than 95%, or may be increased by no less than 1.1 fold, no less than 1.3 fold, no less than 1.5 fold, no less than 2 fold, no less than 3 fold, no less than 5 fold, no less than 10 fold, no less than 20 fold, no less than 22 fold, no less than 30 fold, no less than 50 fold, no less than 100 fold, no less than 500 fold, no less than 1000 fold or no less than 1500 fold. The signal substance may be a radioactive material; for example, the signal substance includes, but is not limited to, 125< I. The animal may include, but is not limited to, a mammal. For example, the animal may include, but is not limited to, a cat, a dog, a horse, a pig, a cow, a sheep, a rabbit, a mouse, a rat, a monkey or a human. The administration may include, but is not limited to, oral administration, intravenous injection, intravenous drip, intraperitoneal injection or topical administration. The tissues or organs may include, but are not limited to, heart, liver, spleen, lung, kidney, brain or bone marrow.

[0218] The compound described herein may have good in vivo safety. The in vivo safety may be that: after the compound disclosed herein is administered to an animal, the release rate of in vivo free toxin in the animal is no more than 50%, no more than 40%, no more than 30%, no more than 20%, no more than 10%, no more than 7%, no more than 5%, no more than 4%, no more than 3%, no more than 2%, no more than 1.9%, no more than 1.8%, no more than 1.7%, no more than 1.6%, no more than 1.5%, no more than 1.4%, no more than 1.3%, no more than 1.2%, no more than 1.1%, no more than 1.0%, no more than 0.9%, no more than 0.8%, no more than 0.7%, no more than 0.6%, no more than 0.5%, no more than 0.4%, no more than 0.3%, no more than 0.2% or no more than 0.1%. For example, the in vivo safety may be that: the compound described herein may be administered at a concentration of no less than 0.5 mg / kg, no less than 1 mg / kg, no less than 2 mg / kg, no less than 3 mg / kg, no less than 4 mg / kg, no less than 5 mg / kg, no less than 10 mg / kg, no less than 20 mg / kg, no less than 30 mg / kg, no less than 50 mg / kg, no less than 70 mg / kg, no less than 100 mg / kg, no less than 200 mg / kg, no less than 500 mg / kg or no less than 1000 mg / kg without causing toxic manifestation in the animal. For example, the animal may include, but is not limited to, a cat, a dog, a horse, a pig, a cow, a sheep, a rabbit, a mouse, a rat, a monkey or a human. The administration may include, but is not limited to, oral administration, intravenous injection, intravenous drip, intraperitoneal injection or topical administration.Pharmaceutical Composition

[0219] The pharmaceutical composition described herein may contain, in addition to the active compound, one or more adjuvants, which may be selected from the group consisting of the following ingredients: fillers (diluents), binders, wetting agents, disintegrants, excipients, and the like. Depending on the method of administration, the composition may contain 0.1 wt.% to 99% wt.% of the active compound.

[0220] The pharmaceutical composition containing the active ingredient may be in a form suitable for oral administration, such as tablet, troche, lozenge, aqueous or oil suspension, dispersible powder or granule, emulsion, hard or soft capsule, or syrup. Oral compositions may be prepared according to any method for preparing pharmaceutical compositions known in the art, and the compositions may contain binders, fillers, lubricants, disintegrants, pharmaceutically acceptable wetting agents, and the like, and may also contain one or more ingredients that may be selected from the group consisting of: sweetening agents, flavouring agents, coloring agents and preservatives.

[0221] Aqueous suspensions may contain the active substance in admixture with excipients suitable for the formulation of aqueous suspensions. Aqueous suspensions may also contain one or more preservatives, for example, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents. Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil. These oil suspensions may contain thickening agents. The sweetening agents and the flavoring agents described above may also be added.

[0222] The pharmaceutical compositions may also be prepared as follows: dispersible powders or granules for preparing aqueous suspensions provide the active ingredient, and water is added to mix the active ingredient with one or more of dispersing agents, wetting agents, suspending agents or preservatives. Other excipients, such as sweetening agents, flavouring agents and coloring agents, may also be added. These compositions are well preserved by the addition of antioxidants such as ascorbic acid. The pharmaceutical composition disclosed herein may also be in the form of an oil-in-water emulsion. The pharmaceutical composition may be in the form of a sterile injectable aqueous solution. Available and acceptable vehicles or solvents 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 the oil phase. For example, the active ingredient is dissolved in a mixture of soybean oil and lecithin. The oil solution may then be added to a mixture of water and glycerol and treated to form a microemulsion. The injection or microemulsion can be locally injected into the bloodstream of a patient in large quantities. Alternatively, it may be desirable to administer solutions and microemulsions in such a way as to maintain a constant circulating concentration of the compound disclosed herein. To maintain such a constant concentration, a device for continuous intravenous drug delivery may be used. For example, the device may be a Deltec CADD-PLUS. TM. 5400 intravenous injection pump.

[0223] The pharmaceutical composition may be in the form of a sterile injectable aqueous or oily suspension for intramuscular and subcutaneous administration. The suspension may be prepared according to the known art using the suitable dispersing agents or wetting agents and suspending agents described above. The sterile injectable formulation may also be a sterile injection or suspension prepared in a parenterally acceptable non-toxic diluent or solvent. Alternatively, a sterile fixed oil may be conveniently used as a solvent or a suspending medium.

[0224] The compound disclosed herein may be administered in the form of a suppository for rectal administration. These pharmaceutical compositions may be prepared by mixing a drug with a suitable non-irritating excipient which may be solid at ordinary temperatures but liquid in the rectum and will therefore melt in the rectum to release the drug. Such materials include cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, and mixtures of polyethylene glycols of various molecular weights and fatty acid esters of polyethylene glycol.

[0225] As is well known to those skilled in the art, the dosage of the drug administered depends on a variety of factors, including but not limited to, the activity of the particular compound employed, the age of the patient, the weight of the patient, the health condition of the patient, the behavior of the patient, the diet of the patient, the time of administration, the mode of administration, the rate of excretion, the combination of drugs, and the like. In addition, the optimal treatment regimen, such as the mode of treatment, a compound described herein or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, and / or the daily amount of the compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof, or the type of the pharmaceutically acceptable salt thereof, can be verified according to conventional treatment schemes.Technical Schemes for Synthesis

[0226] For the synthesis purpose of the present disclosure, the following technical schemes for synthesis are adopted in the present application: Step 1: reacting a compound of general formula (Y1) with a compound of general formula (KI3) in the presence of a condensing agent, optionally under a basic condition, to obtain a compound of general formula (I-E-M) Step 2: removing a protecting group of the compound of general formula (I-E-M) to obtain the compound of general formula (I-E) wherein, Rp is a hydroxy protecting group; R 1< , L 1< and L 2< are defined as in any formula (I-A) in embodiments of the first aspect.

[0227] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0228] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. wherein R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; L 2< is -(C(R 3 a< )(R 3b< )) m -R, wherein 0 or no less than 1 methylene unit of L 2< is independently replaced by -Cy-, -N(R 4< )C(O)-, - C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, - N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein 0 or no less than 1 methylene unit of L 1< is independently replaced by -Cy-, -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cy- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cy- is unsubstituted or independently substituted with no less than 1 substituent R 7< ; for example, wherein, R 3a< and R 5a< form a ring B together with an atom therebetween, wherein the ring B may be selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< ; each R 3b< , each R 4< , each R 5b< and each R 6< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< each independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< ; for example, wherein, R 4< and R 5a< form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< ; each R 3a< , each R 3b< , each R 5b< and each R 6< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< each independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< ; for example, wherein, R 3a< and R 6< form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< ; each R 3b< , each R 4< , each R 5a< and each R 5b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< each independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< ; for example, wherein, R 4< and R 6< independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< ; each R 3a< , each R 3b< , each R 5a< and each R 5b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, - SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; or R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< each independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< ; wherein each R 2< , each R 7< and each R 8< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 1. Step 1: reacting a compound of general formula (Y1-2) with a compound of general formula (KI4) in the presence of or in the absence of a reducing agent under an acidic or basic condition to obtain a compound of general formula (I-E-M) Step 2: removing a protecting group of the compound of general formula (I-E-M) to obtain the compound of general formula (I-E) wherein, Rp is a hydroxy protecting group; R 1< , L 1< and L 2< are defined as in any formula (I-A) in embodiments of the first aspect.

[0229] Reducing agents include, but are not limited to, sodium hydride, calcium hydride, lithium hydride, lithium aluminum hydride, sodium borohydride, lithium borohydride, sodium triethylborohydride, sodium triacetoxyborohydride and sodium cyanoborohydride.

[0230] Reagents that provide acidic conditions include a protic acid and a Lewis acid, wherein the protic acid includes, but is not limited to, hydrochloric acid, sulfuric acid, nitric acid, nitrous acid, sulfurous acid, phosphoric acid, phosphorous acid, formic acid, acetic acid, propionic acid, butyric acid, citric acid, benzoic acid, p-toluenesulfonic acid, p-nitrobenzoic acid, methanesulfonic acid, trifluoromethanesulfonic acid and trifluoroacetic acid, and the Lewis acid includes, but is not limited to, boron trifluoride, zinc chloride, magnesium chloride, aluminum chloride, stannic chloride and ferric chloride.

[0231] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0232] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. Step 1: reacting a compound of general formula (Y2x) or a compound of general formula (Y2y) with a compound of formula (KI4) in the presence of a condensing agent, optionally under a basic condition, to obtain a compound of general formula (II-Ex-M) or general formula (II-Ey-M) Step 2: removing a protecting group of the compound of general formula (II-Ex-M) or general formula (II-Ey-M) to obtain the compound of general formula (II-Ex) or general formula (II-Ey) wherein, Rp is a hydroxy protecting group; wherein L 2< , p, ring A, X 1< and L 1< are defined as in any (II-Ax) in embodiments of the first aspect; or X 2< , q, ring A, X 1< and L 1< are defined as in any (II-Ay) in embodiments of the first aspect.

[0233] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0234] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. reacting a compound of general formula (Y3) with a compound of general formula (KI4) in the presence of a condensing agent, optionally under a basic condition, to obtain the compound of general formula (III-E-M). wherein, R 1< and X are defined as in any (III-A) in embodiments of the first aspect.

[0235] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0236] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. Step 1: reacting a compound of general formula (I-F-M1A) with a compound of general formula (KI3) in the presence of a condensing agent, optionally under a basic condition, to obtain a compound of general formula (I-F-M2A) Step 2: removing a protecting group of the compound of general formula (I-F-M2A) to obtain a compound of general formula (I-F-M3A) Step 3: reacting a compound of general formula (KI1) with the compound of general formula (I-F-M3A) in the presence of a condensing agent, optionally under a basic condition, to obtain the compound of general formula (I-F) wherein, Re is an amino protecting group, preferably Fomc; W, Y, Z, R L1< , R L2< , R 1< , L 1< and L 2< are defined as in any formula (I-F) in embodiments of the sixth aspect.

[0237] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0238] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. wherein R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; L 2< is -(C(R 3 a< )(R 3b< )) m -R, wherein 0 or no less than 1 methylene unit of L 2< is independently replaced by -Cy-, -N(R 4< )C(O)-, - C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, - N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein 0 or no less than 1 methylene unit of L 1< is independently replaced by -Cy-, -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cy- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cy- is unsubstituted or independently substituted with no less than 1 substituent R 7< ; wherein each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; or, R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< each independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or independently substituted with no less than 1 substituent R 8< ; wherein each R 2< , each R 7< and each R 8< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 1. Step 1: reacting a compound of general formula (I-F-M1B) with a compound of general formula (KI3) in the presence of or in the absence of a reducing agent, optionally under an acidic or basic condition, to obtain a compound of general formula (I-F-M2B) Step 2: removing a protecting group of the compound of general formula (I-F-M2B) to obtain a compound of general formula (I-F-M3B) Step 3: reacting a compound of general formula (KI1) with the compound of general formula (I-F-M3B) in the presence of a condensing agent, optionally under a basic condition, to obtain the compound of general formula (I-F) wherein, Re is an amino protecting group, preferably Fomc; W, Y, Z, R L1< , R L2< , R 1< , L 1< and L 2< are defined as in any formula (I-F) in embodiments of the sixth aspect.

[0239] Reducing agents include, but are not limited to, sodium hydride, calcium hydride, lithium hydride, lithium aluminum hydride, sodium borohydride, lithium borohydride, sodium triethylborohydride, sodium triacetoxyborohydride and sodium cyanoborohydride.

[0240] Reagents that provide acidic conditions include a protic acid and a Lewis acid, wherein the protic acid includes, but is not limited to, hydrochloric acid, sulfuric acid, nitric acid, nitrous acid, sulfurous acid, phosphoric acid, phosphorous acid, formic acid, acetic acid, propionic acid, butyric acid, citric acid, benzoic acid, p-toluenesulfonic acid, p-nitrobenzoic acid, methanesulfonic acid, trifluoromethanesulfonic acid and trifluoroacetic acid, and the Lewis acid includes, but is not limited to, boron trifluoride, zinc chloride, magnesium chloride, aluminum chloride, stannic chloride and ferric chloride.

[0241] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0242] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. wherein R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )- and -S-; L 2< is -(C(R 3 a< )(R 3b< )) m -R, wherein 0 or no less than 1 methylene unit of L 2< is independently replaced by -Cy-, -N(R 4< )C(O)-, - C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, - N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein 0 or no less than 1 methylene unit of L 1< is independently replaced by -Cy-, -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cy- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cy- is unsubstituted or independently substituted with no less than 1 substituent R 7< ; wherein each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; or, R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< each independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or independently substituted with no less than 1 substituent R 8< ; wherein each R 2< , each R 7< and each R 8< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 1. Step 1: reacting a compound of general formula (I-E) with a compound of general formula (KI2), optionally under an acidic condition, to obtain a compound of general formula (I-F-M1C) Step 2: removing a protecting group of the compound of general formula (I-F-M1C) to obtain a compound of general formula (I-F-M2C) Step 3: reacting a compound of general formula (KI1) with the compound of general formula (I-F-M2C) in the presence of a condensing agent, optionally under a basic condition, to obtain the compound of general formula (I-F) Re is an amino protecting group, preferably Fomc; W, Y, Z, R L1< , R L2< , R 1< , L 1< and L 2< are defined as in any general formula (I-F) in embodiments of the sixth aspect.

[0243] Reducing agents include, but are not limited to, sodium hydride, calcium hydride, lithium hydride, lithium aluminum hydride, sodium borohydride, lithium borohydride, sodium triethylborohydride, sodium triacetoxyborohydride and sodium cyanoborohydride.

[0244] Reagents that provide acidic conditions include a protic acid and a Lewis acid, wherein the protic acid includes, but is not limited to, hydrochloric acid, sulfuric acid, nitric acid, nitrous acid, sulfurous acid, phosphoric acid, phosphorous acid, formic acid, acetic acid, propionic acid, butyric acid, citric acid, benzoic acid, p-toluenesulfonic acid, p-nitrobenzoic acid, methanesulfonic acid, trifluoromethanesulfonic acid and trifluoroacetic acid, and the Lewis acid includes, but is not limited to, boron trifluoride, zinc chloride, magnesium chloride, aluminum chloride, stannic chloride and ferric chloride.

[0245] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0246] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. Step 1: reacting a compound of general formula (II-F-M1x) or a compound of general formula (II-F-M1y) with a compound of general formula (KI4) in the presence of a condensing agent, optionally under a basic condition, to obtain a compound of general formula (II-F-M2x) or general formula (II-F-M2y) Step 2: removing a protecting group of the compound of general formula (II-F-M2x) or general formula (II-F-M2y) to obtain a compound of general formula (II-F-M3x) or general formula (II-F-M3y) Step 3: reacting a compound of general formula (KI1) with the compound of general formula (II-F-M3x) or general formula (II-F-M3y) in the presence of a condensing agent, optionally under a basic condition, to obtain the compound of general formula (II-Fx) or general formula (II-Fy) wherein, Re is an amino protecting group, preferably Fomc; W, Y, Z, R L1< , R L2< , A, X 1< , L 1< , L 2< and p are defined as in any formula (II-Fx) in embodiments of the sixth aspect, or W, Y, Z, R L1< , R L2< , A, X 1< , L 1< , X 2< and q are defined as in any formula (II-Fy) in embodiments of the sixth aspect.

[0247] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0248] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. Step 1: reacting a compound of general formula (III-F-M1) with a compound of general formula (KI4) in the presence of a condensing agent, optionally under a basic condition, to obtain a compound of general formula (III-F-M2) Step 2: removing a protecting group of the compound of general formula (III-F-M2) to obtain a compound of general formula (III-F-M3) Step 3: reacting a compound of general formula (KI1) with the compound of general formula (III-F-M3) in the presence of a condensing agent, optionally under a basic condition, to obtain the compound of general formula (III-F) wherein, Re is an amino protecting group, preferably Fomc; W, Y, Z, R L1< , R L2< , R 1< and X are defined as in any general formula (III-F) in embodiments of the sixth aspect.

[0249] Reagents that provide basic conditions include organic bases and inorganic bases, wherein the organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, piperidine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and the like, and the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, and the like.

[0250] The condensing agent may be selected from the group consisting of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazol-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazol, O-benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2-(7-azobenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. wherein, Ab is a ligand, and after being reduced, Ab reacts with the general formula (I-F) to obtain the compound of general formula (I-D); reducing agents include, but are not limited to, tris(2-carboxyethyl)phosphine, mercaptoethanol, dithiothreitol, cysteine, reduced glutathione, and the like; in particular, disulfide bonds on the antibody are preferably reduced; W, Y, Z, R L1< , R L2< , R 1< , L 1< and L 2< are defined as in any formula (I-D) in embodiments of the fourth aspect. wherein, Ab is a ligand, and after being reduced, Ab reacts with the general formula (II-F), including general formula (II-Fx) or general formula (II-Fy), to obtain the compound of general formula (II-Dx) or general formula (II-Dy); reducing agents include, but are not limited to, tris(2-carboxyethyl)phosphine, mercaptoethanol, dithiothreitol, cysteine, reduced glutathione, and the like; in particular, disulfide bonds on the antibody are preferably reduced; W, Y, Z, R L1< , R L2< , A, X 1< , L 1< , L 2< and p are defined as in any formula (II-Dx) in embodiments of the fourth aspect, or W, Y, Z, R L1< , R L2< , A, X 1< , L 1< , X 2< and q are defined as in any formula (II-Dy) in embodiments of the fourth aspect. wherein, Ab is a ligand, and after being reduced, Ab reacts with the general formula (III-F) to obtain the compound of general formula (III-D); reducing agents include, but are not limited to, tris(2-carboxyethyl)phosphine, mercaptoethanol, dithiothreitol, cysteine, reduced glutathione, and the like; in particular, disulfide bonds on the antibody are preferably reduced; W, Y, Z, R L1< , R L2< , R 1< and X are defined as in any general formula (III-D) in embodiments of the fourth aspect. Technical Schemes

[0251] 1. A compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure shown as formula (I-A): wherein, R 1< is selected from the group consisting of: -O-, -(R 2< )N-, -P(=O)(R 2< )-, -P(R 2< )- and -S-; L 2< is -(C(R 3 a< )(R 3b< )) m -R, wherein 0 or no less than 1 methylene unit of L 2< is independently replaced by -Cy-, -N(R 4< )C(O)-, - C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, - N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein 0 or no less than 1 methylene unit of L 1< is independently replaced by -Cy-, -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-; -Cy- is selected from the group consisting of: 6-10 membered arylene, 5-8 membered heteroarylene, 3-10 membered heterocyclylene, and 3-10 membered saturated or partially unsaturated carbocyclylene, wherein -Cy- is unsubstituted or independently substituted with no less than 1 substituent R 7< ; wherein each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, - C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; or, R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< or R 4< and R 6< each independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or independently substituted with no less than 1 substituent R 8< ; wherein each R 2< , each R 7< and each R 8< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 1. 2. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< and each R 6< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, -C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, - N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R. 3. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein R 3a< and R 5a< , R 4< and R 5a< , R 3a< and R 6< , or R 4< and R 6< each independently optionally form a ring B together with an atom therebetween, wherein the ring B is selected from the group consisting of: 5-8 membered heteroarylene and 3-10 membered saturated or partially unsaturated heterocyclylene, and the ring B is unsubstituted or substituted with no less than 1 substituent R 8< . 4. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-3, wherein m is 1 or 2. 5. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4, wherein m is 1, and L 2< is -C(R 3a< )(R 3b< )-R. 6. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-5, wherein L 2< is -C(R 3a< )(R 3b< )-R, and 0 methylene units of L 2< are replaced by -Cy-, -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, - P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 7. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4, wherein m is 2, and L 2< is -(C(R 3a< )(R 3b< )) 2 -R. 8. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4 and 7, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, and 0 methylene units of L 2< are replaced by -Cy-, -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, - SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 9. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4 and 7, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, and 1 methylene unit of L 2< is replaced by -Cy-, -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, - SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 10. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4, 7 and 9, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, and 1 methylene unit of L 2< is replaced by -C(O)- or -Cy-. 11. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4, 7 and 9-10, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, and 1 methylene unit of L 2< is replaced by -C(O)-. 12. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4, 7 and 9-11, wherein L 2< is -C(O)-C(R 3a< )(R 3b< )-R. 13. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4, 7 and 9-10, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, and 1 methylene unit of L 2< is replaced by -Cy-. 14. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-4, 7, 9-10 and 13, wherein L 2< is -C(R 3a< )(R 3b< )-Cy-R. 15. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein 0 methylene units of L 2< are replaced by -Cy-, -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, - C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 16. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein 1 methylene unit of L 2< is replaced by -Cy-, -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, - OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, - C(=S)-, -C(=NR 4< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 17. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 16, wherein 1 methylene unit of L 2< is replaced by -C(O)- or -Cy-. 18. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 16-17, wherein 1 methylene unit of L 2< is replaced by -C(O)-. 19. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18, wherein n is 2, 3 or 5. 20. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, wherein n is 2, and L 1< is -(C(R 5a< )(R 5b< )) 2 -. 21. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-20, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 0 methylene units of L 1< are replaced by -Cy-, -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 22. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 1 methylene unit of L 1< is replaced by -Cy-, -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, - P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 23. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 22, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 1 methylene unit of L 1< is replaced by -C(O)- or -C(=S)-. 24. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 22-23, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 1 methylene unit of L 1< is replaced by -C(O)-. 25. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 22-24, wherein L 1< is -C(R 5a< )(R 5b< )-C(O)-. 26. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 22-23, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 1 methylene unit of L 1< is replaced by -C(=S)-. 27. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 22-23 and 26, wherein L 1< is -C(R 5a< )(R 5b< )-C(=S)-. 28. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, wherein n is 3, and L 1< is -(C(R 5a< )(R 5b< )) 3 -. 29. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 28, wherein L 1< is -(C(R 5a< )(R 5b< )) 3 -, and 0 methylene units of L 1< are replaced by -Cy-, -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, - SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 30. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 28, wherein L 1< is -(C(R 5a< )(R 5b< )) 3 -, and 1 methylene unit of L 1< is replaced by -Cy-, -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, - SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 31. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 28 and 30, wherein L 1< is -(C(R 5a< )(R 5b< )) 3 -, and 1 methylene unit of L 1< is replaced by -C(O)-. 32. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 28 and 30-31, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -C(O)-. 33. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, wherein n is 5, and L 1< is -(C(R 5a< )(R 5b< )) 5 -. 34. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 33, wherein L 1< is -(C(R 5a< )(R 5b< )) 5 -, and 1 methylene unit of L 1< is replaced by -NR 6< - or -O-. 35. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 33-34, wherein L 1< is -(C(R 5a< )(R 5b< )) 5 -, and 1 methylene unit of L 1< is replaced by -NR 6< -. 36. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 33-35, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -NR 6< -(C(R 5a< )(R 5b< )) 2- . 37. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 33-34, wherein L 1< is -(C(R 5a< )(R 5b< )) 5 -, and 1 methylene unit of L 1< is replaced by -O-. 38. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 33-34 and 37, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -O-(C(R 5a< )(R 5b< )) 2- . 39. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 33, wherein L 1< is -(C(R 5a< )(R 5b< )) 5 -, and 2 methylene units of L 1< are each independently replaced by -C(O)-, -NR 6< - or -O-. 40. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 33 and 39, wherein L 1< is -(C(R 5a< )(R 5b< )) 5 -, and 2 methylene units of L 1< are each independently replaced by -C(O)- or -NR 6< -. 41. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 33 and 39-40, wherein L 1< is -C(R 5a< )(R 5b< )-C(O)-NR 6< -(C(R 5a< )(R 5b< )) 2 -. 42. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 33 and 39-41, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -NR 6< -C(O)-C(R 5a< )(R 5b< )-. 43. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 33 and 39, wherein L 1< is -(C(R 5a< )(R 5b< )) 5 -, and 2 methylene units of L 1< are each independently replaced by -C(O)- or -O-. 44. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 33, 39 and 43, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -O-C(R 5a< )(R 5b< )-C(O)-. 45. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19 and 33, wherein L 1< is -(C(R 5a< )(R 5b< )) 5 -, and 3 methylene units of L 1< are each independently replaced by -C(O)- or -NR 6< -. 46. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-19, 33 and 45, wherein L 1< is -(C(R 5a< )(R 5b< )) 2 -NR 6< -C(O)-C(O)-. 47. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18, wherein 0 methylene units of L 1< are replaced by -Cy-, -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 48. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18, wherein 1 methylene unit of L 1< is replaced by -Cy-, -N(R 6< )C(O)-, - C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, - N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 49. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18 and 48, wherein 1 methylene unit of L 1< is replaced by -C(O)-, -C(=S)-, - NR 6< - or -O-. 50. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18 and 48-49, wherein 1 methylene unit of L 1< is replaced by -C(O)- or - C(=S)-. 51. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18 and 48-50, wherein 1 methylene unit of L 1< is replaced by -C(O)-. 52. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18, wherein 2 methylene units of L 1< are each independently replaced by -Cy-, -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, - P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 53. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18 and 52, wherein 2 methylene units of L 1< are each independently replaced by -C(O)-, -NR 6< - or -O-. 54. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18 and 52-53, wherein 2 methylene units of L 1< are each independently replaced by -C(O)- or -NR 6< -. 55. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18, wherein 3 methylene units of L 1< are each independently replaced by -Cy-, -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, - P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, -C=N-, -N=C- or -C(=N 2 )-. 56. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-18 and 55, wherein 3 methylene units of L 1< are each independently replaced by -C(O)- or -NR 6< -. 57. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 3, wherein R 3a< and R 5a< independently optionally form a ring B together with an atom therebetween. 58. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 3 and 57, wherein ring B is 3-10 membered saturated or partially unsaturated heterocyclylene. 59. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 3 and 57-58, wherein ring B is 3-6 membered saturated or partially unsaturated heterocyclylene. 60. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 3 and 57-59, wherein ring B is 5 membered saturated or partially unsaturated heterocyclylene. 61. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 3 and 57-60, wherein ring B is 5 membered saturated heterocyclylene. 62. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 3, wherein R 4< and R 5a< independently optionally form a ring B together with an atom therebetween. 63. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 3 and 62, wherein ring B is 3-10 membered saturated or partially unsaturated heterocyclylene. 64. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 3 and 62-63, wherein ring B is 6 membered saturated or partially unsaturated heterocyclylene. 65. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 3 and 62-64, wherein ring B is 6 membered saturated heterocyclylene. 66. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein L 2< is -C(R 3a< )(R 3b< )-R or -(C(R 3a< )(R 3b< )) 2 -R, and L 1< is -(C(R 5a< )(R 5b< )) 2 -, - (C(R 5a< )(R 5b< )) 3 - or -(C(R 5a< )(R 5b< )) 5 -. 67. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 66, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, and L 1< is -(C(R 5a< )(R 5b< )) 2 -. 68. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 66-67, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 1 methylene unit of L 1< is replaced by -C(O)-, -C(=S)-, -NR 6< - or -O-. 69. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 66-68, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 1 methylene unit of L 1< is replaced by -C(O)-. 70. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 66-69, wherein L 2< is -(C(R 3a< )(R 3b< )) 2 -R, and L 1< is -C(R 5a< )(R 5b< )-C(O)-. 71. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 66-70, wherein R 3a< and R 5a< independently optionally form a ring B together with an atom therebetween. 72. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 66-71, wherein ring B is 3-10 membered saturated or partially unsaturated heterocyclylene. 73. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 66-72, wherein ring B is 5 membered saturated heterocyclylene. 74. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 66, wherein L 2< is -C(R 3a< )(R 3b< )-R, and L 1< is -(C(R 5a< )(R 5b< )) 2 -. 75. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 66 and 74, wherein L 2< is -C(R 3a< )(R 3b< )-R, L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 1 methylene unit of L 1< is replaced by -C(O)-, -C(=S)-, -NR 6< - or -O-. 76. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 66 and 74-75, wherein L 2< is -C(R 3a< )(R 3b< )-R, L 1< is -(C(R 5a< )(R 5b< )) 2 -, and 1 methylene unit of L 1< is replaced by -C(O)-. 77. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1, 66 and 74-76, wherein L 2< is -C(R 3a< )(R 3b< )-R, and L 1< is -C(R 5a< )(R 5b< )-C(O)-. 78. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-77, wherein R 1< is selected from the group consisting of: -O-, -(R 2< )N- and -S-. 79. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-78, wherein R 1< is -O-. 80. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-78, wherein R 1< is -(R 2< )N-. 81. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-78 and 80, wherein R 2< is hydrogen or a C 1-6 aliphatic group. 82. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-78 and 80-81, wherein R 1< is -HN-. 83. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-82, wherein -Cy-is 6-10 membered arylene. 84. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-83, wherein -Cy- is phenylene. 85. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1-84, wherein R 7< is hydrogen. 86. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein R 3a< and R 3b< are independently hydrogen, or R 3a< and R 5a< independently optionally form a ring B together with an atom therebetween. 87. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 86, wherein ring B is 3-10 membered saturated or partially unsaturated heterocyclylene. 88. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 86-87, wherein ring B is 5 membered saturated heterocyclylene. 89. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein R 4< is hydrogen, or R 4< and R 5a< independently optionally form a ring B together with an atom therebetween. 90. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein R 4< is hydrogen, or R 4< and R 5a< independently optionally form a ring B together with an atom therebetween. 91. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 1 and 86-90, wherein R 8< is hydrogen. 92. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein R, R a< and R b< are each independently hydrogen. 93. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 1, wherein the ligand-drug conjugate comprises the following group of structures: 94. A compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure shown as formula (II-A): wherein, X 1< is selected from the group consisting of: N, P, and saturated or unsaturated C; when X 1< is saturated C, X 1< is substituted with R n< ; when X 1< is saturated C, ring A is selected from the group consisting of: 3-10 membered saturated or partially unsaturated heterocyclyl, and 3-10 membered saturated or partially unsaturated carbocyclyl, wherein ring A is substituted with 0 or no less than 1 substituent R 1a< ; or, when X 1< is unsaturated C, ring A is selected from the group consisting of: 6-10 membered aryl, 5-8 membered heteroaryl, 3-10 membered partially unsaturated heterocyclyl, and 3-10 membered partially unsaturated carbocyclyl, wherein ring A is substituted with 0 or no less than 1 substituent R 1b< ; or, when X 1< is N or P, ring A is selected from the group consisting of: 5-8 membered heteroaryl and 3-10 membered saturated or partially unsaturated heterocyclyl, wherein ring A is substituted with 0 or no less than 1 substituent R 1c< ; when ring A is selected from the group consisting of: 6-10 membered aryl, 5-8 membered heteroaryl, and 3-10 membered saturated or partially unsaturated carbocyclyl, ring A is substituted with p L 2< , wherein L 2< is not R n< ; or, when ring A is 3-10 membered saturated or partially unsaturated heterocyclyl, ring A is substituted with p L 2< , or ring A comprises q ring-forming heteroatom X 2< , and X 2< is used for direct or indirect linking of a ligand; X 2< is selected from the group consisting of: N and P; L 2< is -R 2< -L 3< -, and R 2< is used for direct or indirect linking of a ligand; L 3< is -(C(R 3a< )(R 3b< )) m -, wherein when L 3< comprises a methylene unit, 0 or no less than 1 methylene unit of L 3< is independently replaced by -N(R 4< )C(O)-, -C(O)N(R 4< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4< -, -O-, -S-, -SO-, -SO 2 -, -P(R 4< )-, -P(=O)(R 4< )-, -N(R 4< )SO 2 -, -SO 2 N(R 4< )-, -C(=S)-, -C(=NR 4< )-, -N=N-, - C=N-, -N=C- or -C(=N 2 )-; R 2< is selected from the group consisting of: -O-, -(R 2a< )N-, -S- and -P(=O)(R 2a< )-; L 1< is -(C(R 5a< )(R 5b< )) n -, wherein when L 1< comprises a methylene unit, 0 or no less than 1 methylene unit of L 1< is independently replaced by -N(R 6< )C(O)-, -C(O)N(R 6< )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6< -, -O-, -S-, -SO-, -SO 2 -, -P(R 6< )-, -P(=O)(R 6< )-, -N(R 6< )SO 2 -, -SO 2 N(R 6< )-, -C(=S)-, -C(=NR 6< )-, -N=N-, - C=N-, -N=C- or -C(=N 2 )-; wherein each R 1a< , each R 1b< , each R 1c< , each R 2a< , each R 3a< , each R 3b< , each R 4< , each R 5a< , each R 5b< , each R 6< and each R n< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, - OR, -SR, -N(R a< )(R b< ), -C(O)R, -CO 2 R, -C(O)C(O)R, -C(O)CH 2 C(O)R, -S(O)R, -S(O) 2 R, - C(O)N(R a< )(R b< ), -SO 2 N(R a< )(R b< ), -OC(O)R, -N(R)SO 2 R, or a C 1-6 aliphatic group optionally substituted with R; wherein each R, each R a< and each R b< are each independently hydrogen, protium, deuterium, tritium, halogen, -NO 2 , -CN, -OH, -SH, -NH 2 , -C(O)H, -CO 2 H, -C(O)C(O)H, -C(O)CH 2 C(O)H, -S(O)H, - S(O) 2 H, -C(O)NH 2 , -SO 2 NH 2 , -OC(O)H, -N(H)SO 2 H or a C 1-6 aliphatic group; m and n are each independently selected from the group consisting of integers ≥ 0, and p and q are each independently selected from the group consisting of integers ≥ 1. 95. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to technical scheme 94, wherein X 1< is saturated C. 96. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 94-95, wherein ring A is selected from the group consisting of: 3-10 membered saturated heterocyclyl and 3-10 membered saturated carbocyclyl. 97. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 94-96, wherein ring A is 3-10 membered saturated carbocyclyl. 98. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 94-97, wherein ring A is 3-6 membered saturated carbocyclyl. 99. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 94-98, wherein ring A is 4 membered saturated carbocyclyl. 100. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 94-98, wherein ring A is 6 membered saturated carbocyclyl. 101. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 94-96, wherein ring A is 3-10 membered saturated heterocyclyl. 102. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 94-96 and 101, wherein ring A is 3-6 membered saturated heterocyclyl. 103. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically acceptable salt thereof according to any one of technical schemes 94-96 and 101-102, wherein ring A is 3 membered saturated heterocyclyl. 104. The compound or the tautomer, the mesomer, the racemate, the enantiomer or the diastereoisomer thereof, or the mixture thereof, or the pharmaceutically accep...

Claims

1. A compound of formula: or a pharmaceutically acceptable salt thereof, wherein n is the average connection number, and is from 1 to 10.

2. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 1, wherein n is 3 to 8.

3. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 1, wherein n is 6 to 10.

4. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 1, wherein n is 6 to 7.

5. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 1, wherein n is 7 to 9.

6. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 1, wherein n is 7 to 8.

7. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 1, wherein n is 8 to 9.

8. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 1, wherein n is 8.

9. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to any one of claims 1 to 8, wherein trastuzumab comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 33, and a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 37.

10. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to any one of claims 1 to 8, wherein trastuzumab comprises: a light chain variable region (VL) comprising an amino acid sequence set forth in SEQ ID NO: 25, and a heavy chain variable region (VH) comprising an amino acid sequence set forth in SEQ ID NO: 29.

11. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to any one of claims 1 to 8, wherein trastuzumab comprises: a light chain, wherein the LCDR1 comprises an amino acid sequence set forth in SEQ ID NO: 1, the LCDR2 comprises an amino acid sequence set forth in SEQ ID NO: 5, and the LCDR3 comprises an amino acid sequence set forth in SEQ ID NO: 9, and a heavy chain, wherein the HCDR1 comprises an amino acid sequence set forth in SEQ ID NO: 13, the HCDR2 comprises an amino acid sequence set forth in SEQ ID NO: 17, and the HCDR3 comprises an amino acid sequence set forth in SEQ ID NO: 21; all CDRs being defined according to Kabat.

12. A pharmaceutical composition, comprising the compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 11, and a pharmaceutically acceptable carrier.

13. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 11, and / or the pharmaceutical composition according to claim 12, for use in treating and / or preventing a tumour.

14. The compound or pharmaceutical composition for use according to claim 13, wherein the tumour is selected from the group consisting of tumours associated with expression of the following: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 and EGFR.

15. The compound or pharmaceutical composition for use according to any one of claims 13 or 14, wherein the tumour is selected from the group consisting of: lung cancer, kidney cancer, urinary tract carcinoma, colorectal cancer, prostatic cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer and esophageal cancer.