Anti-tumor compound as well as preparation method and application thereof

Abstract

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

Description

[0001] This application is a divisional application of Chinese patent application filed on September 29, 2021, with application number 202180018263.3 and entitled "An antitumor compound and its preparation method and application". Technical Field

[0002] This application relates to the field of biomedicine, specifically to an antitumor compound, its preparation method, and its application. Background Technology

[0003] Currently, camptothecin derivatives are among the small molecules with cytotoxicity used in antibody-drug conjugates (ADCs), exhibiting antitumor activity by inhibiting topoisomerase I. Camptothecin derivatives can be applied to antibody-drug conjugates (ADCs). However, further development of camptothecin derivatives and ADC drugs with improved efficacy and / or safety is still needed. Summary of the Invention

[0004] This application provides a compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or 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 the in vitro proliferation of tumor cells; (2) having targeted inhibition; (3) having plasma stability; (4) having in vivo tumor suppression effect; (5) having a bystander effect; (6) having antitransporter transport capability; (7) having in vivo tumor targeting capability; and (8) having good in vivo safety.

[0005] On one hand, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises the structure shown in formula (II-A):

[0006]

[0007] Where X 1 For saturated C, the X 1 R n replace;

[0008] Ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or at least 1 substituent R. 1a replace;

[0009] When ring A is a 3- to 10-membered saturated or partially unsaturated carbon cyclic group, ring A is divided by p L... 2 Instead, the L 2 Not for Rn ;

[0010] Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 replace;

[0011] L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0012] L 3 -(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Each of the zero or at least one methylene unit is independently converted to -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0013] R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-;

[0014] L 1 -(C(R) 5a (R) 5b )) n -, where L 1 When containing a methylene unit, the L 1 Each of the zero or at least one methylene unit is independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6)-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0015] Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0016] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0017] m and n are each independently selected from integers at least 0, and p is an integer at least 1.

[0018] On the one hand, this application provides a general formula (II-E) x The compound shown in the diagram, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein:

[0019] ,

[0020] Where X 1 For saturated C, the X 1 Rn replace;

[0021] Ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or at least 1 substituent R. 1a replace;

[0022] When ring A is a 3- to 10-membered saturated or partially unsaturated carbon cyclic group, ring A is divided by p L... 2 Instead, the L 2 Not for R n ;

[0023] Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 replace;

[0024] L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0025] L 3 -(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Each of the zero or at least one methylene unit is independently converted to -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0026] R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-;

[0027] L 1 -(C(R) 5a (R) 5b ))n -, where L 1 When containing a methylene unit, the L 1 Each of the zero or at least one methylene unit is independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0028] Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0029] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0030] m and n are each independently selected from integers at least 0, and p is an integer at least 1.

[0031] On the one hand, this application provides a compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, comprising the formula (II-C). x The structure shown is as follows:

[0032] ,

[0033] The L is -L a -L b -L c -;

[0034] The -L a -Selected from the following groups:

[0035] , ,and ;

[0036] Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp -, Z is -(C(R) za (R) zb )) zn ;

[0037] Where wn is selected from integers that are at least 0.

[0038] The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0039] Where yn is selected from integers that are at least 0, and yp is 0 or 1;

[0040] Where zn is selected from integers that are at least 0.

[0041] Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0042] -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace;

[0043] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or R r Optional substitution of C 1-6 Aliphatic groups;

[0044] Each Rr R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0045] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0046] The -L c -Selected from the following groups:

[0047] , , , , , ,and ;

[0048] Where R L1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0049] Where X 1 For saturated C, the X 1 R n replace;

[0050] Ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or at least 1 substituent R. 1a replace;

[0051] When ring A is a 3- to 10-membered saturated or partially unsaturated carbon cyclic group, ring A is divided by p L... 2 Instead, the L 2 Not for R n ;

[0052] Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L2 replace;

[0053] L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0054] L 3 -(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Each of the zero or at least one methylene unit is independently converted to -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0055] R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-;

[0056] L 1 -(C(R) 5a (R) 5b )) n -, where L 1 When containing a methylene unit, the L 1 Each of the zero or at least one methylene unit is independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6-, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0057] Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0058] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0059] m and n are each independently selected from integers at least 0, and p is an integer at least 1.

[0060] On one hand, this application provides a compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, comprising the structure shown in formula (II-Dx):

[0061] ,

[0062] Where Ab is the ligand, and the average number of connections N a Integers or decimals from 1 to 10;

[0063] The L is -L a -L b -L c -;

[0064] The -L a -Selected from the following groups:

[0065] , ,and ;

[0066] Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp -, Z is -(C(R) za (R) zb )) zn ;

[0067] Where wn is selected from integers that are at least 0.

[0068] The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0069] Where yn is selected from integers that are at least 0, and yp is 0 or 1;

[0070] Where zn is selected from integers that are at least 0.

[0071] Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR)zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0072] -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace;

[0073] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or R r Optional substitution of C 1-6 Aliphatic groups;

[0074] Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0075] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0076] The -L c -Selected from the following groups:

[0077] , , , , , ,and ;

[0078] Where R L1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0079] Where X 1 For saturated C, the X 1 R n replace;

[0080] Ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or at least 1 substituent R. 1a replace;

[0081] When ring A is a 3- to 10-membered saturated or partially unsaturated carbon cyclic group, ring A is divided by p L... 2 Instead, the L 2 Not for R n ;

[0082] Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 replace;

[0083] L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0084] L 3 -(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Each of the zero or at least one methylene unit is independently converted to -N(R)4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0085] R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-;

[0086] L 1 -(C(R) 5a (R) 5b )) n -, where L 1 When containing a methylene unit, the L 1 Each of the zero or at least one methylene unit is independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0087] Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0088] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0089] m and n are each independently selected from integers at least 0, and p is an integer at least 1.

[0090] On the one hand, this application provides a general formula (II-F) x The compound shown in the diagram, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein:

[0091] ,

[0092] The L x For L ax -L b -L c -;

[0093] The L ax -Selected from the following groups:

[0094] , ,and ;

[0095] Where R hal It is iodine or bromine;

[0096] Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp -, Z is -(C(R) za (R)zb )) zn ;

[0097] Where wn is selected from integers that are at least 0.

[0098] The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0099] Where yn is selected from integers that are at least 0, and yp is 0 or 1;

[0100] Where zn is selected from integers that are at least 0.

[0101] Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0102] -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace;

[0103] Each R wa R wb R za R zb Rwx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or by R r Optional substitution of C 1-6 Aliphatic groups;

[0104] Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0105] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0106] The -L c -Selected from the following groups:

[0107] , , , , , ,and ;

[0108] Where R L1 R L2Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0109] Where X 1 For saturated C, the X 1 R n replace;

[0110] Ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or at least 1 substituent R. 1a replace;

[0111] When ring A is a 3- to 10-membered saturated or partially unsaturated carbon cyclic group, ring A is divided by p L... 2 Instead, the L 2 Not for R n ;

[0112] Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 replace;

[0113] L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0114] L 3 -(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Each of the zero or at least one methylene unit is independently converted to -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR)4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0115] R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-;

[0116] L 1 -(C(R) 5a (R) 5b )) n -, where L 1 When containing a methylene unit, the L 1 Each of the zero or at least one methylene unit is independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0117] Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0118] Where each R, Ra R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0119] m and n are each independently selected from integers at least 0, and p is an integer at least 1.

[0120] On one hand, this application provides a compound or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, comprising a structure comprising the following groups:

[0121] (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), and (II-A-12).

[0122] On one hand, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises the structure shown in formula (III-A):

[0123]

[0124] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-;

[0125] X is -L 1 -CH2-C(O)-;

[0126] L 1 -(C(R) 3a (R) 3b)) m -, where L 1 The zero or at least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b - or -C(=N2)- substitution;

[0127] Each R 2 R 3a R 3b R 4b Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0128] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0129] m is selected from an integer that is at least 0, and n is selected from an integer that is at least 1;

[0130] When R 1 When L is -O- or -HN-, 1 At least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b )- or -C(=N2)- substitution, or each R 3a R 3b They are not both hydrogen.

[0131] On one hand, this application provides a compound of general formula (III-E) or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0132]

[0133] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-;

[0134] X is -L 1 -CH2-C(O)-;

[0135] L 1 -(C(R) 3a (R) 3b )) m -, where L 1 The zero or at least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b - or -C(=N2)- substitution;

[0136] Each R 2 R 3a R 3b R 4b Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0137] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0138] m is selected from an integer that is at least 0, and n is selected from an integer that is at least 1;

[0139] When R 1 When L is -O- or -HN-, 1At least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b )- or -C(=N2)- substitution, or each R 3a R 3b They are not both hydrogen.

[0140] On the one hand, this application provides a compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, comprising the structure shown in formula (III-C):

[0141]

[0142] The L is -L a -L b -L c -;

[0143] The -L a -Selected from the following groups:

[0144] , ,and ;

[0145] Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp Z is -(C(R) za (R) zb )) zn ,;

[0146] Where wn is selected from integers that are at least 0.

[0147] The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0148] Where yn is selected from integers that are at least 0, and yp is 0 or 1;

[0149] Where zn is selected from integers that are at least 0.

[0150] Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0151] -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace;

[0152] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or by R rOptional substitution of C 1-6 Aliphatic groups;

[0153] Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0154] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0155] The -L c -Selected from the following groups:

[0156] , , , , , ,and ;

[0157] Where R L1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0158] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-;

[0159] X is -L 1 -CH2-C(O)-;

[0160] L 1 -(C(R) 3a (R) 3b )) m -, where L 1 The zero or at least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-.4b - or -C(=N2)- substitution;

[0161] Each R 2 R 3a R 3b R 4b Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0162] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0163] m is selected from an integer that is at least 0, and n is selected from an integer that is at least 1;

[0164] When R 1 When L is -O- or -HN-, 1 At least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b )- or -C(=N2)- substitution, or each R 3a R 3b They are not both hydrogen.

[0165] On the one hand, this application provides a compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, comprising the structure shown in formula (III-D):

[0166]

[0167] Where Ab is the ligand, and the average number of connections N a Integers or decimals from 1 to 10;

[0168] The L is -L a -L b -L c -;

[0169] The -L a -Selected from the following groups:

[0170] , ,and ;

[0171] Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp Z is -(C(R) za (R) zb )) zn ,;

[0172] Where wn is selected from integers that are at least 0.

[0173] The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0174] Where yn is selected from integers that are at least 0, and yp is 0 or 1;

[0175] Where zn is selected from integers that are at least 0.

[0176] Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(Rzx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0177] -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace;

[0178] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or by R r Optional substitution of C 1-6 Aliphatic groups;

[0179] Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0180] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0181] The -L c -Selected from the following groups:

[0182] , , , , , ,and ;

[0183] Where R L1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0184] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-;

[0185] X is -L 1 -CH2-C(O)-;

[0186] L 1 -(C(R) 3a (R) 3b )) m -, where L 1 The zero or at least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b - or -C(=N2)- substitution;

[0187] Each R 2 R 3a R 3b R 4b Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(Ra (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0188] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0189] m is selected from an integer that is at least 0, and n is selected from an integer that is at least 1;

[0190] When R 1 When L is -O- or -HN-, 1 At least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b )- or -C(=N2)- substitution, or each R 3a R 3b They are not both hydrogen.

[0191] On one hand, this application provides a compound of general formula (III-F) or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0192] ,

[0193] The L x For L ax -L b -L c -;

[0194] The L ax -Selected from the following groups:

[0195] , ,and ;

[0196] Where R hal It is iodine or bromine;

[0197] Where W is -(C(R) wa (R) wb)) wn -, Y is -(OCH2CH2) yn -O yp Z is -(C(R) za (R) zb )) zn ,;

[0198] Where wn is selected from integers that are at least 0.

[0199] The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0200] Where yn is selected from integers that are at least 0, and yp is 0 or 1;

[0201] Where zn is selected from integers that are at least 0.

[0202] Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0203] -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace;

[0204] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or R r Optional substitution of C 1-6 Aliphatic groups;

[0205] Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0206] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0207] The -L c -Selected from the following groups:

[0208] , , , , , ,and ;

[0209] Where RL1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0210] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-;

[0211] X is -L 1 -CH2-C(O)-;

[0212] L 1 -(C(R) 3a (R) 3b )) m -, where L 1 The zero or at least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b - or -C(=N2)- substitution;

[0213] Each R 2 R 3a R 3b R 4b Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[0214] Where each R, R a R bEach can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0215] m is selected from an integer that is at least 0, and n is selected from an integer that is at least 1;

[0216] When R 1 When L is -O- or -HN-, 1 At least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b )- or -C(=N2)- substitution, or each R 3a R 3b They are not both hydrogen.

[0217] On one hand, this application provides a compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the ligand-drug conjugate comprises a structure comprising the following group:

[0218] (III-A-1) (III-A-2) (III-A-3), (III-A-4) (III-A-5) (III-A-6) (III-A-7) (III-A-8) (III-A-9) (III-A-10) (III-A-11) (III-A-12) (III-A-13) (III-A-14) (III-A-15) (III-A-16), and (III-A-17).

[0219] On the one hand, this application provides a method for preparing the compound of this application or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, comprising reacting a ligand Ab with a compound of formula (II-F) of this application. x The structure shown is contacted as indicated.

[0220] On the one hand, this application provides a method for preparing the compound of this application or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically usable salts thereof, comprising contacting the ligand Ab with the structure shown in formula (III-F) of this application.

[0221] On the one hand, this application provides a pharmaceutical composition comprising the compound of this application or its tautomers, mesosomes, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier.

[0222] On the one hand, this application provides the use of the compound of this application or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, and / or pharmaceutical compositions of this application in the preparation of medicaments for the treatment and / or prevention of tumors.

[0223] Other aspects and advantages of this application will readily be apparent to those skilled in the art from the detailed description below. Only exemplary embodiments of this application are shown and described in the following detailed description. As will be appreciated by those skilled in the art, the content of this application enables them to make modifications to the disclosed specific embodiments without departing from the spirit and scope of the invention to which this application pertains. Accordingly, the descriptions in the accompanying drawings and specification of this application are merely exemplary and not restrictive. Attached Figure Description

[0224] The features and advantages of the invention described in detail below, along with the accompanying drawings, will provide a better understanding of the specific embodiments and their accompanying drawings. A brief description of the drawings is as follows:

[0225] Figures 1-16 The images shown are graphs illustrating the in vivo tumor inhibition results of the compounds in this application. Detailed Implementation

[0226] The following specific embodiments illustrate the implementation of the invention. Those skilled in the art can easily understand other advantages and effects of the invention from the content disclosed in this specification.

[0227] Terminology Definition

[0228] In this application, the term "ligand" generally refers to a macromolecular compound that can recognize and bind to antigens or receptors associated with target cells. The role of a ligand can be to present a drug to a target cell population that has bound the ligand. These ligands include, but are not limited to, protein hormones, lectins, growth factors, antibodies, or other molecules that can bind to cells, receptors, and / or antigens. In this application, a ligand can be represented as Ab. The ligand antigen forms a linker bond with a linker unit through a heteroatom on the ligand. It can be an antibody or its antigen-binding fragment, and the antibody can be selected from chimeric antibodies, humanized antibodies, fully human antibodies, or murine antibodies; the antibody can be a monoclonal antibody. For example, the antibody can be an antibody targeting the following targets: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70, or EGFR. For example, the antibody may be an antibody targeting the following targets: 5T4, AGS-16, ANGPTL4, ApoE, CD19, CTGF, CXCR5, FGF2, MCPT8, MFI2, MS4A7, NCA, Sema5b, SLITRK6, STC2, TGF, 0772P, 5T4, ACTA2, ADGRE1, AG-7, AIF1, AKR1C1, AKR1C2, ASLG659, Axl, B7H3, BAFF-R , BCMA, BMPR1B, BNIP3, C1QA, C1QB, CA6, CADM1, CCD79b, CCL5, CCR5, CCR7, CD1lc, CD123, CD138, CD142, CD14 7. 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, CDllb, CEA, CEACAM5, c-Met, COL6A3, COL7A1, CRIPTO, CSF1R, CTSD, CTSS, CXCL11, CXCL10, DDIT4, DL L3, DLL4, DR5, E16, EFNA4, EGFR, EGFRvIII, EGLN, EGLN3, EMR2, ENPP3, EpCAM, EphA2, EphB2R, ETBR, FcRH2, F cRHl, 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, MMP 14, MMP16, MPF, MSG783, MSLN, MUC-1, NaPi2b, Napi3b, Nectin-4, Nectin-4, NOG, P2X5, pCAD, P-Cadherin, PDGFRA, PDK1, PD-L1, PFKFB3, PGF, PGK1, PIK3AP1, PIK3CD, PLOD2, PSCA, PSCAhlg, PSMA, PSMA, PTK7, P-cadherin, RNF43, NaPi2b, ROR1, ROR2, SERPINE1, SLC39A6, SLTRK6, STAT1, STEAP1, STEAP2, TCF4, TENB2, TGFB1, TGFB2, TGFBR1, TNFRSF21, TNFSF9, Trop-2, TrpM4, Tyro7, UPK1B, VEGFA, WNT5A, Epidermal Growth Factor, Short Proteoglycans, Mesothelin, Sodium Phosphate Cotransporter 2B, Sealin 18.2, Endothelial Peptide Receptor, Mucins (such as Mucin 1 and Mucin 16), Guanylate cyclase C, Integrin a4p7, Integrin a5p6, Trophoblast Cell Glycoproteins, or Tissue Factor.

[0229] In this application, the term "cytotoxic drug" generally refers to a toxic drug that possesses a strong chemical molecule within tumor cells that disrupts their normal growth. Cytotoxic drugs can kill tumor cells at sufficiently high concentrations. The "cytotoxic drug" may include toxins, such as small molecule toxins or enzyme-active toxins derived from bacteria, fungi, plants, or animals, and radioactive isotopes (e.g., At). 211 I 131 I 125 Y 90 Re 186 Re 188 、Sm 153 Bi 212 P 32Or radioactive isotopes of Lu), toxic drugs, chemotherapeutic drugs, antibiotics and ribolysins, for example, can be toxic drugs, including but not limited to camptothecin derivatives, for example, can be camptothecin derivative essanotecan (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).

[0230] In this application, the term "connector structure" generally refers to a chemical structural fragment or bond that is connected to a ligand at one end and to a cytotoxic drug at the other end. It may also refer to connecting other connectors before being connected to the cytotoxic drug. The direct or indirect connection to the ligand can mean that the group is directly connected to the ligand via a covalent bond, or it can mean that the ligand is connected via a connector structure. For example, the connector structure can be the -L described in this application. ax -L b -L c -and or -L a -L b -L c -The structure shown. For example, chemical structural fragments or bonds containing acid-labile linker structures (e.g., hydrazones), protease-sensitive (e.g., peptidase-sensitive) linker structures, light-labile linker structures, dimethyl linker structures, or disulfide linker structures can be used as linker structures.

[0231] In this application, the term "optionally linked to other molecular parts" generally means that the structure is not linked to any other chemical structure, or that the structure is linked to one or more other chemical structures different from the structure (e.g., ligands described in this application) (e.g., linked by chemical bonds or by a linker structure).

[0232] In this application, the term "ligand-drug conjugate" generally refers to a ligand linked to a biologically active cytotoxic drug via a stable linker unit. In this application, "ligand-drug conjugate" can be an antibody-drug conjugate (ADC), where an ADC refers to a monoclonal antibody or antibody fragment linked to a biologically active cytotoxic drug via a stable linker unit.

[0233] In this application, the term "antibody or antigen-binding fragment thereof" generally refers to an immunologically binding agent extending to all antibodies from all species, including dimer, trimer, and multimer antibodies; bispecific antibodies; chimeric antibodies; fully human antibodies; humanized antibodies; recombinant and modified antibodies, and fragments thereof. The term "antibody or fragment thereof" can refer to any antibody-like molecule having an antigen-binding region, including small molecule fragments such as Fab′, Fab, F(ab′)2, single-domain antibodies (DABs), Fv, scFv (single-chain Fv), linear antibodies, biantibodies, etc. The term "antigen-binding fragment" can refer to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. For example, fragments of full-length antibodies can be used to perform the antigen-binding function of an antibody. Techniques for preparing and using various antibody-based constructs and fragments are well known in the art. The antibodies may include: anti-HER2 (ErbB2) antibody, anti-EGFR antibody, anti-B7-H3 antibody, anti-c-Met antibody, anti-HER3 (ErbB3) antibody, anti-HER4 (ErbB4) antibody, anti-CD20 antibody, anti-CD22 antibody, anti-CD30 antibody, anti-CD33 antibody, anti-CD44 antibody, anti-CD56 antibody, anti-CD70 antibody, anti-CD73 antibody, anti-CD105 antibody, anti-CEA antibody, anti-A33 antibody, anti-Cripto antibody, anti-EphA2 antibody, anti-G250 antibody, anti-MUCl antibody, anti-Lewis Y antibody, anti-TROP2 antibody, and anti-Claudin antibody. 18.2 Antibody, anti-VEGFR antibody, anti-GPNMB antibody, anti-Integrin antibody, anti-PSMA antibody, anti-Tenascin-C antibody, anti-SLC44A4 antibody or anti-Mesothelin antibody, for example, trastuzumab or pertuzumab.

[0234] In this application, the term "chimeric antibody" generally refers to an antibody formed by fusing the variable region of a murine antibody with the constant region of a human antibody, which can alleviate the immune response induced by murine antibodies. To establish a chimeric antibody, a hybridoma that secretes murine-specific monoclonal antibodies can be created. The variable region gene can then be cloned from the murine hybridoma cells, and the constant region gene of a human antibody can be cloned as needed. The murine variable region gene and the human constant region gene can be linked to form a chimeric gene, which is then inserted into an expression vector. The chimeric antibody molecule can then be expressed in eukaryotic or prokaryotic systems.

[0235] In this application, the term "humanized antibody," also known as a CDR-grafted antibody, generally refers to an antibody generated by grafting a mouse CDR sequence into a human antibody variable region framework, i.e., an antibody generated within a different type of human germline antibody framework sequence. This can overcome the heterologous response induced by chimeric antibodies carrying a large amount of mouse protein components. Such framework sequences can be obtained from public DNA databases containing germline antibody gene sequences or from publicly available references. For example, germline DNA sequences of human heavy chain and light chain variable region genes can be found in the VBase human germline sequence database.

[0236] In this application, the terms "fully human antibody," "fully human antibody," or "completely human antibody," also known as "fully human monoclonal antibody," refer to antibodies whose variable and constant regions can both be human-derived, thus eliminating immunogenicity and toxic side effects. The development of monoclonal antibodies has gone through four stages: murine monoclonal antibodies, chimeric monoclonal antibodies, humanized monoclonal antibodies, and fully human monoclonal antibodies. The antibody or ligand described in this application can be a fully human monoclonal antibody. Related technologies for the preparation of fully human antibodies include: human hybridoma technology, EBV-transformed B lymphocyte technology, phage display technology, transgenic mouse antibody preparation technology, and single B cell antibody preparation technology, etc.

[0237] In this application, the term “CDR” generally refers to one of the six hypervariable regions within the variable domain of an antibody that primarily facilitate antigen binding. One of the most common definitions of the six CDRs is provided by Kabat EA 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 in this application, the Kabat definition of CDR can be applied to CDR1, CDR2, and CDR3 (CDR L1, CDR L2, CDR L3 or L1, L2, L3) of light chain variable structural domains, and CDR1, CDR2, and CDR3 (CDR H1, CDR H2, CDR H3 or H1, H2, H3) of heavy chain variable structural domains.

[0238] In this application, the term "methylene" generally refers to a residue derived from a group containing one carbon atom by removing two hydrogen atoms. The methylene group can be substituted or unsubstituted, substituted or non-substituted. The term "alkylene" generally refers to a saturated straight-chain or branched aliphatic hydrocarbon group having two residues derived from the removal of two hydrogen atoms from the same carbon atom or two different carbon atoms of a parent alkane. It can be a straight-chain or branched group containing 1 to 20 carbon atoms, for example, containing 1 to 12 carbon atoms, such as an alkylene group containing 1 to 6 carbon atoms. Non-limiting examples of alkylene groups include, but are not limited to, methylene (-CH2-), 1,1-ethylene (-CH(CH3)-), 1,2-ethylene (-CH2CH2)-, 1,1-propylene (-CH(CH2CH3)-), 1,2-propylene (-CH2CH(CH3)-), 1,3-propylene (-CH2CH2CH2-), 1,4-butylene (-CH2CH2CH2CH2-), and 1,5-butylene (-CH2CH2CH2CH2CH2-). The alkylene group can be substituted or unsubstituted, alternative or non-alternative. For example, when substituted, the substituent can be replaced at any usable connection point. The substituent is preferably independently selected independently from one or more substituents chosen from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocyclic, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, and oxo, for example, it can be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0239] In this application, the term "arylene" generally refers to a residue having two hydrogen atoms removed from the same carbon atom or two different carbon atoms of an aromatic ring. The term "aromatic ring" can refer to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (i.e., a ring sharing adjacent carbon atom pairs) having a conjugated π-electron system, and can be 6- to 10-membered, such as benzene and naphthalene. The aromatic ring can be fused to a heteroaryl, heterocyclic, or cycloalkyl ring, wherein the ring attached to the parent structure is an aryl ring. The aryl group can be substituted or unsubstituted, and when 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, hydroxyl, nitro, cyano, cycloalkyl, heterocyclic alkyl, aryl, heteroaryl, cycloalkoxy, heterocyclic alkoxy, cycloalkylthio, and heterocyclic alkylthio.

[0240] In this application, the term "hybrid aryl" generally refers to a residue having two hydrogen atoms removed from the same carbon atom or two different carbon atoms of a heteroaryl ring. The term "heteroaryl ring" refers to a heteroaryl 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. The heteroaryl group may be 5 to 10-membered, or 5- or 6-membered, such as furanyl, thiophene, pyridinyl, pyrroleyl, N-alkylpyrroleyl, pyrimidinyl, pyrazinyl, imidazolyl, tetrazolyl, etc. The heteroaryl ring may be fused to an aryl, heterocyclic, or cycloalkyl ring, wherein the ring connected to the parent structure is the heteroaryl ring. The heteroaryl group can be optionally substituted or unsubstituted. When 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, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, and heterocycloalkylthio.

[0241] In this application, the term "hypo-heterocyclic group" generally refers to a stable, non-aromatic 3-7 membered monocyclic structure, a fused 7-10 membered bicyclic heterocyclic structure, or a bridged 6-10 membered bicyclic heterocyclic structure. These cyclic structures can be saturated or partially saturated, and in addition to a carbon atom, they contain one or more heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen. For example, it may contain 1-4 heteroatoms as defined above. When used to refer to atoms on a heterocyclic structure, the term "nitrogen" can include nitrogen that has undergone a supersubstitution reaction. The hypo-heterocyclic group can be substituted or unsubstituted.

[0242] In this application, the term "carbocyclic group" generally refers to a residue having two hydrogen atoms removed from the same carbon atom or two different carbon atoms of a carbide ring. The term "carbide ring" generally refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon containing 3 to 20 carbon atoms, 3 to 12 carbon atoms, 3 to 10 carbon atoms, or 3 to 8 carbon atoms. Non-limiting examples of monocyclic carbocyclic rings include cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclohexadiene, cycloheptane, cycloheptanetriene, cyclooctane, etc.; polycyclic carbocyclic rings may include spirocyclic, fused, and bridged ring carbocyclic rings. The carbocyclic group can be substituted or unsubstituted.

[0243] In this application, the term "partially unsaturated" generally refers to a cyclic structure in which the cyclic molecules contain at least one double or triple bond. The term "partially unsaturated" encompasses cyclic structures with multiple unsaturations, but is not intended to include aromatic or heteroaromatic rings as defined in this application. The term "unsaturated" indicates that a portion has one or more degrees of unsaturation.

[0244] In this application, the term "halogen" generally refers to fluorine, chlorine, bromine, or iodine, for example, fluorine or chlorine.

[0245] In this application, the term "aliphatic group" generally refers to a straight-chain, branched, or cyclic hydrocarbon having 1-12 carbon atoms, which is either fully saturated or contains one or more unsaturated units, but the unsaturated units are not aromatic groups. For example, applicable aliphatic groups may include substituted or unsubstituted straight-chain, branched, or cyclic alkyl, alkenyl, ynyl, and mixtures of these groups; such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl. For example, aliphatic groups have 1-12, 1-8, 1-6, 1-4, or 1-3 carbon atoms.

[0246] In this application, the terms “optional” or “optionally” generally mean that the event or environment described below may but does not have to occur, and the description includes situations in which the event or environment occurs or does not occur. For example, “optionally alkyl-substituted heterocyclic group” means that an alkyl group may but does not have to be present, and the description can include cases where the heterocyclic group is substituted with an alkyl group and cases where the heterocyclic group is not substituted with an alkyl group.

[0247] In this application, the term "substituted" generally refers to one or more hydrogen atoms in a group, for example, up to five, or for example, one to three hydrogen atoms, independently substituted by the corresponding number of substituents. Substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without much effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when bonded to a carbon atom with an unsaturated bond (such as an alkene).

[0248] In this application, the term "replaced" for zero or more (e.g., zero or at least one, zero or one, zero) methylene units generally means that when the structure contains one or more methylene units, the one or more methylene units may not be replaced, or may be 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-, -SO2-, -PH-, -P(=O)H-, -NHSO2-, -SO2NH-, -C(=S)-, -C(=NH)-, -N=N-, -C=N-, -N=C- or -C(=N2)-).

[0249] One or more hydrogen atoms in a group, for example, up to five, or for example, one to three hydrogen atoms, are independently replaced by the corresponding number of substituents. The substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without much effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when bonded to a carbon atom with an unsaturated bond (such as an alkene).

[0250] In this application, the term "compound" generally refers to a substance having two or more different elements. For example, the compound in this application can be an organic compound, a compound with a molecular weight of less than 500, less than 1000, more than 1000, or more than 10,000 or 100,000. In this application, a compound can also refer to a compound linked by chemical bonds. For example, it can be a compound in which one or more molecules with a molecular weight of less than 1000 are linked by chemical bonds to a biological macromolecule, such as a polysaccharide, protein, nucleic acid, polypeptide, etc. For example, the compound in this application can include a compound in which a protein is linked to one or more molecules with a molecular weight of less than 1000, a compound in which a protein is linked to one or more molecules with a molecular weight of less than 10,000, or a compound in which a protein is linked to one or more molecules with a molecular weight of less than 100,000.

[0251] Unless otherwise specified, the structures described in this application may also include compounds that differ only in the presence or absence of one or more isotopically enriched atoms. For example, compounds whose structures are identical to those of this application except that hydrogen atoms are replaced by deuterium or tritium, or carbon atoms are replaced by carbon-13 or carbon-14, are within the scope of this application.

[0252] In this application, the term "pharmaceutical composition" generally refers to a mixture containing one or more of the compounds described in this application or their physiologically / pharmacologically acceptable salts or prodrugs, along with other chemical components, such as physiologically / pharmacologically acceptable carriers and excipients. Pharmaceutical compositions can facilitate administration to organisms, promote the absorption of the active ingredient, and thereby exert its biological activity. Conventional methods for preparing pharmaceutical compositions can be found in the Chinese Pharmacopoeia.

[0253] In this application, the terms "pharmaceutically acceptable salt" or "medicinal salt" generally refer to salts of compounds or ligand-drug conjugates of this application, or salts of compounds described in this application, which are safe and / or effective when used in mammals and have the desired biological activity. The antibody-antibody-drug conjugates of this application can form salts with acids. Non-limiting examples of pharmaceutically acceptable salts include: hydrochloride, hydrobromide, hydroiodide, sulfate, hydrogen sulfate, citrate, acetate, succinate, ascorbate, oxalate, nitrate, sorbate, hydrogen phosphate, dihydrogen phosphate, salicylate, hydrogen citrate, tartrate, maleate, fumarate, formate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, and p-toluenesulfonate.

[0254] In this application, the terms "solvent" or "solvent compound" generally refer to the ligand-drug conjugate of this application forming a pharmaceutically usable solvate with one or more solvent molecules, non-limiting examples of which include water, ethanol, acetonitrile, isopropanol, DMSO, and ethyl acetate.

[0255] The term "drug loading" typically refers to the average amount of cytotoxic drug loaded onto each ligand, or it can be expressed as the ratio of cytotoxic drug to antibody. The range of cytotoxic drug loading can be 0-12 cytotoxic drugs per ligand (Ab), for example, 1-10 cytotoxic drugs. In the embodiments of this application, drug loading is expressed as N. a Examples can be the average of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. The drug loading of each ADC molecule after the coupling reaction can be identified using conventional methods such as UV / visible spectroscopy, mass spectrometry, ELISA, and HPLC characterization.

[0256] The pharmaceutical composition may be in the form of a sterile injectable aqueous or oil suspension for intramuscular and subcutaneous administration. This suspension may be formulated using suitable dispersants or wetting agents and suspending agents as described above, according to known techniques. The sterile injectable formulation may also be a sterile injectable solution or suspension prepared in a non-toxic, parenteral-acceptable diluent or solvent, such as a solution prepared in 1,3-butanediol. Furthermore, a sterile fixative oil may be conveniently used as a solvent or suspension medium. For example, any blended fixative oil, including synthetic mono- or diglycerides of glycerol, may be used. Additionally, fatty acids such as oleic acid may also be used to prepare the injectable formulation.

[0257] In this application, the term "comprising" generally means including the explicitly specified features, but does not exclude other elements. The terms "above" and "below" generally refer to situations that include the stated number.

[0258] In this application, the term "about" generally refers to a variation within a range of 0.5% to 10% above or below a specified value, such as a variation within a range of 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% above or below a specified value. Invention Details

[0260] In a first aspect, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (IA):

[0261]

[0262] Where R 1 It can be selected from the following groups: -O-, -(R 2 )N-,-P(=O)(R 2 )-, and -S-;

[0263] L 2 It can be -(C(R) 3a (R) 3b )) m -R, m can be selected from integers greater than 1;

[0264] Where L 2 Zero or more methylene units can be independently converted by -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0265] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be selected from integers greater than 1;

[0266] Where L 1Zero or more methylene units can be independently converted by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0267] -Cy- can be selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic groups, wherein -Cy- is unsubstituted or can be independently substituted by one or more substituents R. 7 replace;

[0268] Each R 3a R 3b R 4 R 5a R 5b R 6 Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each, independently and optionally together with the atoms between them, can form a ring B, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R.8 replace;

[0269] Each R 2 R 7 R 8 Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0270] Where each R, R a R b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0271] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (IA):

[0272]

[0273] Where R 1 It can be selected from the following groups: -O-, -(R 2 )N-,-P(=O)(R 2 )-, and -S-;

[0274] L 2 It can be -(C(R) 3a (R) 3b )) m -R, m can be selected from integers greater than 1;

[0275] Where L 2 Zero or more methylene units can be independently converted by -Cy-, -N(R) 4)C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0276] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be selected from integers greater than 1;

[0277] Where L 1 Zero or more methylene units can be independently converted by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0278] -Cy- can be selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic groups, wherein -Cy- is unsubstituted or can be independently substituted by one or more substituents R. 7 replace;

[0279] Each R 3a R 3b R 4 R 5a R 5b R 6 Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0280] Each R 2 R 7 R 8 Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0281] Where each R, R a R b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0282] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (IA).

[0283] For example, where R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6Each, independently and optionally together with the atoms between them, can form a ring B, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 Replace, each R 3a R 3b R 4 R 5a R 5b R 6 Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each, independently and optionally together with the atoms between them, can form a ring B, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 replace;

[0284] For example, where R 3a With R 5a Together with the atoms between them, a ring B can be formed, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 Replace, each R 3b R 4 R 5b R 6 Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each, independently and optionally together with the atoms between them, can form a ring B, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 replace;

[0285] For example, where R 4 With R 5a Together with the atoms between them, a ring B can be formed, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 Replace, each R 3a R 3b R 5b R 6 Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6Each, independently and optionally together with the atoms between them, can form a ring B, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 replace;

[0286] For example, where R 3a With R 6 Together with the atoms between them, a ring B can be formed, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 Replace, each R 3b R 4 R 5a R 5b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each, independently and optionally together with the atoms between them, can form a ring B, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 replace;

[0287] For example, where R 4 With R 6 Each, independently and optionally together with the atoms between them, can form a ring B, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 Replace, each R 3a R 3b R5a R 5b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each, independently and optionally together with the atoms between them, can form a ring B, which can be selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or can be substituented by more than one R. 8 replace;

[0288] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (IA):

[0289]

[0290] Where R 1 It can be -O-;

[0291] L 2 It can be -(C(R) 3a (R) 3b )) m -R, m can be selected from integers from 1 to 3;

[0292] Where L 2 The 0 methylene units can be replaced;

[0293] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be an integer from 2 to 4;

[0294] Where L 1 The 0, 1, or 2 methylene units can be -N(R) 6 )C(O)-, -C(O)-, -OC(O)-, -NR 6 -, -O-, or -C(=S)- can be substituted;

[0295] Each R 3a R 3b R 5a R 5b R 6 Each can be independently hydrogen, halogen, or C that can be optionally substituted by R. 1-6 Aliphatic groups, or R 3a With R 5a Together with the atoms between them, they can form a ring B, which can be selected from a 5-membered saturated hypoheterocyclic group, wherein the ring B is unsubstituted.

[0296] R can be hydrogen or halogen.

[0297] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (IA):

[0298]

[0299] Where R 1 It can be -O-;

[0300] L 2 It can be -(C(R) 3a (R) 3b )) m -R, m can be an integer selected from 1 or 2;

[0301] Where L 2 The 0 methylene units can be replaced;

[0302] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be an integer selected from 2 or 3;

[0303] Where L 1 One or two methylene units can be replaced by -C(O)-;

[0304] Each R 3a R 3b R 5a R 5b Each can be independently hydrogen, or R3a With R 5a Together with the atoms between them, they can form a ring B, which can be selected from a 5-membered saturated subheterocyclic group having one nitrogen atom, wherein the ring B is unsubstituted.

[0305] R can be hydrogen.

[0306] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (IA):

[0307]

[0308] Where R 1 It can be -O-;

[0309] L 2 It can be -(C(R) 3a (R) 3b )) m -R, m can be an integer selected from 1 or 2;

[0310] Where L 2 The 0 methylene units can be replaced;

[0311] L 1 It can be -(C(R) 5a (R) 5b ))2-;

[0312] Where L 1 One methylene unit can be replaced by -C(O)-;

[0313] Each R 3a R 3b R 5a R 5b Each can be independently hydrogen, or R 3a With R 5a Together with the atoms between them, they can form a ring B, which can be selected from a 5-membered saturated subheterocyclic group having one nitrogen atom, wherein the ring B is unsubstituted.

[0314] R can be hydrogen.

[0315] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure from the group consisting of:

[0316] (IA-1) (IA-2) (IA-3) (IA-4) (IA-5)

[0317] (IA-6) (IA-7) (IA-8) (IA-9) (IA-10) (IA-11) (IA-12) (IA-13) (IA-14) (IA-15) (IA-16) (IA-17)

[0318] Where R 1 It can be selected from the following groups: -O-, -HN-, -P(=O)H-, and -S-.

[0319] In another embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (II-A):

[0320]

[0321] Where X 1 It can be selected from the following group: N, P, and saturated or unsaturated C, when X 1 When C can be saturated, X 1 It can be R n Substitution; the ring A optionally connects the structure shown in formula (II-A) to other molecular moieties;

[0322] When X 1 When the C group is saturated, ring A can be selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A can be substituted with 0 or more R groups. 1a replace;

[0323] Or, when X 1When the carbon atom is unsaturated, ring A can be selected from the group consisting of 6- to 10-membered aryl groups, 5- to 8-membered heteroaryl groups, 3- to 10-membered partially unsaturated heterocyclic groups, and 3- to 10-membered partially unsaturated carbocyclic groups, wherein ring A can be substituted with 0 or more R groups. 1b replace;

[0324] Or, when X 1 When it can be N or P, ring A can be selected from the group consisting of 5 to 8-membered heteroaryl groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein ring A can be 0 or 1 or more substituents R. 1c replace;

[0325] When ring A can be selected from the group consisting of 6 to 10 aryl groups, 5 to 8 heteroaryl groups, and 3 to 10 saturated or partially unsaturated carbocyclic groups, ring A can be p L 2 Instead, the L 2 It cannot be R n ;

[0326] Alternatively, when ring A can be a 3- to 10-membered saturated or partially unsaturated heterocyclic group, ring A can be p L-membered heterocyclic groups. 2 Substitution, or the ring A may contain q cyclic heteroatoms X 2 And the X 2 Used to connect the structure shown in formula (II-A) with other molecular parts;

[0327] X 2 It can be selected from the following groups: N, and P;

[0328] L 2 It can be -R 2 -L 3 -, the R 2 Used to connect the structure shown in formula (II-A) with other molecular parts;

[0329] L 3 It can be -(C(R) 3a (R) 3b )) m -, where L 3 When it may contain a methylene unit, the L 3 Zero or more methylene units can be independently converted by -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4)-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0330] R 2 It can be selected from the following groups: -O-, -(R 2a -N-, -S-, and -P(=O)(R 2a )-;

[0331] L 1 It can be -(C(R) 5a (R) 5b )) n -, where L 1 When it may contain a methylene unit, the L 1 Zero or more methylene units can be independently converted by -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0332] Each R 1a R 1b R 1c R 2a R 3a R 3b R 4 R 5a R 5b R 6 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b-OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0333] Where each R, R a R b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0334] m and n can each be independently selected from integers greater than 0, and p and q can each be independently selected from integers greater than 1.

[0335] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (II-Ax):

[0336]

[0337] X 1 The X can be saturated C. 1 It can be R n replace;

[0338] Ring A may be selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A may be substituted with 0 or more substituents R. 1a replace;

[0339] The ring A can be p L. 2 Replacement, p can be selected from integers greater than 1, the L 2 It cannot be R n ;

[0340] L 2 It can be -R 2 -L 3 -;

[0341] L 3 It can be -(C(R) 3a (R) 3b )) m -, m can be selected from integers greater than or equal to 0.

[0342] Where L 3When it may contain a methylene unit, the L 3 Zero or more methylene units can be independently converted by -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0343] R 2 It can be selected from the following groups: -O-, -(R 2a -N-, -S-, and -P(=O)(R 2a )-;

[0344] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be selected from integers greater than or equal to 0.

[0345] Where L 1 When it may contain a methylene unit, the L 1 Zero or more methylene units can be independently converted by -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0346] Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R6 R n Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0347] Where each R, R a R b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0348] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (II-Ay):

[0349]

[0350] X 1 The X can be saturated C. 1 It can be R n replace;

[0351] Ring A can be a 3- to 10-membered saturated or partially unsaturated heterocyclic group, wherein ring A can be either unsubstituted or can be substituted by one or more substituents R. 1a replace;

[0352] The ring A may contain q cyclic heteroatoms X. 2 And the X 2 Used for direct or indirect ligand connection; q can be selected from integers greater than 1, X 2 It can be selected from the following groups: N, and P;

[0353] L 1 It can be -(C(R) 5a(R) 5b )) n -, n can be selected from integers greater than or equal to 0.

[0354] Where L 1 Zero or more methylene units can be independently converted by -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0355] Each R 1a R 5a R 5b R 6 R n Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0356] Where each R, R a R b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0357] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (II-Ax):

[0358]

[0359] X 1 It can be unsaturated C;

[0360] Ring A may be selected from the group consisting of 6- to 10-membered aryl groups, 5- to 8-membered heteroaryl groups, 3- to 10-membered partially unsaturated heterocyclic groups, and 3- to 10-membered partially unsaturated carbocyclic groups, wherein ring A is either unsubstituted or can be substituted by one or more substituents R. 1b replace;

[0361] The ring A can be p L. 2 Replacement, where p can be selected from integers greater than 1;

[0362] L 2 It can be -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0363] L 3 It can be -(C(R) 3a (R) 3b )) m -, m can be selected from integers greater than or equal to 0.

[0364] Where L 3 Zero or more methylene units can be independently converted by -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0365] R 2 It can be selected from the following groups: -O-, -(R 2a -N-, -S-, and -P(=O)(R 2a )-;

[0366] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be selected from integers greater than or equal to 0.

[0367] Where L 1 Zero or more methylene units can be independently converted by -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0368] Each R 1b R 2a R 3a R 3b R 4 R 5a R 5b R 6 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0369] Where each R, R a R bEach can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0370] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (II-Ay):

[0371]

[0372] X 1 It can be unsaturated C.

[0373] Ring A can be a 3- to 10-membered partially unsaturated heterocyclic group, wherein ring A is either unsubstituted or can be substituted by one or more substituents R. 1b replace;

[0374] The ring A may contain q cyclic heteroatoms X. 2 And the X 2 Used for direct or indirect ligand connection; q can be selected from integers greater than 1, X 2 It can be selected from the following groups: N, and P;

[0375] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be selected from integers greater than or equal to 0.

[0376] Where L 1 Zero or more methylene units can be independently converted by -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0377] Each R 1b R 5a R 5b R 6 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0378] Where each R, R a R b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0379] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (II-Ax):

[0380]

[0381] X 1 It can be N or P;

[0382] Ring A may be selected from the group consisting of 5- to 8-membered heteroaryl groups and 3- to 10-membered saturated or partially unsaturated heterocyclic groups, wherein ring A may not be substituted or may be substituted by one or more substituents R. 1c replace;

[0383] The ring A can be p L. 2 Replacement, where p can be selected from integers greater than 1;

[0384] L 2 It can be -R 2 -L 3 -, the R2 Used for direct or indirect ligand connection;

[0385] L 3 It can be -(C(R) 3a (R) 3b )) m -, m can be selected from integers greater than or equal to 0.

[0386] Where L 3 Zero or more methylene units can be independently converted by -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0387] R 2 It can be selected from the following groups: -O-, -(R 2a -N-, -S-, and -P(=O)(R 2a )-;

[0388] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be selected from integers greater than or equal to 0.

[0389] Where L 1 Zero or more methylene units can be independently converted by -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0390] Each R 1c R 2a R 3a R 3b R 4 R 5a R 5b R 6 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0391] Where each R, R a R b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0392] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (II-Ay):

[0393]

[0394] X 1 It can be N or P;

[0395] Ring A can be a 3- to 10-membered saturated or partially unsaturated heterocyclic group, wherein ring A can be either unsubstituted or can be substituted by one or more substituents R. 1c replace;

[0396] The ring A may contain q cyclic heteroatoms X. 2 And the X 2 Used for direct or indirect ligand connection; q can be selected from integers greater than 1, X 2 It can be selected from the following groups: N, and P;

[0397] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be selected from integers greater than or equal to 0.

[0398] Where L 1 Zero or more methylene units can be independently converted by -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0399] Each R 1c R 5a R 5b R 6 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0400] Where each R, R a R b Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0401] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (II-Ax):

[0402]

[0403] X 1 The X can be saturated C. 1 It can be R n replace;

[0404] Ring A can be selected from the following group: 3 to 6 saturated heterocyclic groups, and 3 to 6 saturated or partially unsaturated carbocyclic groups;

[0405] p can be 1, and the L 2 It cannot be R n ;

[0406] L 2 It can be -R 2 -L 3 -;

[0407] L 3 It can be -(C(R) 3a (R) 3b )) m -, m can be selected from integers from 0 to 2, where when L 3 When it may contain a methylene unit, the L 3 One or two methylene units can be replaced by -C(O)- or -C(=S)-;

[0408] R 2 It can be selected from -O-;

[0409] L 1 It can be -(C(R) 5a (R) 5b )) n - n can be selected from 0 or 1;

[0410] Where L 1 When it may contain a methylene unit, the L 1 One or two methylene units can be replaced by -C(O)- or -C(=S)-;

[0411] Each R 3a R 3b R 5a R 5b R n Each can be hydrogen, halogen, or C that can be optionally substituted by R. 1-6Aliphatic groups;

[0412] Each R can be either hydrogen or halogen.

[0413] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (II-Ax):

[0414]

[0415] X 1 It can be saturated C and the X 1 Connect R n The R n It can be H;

[0416] Ring A can be selected from the following group: 5-membered saturated heterocyclic groups with 1 nitrogen heteroatom, and 4- to 6-membered saturated carbocyclic groups;

[0417] p can be 1;

[0418] L 2 It can be -R 2 -L 3 -, the L 3 Directly connected to ring A;

[0419] L 3 It can be -(C(R) 3a (R) 3b )) m -, m can be 0 or 2;

[0420] R 2 It can be -O-;

[0421] L 1 It can be -C(O)-;

[0422] Each R 3a R 3b Each can be hydrogen on its own.

[0423] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (II-Ay):

[0424]

[0425] X 1 The X can be saturated C. 1 It can be Rn replace;

[0426] Ring A can be a 3- to 6-membered saturated heterocyclic group;

[0427] The ring A may contain one cyclic heteroatom N, and the N is used to directly or indirectly connect to a ligand;

[0428] L 1 It can be -(C(R) 5a (R) 5b )) n -, n can be selected from 0 or 1;

[0429] Where L 1 One or two methylene units can be replaced by -C(O)- or -C(=S)-;

[0430] Each R 5a R 5b R n Each can be hydrogen, halogen, or C that can be optionally substituted by R. 1-6 Aliphatic groups;

[0431] Each R can be either hydrogen or halogen.

[0432] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (II-Ay):

[0433]

[0434] X 1 The X can be saturated C. 1 It can be replaced by H;

[0435] Ring A can be a 5-membered saturated heterocyclic group with one N heteroatom;

[0436] The ring A may contain one cyclic heteroatom N, and the N is used to directly or indirectly connect to a ligand;

[0437] L 1 It can be -C(O)-.

[0438] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (II-Ax):

[0439]

[0440] X 1 It can be unsaturated C;

[0441] Ring A may be selected from the group consisting of: 6-membered aryl, 5- to 8-membered heteroaryl, 3- to 10-membered partially unsaturated heterocyclic groups, and 3- to 10-membered partially unsaturated carbocyclic groups, wherein ring A is either unsubstituted or independently substituted by one substituent R. 1b replace;

[0442] p can be 1;

[0443] L 2 It can be -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0444] L 3 It can be -C(R) 3a (R) 3b )-;

[0445] R 2 Can be selected from -O-, -(R 2a )N-, or -S-;

[0446] L 1 It can be -C(R) 5a (R) 5b )-;

[0447] Where L 1 One or two methylene units can be replaced by -C(O)- or -C(=S)-;

[0448] Each R 1b R 2a R 3a R 3b R 5a R 5b Each can be hydrogen, halogen, or C that can be optionally substituted by R. 1-6 Aliphatic groups;

[0449] Each R can be either hydrogen or halogen.

[0450] For example, the compound may comprise the structure shown in formula (II-Ax):

[0451] X 1 It can be unsaturated C;

[0452] Ring A can be selected from the group consisting of 6-membered aryl and 5 to 8-membered heteroaryl;

[0453] p can be 1;

[0454] L 2 It can be -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0455] L 3 It can be -C(R) 3a (R) 3b )-;

[0456] R 2 Can be selected from -O-, -(R 2a )N-, or -S-;

[0457] L 1 It can be -C(R) 5a (R) 5b )-;

[0458] Where L 1 One or two methylene units can be replaced by -C(O)- or -C(=S)-;

[0459] Each R 2a R 3a R 3b R 5a R 5b Each can be hydrogen, halogen, or C that can be optionally substituted by R. 1-6 Aliphatic groups;

[0460] Each R can be either hydrogen or halogen.

[0461] For example, the compound may comprise the structure shown in formula (II-Ax):

[0462] X 1 It can be unsaturated C;

[0463] Ring A can be a 6-membered aryl group;

[0464] p can be 1;

[0465] L 2 It can be -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0466] L 3 It can be -C(R) 3a (R) 3b )-;

[0467] R 2 It can be -O-;

[0468] L 1 It can be -C(O)-;

[0469] Each R 3a R 3b R 5a R 5b Each can be either hydrogen or C. 1-6 Aliphatic groups.

[0470] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (II-Ay):

[0471] X 1 It can be unsaturated C.

[0472] Ring A can be a 5-membered partially unsaturated heterocyclic group;

[0473] The ring A may contain one cyclic heteroatom N, and the N is used to directly or indirectly connect to a ligand;

[0474] L 1 It can be -C(R) 5a (R) 5b ),

[0475] Where L 1 One or two methylene units can be replaced by -C(O)- or -C(=S)-;

[0476] Each R 5a R 5b Each can be hydrogen, halogen, or C that can be optionally substituted by R. 1-6 Aliphatic groups;

[0477] Each R can be hydrogen or halogen independently.

[0478] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (II-Ax):

[0479] X 1 It can be N;

[0480] Ring A can be a 6-membered saturated heterocyclic group;

[0481] p can be 1;

[0482] L 2 It can be -R2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[0483] L 3 It can be -(C(R) 3a (R) 3b )) m -, m can be 1 or 2

[0484] Where L 3 One or two methylene units can be replaced by -C(O)- or -C(=S)-;

[0485] R 2 It can be selected from the following groups: -O-, -(R 2a N- and -S-;

[0486] L 1 It can be -C(R) 5a (R) 5b )-,

[0487] Where L 1 One methylene unit can be replaced by -C(O)- or -C(=S)-;

[0488] Each R 2a R 3a R 3b R 5a R 5b Each can be hydrogen, halogen, or C that can be optionally substituted by R. 1-6 Aliphatic groups;

[0489] Each R can be either hydrogen or halogen.

[0490] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (II-Ay):

[0491] X 1 It can be N,

[0492] Ring A can be a 5-membered partially unsaturated heterocyclic group;

[0493] The ring A may contain one cyclic heteroatom N, and the N is used to directly or indirectly connect to a ligand;

[0494] L 1 It can be -C(R) 5a (R) 5b ),

[0495] Where L 1 One or more methylene units can be replaced by -C(O)- or -C(=S)-;

[0496] Each R 5a R 5b Each can be hydrogen, halogen, or C that can be optionally substituted by R. 1-6 Aliphatic groups;

[0497] Each R can be hydrogen or halogen independently.

[0498] In one embodiment, this application provides a compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise a structure of the group consisting of:

[0499] (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)

[0500] (II-A-11) (II-A-12)

[0501] Where R 2 It can be selected from the following groups: -O-, -HN-, -P(=O)H-, and -S-.

[0502] In another embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0503]

[0504] Where R 1 It can be selected from the following groups: -O-, -(R 2 )N-,-P(=O)(R 2 )-, and -S-;

[0505] X can be selected from the following group: -L1 -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 -;

[0506] L 1 It can be -(C(R) 3a (R) 3b )) m -, where L 1 When it may contain a methylene unit, the L 1 The zero or one or more methylene units can be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 4b - or -C(=N2)- substitution;

[0507] L 0 It can be -C(R) 2a (R) 2b )-, or L 0 It can be -C(=S)- or -C(=NR) 4a - or -C(=N2)-;

[0508] L 2 It can be -C(R) 5a (R) 5b )-, where L 2 The 0 or 1 methylene unit can be -N(R 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 Substitute with -, -N=N-, -C=N-, -N=C-, or -C(=N2)-.

[0509] L 3 It can be -(C(R) 7a (R) 7b )) n -, where L 3One or more methylene units can be independently converted by -N(R) 8 )C(O)-、-C(O)N(R 8 -, -OC(O)-, -C(O)O-, -NR 8 -, -O-, -S-, -SO-, -SO2-, -P(R 8 )-、-P(=O)(R 8 )-、-N(R 8 SO2-, -SO2N(R) 8 Substitute with -, -N=N-, -C=N-, or -N=C-, while L 3 The zero or one or more methylene units can also be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 8 - or -C(=N2)- substitution;

[0510] Each R 1a R 1b R 2 R 2a R 2b R 3a R 3b R 4a R 4b R 5a R 5b R 6 R 7a R 7b R 8 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0511] Where each R, R a R bEach independently may be hydrogen, protium, deuterium, tritium, a halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 an aliphatic group;

[0512] m may be selected from integers of 0 or more, and n may be selected from integers of 1 or more;

[0513] When R 1 may be -O- or -HN-, and X may be -L 1 -CH2-C(O)-, where when L 1 may contain methylene units, each of the L 1 methylene units may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b )-, or -C(=N2)-, or in each -C(R 1 )(R 3a )(R 3b )- of L 3a R 3b and R

[0514] When R 1 may be -HN-, and X may be -L 1 -L 0 -, and L 0 may be -CH2-, each of the L 1 methylene units may be independently replaced by -C(O)-, -C(=S)-, -C(=NR 4b )-, or -C(=N2)-, or each R<00​​​​​​​​​​​​​​​​​​​​​​​​​​)C(O)-, -OC(O)-, -C(O)O-, -S-, -SO-, -SO2-, -P(R 8 )-、-P(=O)(R 8 )-、-N(R 8 SO2-, -SO2N(R) 8 -, -N=N-, -C=N-, or -N=C- can be substituted.

[0517] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0518]

[0519] Where R 1 It can be selected from the following groups: -O-, -(R 2 N- and -S-;

[0520] X can be -L 1 -C(R 1a (R) 1b )-C(S)-;

[0521] L 1 It can be -(C(R) 3a (R) 3b )) m -, m can be selected from integers greater than or equal to 0;

[0522] Where L 1 The zero or one or more methylene units can be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 4b - or -C(=N2)- substitution;

[0523] R 2 It can be halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0524] Each R1a R 1b R 3a R 3b R 4b Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0525] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0526] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0527]

[0528] R 1 It can be -S- or -(R) 2 )N-;

[0529] X can be -L 1 -C(R 1a (R) 1b )-C(O)-;

[0530] L 1 It can be -(C(R) 3a (R) 3b )) m -, m can be selected from integers greater than or equal to 0;

[0531] Where L 1The zero or one or more methylene units can be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 4b - or -C(=N2)- substitution;

[0532] R 2 It can be halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0533] Each R 1a R 1b R 3a R 3b R 4b Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0534] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0535] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0536]

[0537] Where R 1 It can be -O- or -HN-.

[0538] X can be -L 1 -CH2-C(O)-;

[0539] L 1 It can be -(C(R) 3a (R) 3b )) m - m can be selected from integers greater than 1;

[0540] Where L 1 One or more methylene units can be independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b - or -C(=N2)- substitution;

[0541] Each R 3a R 3b R 4b Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0542] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0543] In one embodiment, the present application provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0544]

[0545] where R 1 may be -O- or -HN-,

[0546] X may be -L 1 -CH2-C(O)-;

[0547] L 1 may be -(C(R 3a )(R 3b )) m -, m may be selected from integers greater than or equal to 0;

[0548] In each -C(R 3a )(R 3b )-, R 3a , R 3b are not simultaneously hydrogen, or one or more methylene units of L 1 may each independently be replaced by -C(O)-, -C(=S)-, -C(=NR 4b )- or -C(=N2)-;

[0549] where each R 3a , R 3b , R 4b are each independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R a )(R b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a )(R b ), -SO2N(R a )(R b ), -OC(O)R, -N(R)SO2R, or an aliphatic group optionally substituted by R 1-6 ;

[0550] where each R, R a , R bEach can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0551] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0552]

[0553] Where R 1 It can be -O-, -S-, or -(R) 2 )N-,

[0554] X can be -L 1 -L 0 -;

[0555] L 0 It can be -C(R) 2a (R) 2b )-, or L 0 It can be -C(=S)- or -C(=NR) 4a - or -C(=N2)-;

[0556] L 1 It can be -(C(R) 3a (R) 3b )) m -, m can be selected from integers greater than or equal to 0;

[0557] Where L 1 The zero or one or more methylene units can be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 4b - or -C(=N2)- substitution;

[0558] R 2 It can be halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a(R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0559] Each R 2a R 2b R 3a R 3b R 4a R 4b Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0560] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0561] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0562]

[0563] Where R 1 It can be -HN-,

[0564] X can be -L 1 -L 0 -;

[0565] L 0 It can be -C(R) 2a (R) 2b )-, or L0 It can be -C(=S)- or -C(=NR) 4a - or -C(=N2)-;

[0566] L 1 It can be -(C(R) 3a (R) 3b )) m -, m can be selected from integers greater than 0, each R 3a R 3b It can be hydrogen at different times;

[0567] Where L 1 The zero or one or more methylene units can be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 4b - or -C(=N2)- substitution;

[0568] Each R 2a R 2b R 3a R 3b R 4a R 4b Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0569] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0570] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0571]

[0572] Where X can be -L 3 -L 2 -,

[0573] L 2 It can be -C(R) 5a (R) 5b )-, where L 2 The 0 or 1 methylene unit can be -N(R 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 Substitute with -, -N=N-, -C=N-, -N=C-, or -C(=N2)-.

[0574] R 1 It can be -S- or -(R) 2 )N-, or R 1 It can be -O- and L 2 It cannot be -C(O)-, or R 1 It can be -NH- and L 2 It cannot be -C(O)-;

[0575] L 3 It can be -(C(R) 7a (R) 7b )) n -, n can be selected from integers greater than 1;

[0576] Where L 3 One or more methylene units can be independently converted by -N(R) 8 )C(O)-、-C(O)N(R 8 -, -OC(O)-, -C(O)O-, -NR 8 -, -O-, -S-, -SO-, -SO2-, -P(R8 )-、-P(=O)(R 8 )-、-N(R 8 SO2-, -SO2N(R) 8 Substitute with -, -N=N-, -C=N-, or -N=C-, while L 3 The zero or one or more methylene units can also be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 8 - or -C(=N2)- substitution;

[0577] R 2 It can be halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0578] Each R 5a R 5b R 6 R 7a R 7b R 8 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0579] Where each R, R a R bEach can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0580] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0581]

[0582] Where R 1 It can be -O-,

[0583] X can be -L 3 -L 2 -,;

[0584] Where L 2 It can be -C(O)-;

[0585] L 3 It can be -(C(R) 7a (R) 7b )) n -, n can be selected from integers greater than or equal to 0;

[0586] Where L 3 One or more methylene units can be independently converted by -N(R) 8 )C(O)-、-C(O)N(R 8 -, -OC(O)-, -C(O)O-, -NR 8 -, -O-, -S-, -SO-, -SO2-, -P(R 8 )-、-P(=O)(R 8 )-、-N(R 8 SO2-, -SO2N(R) 8 Substitute with -, -N=N-, -C=N-, or -N=C-, while L 3 The zero or one or more methylene units can also be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 8 - or -C(=N2)- substitution;

[0587] Each R 7a R 7b R8 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0588] Where R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups,

[0589] When L 3 One methylene unit can be -NR 8 When replaced, the R 8 It cannot be C that can be replaced by -NH2. 1-6 Aliphatic groups.

[0590] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0591]

[0592] Chinese R 1 It can be -HN-,

[0593] X can be -L 3 -L 2 -;

[0594] Where L 2 It can be -C(O)-,

[0595] L 3 It can be -(C(R) 7a (R) 7b )) n-, n can be selected from integers greater than 1;

[0596] The L 3 One or more methylene units can be -N(R) 8 )C(O)-, -OC(O)-, -C(O)O-, -S-, -SO-, -SO2-, -P(R 8 )-、-P(=O)(R 8 )-、-N(R 8 SO2-, -SO2N(R) 8 Substitute L with -, -N=N-, -C=N-, or -N=C-, where L 3 The zero or one or more methylene units can each be independently converted to -C(O)N(R) 8 )-、-NR 8 - or -O- can be used as a substitute, while L 3 The zero or one or more methylene units can also be independently converted by -C(O)-, -C(=S)-, -C(=NR)-. 8 - or -C(=N2)- substitution;

[0597] Each R 7a R 7b R 8 Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C that can be optionally replaced by R 1-6 Aliphatic groups;

[0598] Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0599] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0600]

[0601] R 1 It can be -O-, -S-, or -(R) 2 )N-;

[0602] X can be -L 1 -C(R 1a (R) 1b )-C(S)-;

[0603] L 1 It can be -(C(R) 3a (R) 3b )) m -, m can be 0, 1 or 2;

[0604] Where L 1 One or two methylene units can be replaced by -C(O)-;

[0605] Each R 1a R 1b R 2 R 3a R 3b Each can be hydrogen or, optionally, C that can be substituted by R. 1-6 Aliphatic groups;

[0606] Each R can be hydrogen.

[0607] For example, the compound may comprise the structure shown in formula (III-A):

[0608] R 1 It can be -O-;

[0609] X can be -L 1 -C(R 1a (R) 1b )-C(S)-;

[0610] L 1 It can be -(CH2) m -, m can be 1 or 2;

[0611] Where L 1 One or two methylene units can be replaced by -C(O)-;

[0612] Each R 1aR 1b Each can be hydrogen or, optionally, C that can be substituted by R. 1-6 Aliphatic groups;

[0613] Each R can be hydrogen.

[0614] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0615]

[0616] R 1 It can be -S- or -(R) 2 )N-;

[0617] X can be -L 1 -C(R 1a (R) 1b )-C(O)-;

[0618] L 1 It can be -(C(R) 3a (R) 3b )) m -, m can be 0, 1, or 2.

[0619] Where L 1 One or two methylene units can be replaced by -C(O)-;

[0620] R 2 It can be C 1-6 Aliphatic groups;

[0621] Each R 1a R 1b R 3a R 3b Each can be either hydrogen or C. 1-6 Aliphatic groups.

[0622] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0623]

[0624] R 1 It can be -S- or -(R) 2 )N-;

[0625] X can be -L 1 -C(R 1a (R) 1b )-C(O)-;

[0626] L 1 It can be -(C(R) 3a (R) 3b )) m -, m can be 1 or 2;

[0627] Where L 1 One or two methylene units can be replaced by -C(O)-;

[0628] R 2 It can be C 1-6 Aliphatic groups;

[0629] Each R 1a R 1b R 3a R 3b Each can be either hydrogen or C. 1-6 Aliphatic groups.

[0630] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0631]

[0632] When R 1 It can be -S- or -(R) 2 )N-;

[0633] X can be -L 1 -C(R 1a (R) 1b )-C(O)-;

[0634] L 1 It can be -(C(R) 3a (R) 3b )) m -, where m can be 0, 1, or 2.

[0635] Where L 1 One or two methylene units can be replaced by -C(O)-;

[0636] R 2 It can be C 1-6 Aliphatic groups;

[0637] Each R 1a R1b R 3a R 3b Each can be either hydrogen or C. 1-6 Aliphatic groups;

[0638] Or when R 1 It can be -O-;

[0639] X can be -L 1 -CH2-C(O)-;

[0640] L 1 It can be -(C(R) 3a (R) 3b ))2-hour;

[0641] Where L 1 One or two methylene units can be replaced by -C(O)-;

[0642] Each R 3a R 3b Each can be hydrogen or C independently. 1-6 Aliphatic groups;

[0643] Each R 3a R 3b It can be hydrogen or L at different times. 1 One methylene unit can be replaced by -C(O)-;

[0644] Each R 3a R 3b Each can be hydrogen or C independently. 1-6 Aliphatic groups.

[0645] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0646]

[0647] R 1 It can be -O-;

[0648] X can be -L 1 -CH2-C(O)-;

[0649] L 1 It can be -(C(R) 3a (R) 3b ))2-;

[0650] Where L 1One or two methylene units can be replaced by -C(O)-;

[0651] Each R 3a R 3b Each can be hydrogen or C independently. 1-6 Aliphatic groups;

[0652] Each R 3a R 3b It can be hydrogen or L at different times. 1 One methylene unit can be replaced by -C(O)-;

[0653] Each R 3a R 3b Each can be hydrogen or C independently. 1-6 Aliphatic groups.

[0654] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0655]

[0656] When R 1 It can be -S- or -(R) 2 )N-;

[0657] X can be -L 1 -C(R 1a (R) 1b )-C(O)-;

[0658] L 1 It can be -(C(R) 3a (R) 3b )) m -, where m can be 0, 1, or 2.

[0659] Where L 1 One or two methylene units can be replaced by -C(O)-;

[0660] R 2 It can be C 1-6 Aliphatic groups;

[0661] Each R 1a R 1b R 3a R 3b Each can be either hydrogen or C. 1-6 Aliphatic groups;

[0662] Or when R1 It can be -O-

[0663] X can be -L 1 When it is -CH2-C(O)-

[0664] L 1 can be -C(R 3a )(R 3b )-, in each -C(R 3a )(R 3b )- R 3a , R 3b cannot be hydrogen at the same time;

[0665] where each R 3a , R 3b can be independently hydrogen or C 1-6 aliphatic group.

[0666] In one embodiment, the present application provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0667]

[0668] R 1 can be -O-;

[0669] X can be -L 1 -CH2-C(O)-;

[0670] L 1 can be -(C(R 3a )(R 3b ))2-;

[0671] where 0 or 1 methylene unit of L 1 can be replaced by -C(O)-;

[0672] where each R 3a , R 3b can be independently hydrogen or C 1-6 aliphatic group;

[0673] In each -C(R 3a )(R 3b )- R 3a , R 3b cannot be hydrogen at the same time, or 1 methylene unit of L 1 can be replaced by -C(O)-;

[0674] where each R 3a , R3b Each independently can be hydrogen, or C 1-6 an aliphatic group.

[0675] In one embodiment, the present application provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (III-A):

[0676]

[0677] R 1 can be -O-;

[0678] X can be -L 1 -CH2-C(O)-;

[0679] L 1 can be -(CH2)2-;

[0680] wherein one methylene unit of L 1 can be replaced by -C(O)-.

[0681] In one embodiment, the present application provides a compound or its tautomer, mesomer, racemate, enantiomer, diastereoisomer, or a mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure represented by formula (III-A):

[0682]

[0683] wherein R 1 can be -O-,

[0684] X can be -L 1 -CH2-C(O)-;

[0685] L 1 can be -(C(R 3a )(R 3b )) m -, m can be an integer selected from 1 to 5, and in each -C(R 3a )(R 3b )-, R 3a , R 3b cannot both be hydrogen at the same time;

[0686] wherein each R 3a , R 3b each independently can be hydrogen, halogen or an optionally R-substituted C 1-6 aliphatic group;

[0687] wherein each R can be hydrogen or halogen.

[0688] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0689]

[0690] Where R 1 It can be -O-,

[0691] X can be -L 1 -CH2-C(O)-;

[0692] L 1 It can be -C(R) 3a (R) 3b )-, R 3a R 3b It can be hydrogen at different times;

[0693] Each R 3a R 3b Each can be either hydrogen or C. 1-6 Aliphatic groups.

[0694] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0695]

[0696] Where R 1 It can be -O- or -(R) 2 )N-,

[0697] X can be -L 1 -L 0 -;

[0698] L 0 It can be -CH2- or L 0 It can be -C(=S)-;

[0699] L 1 It can be -(CH2) m -, m can be an integer from 0 to 2;

[0700] Where L 1 One or two methylene units can be replaced by -C(O)- or -C(=S)-;

[0701] R 2 It can be C 1-6 Aliphatic groups.

[0702] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0703]

[0704] Where R 1 It can be -NH-,

[0705] X can be -L 1 -L 0 -;

[0706] L 0 It can be -CH2- or L 0 It can be -C(=S)-;

[0707] L 1 It can be -(CH2) m -, m can be an integer from 0 to 2;

[0708] Where L 1 One or two methylene units can be replaced by -C(O)- or -C(=S)-.

[0709] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0710]

[0711] R 1 It can be -S-, or -(R) 2 )N-;

[0712] X can be -L 3 -L 2 -,;

[0713] Where L 2 It can be -C(O)-;

[0714] L 3 It can be -(CH2) n -, n can be 4 or 5;

[0715] Where L 3 One methylene unit can be -NR8 -, -O-, -S- or -SO- can be substituted;

[0716] R 2 It can be C 1-6 Aliphatic groups.

[0717] For example, the compound may comprise the structure shown in formula (III-A):

[0718] R 1 It can be -S- or -(R) 2 )N-;

[0719] X can be -L 3 -L 2 -,;

[0720] Where L 2 It can be -C(O)-;

[0721] L 3 It can be -(CH2) n -, n can be 4 or 5;

[0722] Where L 3 One methylene unit can be replaced by -O-;

[0723] R 2 It can be C 1-6 Aliphatic groups.

[0724] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0725]

[0726] Where R 1 It can be -O-,

[0727] X can be -L 3 -L 2 -,;

[0728] Where L 2 It can be -C(O)-;

[0729] L 3 It can be -(C(R) 7a (R) 7b )) n -, n can be 4 or 5;

[0730] Where L 3 One methylene unit can be -NR8 - or -O- can be substituted, while L 3 The 0 or 1 methylene units can also be independently replaced by -C(O)- or -C(=S)-;

[0731] Each R 7a R 7b R 8 Each can be hydrogen or C independently. 1-6 Aliphatic groups.

[0732] For example, the compound may comprise the structure shown in formula (III-A):

[0733] R 1 It can be -O-,

[0734] X can be -L 3 -L 2 -,;

[0735] Where L 2 It can be -C(O)-;

[0736] L 3 It can be -(C(R) 7a (R) 7b ))4-;

[0737] Where L 3 One methylene unit can be -NR 8 - or -O- alternative;

[0738] Each R 7a R 7b R 8 Each can be either hydrogen or C. 1-6 Aliphatic groups.

[0739] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0740]

[0741] Where R 1 It can be -O-,

[0742] X can be -L 3 -L 2 -,;

[0743] Where L 2 It can be -C(O)-;

[0744] L 3 It can be -(C(R) 7a (R) 7b ))4-;

[0745] Where L 3 One methylene unit can be -NR 8 Substitute;

[0746] Each R 7a R 7b R 8 Each can be either hydrogen or C. 1-6 Aliphatic groups.

[0747] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise the structure shown in formula (III-A):

[0748]

[0749] Where R 1 It can be -NH-,

[0750] X can be -L 3 -L 2 -,;

[0751] Where L 2 It can be -C(O)-;

[0752] L 3 It can be -(CH2) n -, n can be 4 or 5;

[0753] Where L 3 One methylene unit can be replaced by -S-.

[0754] In one embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound may comprise a structure from the group consisting of:

[0755] (III-A-1) (III-A-2) (III-A-3) (III-A-4) (III-A-5) (III-A-6) (III-A-7) (III-A-8) (III-A-9)

[0756] (III-A-10) (III-A-11) (III-A-12) (III-A-13) (III-A-14) (III-A-15)

[0757] (III-A-16) (III-A-17)

[0758] Where R 2 C can be any C that can be replaced by R. 1-6 Aliphatic groups, where R can be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; or R in them 2 It can be halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0759] For example, R 2 It can be any one or more of hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 The aliphatic group can be optionally substituted with a methyl group. For example, R 2 It can be hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C1-6 The ethyl group is optionally substituted with an aliphatic group. For example, R 2 It can be hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 The propyl group, which may be optionally substituted with an aliphatic group.

[0760] In a second aspect, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise the structure shown in formula (IB):

[0761]

[0762] Among them, X a Nitrogen can be generated by removing two hydrogen atoms from the amino group of cytotoxic drugs;

[0763] The L can be -L a -L b -L c -;

[0764] The -L a - You can choose from the following groups:

[0765]

[0766] Where W can be -(C(R) wa (R) wb )) wn -, Y can be -(OCH2CH2) yn -O yp -, Z can be -(C(R) za (R) zb )) zn ;

[0767] Where wn can be selected from integers greater than or equal to 0.

[0768] One or more methylene units of W can be independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(Rwx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0769] Where yn can be selected from integers greater than 0, and yp can be 0 or 1;

[0770] Where zn can be selected from integers greater than or equal to 0.

[0771] Zero or more methylene units of Z can be independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0772] -Cyr- can be selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or can be independently substituted by one or more substituents R. cx replace;

[0773] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r-S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r Or it can be R r Optional substitution of C 1-6 Aliphatic groups;

[0774] Each R r R ra R rb Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0775] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0776] The -L c - You can choose from the following groups:

[0777] , , , , , ,and ;

[0778] Where R L1 R L2 Each can be independently selected from the following groups: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0779] R 1 L 1 L 2 As defined in any of the formulas (IA) in the implementation of the first aspect.

[0780] In another embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise the structure shown in formula (II-Bx) or formula (II-By):

[0781] , ,

[0782] Among them, X a Nitrogen can be generated by removing two hydrogen atoms from the amino group of cytotoxic drugs;

[0783] The L can be -L a -L b -L c -;

[0784] The -L a - You can choose from the following groups:

[0785]

[0786] Where W can be -(C(R) wa (R) wb )) wn -, Y can be -(OCH2CH2) yn -O yp -, Z can be -(C(R) za (R) zb )) zn ;

[0787] Where wn can be selected from integers greater than or equal to 0.

[0788] One or more methylene units of W can be independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0789] Where yn can be selected from integers greater than 0, and yp can be 0 or 1;

[0790] Where zn can be selected from integers greater than or equal to 0.

[0791] Zero or more methylene units of Z can be independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0792] -Cyr- can be selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or can be independently substituted by one or more substituents R. cx replace;

[0793] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r Or it can be R r Optional substitution of C 1-6 Aliphatic groups;

[0794] Each R r R ra R rb Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0795] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0796] The -L c - You can choose from the following groups:

[0797] , , , , , ,and ;

[0798] Where R L1 R L2 Each can be independently selected from the following groups: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0799] L 2 p, ring A, X 1 L 1 As defined in any of the formulas (II-Ax) in the embodiments of the first aspect;

[0800] or X 2 , q, ring A, X 1 L 1 As defined in any of the formulas (II-Ay) in the embodiments of the first aspect.

[0801] In another embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise the structure shown in formula (III-B):

[0802]

[0803] Among them, X a Nitrogen can be generated by removing two hydrogen atoms from the amino group of cytotoxic drugs;

[0804] The L can be -L a -L b -L c -;

[0805] The -L a - You can choose from the following groups:

[0806]

[0807] Where W can be -(C(R) wa (R) wb )) wn -, Y can be -(OCH2CH2) yn -O yp Z can be -(C(R) za (R) zb )) zn ,;

[0808] Where wn can be selected from integers greater than or equal to 0.

[0809] One or more methylene units of W can be independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0810] Where yn can be selected from integers greater than 0, and yp can be 0 or 1;

[0811] zn can be selected from integers greater than or equal to 0.

[0812] Zero or more methylene units of Z can be independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx)-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0813] -Cyr- can be selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or can be independently substituted by one or more substituents R. cx replace;

[0814] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r Or it can be R r Optional substitution of C 1-6 Aliphatic groups;

[0815] Each R r R ra R rbEach can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0816] The -L b - indicates a peptide residue consisting of 2 to 7 amino acids;

[0817] The -L c - You can choose from the following groups:

[0818] , , , , , ,and ;

[0819] Where R L1 R L2 Each can be independently selected from the following groups: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups;

[0820] Where R 1 X is as defined in any formula (III-A) in the implementation of the first aspect.

[0821] In another implementation, where wn can be selected from integers from 2 to 6, and 0 or 1 methylene units of W can each be independently converted to -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx -, -C(O)-, -NR wx - or -O- as a substitute.

[0822] For example, wn can be 1, 2, 3, or 6, and each methylene unit of W can be independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )- or -C(O)- substitution.

[0823] In another implementation, yn can be selected from integers from 0 to 12, and yp can be 0 or 1.

[0824] For example, yn can be 0, 4 or 8, and yp can be 0 or 1.

[0825] In another implementation, zn can be selected from integers from 0 to 10, and 0 or 1 methylene units of Z can each be independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )- or -C(O)- substitution.

[0826] For example, zn can be 1, 2, or 3, and each methylene unit of Z can be independently converted to -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )- or -C(O)- substitution.

[0827] In another embodiment, -Cyr- can be selected from the group consisting of 6 to 10 arylene groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein -Cyr- is unsubstituted or can be independently substituted by 1 to 3 substituents R. cx replace.

[0828] For example, -Cyr- can be a 3- to 10-membered saturated carbocyclic group, wherein -Cyr- is unsubstituted or can be independently substituted by 1 to 3 substituents R. cx replace.

[0829] In another implementation, each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R)rb -OC(O)R r -N(R)SO2R r Or it can be R r Optional substitution of C 1-6 Aliphatic groups; wherein each R r R ra R rb Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0830] For example, where each R wa R wb R za R zb R wx R zx ,R cx Each can be independently of hydrogen, halogen, -OR r Or it can be R r Optional substitution of C 1-6 Aliphatic groups; wherein each R r Each can be independently hydrogen, halogen, or C 1-6 Aliphatic groups.

[0831] In another implementation, the -L b - indicates a peptide residue consisting of 2 to 7 amino acids, wherein -L b - The peptide residues can be peptide residues formed from amino acids selected from the following group: phenylalanine, glycine, alanine, valine, citrulline, lysine, serine, glutamic acid, and aspartic acid.

[0832] For example, the -L b - indicates a peptide residue consisting of 2 to 4 amino acids, wherein -L b - The peptide residues can be peptide residues that can be formed from amino acids selected from the following group: phenylalanine, glycine, alanine, valine, citrulline, and lysine.

[0833] For example, the -L b - You can choose from the following groups:

[0834] , , , , ,and .

[0835] For example, the -L b -can be

[0836] .

[0837] In another implementation, the -L c - You can choose from the following groups:

[0838] , , , , , ,and .

[0839] For example, the -L c - You can choose from the following groups:

[0840]

[0841] The -L c -can be

[0842] .

[0843] In another implementation, where R L1 R L2 Each can be independently selected from the following groups: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups.

[0844] For example, where R L1 R L2 Each can be independently selected from the following groups: hydrogen, halogens, -OH and C. 1-6 Aliphatic groups.

[0845] In another implementation, where -L a -can be .

[0846] In another implementation, -L b - You can choose from the following groups: , , , , , , , ,and .

[0847] For example, -L b - You can choose from the following groups: , , ,and .

[0848] In one implementation, -L c -can be .

[0849] In one implementation, where -L a -L b -L c - You can choose from the following groups: , , ,and .

[0850] Among them, cytotoxic drugs are shown in formula (EXA):

[0851] .

[0852] In a third aspect, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise the structure shown in formula (IC):

[0853]

[0854] Where L can be -L a -L b -L c -, L a L b L c As defined in any of the formulas (IB) in the implementation of the second aspect;

[0855] R 1 L 1 L 2 As defined in any of the formulas (IA) in the implementation of the first aspect.

[0856] In another embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise the structure shown in formula (II-Cx) or formula (II-Cy):

[0857] ,

[0858] Where L can be -L a -L b -L c -, L a L b L c As defined by any formula (II-Bx) in the implementation of the second aspect;

[0859] L 2 p, ring A, X 1 L 1 As defined in any of the formulas (II-Ax) in the embodiments of the first aspect;

[0860] or X 2 , q, ring A, X 1 L 1 As defined in any of the formulas (II-Ay) in the embodiments of the first aspect.

[0861] In another embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise the structure shown in formula (III-C):

[0862]

[0863] Where L can be -L a -L b -L c -, L a L b L c As defined in any of the formulas (III-B) in the implementation of the second aspect;

[0864] Where R 1 X is as defined in any formula (III-A) in the implementation of the first aspect.

[0865] In a fourth aspect, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise the structure shown in formula (ID):

[0866]

[0867] Where Ab can be a ligand, and the average number of connections N a It can be an integer or a decimal number from 1 to 10;

[0868] L can be -L a -L b -L c -, L a L b L c As defined in any of the formulas (IB) in the implementation of the second aspect;

[0869] R 1 L 1 L 2 As defined in any of the formulas (IA) in the implementation of the first aspect.

[0870] In another embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise a structure represented by formula (II-Dx) or formula (II-Dy).

[0871] ,

[0872] Where Ab can be a ligand, and the average number of connections N a It can be an integer or a decimal number from 1 to 10;

[0873] L can be -L a -L b -L c -, L a L b L c As defined in any of the formulas (II-Bx) in the implementation of the second aspect;

[0874] L 2 Ring A, X 1 L 1 As defined in any of the formulas (II-Ax) in the embodiments of the first aspect;

[0875] or X 2 Ring A, X 1 L 1 As defined in any of the formulas (II-Ay) in the embodiments of the first aspect.

[0876] In another embodiment, this application provides a compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, which may comprise the structure shown in formula (III-D).

[0877]

[0878] Where Ab can be a ligand, and the average number of connections N a It can be an integer or a decimal number from 1 to 10;

[0879] L can be -L a -L b -L c -, L a L b L c As defined in any of the formulas (III-B) in the implementation of the second aspect;

[0880] Where R 1 X is as defined in any formula (III-A) in the implementation of the first aspect.

[0881] In another embodiment, the ligand Ab can be an antibody or its antigen-binding fragment.

[0882] For example, the ligand Ab can be selected from the group consisting of chimeric antibodies, humanized antibodies, and fully human antibodies.

[0883] For example, the ligand Ab targets the following groups: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70, and EGFR.

[0884] For example, the ligand Ab targets the following groups: For example, the antibody may be an antibody targeting the following targets: 5T4, AGS-16, ANGPTL4, ApoE, CD19, CTGF, CXCR5, FGF2, MCPT8, MFI2, MS4A7, NCA, Sema5b, SLITRK6, STC2, TGF, O772P, 5T4, ACTA2, ADGRE1, AG-7, AIF1, AKR1C1, AKR1C2, ASLG659, Axl, B7H3, BAFF-R, BCMA, BMPR1B, BNIP3, C1QA, C1QB, CA6, CADM1, CCD79b, CCL5, CCR5, CCR7, CD1lc, CD123, CD138, CD142, CD147, CD166, CD19, CD19,CD22, CD21, CD20, CD205, CD22, CD223, CD228, CD25, CD30, CD33, CD37, CD38, CD40, CD45, CD45(PTPRC), CD46, CD47, CD49D(ITGA4), CD56, CD66e, CD70, C D71, CD72, CD74, CD79a, CD79b, CD80, CDCP1, CDH11, CDllb, CEA, CEACAM5, c-Met, COL6A3, COL7A1, CRIPTO, CSF1R, CTSD, CTSS, CXCL11, CXCL10, DDIT4, D LL3, DLL4, DR5, E16, EFNA4, EGFR, EGFRvIII, EGLN, EGLN3, EMR2, ENPP3, EpCAM, EphA2, EphB2R, ETBR, FcRH2, FcRHl, FGFR2, FGFR3, FLT3, FOLR-α, GD2, GE DA, 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, KIS S1R, KRT33A, LIV-1, LOX, LRP-1, LRRC15, LUM, LY64, LY6E, Ly86, LYPD3, MDP, MMP10, MMP14, MMP16, MPF, MSG783, MSLN, MUC-1, NaPi2b, Napi3b, Nectin-4, Nectin-4, NOG, P2X5, pCAD, P-Cadherin, PDGFRA, PDK1, PD-L1, PFKFB3, PGF, PGK1, PIK3AP1, PIK3CD, PLOD2, PSCA, PSCAhlg, PSMA, PSMA, PTK7, P-cadherin RNF43, NaPi2b, ROR1, ROR2, SERPINE1, SLC39A6, SLTRK6, STAT1, STEAP1, STEAP2, TCF4, TENB2, TGFB1, TGFB2, TGFBR1, TNFRSF21, TNFSF9, Trop-2, TrpM4, Tyro7, UPK1B, VEGFA, WNT5A, epidermal growth factor, short proteoglycans, mesothelin, sodium phosphate cotransporter 2B, occlusive protein 18.2, endothelial peptide receptors, mucins (such as mucin 1 and mucin 16), guanylate cyclase C, integrin a4p7, integrin a5p6, trophoblast cell glycoproteins, and tissue factor.

[0885] In another implementation, the average number of connections N a It can be an integer or a decimal from 2 to 8. For example, the average number of connections N a It can be an integer or a decimal from 3 to 8. For example, the average number of connections N a It can 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.

[0886] Fifthly, this application provides a compound of general formula (IE) or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0887]

[0888] Among them, R 1 L 1 L 2 As defined in any of the formulas (IA) in the implementation of the first aspect.

[0889] In another embodiment, this application provides a general formula (II-E) x ) or general formula (II-E) y The compound shown in the diagram, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein:

[0890] , ,

[0891] Among them, L 2 p, ring A, X 1 L 1 As defined in any of the formulas (II-Ax) in the embodiments of the first aspect;

[0892] or X 2 , q, ring A, X 1 L 1 As defined in any of the formulas (II-Ay) in the embodiments of the first aspect.

[0893] In another embodiment, this application provides a compound of general formula (III-E) or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0894]

[0895] Where R 1 X is as defined in any formula (III-A) in the implementation of the first aspect.

[0896] In a sixth aspect, this application provides a compound of general formula (IF) or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0897]

[0898] Wherein, the L x -L can be used ax -L b -L c -;

[0899] The L ax - You can choose from the following groups:

[0900]

[0901] Where R hal It can be iodine or bromine;

[0902] Where W can be -(C(R) wa (R) wb )) wn -, Y can be -(OCH2CH2) yn -O yp -, Z can be -(C(R) za (R) zb )) zn ;

[0903] Where wn can be selected from integers greater than or equal to 0.

[0904] One or more methylene units of W can be independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0905] Where yn can be selected from integers greater than 0, and yp can be 0 or 1;

[0906] Where zn can be selected from integers greater than or equal to 0.

[0907] Zero or more methylene units of Z can be independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0908] -Cyr- can be selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or can be independently substituted by one or more substituents R. cx replace;

[0909] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r Or it can be Rr Optional substitution of C 1-6 Aliphatic groups;

[0910] Each R r R ra R rb Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0911] L b L c As defined in any of the formulas (IB) in the implementation of the second aspect;

[0912] R 1 L 1 L 2 As defined in any of the formulas (IA) in the implementation of the first aspect.

[0913] In another embodiment, this application provides a general formula (II-F) x ) or general formula (II-F) y The compound shown in the diagram, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein:

[0914] , ,

[0915] Wherein, the L x -L can be used ax -L b -L c -;

[0916] The L ax - You can choose from the following groups:

[0917]

[0918] Where R hal It can be iodine or bromine;

[0919] Where W can be -(C(R) wa (R) wb )) wn -, Y can be -(OCH2CH2) yn -O yp-, Z can be -(C(R) za (R) zb )) zn ;

[0920] Where wn can be selected from integers greater than or equal to 0.

[0921] One or more methylene units of W can be independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0922] Where yn can be selected from integers greater than 0, and yp can be 0 or 1;

[0923] Where zn can be selected from integers greater than or equal to 0.

[0924] Zero or more methylene units of Z can be independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0925] -Cyr- can be selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or can be independently substituted by one or more substituents R. cx replace;

[0926] Each R wa Rwb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r Or it can be R r Optional substitution of C 1-6 Aliphatic groups;

[0927] Each R r R ra R rb Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0928] L b L c As defined in any of the formulas (II-Bx) in the implementation of the second aspect;

[0929] Among them, L 2 p, ring A, X 1 L 1 As defined in any of the formulas (II-Ax) in the embodiments of the first aspect;

[0930] or X 2 , q, ring A, X 1 L 1 As defined in any of the formulas (II-Ay) in the embodiments of the first aspect.

[0931] In another embodiment, this application provides a compound of general formula (III-F) or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0932] ,

[0933] Wherein, the L x -L can be used ax -L b -L c -;

[0934] The L ax - You can choose from the following groups:

[0935]

[0936] Where R hal It can be iodine or bromine;

[0937] Where W can be -(C(R) wa (R) wb )) wn -, Y can be -(OCH2CH2) yn -O yp -, Z can be -(C(R) za (R) zb )) zn ;

[0938] Where wn can be selected from integers greater than or equal to 0.

[0939] One or more methylene units of W can be independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0940] Where yn can be selected from integers greater than 0, and yp can be 0 or 1;

[0941] Where zn can be selected from integers greater than or equal to 0.

[0942] Zero or more methylene units of Z can be independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[0943] -Cyr- can be selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or can be independently substituted by one or more substituents R. cx replace;

[0944] Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r Or it can be R r Optional substitution of C 1-6 Aliphatic groups;

[0945] Each R r R ra R rb Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[0946] L b L c As defined in any of the formulas (III-B) in the implementation of the second aspect;

[0947] Where R 1 X is as defined in any formula (III-A) in the implementation of the first aspect.

[0948] In another embodiment, the L ax - You can choose from the following groups:

[0949]

[0950] Where R hal It can be iodine or bromine;

[0951] Where W can be -(C(R) wa (R) wb )) wn -, Y can be -(OCH2CH2) yn -O yp -, Z can be -(C(R) za (R) zb )) zn .

[0952] In another implementation, where wn can be selected from integers from 2 to 6, and 0 or 1 methylene units of W can each be independently converted to -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx -, -C(O)-, -NR wx - or -O- as a substitute.

[0953] For example, wn can be 1, 2, 3, or 6, and each methylene unit of W can be independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )- or -C(O)- substitution.

[0954] In another implementation, yn can be selected from integers from 0 to 12, and yp can be 0 or 1.

[0955] For example, yn can be 0, 4 or 8, and yp can be 0 or 1.

[0956] In another implementation, zn can be selected from integers from 0 to 10, and 0 or 1 methylene units of Z can each be independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )- or -C(O)- substitution.

[0957] For example, zn can be 1, 2, or 3, and each methylene unit of Z can be independently converted to -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )- or -C(O)- substitution.

[0958] In another embodiment, -Cyr- can be selected from the group consisting of 6 to 10 arylene groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein -Cyr- is unsubstituted or can be independently substituted by 1 to 3 substituents R. cx replace.

[0959] For example, -Cyr- can be a 3- to 10-membered saturated carbocyclic group, wherein -Cyr- is unsubstituted or can be independently substituted by 1 to 3 substituents R. cx replace.

[0960] In another implementation, each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R)rb -OC(O)R r -N(R)SO2R r Or it can be R r Optional substitution of C 1-6 Aliphatic groups; wherein each R r R ra R rb Each can independently be hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups.

[0961] For example, where each R wa R wb R za R zb R wx R zx ,R cx Each can be independently of hydrogen, halogen, -OR r Or it can be R r Optional substitution of C 1-6 Aliphatic groups; wherein each R r Each can be independently hydrogen, halogen, or C 1-6 Aliphatic groups.

[0962] In another implementation, L ax -can be .

[0963] In another implementation, where L ax -L b -L c - You can choose from the following groups:

[0964] , , ,and .

[0965] The compounds disclosed in this application

[0966] In one embodiment, the compounds disclosed in this application include, but are not limited to:

[0967]

[0968]

[0969]

[0970]

[0971]

[0972]

[0973]

[0974]

[0975]

[0976]

[0977]

[0978]

[0979]

[0980]

[0981]

[0982]

[0983]

[0984]

[0985]

[0986]

[0987]

[0988]

[0989]

[0990]

[0991]

[0992]

[0993]

[0994]

[0995]

[0996]

[0997]

[0998]

[0999]

[1000]

[1001] The average number of connections n in the above list can be an integer or a decimal from 1 to 10. The average number of connections n in the above list can be an integer or a decimal from 2 to 8. For example, the average number of connections n can be an integer or a decimal from 3 to 8. For example, the average number of connections n can 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.

[1002] In one embodiment, the compounds disclosed in this application include, but are not limited to:

[1003]

[1004]

[1005]

[1006]

[1007]

[1008]

[1009]

[1010]

[1011]

[1012]

[1013]

[1014]

[1015]

[1016]

[1017]

[1018]

[1019]

[1020]

[1021]

[1022]

[1023]

[1024]

[1025]

[1026]

[1027]

[1028]

[1029]

[1030]

[1031]

[1032] The average number of connections n in the above list can be an integer or a decimal from 1 to 10. The average number of connections n in the above list can be an integer or a decimal from 2 to 8. For example, the average number of connections n can be an integer or a decimal from 3 to 8. For example, the average number of connections n can 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.

[1033] In one embodiment, the compounds disclosed in this application include, but are not limited to:

[1034]

[1035]

[1036]

[1037]

[1038]

[1039]

[1040]

[1041]

[1042]

[1043]

[1044]

[1045]

[1046]

[1047]

[1048]

[1049]

[1050]

[1051]

[1052]

[1053]

[1054]

[1055]

[1056]

[1057]

[1058]

[1059]

[1060]

[1061]

[1062] The average number of connections n in the above list can be an integer or a decimal from 1 to 10. The average number of connections n in the above list can be an integer or a decimal from 2 to 8. For example, the average number of connections n can be an integer or a decimal from 3 to 8. For example, the average number of connections n can 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.

[1063] ligands

[1064] The ligands described in this application may be protein hormones, lectins, growth factors, antibodies, or other molecules capable of binding to cells, receptors, and / or antigens. For example, the ligands in this application may be antibodies or their antigen-binding fragments.

[1065] In this application, the ligand may comprise at least one CDR in the variable region (VL) of the antibody light chain. The CDR may be as defined by Kabat.

[1066] In this application, the antigen-binding protein may comprise LCDR1, and LCDR1 may comprise the amino acid sequence shown in any one of SEQ ID NO: 1-4. The CDR may be defined according to Kabat.

[1067] In this application, the antigen-binding protein may comprise LCDR2, and LCDR2 may comprise the amino acid sequence shown in any one of SEQ ID NO: 5-8. The CDR may be defined according to Kabat.

[1068] In this application, the antigen-binding protein may comprise LCDR3, and LCDR3 may comprise the amino acid sequence shown in any one of SEQ ID NO: 9-12. The CDR may be defined according to Kabat.

[1069] In this application, the isolated antigen-binding protein may comprise LCDR1-3. LCDR1 may comprise the amino acid sequence shown in any one of SEQ ID NO: 1-4; LCDR2 may comprise the amino acid sequence shown in any one of SEQ ID NO: 5-8; and LCDR3 may comprise the amino acid sequence shown in any one of SEQ ID NO: 9-12. The CDR may be defined according to Kabat.

[1070] For example, the antigen-binding protein described in this application may contain the same LCDR1-3 as Trastuzumab, wherein LCDR1 may contain the amino acid sequence shown in SEQ ID NO:1; LCDR2 may contain the amino acid sequence shown in SEQ ID NO:5; and LCDR3 may contain the amino acid sequence shown in SEQ ID NO:9. For example, the antigen-binding protein described in this application may contain the same LCDR1-3 as Pertuzumab, wherein LCDR1 may contain the amino acid sequence shown in SEQ ID NO:2; LCDR2 may contain the amino acid sequence shown in SEQ ID NO:6; and LCDR3 may contain the amino acid sequence shown in SEQ ID NO:10. The CDR may be defined according to Kabat.

[1071] For example, the antigen-binding protein described in this application may contain the same LCDR1-3 as Sacituzumab, wherein LCDR1 may contain the amino acid sequence shown in SEQ ID NO:3; LCDR2 may contain the amino acid sequence shown in SEQ ID NO:7; and LCDR3 may contain the amino acid sequence shown in SEQ ID NO:11. The CDR may be defined according to Kabat.

[1072] For example, the antigen-binding protein described in this application may contain the same LCDR1-3 as Zolbetuximab, wherein LCDR1 may contain the amino acid sequence shown in SEQ ID NO:4; LCDR2 may contain the amino acid sequence shown in SEQ ID NO:8; and LCDR3 may contain the amino acid sequence shown in SEQ ID NO:12. The CDR may be defined according to Kabat.

[1073] The antigen-binding protein described in this application may contain at least one CDR in the variable region (VH) of the antibody heavy chain. The CDR may be as defined by Kabat.

[1074] In this application, the antigen-binding protein may comprise HCDR1, and HCDR1 may comprise the amino acid sequence shown in any one of SEQ ID NO: 13-16. The CDR may be defined according to Kabat.

[1075] In this application, the antigen-binding protein may comprise HCDR2, and HCDR2 may comprise the amino acid sequence shown in any one of SEQ ID NO: 17-20. The CDR may be defined according to Kabat.

[1076] In this application, the antigen-binding protein may comprise HCDR3, and HCDR3 may comprise the amino acid sequence shown in any one of SEQ ID NO: 21-24. The CDR may be defined according to Kabat.

[1077] In this application, the isolated antigen-binding protein may comprise HCDR1-3. Specifically, HCDR1 may comprise the amino acid sequence shown in any one of SEQ ID NO: 13-16; HCDR2 may comprise the amino acid sequence shown in any one of SEQ ID NO: 17-20; and HCDR3 may comprise the amino acid sequence shown in any one of SEQ ID NO: 21-24. The CDR may be defined according to Kabat.

[1078] For example, the antigen-binding protein described in this application may contain the same HCDR1-3 as Trastuzumab, wherein HCDR1 may contain the amino acid sequence shown in SEQ ID NO:13; HCDR2 may contain the amino acid sequence shown in SEQ ID NO:17; and HCDR3 may contain the amino acid sequence shown in SEQ ID NO:21. The CDR may be defined according to Kabat.

[1079] For example, the antigen-binding protein described in this application may contain the same HCDR1-3 as Pertuzumab, wherein HCDR1 may contain the amino acid sequence shown in SEQ ID NO:14; HCDR2 may contain the amino acid sequence shown in SEQ ID NO:18; and HCDR3 may contain the amino acid sequence shown in SEQ ID NO:22. The CDRs may be defined according to Kabat.

[1080] For example, the antigen-binding protein described in this application may contain the same HCDR1-3 as Sacituzumab, wherein HCDR1 may contain the amino acid sequence shown in SEQ ID NO:15; HCDR2 may contain the amino acid sequence shown in SEQ ID NO:19; and HCDR3 may contain the amino acid sequence shown in SEQ ID NO:23. The CDRs may be defined according to Kabat.

[1081] For example, the antigen-binding protein described in this application may contain the same HCDR1-3 as Zolbetuximab, wherein HCDR1 may contain the amino acid sequence shown in SEQ ID NO:16; HCDR2 may contain the amino acid sequence shown in SEQ ID NO:20; and HCDR3 may contain the amino acid sequence shown in SEQ ID NO:24. The CDRs may be defined according to Kabat.

[1082] In this application, the isolated antigen-binding proteins may comprise LCDR1-3 and HCDR1-3. Specifically, LCDR1 may comprise the amino acid sequence shown in any one of SEQ ID NO: 1-4; LCDR2 may comprise the amino acid sequence shown in any one of SEQ ID NO: 5-8; LCDR3 may comprise the amino acid sequence shown in any one of SEQ ID NO: 9-12; HCDR1 may comprise the amino acid sequence shown in any one of SEQ ID NO: 13-16; HCDR2 may comprise the amino acid sequence shown in any one of SEQ ID NO: 17-20; and HCDR3 may comprise the amino acid sequence shown in any one of SEQ ID NO: 21-24. The CDR may be defined according to Kabat.

[1083] For example, the antigen-binding protein described in this application may contain the same LCDR1-3 and HCDR1-3 as Trastuzumab. Specifically, LCDR1 may contain the amino acid sequence shown in SEQ ID NO:1; LCDR2 may contain the amino acid sequence shown in SEQ ID NO:5; LCDR3 may contain the amino acid sequence shown in SEQ ID NO:9; HCDR1 may contain the amino acid sequence shown in SEQ ID NO:13; HCDR2 may contain the amino acid sequence shown in SEQ ID NO:17; and HCDR3 may contain the amino acid sequence shown in SEQ ID NO:21. The CDRs may be defined according to Kabat.

[1084] For example, the antigen-binding protein described in this application may contain the same LCDR1-3 and HCDR1-3 as Pertuzumab. Specifically, LCDR1 may contain the amino acid sequence shown in SEQ ID NO:2; LCDR2 may contain the amino acid sequence shown in SEQ ID NO:6; LCDR3 may contain the amino acid sequence shown in SEQ ID NO:10; HCDR1 may contain the amino acid sequence shown in SEQ ID NO:14; HCDR2 may contain the amino acid sequence shown in SEQ ID NO:18; and HCDR3 may contain the amino acid sequence shown in SEQ ID NO:22. The CDRs may be defined according to Kabat.

[1085] For example, the antigen-binding protein described in this application may contain the same LCDR1-3 and HCDR1-3 as Sacituzumab. Specifically, LCDR1 may contain the amino acid sequence shown in SEQ ID NO:3; LCDR2 may contain the amino acid sequence shown in SEQ ID NO:7; LCDR3 may contain the amino acid sequence shown in SEQ ID NO:11; HCDR1 may contain the amino acid sequence shown in SEQ ID NO:15; HCDR2 may contain the amino acid sequence shown in SEQ ID NO:19; and HCDR3 may contain the amino acid sequence shown in SEQ ID NO:23. The CDRs may be defined according to Kabat.

[1086] For example, the antigen-binding protein described in this application may contain the same LCDR1-3 and HCDR1-3 as Zolbetuximab. Specifically, LCDR1 may contain the amino acid sequence shown in SEQ ID NO:4; LCDR2 may contain the amino acid sequence shown in SEQ ID NO:8; LCDR3 may contain the amino acid sequence shown in SEQ ID NO:12; HCDR1 may contain the amino acid sequence shown in SEQ ID NO:16; HCDR2 may contain the amino acid sequence shown in SEQ ID NO:20; and HCDR3 may contain the amino acid sequence shown in SEQ ID NO:24. The CDRs may be defined according to Kabat.

[1087] In this application, the antigen-binding protein may include a light chain variable region (VL), and the VL may contain the amino acid sequence shown in any one of SEQ ID NO: 25-28.

[1088] In this application, the antigen-binding protein may include a heavy chain variable region VH, and the VH may contain the amino acid sequence shown in any one of SEQ ID NO: 29-32.

[1089] In this application, the antigen-binding protein may comprise a light chain variable region (VL) and a heavy chain variable region (VH). Specifically, the VL may comprise the amino acid sequence shown in any one of SEQ ID NO: 25-28, and the VH may comprise the amino acid sequence shown in any one of SEQ ID NO: 29-32.

[1090] For example, the antigen-binding protein described in this application may contain the same light chain variable region VL and heavy chain variable region VH as Trastuzumab. Specifically, the VL may contain the amino acid sequence shown in SEQ ID NO: 25, and the VH may contain the amino acid sequence shown in SEQ ID NO: 29.

[1091] For example, the antigen-binding protein described in this application may contain the same light chain variable region VL and heavy chain variable region VH as Pertuzumab. Specifically, the VL may contain the amino acid sequence shown in SEQ ID NO: 26, and the VH may contain the amino acid sequence shown in SEQ ID NO: 30.

[1092] For example, the antigen-binding protein described in this application may contain the same light chain variable region VL and heavy chain variable region VH as Sacituzumab. Specifically, the VL may contain the amino acid sequence shown in SEQ ID NO: 27, and the VH may contain the amino acid sequence shown in SEQ ID NO: 31.

[1093] For example, the antigen-binding protein described in this application may contain the same light chain variable region VL and heavy chain variable region VH as Zolbetuximab. Specifically, the VL may contain the amino acid sequence shown in SEQ ID NO: 28, and the VH may contain the amino acid sequence shown in SEQ ID NO: 32.

[1094] In this application, the antigen-binding protein may comprise a light chain, and the light chain may comprise an amino acid sequence represented by any one of SEQ ID NO:33-36.

[1095] In this application, the antigen-binding protein may comprise a heavy chain, and the heavy chain may comprise an amino acid sequence shown in any one of SEQ ID NO:37-40.

[1096] In this application, the antigen-binding protein may comprise an antibody light chain and an antibody heavy chain, wherein the light chain may comprise any of the amino acid sequences shown in SEQ ID NO: 33-36, and the heavy chain may comprise any of the amino acid sequences shown in SEQ ID NO: 37-40.

[1097] For example, the antigen-binding protein described in this application may contain the same antibody light chain and antibody heavy chain as Trastuzumab, wherein the light chain may contain the amino acid sequence shown in SEQ ID NO: 33, and the heavy chain may contain the amino acid sequence shown in SEQ ID NO: 37.

[1098] For example, the antigen-binding protein described in this application may contain the same antibody light chain and antibody heavy chain as Pertuzumab, wherein the light chain may contain the amino acid sequence shown in SEQ ID NO: 34, and the heavy chain may contain the amino acid sequence shown in SEQ ID NO: 38.

[1099] For example, the antigen-binding protein described in this application may contain the same antibody light chain and antibody heavy chain as Sacituzumab, wherein the light chain may contain the amino acid sequence shown in SEQ ID NO: 35, and the heavy chain may contain the amino acid sequence shown in SEQ ID NO: 39.

[1100] For example, the antigen-binding protein described in this application may contain the same antibody light chain and antibody heavy chain as Zolbetuximab, wherein the light chain may contain the amino acid sequence shown in SEQ ID NO: 36, and the heavy chain may contain the amino acid sequence shown in SEQ ID NO: 40.

[1101] Prevention and / or prevention of tumors

[1102] On the other hand, this application provides the use of the compound described herein, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the preparation of a medicament for treating and / or preventing tumors. The tumor may be selected from tumors associated with the expression of the following groups: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70, or EGFR. The tumor may be selected from the following groups: lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer, and esophageal cancer.

[1103] On the other hand, this application provides methods for treating and / or preventing tumors, comprising administering to a subject in need the compound described in this application or its tautomers, racemates, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, and / or pharmaceutical compositions comprising thereof. The tumor may be selected from tumors associated with expression of the following groups: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70, or EGFR. The tumor may be selected from the following groups: lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer, and esophageal cancer.

[1104] On the other hand, this application provides a compound described herein, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, and / or pharmaceutical compositions comprising thereof, for the treatment and / or prevention of tumors. The tumor may be selected from tumors associated with expression of the following groups: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70, or EGFR. The tumor may be selected from the following groups: lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer, and esophageal cancer.

[1105] For example, the tumor may be selected from tumors associated with the expression of the following groups: 5T4, AGS-16, ANGPTL4, ApoE, CD19, CTGF, CXCR5, FGF2, MCPT8, MFI2, MS4A7, NCA, Sema5b, SLITRK6, STC2, TGF, O772P, 5T4, ACTA2, ADGRE1, AG-7, AIF1, AKR1C1, AKR1C2, ASLG659, Axl, B7H3, BAFF-R, BCMA, BMPR1B, BNIP3, C1QA, C1QB, CA6, CADM1, CCD79b, CCL5, CCR5, CCR7, CD1lc, CD123, CD138, CD142, CD147, CD166, CD19, CD19,CD22, CD21, CD20, CD205, CD22, CD223, CD228, CD25, CD30, CD33, CD37, CD38, CD40, CD45, CD45(PTPRC), CD46, CD47, CD49D(ITGA4), CD56, CD66e, CD70, C D71, CD72, CD74, CD79a, CD79b, CD80, CDCP1, CDH11, CDllb, CEA, CEACAM5, c-Met, COL6A3, COL7A1, CRIPTO, CSF1R, CTSD, CTSS, CXCL11, CXCL10, DDIT4, D LL3, DLL4, DR5, E16, EFNA4, EGFR, EGFRvIII, EGLN, EGLN3, EMR2, ENPP3, EpCAM, EphA2, EphB2R, ETBR, FcRH2, FcRHl, FGFR2, FGFR3, FLT3, FOLR-α, GD2, GE DA, 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, KIS S1R, KRT33A, LIV-1, LOX, LRP-1, LRRC15, LUM, LY64, LY6E, Ly86, LYPD3, MDP, MMP10, MMP14, MMP16, MPF, MSG783, MSLN, MUC-1, NaPi2b, Napi3b, Nectin-4, Nectin-4, NOG, P2X5, pCAD, P-Cadherin, PDGFRA, PDK1, PD-L1, PFKFB3, PGF, PGK1, PIK3AP1, PIK3CD, PLOD2, PSCA, PSCAhlg, PSMA, PSMA, PTK7, P-cadherin RNF43, NaPi2b, ROR1, ROR2, SERPINE1, SLC39A6, SLTRK6, STAT1, STEAP1, STEAP2, TCF4, TENB2, TGFB1, TGFB2, TGFBR1, TNFRSF21, TNFSF9, Trop-2, TrpM4, Tyro7, UPK1B, VEGFA, WNT5A, epidermal growth factor, short proteoglycans, mesothelin, sodium phosphate cotransporter 2B, occlusive protein 18.2, endothelial peptide receptors, mucins (such as mucin 1 and mucin 16), guanylate cyclase C, integrin a4p7, integrin a5p6, trophoblast cell glycoproteins, and tissue factor.

[1106] The compounds described in this application can possess inhibitory activity against the in vitro proliferation of tumor cells. This inhibitory activity can be defined as a decrease in the proliferation capacity of tumor cells by more than 1%, 2%, 4%, 5%, 8%, 10%, 15%, 18%, 20%, 25%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% when the compound is added to the culture medium of tumor cells, compared to the addition of a negative control or control drug. For example, the inhibitory activity can be defined as an effect on the IC50 of tumor cells. 50 The value (nM) can be below 10000, below 5000, below 4000, below 3000, below 2000, below 1000, below 500, below 400, below 300, below 200, below 150, below 120, below 110, below 100, below 99, below 98, below 97, below 95, below 90, below 80, below 75, below 70, below 65, below 62, below 60, below 50, below 40, below 30, below 25, below 23, below 22, below 20, below 19, below 18, below 18.5, below 17, below 15, below 12, below 10, below 9. Below 8.5, below 7, below 6.7, below 6, below 5.9, below 5.5, below 5.0, below 4.8, below 4.5, below 4.4, below 4, below 3.5, below 3, below 2.5, below 2, below 1.5, below 1.0, below 0.5, below 0.3, below 0.29, below 0.25, below 0.21, below 0.20, below 0.18, below 0.17, below 0.15, below 0.12, below 0.10, below 0.09, below 0.08, below 0.07, below 0.06, below 0.05, below 0.04, below 0.03, below 0.02, or below 0.01. For example, the tumor cells may include, but are not limited to, solid tumor cells, such as gastric cancer cells or breast cancer cells, such as NCI-N87 cells, JIMT-1 cells or MBA-MB-231 cells.

[1107] The compounds described in this application may possess targeted inhibitory properties. This targeted inhibitory property can be defined as follows: when the compound is added to a culture medium containing tumor cells highly expressing a specific target, compared to the addition of a negative control or control drug, the proliferation capacity of the tumor cells highly expressing the specific target decreases by more than 1%, 2%, 4%, 5%, 8%, 10%, 15%, 18%, 20%, 25%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. For example, the targeted inhibitory property can be defined as an IC50 effect on tumor cells highly expressing a specific target. 50 The value (nM) can be below 10000, below 5000, below 4000, below 3000, below 2000, below 1000, below 500, below 400, below 300, below 200, below 185, below 150, below 120, below 110, below 100, below 99, below 98, below 97, below 95, below 91, below 80, below 74, below 70, below 65, below 62, below 60, below 50, below 40, below 30, below 25, below 23, below 22, below 20, below 19, below 18, below 18.5, below 17, below 15, below 12, below 10, 9 Below, below 8.5, below 7, below 6.7, below 6, below 5.9, below 5.5, below 5.0, below 4.8, below 4.5, below 4.4, below 4, below 3.5, below 3, below 2.5, below 2, below 1.5, below 1.0, below 0.5, below 0.3, below 0.29, below 0.25, below 0.21, below 0.20, below 0.18, below 0.17, below 0.15, below 0.12, below 0.10, below 0.09, below 0.08, below 0.07, below 0.06, below 0.05, below 0.04, below 0.03, below 0.02, or below 0.01. For example, tumor cells that highly express the specific target may include, but are not limited to, solid tumor cells. For instance, tumor cells that highly express the specific target may include, but are not limited to, gastric cancer cells or breast cancer cells. For example, tumor cells that highly express the specific target may include, but are not limited to, NCI-N87 cells or JIMT-1 cells. The specific target may include, but is not limited to, HER2 or TROP2.

[1108] The compounds described in this application may possess plasma stability. This plasma stability means that when the compound is added to plasma, the release rate of the cytotoxic drug released by the compound does not exceed 50%, 40%, 30%, 20%, 10%, 7%, 5%, 4%, 3%, 2%, 1.9%, 1.8%, 1.7%, 1.6%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1.0%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1%.

[1109] The compounds described in this application can have an in vivo tumor-suppressing effect. This tumor-suppressing effect can be demonstrated by the following: when the compounds of this application are administered to animals, compared to the addition of a negative control or control drug, the tumor volume of the animals is reduced by more than 1%, 2%, 4%, 5%, 8%, 10%, 15%, 18%, 20%, 25%, 40%, 50%, 55%, 60%, 70%, 73%, or 75% at 1, 3, 5, 7, 14, 20, 21, or 30 days, respectively. The tumor volume of the animal decreased by more than 1.1 times, 1.3 times, 1.5 times, 2 times, 3 times, 5 times, 10 times, 20 times, 22 times, 30 times, 50 times, 100 times, 500 times, 1000 times, or 1500 times or more at 1 day, 3 days, 5 days, 7 days, 14 days, 20 days, 21 days, or 30 days, or compared to the administration of a negative control or control drug. The animal may include, but is not limited to, mammals, such as cats, dogs, horses, pigs, cows, sheep, rabbits, mice, rats, monkeys, or humans. The administration may include, but is not limited to, oral administration, intravenous injection, intravenous infusion, intraperitoneal injection, or local administration.

[1110] The compounds described in this application may exhibit a bystander effect. This bystander effect can mean that the compounds of this application have no significant inhibitory effect on the cell proliferation of tumor cells with low expression of a specific target, but in co-culture of tumor cells with low expression of a specific target and tumor cells with high expression of a specific target, the compounds of this application can simultaneously inhibit the cell proliferation of both types of tumor cells. For example, in co-culture of tumor cells with low expression of a specific target and tumor cells with high expression of a specific target, the inhibitory activity can be defined as an IC50 value against tumor cells with low expression of a specific target. 50The value (nM) can be below 10000, below 5000, below 4000, below 3000, below 2000, below 1000, below 500, below 400, below 300, below 200, below 185, below 150, below 120, below 110, below 100, below 99, below 98, below 97, below 95, below 91, below 80, below 74, below 70, below 65, below 62, below 60, below 50, below 40, below 30, below 25, below 23, below 22, below 20, below 19, below 18, below 18.5, below 17, below 15, below 12, below 10, 9 Below, below 8.5, below 7, below 6.7, below 6, below 5.9, below 5.5, below 5.0, below 4.8, below 4.5, below 4.4, below 4, below 3.5, below 3, below 2.5, below 2, below 1.5, below 1.0, below 0.5, below 0.3, below 0.29, below 0.25, below 0.21, below 0.20, below 0.18, below 0.17, below 0.15, below 0.12, below 0.10, below 0.09, below 0.08, below 0.07, below 0.06, below 0.05, below 0.04, below 0.03, below 0.02, or below 0.01. Compared to tumor cells that highly express a specific target, tumor cells with low expression of that target may exhibit a reduction in the expression of that specific target by more than 1%, 2%, 4%, 5%, 8%, 10%, 15%, 18%, 20%, 25%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%. For example, tumor cells with high expression of the specific target may include, but are not limited to, solid tumor cells, such as gastric cancer cells or breast cancer cells, and may include, but are not limited to, NCI-N87 cells or JIMT-1 cells. Similarly, tumor cells with low expression of the specific target may include, but are not limited to, solid tumor cells, such as breast cancer cells, and may include, but are not limited to, HCC1187 cells.

[1111] The compounds described in this application may possess antitransporter transport capabilities. This antitransporter capability can be defined as a reduction in the efflux ratio of the compound compared to a standard of the transport substrate, which is 1% or more, 2% or more, 4% or more, 5% or more, 8% or more, 10% or more, 15% or more, 18% or more, 20% or more, 25% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 95% or more. For example, the efflux ratio test can be a method commonly used by those skilled in the art, or it may be described in the embodiments of this application.

[1112] The compounds described in this application may possess in vivo tumor-targeting capability. This in vivo targeting capability can refer to the distribution of the labeled compound in the tumor tissue of an animal, compared to other tissues and organs, being increased by more than 1%, 2%, 4%, 5%, 8%, 10%, 15%, 18%, 20%, 25%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or by more than 1.1 times, 1.3 times, 1.5 times, 2 times, 3 times, 5 times, 10 times, 20 times, 22 times, 30 times, 50 times, 100 times, 500 times, 1000 times, or 1500 times. The signaling substance may be a radioactive substance, and for example, the signaling substance includes, but is not limited to, radioactive substances. 125 I. The animal may include, but is not limited to, mammals, such as cats, dogs, horses, pigs, cows, sheep, rabbits, mice, rats, monkeys, or humans. The administration may include, but is not limited to, oral administration, intravenous injection, intravenous infusion, intraperitoneal injection, or local administration. The tissue or organ may include, but is not limited to, the heart, liver, spleen, lungs, kidneys, brain, or bone marrow.

[1113] The compounds described in this application can exhibit good in vivo safety. This in vivo safety can be defined as the release rate of free toxins in animals after administration of the compounds to animals not exceeding 50%, 40%, 30%, 20%, 10%, 7%, 5%, 4%, 3%, 2%, 1.9%, 1.8%, 1.7%, 1.6%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1.0%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1%. For example, the in vivo safety can be defined as the absence of toxic effects in animals. The application concentration of the compound described in this application can be 0.5 mg / kg or higher, 1 mg / kg or higher, 2 mg / kg or higher, 3 mg / kg or higher, 4 mg / kg or higher, 5 mg / kg or higher, 10 mg / kg or higher, 20 mg / kg or higher, 30 mg / kg or higher, 50 mg / kg or higher, 70 mg / kg or higher, 100 mg / kg or higher, 200 mg / kg or higher, 500 mg / kg or higher, or 1000 mg / kg or higher. For example, the animals may include, but are not limited to, cats, dogs, horses, pigs, dairy cows, sheep, rabbits, mice, rats, monkeys, or humans. The application may include, but is not limited to, oral administration, intravenous injection, intravenous infusion, intraperitoneal injection, or local administration.

[1114] Pharmaceutical Composition

[1115] In addition to the active compound, the pharmaceutical composition described in this application may contain one or more excipients, which may be selected from the group consisting of fillers (diluents), binders, wetting agents, disintegrants, and excipients. Depending on the method of administration, the composition may contain 0.1 to 99% by weight of the active compound.

[1116] Pharmaceutical compositions containing active ingredients may be in oral forms, such as tablets, sugar lozenges, tablets, aqueous or oil suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups. Oral compositions may be prepared according to any method known in the art for preparing pharmaceutical compositions, and may contain binders, fillers, lubricants, disintegrants, or pharmaceutically acceptable wetting agents, and may also contain one or more ingredients selected from the group consisting of sweeteners, flavoring agents, coloring agents, and preservatives.

[1117] Aqueous suspensions may contain active substances and excipients suitable for mixing. Aqueous suspensions may also contain one or more preservatives, such as one or more colorants, one or more flavoring agents, and one or more sweeteners. Oil suspensions can be prepared by suspending the active ingredient in vegetable oil. Oil suspensions may contain thickeners. The aforementioned sweeteners and flavoring agents may also be added.

[1118] The pharmaceutical composition may also provide the active ingredient as a dispersible powder or granules for preparing an aqueous suspension, by adding one or more of a water-mixing dispersant, wetting agent, suspending agent, or preservative. Other excipients such as sweeteners, flavoring agents, and coloring agents may also be added. These compositions are preserved by adding antioxidants such as ascorbic acid. The pharmaceutical compositions of this application may also be in the form of an oil-in-water emulsion.

[1119] The pharmaceutical composition may be in the form of a sterile injectable aqueous solution. Acceptable solvents or media that can be used include water, Ringer's solution, and isotonic sodium chloride solution. The sterile injectable formulation may be a sterile injectable oil-in-water microemulsion in which the active ingredient is dissolved in the oil phase. For example, the active ingredient may be dissolved in a mixture of soybean oil and lecithin. The oil solution may then be treated with a mixture of water and glycerol to form a microemulsion. The injection solution or microemulsion may be injected into the patient's bloodstream via local large-volume injection. Alternatively, the solution and microemulsion may be administered in a manner that maintains a constant circulating concentration of the compound of this application. To maintain such a constant concentration, a continuous intravenous delivery device may be used. For example, the device may be a Deltec CADD-PLUS™ 5400 intravenous infusion pump.

[1120] The pharmaceutical composition may be in the form of a sterile injectable aqueous or oil suspension for intramuscular and subcutaneous administration. This suspension may be formulated using suitable dispersants or wetting agents and suspending agents described above, according to known techniques. The sterile injectable formulation may also be a sterile injectable solution or suspension prepared in a parenteral-acceptable, non-toxic diluent or solvent. Alternatively, a sterile fixative oil may be conveniently used as a solvent or suspension medium.

[1121] The compounds of this application may be administered in suppository form for rectal administration. These pharmaceutical compositions can be prepared by mixing the drug with a suitable, non-irritating excipient that is solid at normal temperatures but liquid in the rectum, and thus dissolves in the rectum to release the drug. Such substances include cocoa butter, glycerin gelatin, hydrogenated vegetable oils, polyethylene glycol of various molecular weights, and mixtures of fatty acid esters of polyethylene glycol.

[1122] As is well known to those skilled in the art, the dosage of a drug depends on a variety of factors, including but not limited to: the activity of the specific compound used, the patient's age, the patient's weight, the patient's health status, the patient's behavior, the patient's diet, the timing of administration, the route of administration, the rate of excretion, and the combination of drugs; in addition, the optimal mode of treatment, such as the treatment regimen, the compound described in this application or its tautomers, mesosomes, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, and / or the daily dosage or type of pharmaceutically acceptable salt of the compound or its tautomers, mesosomes, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, can be verified based on conventional treatment protocols.

[1123] Synthesis technology solution

[1124] To achieve the synthetic objective of this disclosure, the present application employs the following synthetic technique:

[1125] Option 1A:

[1126] The preparation method of the compound represented by the general formula (IE) of this disclosure or a pharmaceutically acceptable salt or solvate thereof, the method comprising:

[1127]

[1128] Step 1: Compounds of general formula (Y1) and (KI3) are reacted under alkaline conditions in the presence of a condensing agent to obtain compound of general formula (IEM).

[1129] Step 2: Remove the protecting group from the general formula (IEM) compound to obtain the general formula (IE) compound.

[1130] in:

[1131] Rp is a hydroxyl protecting group;

[1132] R 1 L 1 L 2 As defined in any of the formulas (IA) in the implementation of the first aspect.

[1133] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1134] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1135] Option 1B

[1136] The preparation method of the compound represented by the general formula (IE) of this disclosure or a pharmaceutically acceptable salt or solvate thereof, the method comprising:

[1137]

[1138] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-;

[1139] L 2 -(C(R) 3a (R) 3b )) m -R,

[1140] Where L 2 Zero or more methylene units are each independently converted by -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1141] L 1 -(C(R) 5a (R) 5b )) n -,

[1142] Where L 1 Zero or more methylene units are each independently converted by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1143] -Cy- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cy- is unsubstituted or independently substituted by one or more substituents R. 7 replace;

[1144] For example, where R 3a With R 5a Together with the atoms between them, they form a ring B, which is selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or has one or more substituents R. 8 Replace, each R 3b R 4 R 5b R 6 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups, or R3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each and each optionally, independently, together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or formed by one or more substituents R. 8 replace;

[1145] For example, where R 4 With R 5a Together with the atoms between them, they form a ring B, which is selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or has one or more substituents R. 8 Replace, each R 3a R 3b R 5b R 6 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each and each optionally, independently, together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or formed by one or more substituents R. 8 replace;

[1146] For example, where R 3a With R 6Together with the atoms between them, they form a ring B, which is selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein the ring B is unsubstituted or has one or more substituents R. 8 Replace, each R 3b R 4 R 5a R 5b Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each and each optionally, independently, together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or formed by one or more substituents R. 8 replace;

[1147] For example, where R 4 With R 6 Each and each optionally, independently, together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or formed by one or more substituents R. 8 Replace, each R 3a R 3b R 5a R 5b Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b-SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each and each optionally, independently, together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or formed by one or more substituents R. 8 replace;

[1148] Each R 2 R 7 R 8 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[1149] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[1150] m and n are each independently selected from integers greater than or equal to 1.

[1151] Step 1: Compounds of general formula (Y1-2) and compound of general formula (KI4) react under acidic or basic conditions with or without a reducing agent to obtain compound of general formula (IEM).

[1152] Step 2: Remove the protecting group from the general formula (IEM) compound to obtain the general formula (IE) compound.

[1153] in:

[1154] Rp is a hydroxyl protecting group;

[1155] R 1 L 1 L 2 As defined in any of the formulas (IA) in the implementation of the first aspect.

[1156] Reducing agents include, but are not limited to, sodium hydride, calcium hydride, lithium hydride, lithium aluminum hydride, sodium borohydride, lithium borohydride, triethylborohydride, triacetoxyborohydride, and sodium cyanoborohydride.

[1157] The reagents providing acidic conditions include protic acids and Lewis acids, wherein the protic acids include, but are 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 acids include, but are not limited to, boron trifluoride, zinc chloride, magnesium chloride, aluminum chloride, tin chloride, and ferric chloride.

[1158] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, methyl acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1159] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1160] Option 2:

[1161] This disclosure includes a method for preparing a compound of formula (II-E) or formula (II-Ex) or a pharmaceutically acceptable salt or solvate thereof, the method comprising:

[1162]

[1163] Step 1: A compound of general formula (Y2x) or a compound of general formula (Y2y) and a compound of general formula (KI4) are reacted, optionally under basic conditions, in the presence of a condensing agent, to give a compound of general formula (II-Ex-M) or general formula (II-Ey-M).

[1164] Step 2: Remove the protecting group from 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).

[1165] in:

[1166] Rp is a hydroxyl protecting group;

[1167] Among them, L 2 p, ring A, X 1 L 1 As defined in any of (II-Ax) of the embodiments of the first aspect;

[1168] or X 2 , q, ring A, X 1 L 1 As defined in any of the embodiments of the first aspect (II-Ay).

[1169] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1170] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1171] Option 3:

[1172] This disclosure includes a method for preparing the compound of formula (III-E) or a pharmaceutically acceptable salt or solvate thereof, the method comprising:

[1173]

[1174] Compounds of general formula (Y3) and (KI4) react, optionally under basic conditions, in the presence of a condensing agent, to give compounds of general formula (III-E).

[1175] in:

[1176] R 1 X is as defined in any of (III-A) of the embodiments of the first aspect.

[1177] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1178] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1179] Option 4A

[1180] The preparation method of the compound of formula (IF) disclosed herein or a pharmaceutically acceptable salt or solvate thereof, the method comprising:

[1181]

[1182] Step 1: Compounds of general formula (IF-M1A) and general formula (KI3) are reacted under alkaline conditions in the presence of a condensing agent to obtain compound of general formula (IF-M2A).

[1183] Step 2: Remove the protecting group from the compound of general formula (IF-M2A) to obtain the compound of general formula (IF-M3A).

[1184] Step 3: Compounds of general formula (KI1) and (IF-M3A) are reacted in the presence of a condensing agent, optionally under alkaline conditions, to give compound of general formula (IF).

[1185] in:

[1186] Re is an amino protecting group, preferably Fomc.

[1187] W, Y, Z, R L1 R L2 R 1 L 1 L 2 As defined in any of the formulas (IF) in the implementation of the sixth aspect.

[1188] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1189] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1190] Option 4B

[1191] The preparation method of the compound of formula (IF) disclosed herein or a pharmaceutically acceptable salt or solvate thereof, the method comprising:

[1192]

[1193] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-;

[1194] L 2 -(C(R) 3a (R) 3b )) m -R,

[1195] Where L 2 Zero or more methylene units are each independently converted by -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4-, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1196] L 1 -(C(R) 5a (R) 5b )) n -,

[1197] Where L 1 Zero or more methylene units are each independently converted by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1198] -Cy- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cy- is unsubstituted or independently substituted by one or more substituents R. 7 replace;

[1199] Each R 3a R 3b R 4 R 5a R 5b R 6 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R)a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each, independently and optionally together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or independently formed by one or more substituents R. 8 replace;

[1200] Each R 2 R 7 R 8 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[1201] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[1202] m and n are each independently selected from integers greater than or equal to 1.

[1203] Step 1: Compounds of general formula (IF-M1B) and compound of general formula (KI3) are reacted under acidic or basic conditions, with or without a reducing agent, to obtain compound of general formula (IF-M2B).

[1204] Step 2: Remove the protecting group from the compound of general formula (IF-M2B) to obtain the compound of general formula (IF-M3B).

[1205] Step 3: The compound of general formula (KI1) and the compound of general formula (IF-M3B) react in the presence of a condensing agent, optionally under basic conditions, to obtain the compound of general formula (IF).

[1206] in:

[1207] Re is an amino protecting group, preferably Fomc.

[1208] W, Y, Z, R L1 R L2 R 1 L 1 L 2 As defined in any of the formulas (IF) in the implementation of the sixth aspect.

[1209] Reducing agents include, but are not limited to, sodium hydride, calcium hydride, lithium hydride, lithium aluminum hydride, sodium borohydride, lithium borohydride, triethylborohydride, triacetoxyborohydride, and sodium cyanoborohydride.

[1210] The reagents providing acidic conditions include protic acids and Lewis acids, wherein the protic acids include, but are 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 acids include, but are not limited to, boron trifluoride, zinc chloride, magnesium chloride, aluminum chloride, tin chloride, and ferric chloride.

[1211] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, methyl acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1212] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1213] Option 4C

[1214] The preparation method of the compound of formula (IF) disclosed herein or a pharmaceutically acceptable salt or solvate thereof, the method comprising:

[1215]

[1216] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-;

[1217] L 2 -(C(R) 3a (R) 3b )) m -R,

[1218] Where L 2 Zero or more methylene units are each independently converted by -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1219] L 1 -(C(R) 5a (R) 5b )) n -,

[1220] Where L 1 Zero or more methylene units are each independently converted by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1221] -Cy- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cy- is unsubstituted or independently substituted by one or more substituents R. 7 replace;

[1222] Each R 3a R 3b R 4 R 5a R 5b R 6 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R4 With R 6 Each, independently and optionally together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or independently formed by one or more substituents R. 8 replace;

[1223] Each R 2 R 7 R 8 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[1224] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[1225] m and n are each independently selected from integers greater than or equal to 1.

[1226] Step 1: The compound of general formula (IE) and the compound of general formula (KI2) are reacted under optional acidic conditions to give the compound of general formula (IF-M1C).

[1227] Step 2: Remove the protecting group from the compound of general formula (IF-M1C) to obtain the compound of general formula (IF-M2C).

[1228] Step 3: The compound of general formula (KI1) and the compound of general formula (IF-M2C) react in the presence of a condensing agent, optionally under basic conditions, to obtain the compound of general formula (IF).

[1229] Re is an amino protecting group, preferably Fomc.

[1230] W, Y, Z, RL1 R L2 R 1 L 1 L 2 As defined in any of the general formulas (IF) in the implementation of the sixth aspect.

[1231] Reducing agents include, but are not limited to, sodium hydride, calcium hydride, lithium hydride, lithium aluminum hydride, sodium borohydride, lithium borohydride, triethylborohydride, triacetoxyborohydride, and sodium cyanoborohydride.

[1232] The reagents providing acidic conditions include protic acids and Lewis acids, wherein the protic acids include, but are 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 acids include, but are not limited to, boron trifluoride, zinc chloride, magnesium chloride, aluminum chloride, tin chloride, and ferric chloride.

[1233] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, methyl acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1234] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1235] Option 5

[1236] This disclosure includes a method for preparing a compound of formula (II-Fx) or formula (II-Fy) or a pharmaceutically acceptable salt or solvate thereof, the method comprising:

[1237]

[1238] Step 1: Compounds of general formula (II-F-M1x) or general formula (II-F-M1y) and general formula (KI4) are reacted under alkaline conditions in the presence of a condensing agent to give compounds of general formula (II-F-M2x) or general formula (II-F-M2y).

[1239] Step 2: Deprotecting compounds of general formula (II-F-M2x) or general formula (II-F-M2y) yield compounds of general formula (II-F-M3x) or general formula (II-F-M3y).

[1240] Step 3: The compound of general formula (KI1) and the compound of general formula (II-F-M3x) or the compound of general formula (II-F-M3y) are reacted in the presence of a condensing agent, optionally under basic conditions, to give the compound of general formula (II-Fx) or the compound of general formula (II-Fy).

[1241] in:

[1242] Re is an amino protecting group, preferably Fomc.

[1243] W, Y, Z, R L1 R L2 A, X 1 L 1 L 2 p is as defined in any formula (II-Fx) in the implementation of the sixth aspect, or W, Y, Z, R L1 R L2 A, X 1 L 1 X 2 q is as defined in any formula (II-Fy) in the implementation of the sixth aspect.

[1244] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1245] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1246] Option Six

[1247] This disclosure includes a method for preparing the compound of formula (III-F) or its pharmaceutically acceptable salt or solvate, the method comprising:

[1248]

[1249] Step 1: Compounds of general formula (III-F-M1) and (KI4) are reacted under alkaline conditions in the presence of a condensing agent to give compound of general formula (III-F-M2).

[1250] Step 2: Deprotecting the compound of general formula (III-F-M2) yields the compound of general formula (III-F-M3).

[1251] Step 3: The compound of general formula (KI1) and the compound of general formula (III-F-M3), or in the presence of a condensing agent, optionally under basic conditions, react to give the compound of general formula (III-F).

[1252] in:

[1253] Re is an amino protecting group, preferably Fomc.

[1254] W, Y, Z, R L1 R L2 R 1 X is as defined in any of the general formulas (III-F) in the implementation of the sixth aspect.

[1255] The reagents that provide alkaline conditions include organic and inorganic bases. The organic bases include, but are not limited to, triethylamine, diethylamine, N-methylmorpholine, pyridine, hexahydropyridine, N,N-diisopropylethylamine, n-butyllithium, diisopropylaminolithium, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, etc.; the inorganic bases include, but are not limited to, sodium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, etc.

[1256] The condensing agent may be selected from 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride, 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N N',N'-Tetramethylurea hexafluorophosphate, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate, preferably 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride or 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1257] Option 7

[1258] A method for a compound represented by general formula (ID) disclosed herein includes the following steps:

[1259]

[1260] in:

[1261] Ab is a ligand. After Ab is reduced, it reacts with the general formula (IF) to obtain the general formula (ID).

[1262] Reducing agents include, but are not limited to, tris(2-carboxyethyl)phosphine, mercaptoethanol, dithiothreitol, cysteine, reduced glutathione, etc.; in particular, reducing disulfide bonds on antibodies is preferred.

[1263] W, Y, Z, R L1 R L2 R 1 L 1 L 2 As defined in any of the formulas (ID) in the implementation of the fourth aspect.

[1264] Option 8

[1265]

[1266] in:

[1267] Ab is a ligand. After reduction, Ab reacts with general formula (II-F), including general formula (II-Fx) or general formula (II-Fy), to obtain general formula (II-Dx) or general formula (II-Dy).

[1268] Reducing agents include, but are not limited to, tris(2-carboxyethyl)phosphine, mercaptoethanol, dithiothreitol, cysteine, reduced glutathione, etc.; in particular, reducing disulfide bonds on antibodies is preferred.

[1269] W, Y, Z, R L1 R L2 A, X 1 L 1 L 2 p is as defined in any formula (II-Dx) in the implementation of the fourth aspect, or W, Y, Z, R L1 R L2 A, X 1 L 1 X 2 q is as defined in any of the formulas (II-Dy) in the implementation of the fourth aspect.

[1270] Option Nine

[1271]

[1272] in:

[1273] Ab is a ligand. After reduction of Ab, it reacts with general formula (III-F) to give general formula (III-D).

[1274] Reducing agents include, but are not limited to, tris(2-carboxyethyl)phosphine, mercaptoethanol, dithiothreitol, cysteine, reduced glutathione, etc.; in particular, reducing disulfide bonds on antibodies is preferred.

[1275] W, Y, Z, R L1 R L2 R 1 X is as defined in any of the general formulas (III-D) in the implementation of the fourth aspect.

[1276] Technical solution

[1277] 1. A compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises the structure shown in formula (IA):

[1278]

[1279] Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-,-P(R 2 )-, and -S-;

[1280] L 2 -(C(R) 3a (R) 3b )) m -R,

[1281] Where L 2 Zero or more methylene units are each independently converted by -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1282] L 1 -(C(R) 5a (R) 5b )) n -,

[1283] Where L 1 Zero or more methylene units are each independently converted by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1284] -Cy- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cy- is unsubstituted or independently substituted by one or more substituents R. 7 replace;

[1285] Each R 3a R 3b R 4 R 5a R 5b R 6 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups, or R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each, independently and optionally together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or independently formed by one or more substituents R. 8 replace;

[1286] Each R 2 R 7 R 8 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6Aliphatic groups;

[1287] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[1288] m and n are each independently selected from integers greater than or equal to 1.

[1289] 2. The compound according to technical solution 1, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein each R 3a R 3b R 4 R 5a R 5b R 6 Each of these can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups.

[1290] 3. The compound according to technical solution 1, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein R 3a With R 5a R 4 With R 5a R 3a With R 6 、or R 4 With R 6 Each, independently and optionally together with the atoms between them, forms a ring B, said ring B being selected from the group consisting of 5 to 8-membered heterocyclic groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein said ring B is unsubstituted or independently formed by one or more substituents R. 8 replace.

[1291] 4. The compound according to any one of technical solutions 1-3, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically usable salt, wherein m is 1 or 2.

[1292] 5. The compound according to any one of technical solutions 1-4, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein m is 1, L 2 -C(R) 3a (R) 3b )-R.

[1293] 6. The compound according to any one of technical solutions 1-5, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -C(R) 3a (R) 3b )-R, L 2 The 0 methylene units are -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1294] 7. The compound according to any one of technical solutions 1-4, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein m is 2, L 2 -(C(R) 3a (R) 3b ))2-R.

[1295] 8. The compound according to any one of technical solutions 1-4 and 7, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L2 The 0 methylene units are -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1296] 9. The compound according to any one of technical solutions 1-4 and 7, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L 2 One methylene unit is separated by -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1297] 10. The compound according to any one of technical solutions 1-4, 7, and 9, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L 2 One methylene unit is replaced by -C(O)- or -Cy-.

[1298] 11. The compound according to any one of technical solutions 1-4, 7, 9-10, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or its pharmaceutically acceptable salts, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L 2 One methylene unit is replaced by -C(O)-.

[1299] 12. The compound according to any one of technical solutions 1-4, 7, 9-11, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or its pharmaceutically acceptable salts, wherein L 2 -C(O)-C(R) 3a (R) 3b )-R.

[1300] 13. The compound according to any one of technical solutions 1-4, 7, 9-10, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or its pharmaceutically acceptable salts, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L 2 One methylene unit is replaced by -Cy-.

[1301] 14. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-4, 7, 9-10, and 13, wherein L 2 -(C(R) 3a (R) 3b )-Cy-R.

[1302] 15. The compound according to technical solution 1, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein L 2 The 0 methylene units are -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4-, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1303] 16. The compound according to technical solution 1, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein L 2 One methylene unit is separated by -Cy-, -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1304] 17. The compound according to any one of technical solutions 1 and 16, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 One methylene unit is replaced by -C(O)- or -Cy-.

[1305] 18. The compound according to any one of technical solutions 1, 16-17, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 One methylene unit is replaced by -C(O)-.

[1306] 19. The compound according to any one of technical solutions 1-18, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically usable salt, wherein n is 2, 3, or 5.

[1307] 20. The compound according to any one of technical solutions 1-19, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein n is 2, L 1 -(C(R) 5a (R) 5b ))2-.

[1308] 21. The compound according to any one of technical solutions 1-20, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 -(C(R) 5a (R) 5b ))2-,L 1 The 0 methylene units are -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1309] 22. The compound according to any one of technical solutions 1-19, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 -(C(R) 5a (R) 5b ))2-,L 1 One methylene unit is separated by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1310] 23. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19 and 22, wherein L 1 -(C(R) 5a (R) 5b))2-,L 1 One methylene unit is replaced by -C(O)- or -C(=S)-.

[1311] 24. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19 and 22-23, wherein L 1 -(C(R) 5a (R) 5b ))2-,L 1 One methylene unit is replaced by -C(O)-.

[1312] 25. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-19 and 22-24, wherein L 1 -C(R) 5a (R) 5b )-C(O)-.

[1313] 26. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-19 and 22-23, wherein L 1 -(C(R) 5a (R) 5b ))2-,L 1 One methylene unit is replaced by -C(=S)-.

[1314] 27. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-19, 22-23, and 26, wherein L 1 -C(R) 5a (R) 5b )-C(=S)-.

[1315] 28. The compound according to any one of technical solutions 1-19, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein n is 3, L 1 -(C(R) 5a (R) 5b ))3-.

[1316] 29. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19 and 28, wherein L 1 -(C(R) 5a (R) 5b ))3-,L 1 The 0 methylene units are -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1317] 30. The compound according to any one of technical solutions 1-19 and 28, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 -(C(R) 5a (R) 5b ))3-,L 1 One methylene unit is separated by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1318] 31. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19, 28, and 30, wherein L 1 -(C(R) 5a (R)5b ))3-,L 1 One methylene unit is replaced by -C(O)-.

[1319] 32. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-19, 28, 30-31, wherein L 1 -(C(R) 5a (R) 5b ))2-C(O)-.

[1320] 33. The compound according to any one of technical solutions 1-19, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein n is 5, L 1 -(C(R) 5a (R) 5b ))5-.

[1321] 34. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19 and 33, wherein L 1 -(C(R) 5a (R) 5b ))5-,L 1 One methylene unit is -NR 6 - or -O- alternative.

[1322] 35. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-19 and 33-34, wherein L 1 -(C(R) 5a (R) 5b ))5-,L 1 One methylene unit is -NR 6 - Alternative.

[1323] 36. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19 and 33-35, wherein L 1 -(C(R) 5a (R) 5b ))2-NR 6 -(C(R 5a (R) 5b )) 2- .

[1324] 37. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-19 and 33-34, wherein L 1 -(C(R) 5a (R) 5b ))5-,L 1 One methylene unit is replaced by -O-.

[1325] 38. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-19, 33-34, and 37, wherein L 1 -(C(R) 5a (R) 5b ))2-O-(C(R 5a (R) 5b )) 2- .

[1326] 39. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19 and 33, wherein L 1 -(C(R) 5a (R) 5b ))5-,L 1 The two methylene units are each independently bounded by -C(O)- and -NR-. 6 - or -O- alternative.

[1327] 40. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19, 33, and 39, wherein L 1 -(C(R) 5a (R) 5b ))5-,L 1 The two methylene units are each independently bounded by -C(O)- or -NR 6 -

[1328] 41. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19, 33, 39-40, wherein L 1 -C(R) 5a (R) 5b )-C(O)-NR 6-(C(R 5a (R) 5b ))2-.

[1329] 42. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-19, 33, 39-41, wherein L 1 -(C(R) 5a (R) 5b ))2-NR 6 -C(O)-C(R 5a (R) 5b )-.

[1330] 43. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19, 33, and 39, wherein L 1 -(C(R) 5a (R) 5b ))5-,L 1 The two methylene units are each independently replaced by -C(O)- or -O-.

[1331] 44. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19, 33, 39, and 43, wherein L 1 -(C(R) 5a (R) 5b ))2-OC(R 5a (R) 5b )-C(O)-.

[1332] 45. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19 and 33, wherein L 1 -(C(R) 5a (R) 5b ))5-,L 1 The three methylene units are each independently bounded by -C(O)- or -NR 6 - Alternative.

[1333] 46. ​​The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-19, 33, and 45, wherein L 1 -(C(R) 5a(R) 5b ))2-NR 6 -C(O)-C(O)-.

[1334] 47. The compound according to any one of technical solutions 1-18, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 The 0 methylene units are -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1335] 48. The compound according to any one of technical solutions 1-18, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 One methylene unit is separated by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1336] 49. The compound according to any one of technical solutions 1-18 and 48, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 One methylene unit is separated by -C(O)-, -C(=S)-, -NR 6 - or -O- alternative.

[1337] 50. The compound according to any one of technical solutions 1-18, 48-49, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 One methylene unit is replaced by -C(O)- or -C(=S)-.

[1338] 51. The compound according to any one of technical solutions 1-18, 48-50, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 One methylene unit is replaced by -C(O)-.

[1339] 52. The compound according to any one of technical solutions 1-18, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 The two methylene units are each independently bounded by -Cy- and -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1340] 53. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-18 and 52, wherein L 1 The two methylene units are each independently bounded by -C(O)- and -NR-. 6 - or -O- alternative.

[1341] 54. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 1-18 and 52-53, wherein L 1 The two methylene units are each independently bounded by -C(O)- or -NR 6 - Alternative.

[1342] 55. The compound according to any one of technical solutions 1-18, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 The three methylene units are each independently bounded by -Cy-, -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1343] 56. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 1-18 and 55, wherein L 1 The three methylene units are each independently bounded by -C(O)- or -NR 6 - Alternative.

[1344] 57. The compound according to any one of technical solutions 1 and 3, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 3a With R 5a Each of them independently and optionally forms a ring B together with the atoms between them.

[1345] 58. The compound according to any one of technical solutions 1, 3, and 57, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the ring B is a 3- to 10-membered saturated or partially unsaturated heterocyclic group.

[1346] 59. The compound according to any one of technical solutions 1, 3, 57-58, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically usable salt thereof, wherein the ring B is a 3- to 6-membered saturated or partially unsaturated heterocyclic group.

[1347] 60. The compound according to any one of technical solutions 1, 3, 57-59, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically usable salt thereof, wherein ring B is a 5-membered saturated or partially unsaturated heterocyclic group.

[1348] 61. The compound according to any one of technical solutions 1, 3, 57-60, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is a 5-membered saturated heterocyclic group.

[1349] 62. The compound according to any one of technical solutions 1 and 3, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically acceptable salt, wherein R 4 With R 5a Each of them independently and optionally forms a ring B together with the atoms between them.

[1350] 63. The compound according to any one of technical solutions 1, 3, and 62, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically usable salt thereof, wherein the ring B is a 3- to 10-membered saturated or partially unsaturated heterocyclic group.

[1351] 64. The compound according to any one of technical solutions 1, 3, 62-63, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is a 6-membered saturated or partially unsaturated heterocyclic group.

[1352] 65. The compound according to any one of technical solutions 1, 3, 62-64, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is a 6-membered saturated heterocyclic group.

[1353] 66. The compound according to technical solution 1, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein L 2 -C(R) 3a (R) 3b -R, or -(C(R) 3a (R) 3b ))2-R, L 1 -(C(R) 5a (R) 5b ))2-、-(C(R 5a (R)5b ))3-、or-(C(R) 5a (R) 5b ))5-.

[1354] 67. The compound according to any one of technical solutions 1 and 66, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L 1 -(C(R) 5a (R) 5b ))2-.

[1355] 68. The compound according to any one of technical solutions 1, 66-67, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L 1 -(C(R) 5a (R) 5b ))2-,L 1 One methylene unit is separated by -C(O)-, -C(=S)-, -NR 6 - or -O- alternative.

[1356] 69. The compound according to any one of technical solutions 1, 66-68, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L 1 -(C(R) 5a (R) 5b ))2-,L 1 One methylene unit is replaced by -C(O)-.

[1357] 70. The compound according to any one of technical solutions 1, 66-69, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -(C(R) 3a (R) 3b ))2-R, L 1 -C(R) 5a (R) 5b )-C(O)-.

[1358] 71. The compound according to any one of technical solutions 1, 66-70, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 3a With R 5a Each of them independently and optionally forms a ring B together with the atoms between them.

[1359] 72. The compound according to any one of technical solutions 1, 66-71, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the ring B is a 3- to 10-membered saturated or partially unsaturated heterocyclic group.

[1360] 73. The compound according to any one of technical solutions 1, 66-72, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is a 5-membered saturated heterocyclic group.

[1361] 74. The compound according to any one of technical solutions 1 and 66, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -C(R) 3a (R) 3b )-R, L 1 -(C(R) 5a (R) 5b ))2-.

[1362] 75. The compound according to any one of technical solutions 1, 66, and 74, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -C(R) 3a (R) 3b )-R, L 1 -(C(R) 5a (R) 5b ))2-,L 1 One methylene unit is separated by -C(O)-, -C(=S)-, -NR 6 - or -O- alternative.

[1363] 76. The compound according to any one of technical solutions 1, 66, 74-75, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or its pharmaceutically acceptable salts, wherein L 2 -C(R) 3a (R)3b )-R, L 1 -(C(R) 5a (R) 5b ))2-,L 1 One methylene unit is replaced by -C(O)-.

[1364] 77. The compound according to any one of technical solutions 1, 66, 74-76, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 2 -C(R) 3a (R) 3b )-R, L 1 -C(R) 5a (R) 5b )-C(O)-.

[1365] 78. The compound according to any one of claims 1-77, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 1 Selected from the following groups: -O-, -(R) 2 )N-, and -S-.

[1366] 79. The compound according to any one of claims 1-78, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 1 It is -O-.

[1367] 80. The compound according to any one of claims 1-78, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 1 -(R) 2 )N-.

[1368] 81. The compound according to any one of technical solutions 1-78 and 80, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 2 It is hydrogen or C 1-6 Aliphatic groups.

[1369] 82. The compound according to any one of technical solutions 1-78, 80-81, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 1 It is -HN-.

[1370] 83. The compound according to any one of technical solutions 1-82, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the -Cy- is a 6- to 10-membered arylene.

[1371] 84. The compound according to any one of technical solutions 1-83, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the -Cy- is a phenylene oxide.

[1372] 85. The compound according to any one of claims 1-84, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 7 It is hydrogen.

[1373] 86. The compound according to technical solution 1, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein R 3a R 3b Each is independently hydrogen, or R 3a With R 5a Each of them independently and optionally forms a ring B together with the atoms between them.

[1374] 87. The compound according to any one of technical solutions 1 and 86, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically usable salt, wherein the ring B is a 3- to 10-membered saturated or partially unsaturated heterocyclic group.

[1375] 88. The compound according to any one of technical solutions 1, 86-87, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is a 5-membered saturated heterocyclic group.

[1376] 89. The compound according to technical solution 1, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein R 4 It is hydrogen, or R 4 With R 5a Each of them independently and optionally forms a ring B together with the atoms between them.

[1377] 90. The compound according to technical solution 1, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein R 4 It is hydrogen, or R 4 With R 5a Each of them independently and optionally forms a ring B together with the atoms between them.

[1378] 91. The compound according to any one of technical solutions 1, 86-90, or any tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 8 It is hydrogen.

[1379] 92. The compound according to technical solution 1, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R, R a R b Each is independently hydrogen.

[1380] 93. The compound according to technical solution 1, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the ligand-drug conjugate comprises a structure belonging to the group consisting of:

[1381] (IA-1) (IA-2) (IA-3) (IA-4) (IA-5) (IA-6) (IA-7) (IA-8) (IA-9) (IA-10) (IA-11) (IA-12) (IA-13) (IA-14) (IA-15) (IA-16) (IA-17).

[1382] 94. A compound or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the compound comprises the structure shown in formula (II-A):

[1383]

[1384] Where X 1 Selected from the following group: N, P, and saturated or unsaturated C, when X 1 When C is saturated, X 1 R n replace;

[1385] When X 1 When the C is saturated, ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or more R groups. 1a replace;

[1386] Or, when X 1 When the carbon atom is unsaturated (C), ring A is selected from the group consisting of 6- to 10-membered aryl groups, 5- to 8-membered heteroaryl groups, 3- to 10-membered partially unsaturated heterocyclic groups, and 3- to 10-membered partially unsaturated carbocyclic groups, wherein ring A is substituted with 0 or more substituents R. 1b replace;

[1387] Or, when X 1 When N or P, ring A is selected from the group consisting of 5 to 8-membered heteroaryl groups and 3 to 10-membered saturated or partially unsaturated heterocyclic groups, wherein ring A is substituented by 0 or 1 or more R groups. 1c replace;

[1388] When ring A is selected from the group consisting of 6- to 10-membered aryl, 5- to 8-membered heteroaryl, and 3- to 10-membered saturated or partially unsaturated carbocyclic groups, ring A is subjected to p L 2 Instead, the L 2 Not for R n ;

[1389] Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 Substitution, or the ring A comprising q cyclic heteroatoms X 2 And the X 2 Used for direct or indirect ligand connection;

[1390] X 2 Selected from the following groups: N, and P;

[1391] L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection;

[1392] L 3-(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Zero or more methylene units are each independently converted to -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1393] R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-;

[1394] L 1 -(C(R) 5a (R) 5b )) n -, where L 1 When containing a methylene unit, the L 1 Zero or more methylene units are each independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted;

[1395] Each R 1a R 1b R 1c R 2a R 3a R 3b R4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups;

[1396] Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups;

[1397] m and n are each independently selected from integers greater than 0, and p and q are each independently selected from integers greater than 1.

[1398] 95. The compound according to technical solution 94, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein X 1 C is saturated.

[1399] 96. The compound according to any one of technical claims 94-95, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is selected from the group consisting of 3- to 10-membered saturated heterocyclic groups and 3- to 10-membered saturated carbocyclic groups.

[1400] 97. The compound according to any one of technical solutions 94-96, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically usable salt, wherein ring A is a 3- to 10-membered saturated carbocyclic group.

[1401] 98. The compound according to any one of technical solutions 94-97, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically usable salt, wherein ring A is a 3- to 6-membered saturated carbocyclic group.

[1402] 99. The compound according to any one of technical solutions 94-98, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically usable salt, wherein ring A is a 4-membered saturated carbocyclic group.

[1403] 100. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-98, wherein ring A is a 6-membered saturated carbocyclic group.

[1404] 101. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-96, wherein ring A is a 3- to 10-membered saturated heterocyclic group.

[1405] 102. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-96 and 101, wherein ring A is a 3- to 6-membered saturated heterocyclic group.

[1406] 103. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-96 and 101-102, wherein ring A is a 3-membered saturated heterocyclic group.

[1407] 104. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-96, 101-103, wherein ring A comprises one heteroatom.

[1408] 105. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-96 and 101-104, wherein ring A comprises one nitrogen atom.

[1409] 106. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-96 and 101-102, wherein ring A is a 5-membered saturated heterocyclic group.

[1410] 107. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-96, 101-102, and 106, wherein ring A comprises one heteroatom.

[1411] 108. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-96, 101-102, 106-107, wherein ring A comprises one nitrogen atom.

[1412] 109. The compound according to any one of technical solutions 94-108, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is substituted with 0 substituents R. 1a replace.

[1413] 110. The compound according to technical solution 94, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein X 1 It is unsaturated C.

[1414] 111. The compound according to any one of technical solutions 94 and 110, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically usable salt thereof, wherein ring A is selected from the group consisting of 6 to 10 aryl groups and 5 to 8 heteroaryl groups.

[1415] 112. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 110-111, wherein ring A is a 6- to 10-membered aryl group.

[1416] 113. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 110-112, wherein ring A is phenyl.

[1417] 114. The compound according to any one of technical solutions 110-113, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is substituted with 0 substituents R. 1b replace.

[1418] 115. The compound according to technical solution 94, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein X 1 It can be N or P.

[1419] 116. The compound according to technical solution 94 or 115, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein X 1 Let N be the number of elements in the array.

[1420] 117. The compound according to any one of technical claims 94, 115-116, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is selected from the group consisting of 5- to 8-membered heteroaryl groups and 3- to 10-membered saturated heterocyclic groups.

[1421] 118. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 115-117, wherein ring A is a 3- to 10-membered saturated heterocyclic group.

[1422] 119. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 115-118, wherein ring A is a 3- to 6-membered saturated heterocyclic group.

[1423] 120. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 115-119, wherein ring A is a 6-membered saturated heterocyclic group.

[1424] 121. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 115-120, wherein ring A independently comprises two heteroatoms.

[1425] 122. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 115-121, wherein ring A independently comprises two nitrogen atoms.

[1426] 123. The compound according to any one of technical solutions 115-121, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is substituted with 0 substituents R. 1c replace.

[1427] 124. The compound according to technical solution 94, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein formula (II-A) has the structure shown in formula (II-Ax):

[1428] ;

[1429] Wherein, when ring A is selected from the group consisting of 6- to 10-membered aryl, 5- to 8-membered heteroaryl, and 3- to 10-membered saturated or partially unsaturated carbocyclic groups, ring A is subjected to p L 2 replace;

[1430] Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 replace.

[1431] 125. The compound according to technical solution 94, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein formula (II-A) has the structure shown in formula (II-Ay):

[1432] ;

[1433] Wherein ring A is a 3- to 10-membered saturated or partially unsaturated heterocyclic group, and ring A contains q cyclic heteroatoms X. 2 And the X 2 Used for direct or indirect ligand connection.

[1434] 126. The compound according to technical solution 94, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically usable salt thereof, wherein the ring A is selected from the group consisting of 6 to 10 aryl groups, 5 to 8 heteroaryl groups, and 3 to 10 saturated carbocyclic groups.

[1435] 127. The compound according to any one of technical claims 94 and 126, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the ring A is selected from the group consisting of phenyl and 3 to 6 saturated carbocyclic groups.

[1436] 128. The compound according to any one of technical solutions 94, 126-127, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is a 3- to 6-membered saturated carbocyclic group.

[1437] 129. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 126-128, wherein ring A is a 4-membered saturated carbocyclic group or a 6-membered saturated carbocyclic group.

[1438] 130. The compound according to any one of technical solutions 94, 126-127, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is phenyl.

[1439] 131. The compound according to any one of technical solutions 94, 126-130, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is surrounded by one or more L 2 replace.

[1440] 132. The compound according to any one of technical solutions 94, 126-131, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is surrounded by 1 L 2 replace.

[1441] 133. The compound according to any one of technical solutions 94 and 126, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is a 3- to 10-membered saturated heterocyclic group.

[1442] 134. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 126, and 133, wherein ring A is a 3- to 6-membered saturated heterocyclic group.

[1443] 135. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 126, 133-134, wherein ring A is a 3-membered saturated heterocyclic group.

[1444] 136. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 126, 133-134, wherein ring A is a 5-membered saturated heterocyclic group.

[1445] 137. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 126, 133-134, wherein ring A is a 6-membered saturated heterocyclic group.

[1446] 138. The compound according to any one of technical solutions 133-137, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is surrounded by one or more L... 2 replace.

[1447] 139. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 133-138, wherein ring A is surrounded by 1 L 2 replace.

[1448] 140. The compound according to technical solution 94, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically usable salt thereof, wherein m is 0, 1, or 2.

[1449] 141. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94 and 140, wherein m is 0, L 3 It is a covalent bond.

[1450] 142. The compound or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94 and 140, wherein m is 1, L 3 -C(R) 5a (R) 5b )-.

[1451] 143. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 140, and 142, wherein L 3 The 0 methylene units are -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1452] 144. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94 and 140, wherein m is 2, L 3 -(C(R) 3a (R) 3b ))2-.

[1453] 145. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94, 140, and 144, wherein L 3 The 0 methylene units are -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1454] 146. The compound according to any one of technical solutions 94 and 125, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A comprises one or more cyclic heteroatoms X. 2 And the X 2 Used for direct or indirect ligand connection.

[1455] 147. The compound according to any one of technical solutions 94, 125, and 146, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A comprises one of the cyclic heteroatoms X. 2 .

[1456] 148. The compound according to any one of technical solutions 94, 125, 146-147, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein X 2 Let N be the number of elements in the array.

[1457] 149. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-148, wherein n is 0 or 1.

[1458] 150. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-149, wherein n is 0 and L 1 It is a covalent bond.

[1459] 151. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-149, wherein n is 1, L 1 -C(R) 5a (R) 5b )-.

[1460] 152. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-149 and 151, wherein L 1 One methylene unit is -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6-, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted.

[1461] 153. The compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, according to any one of technical solutions 94-149 and 151-152, wherein L 1 One methylene unit is replaced by -C(O)-.

[1462] 154. The compound according to any one of technical solutions 94-153, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 2 Selected from the following groups: -O-, -(R) 2a )N-, and -S-.

[1463] 155. The compound according to any one of technical solutions 94-154, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 2 It is -O-.

[1464] 156. The compound according to any one of technical solutions 94-153, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 2 -(R) 2a )N-.

[1465] 157. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, according to any one of technical solutions 94-153 and 156, wherein R 2a It is hydrogen.

[1466] 158. The compound or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereo...

Claims

1. A general formula (II-E) x The compound shown in the diagram, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein: ， Where X 1 For saturated C, the X 1 R n replace; Ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or at least 1 substituent R. 1a replace; When ring A is a 3- to 10-membered saturated or partially unsaturated carbon cyclic group, ring A is divided by p L... 2 Instead, the L 2 Not for R n ; Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 replace; L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection; L 3 -(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Each of the zero or at least one methylene unit is independently converted to -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-; L 1 -(C(R) 5a (R) 5b )) n -, where L 1 When containing a methylene unit, the L 1 Each of the zero or at least one methylene unit is independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups; Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; m and n are each independently selected from integers at least 0, and p is an integer at least 1.

2. A compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, comprising the formula (II-D) x The structure shown is as follows: ， in, Ab is the ligand, and the average number of connections N is... a Integers or decimals from 1 to 10; The L is -L a -L b -L c -; The -L a -Selected from the following groups: , ,and ; Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp -, Z is -(C(R) za (R) zb )) zn ; Where wn is selected from integers that are at least 0. The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; Where yn is selected from integers that are at least 0, and yp is 0 or 1; Where zn is selected from integers that are at least 0. Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace; Each R wa R wb R za R zb R wx R zx R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or by R r Optional substitution of C 1-6 Aliphatic groups; Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; The -L b - indicates a peptide residue consisting of 2 to 7 amino acids; The -L c -Selected from the following groups: , , , , , ,and ; Where R L1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups; Where X 1 For saturated C, the X 1 R n replace; Ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or at least 1 substituent R. 1a replace; When ring A is a 3- to 10-membered saturated or partially unsaturated carbon cyclic group, ring A is divided by p L... 2 Instead, the L 2 Not for R n ; Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 replace; L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection; L 3 -(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Each of the zero or at least one methylene unit is independently converted to -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-; L 1 -(C(R) 5a (R) 5b )) n -, where L 1 When containing a methylene unit, the L 1 Each of the zero or at least one methylene unit is independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups; Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; m and n are each independently selected from integers at least 0, and p is an integer at least 1.

3. A general formula (II-F) x The compound shown in the diagram, or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, wherein: ， The L x For L ax -L b -L c -; The L ax -Selected from the following groups: , ,and ; Where R hal It is iodine or bromine; Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp -, Z is -(C(R) za (R) zb )) zn ; Where wn is selected from integers that are at least 0. The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; Where yn is selected from integers that are at least 0, and yp is 0 or 1; Where zn is selected from integers that are at least 0. Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace; Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or by R r Optional substitution of C 1-6 Aliphatic groups; Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; The -L b - indicates a peptide residue consisting of 2 to 7 amino acids; The -L c -Selected from the following groups: , , , , , ,and ; Where R L1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups; Where X 1 For saturated C, the X 1 R n replace; Ring A is selected from the group consisting of 3 to 10 saturated or partially unsaturated heterocyclic groups and 3 to 10 saturated or partially unsaturated carbocyclic groups, wherein ring A is substituented by 0 or at least 1 substituent R. 1a replace; When ring A is a 3- to 10-membered saturated or partially unsaturated carbon cyclic group, ring A is divided by p L... 2 Instead, the L 2 Not for R n ; Alternatively, when ring A is a 3- to 10-member saturated or partially unsaturated heterocyclic group, ring A is divided by p L 2 replace; L 2 -R 2 -L 3 -, the R 2 Used for direct or indirect ligand connection; L 3 -(C(R) 3a (R) 3b )) m -, where L 3 When containing a methylene unit, the L 3 Each of the zero or at least one methylene unit is independently converted to -N(R) 4 )C(O)-、-C(O)N(R 4 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 4 -, -O-, -S-, -SO-, -SO2-, -P(R 4 )-、-P(=O)(R 4 )-、-N(R 4 SO2-, -SO2N(R) 4 -, -C(=S)-, -C(=NR) 4 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; R 2 Selected from the following groups: -O-, -(R) 2a -N-, -S-, and -P(=O)(R 2a )-; L 1 -(C(R) 5a (R) 5b )) n -, where L 1 When containing a methylene unit, the L 1 Each of the zero or at least one methylene unit is independently converted to -N(R) 6 )C(O)-、-C(O)N(R 6 )-, -C(O)-, -OC(O)-, -C(O)O-, -NR 6 -, -O-, -S-, -SO-, -SO2-, -P(R 6 )-、-P(=O)(R 6 )-、-N(R 6 SO2-, -SO2N(R) 6 -, -C(=S)-, -C(=NR) 6 -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; Each R 1a R 2a R 3a R 3b R 4 R 5a R 5b R 6 R n Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups; Where each R, R a R b Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; m and n are each independently selected from integers at least 0, and p is an integer at least 1.

4. The compound according to any one of claims 1-3, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is selected from the group consisting of 3- to 10-membered saturated heterocyclic groups and 3- to 10-membered saturated carbocyclic groups.

5. The compound according to any one of claims 1-3, or its tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or its pharmaceutically usable salt, wherein ring A is a 3- to 6-membered saturated carbocyclic group.

6. The compound according to any one of claims 1-3, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is a 4-membered saturated carbocyclic group.

7. A compound of general formula (III-E) or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein: Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-; X is -L 1 -CH2-C(O)-; L 1 -(C(R) 3a (R) 3b )) m -, where L 1 The zero or at least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b - or -C(=N2)- substitution; Each R 2 R 3a R 3b R 4b Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups; Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; m is selected from an integer that is at least 0, and n is selected from an integer that is at least 1; When R 1 When L is -O- or -HN-, 1 At least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b )- or -C(=N2)- substitution, or each R 3a R 3b They are not both hydrogen.

8. A compound or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, comprising the structure shown in formula (III-D): in, Ab is the ligand, and the average number of connections N is... a Integers or decimals from 1 to 10; The L is -L a -L b -L c -; The -L a -Selected from the following groups: , ,and ; Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp Z is -(C(R) za (R) zb )) zn ,; Where wn is selected from integers that are at least 0. The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; Where yn is selected from integers that are at least 0, and yp is 0 or 1; Where zn is selected from integers that are at least 0. Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace; Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or by R r Optional substitution of C 1-6 Aliphatic groups; Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; The -L b - indicates a peptide residue consisting of 2 to 7 amino acids; The -L c -Selected from the following groups: , , , , , ,and ; Where R L1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups; Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-; X is -L 1 -CH2-C(O)-; L 1 -(C(R) 3a (R) 3b )) m -, where L 1 The zero or at least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b - or -C(=N2)- substitution; Each R 2 R 3a R 3b R 4b Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups; Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; m is selected from an integer that is at least 0, and n is selected from an integer that is at least 1; When R 1 When L is -O- or -HN-, 1 At least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b )- or -C(=N2)- substitution, or each R 3a R 3b They are not both hydrogen.

9. A compound of general formula (III-F) or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein: ， The L x For L ax -L b -L c -; The L ax -Selected from the following groups: , ,and ; Where R hal It is iodine or bromine; Where W is -(C(R) wa (R) wb )) wn -, Y is -(OCH2CH2) yn -O yp Z is -(C(R) za (R) zb )) zn ,; Where wn is selected from integers that are at least 0. The zero or at least one methylene unit of W is independently converted by -Cyr-, -N(R) wx )C(O)-、-C(O)N(R wx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR wx -, -O-, -S-, -SO-, -SO2-, -P(R wx )-、-P(=O)(R wx )-、-N(R wx SO2-, -SO2N(R) wx -, -C(=S)-, -C(=NR) wx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; Where yn is selected from integers that are at least 0, and yp is 0 or 1; Where zn is selected from integers that are at least 0. Zero or at least one methylene unit of Z is independently converted by -Cyr-, -N(R) zx )C(O)-、-C(O)N(R zx )-, -C(O)-, -OC(O)-, -C(O)O-, -NR zx -, -O-, -S-, -SO-, -SO2-, -P(R zx )-、-P(=O)(R zx )-、-N(R zx SO2-, -SO2N(R) zx -, -C(=S)-, -C(=NR) zx -, -N=N-, -C=N-, -N=C- or -C(=N2)- can be substituted; -Cyr- is selected from the group consisting of 6- to 10-membered arylene, 5- to 8-membered heteroarylene, 3- to 10-membered heterocyclic, and 3- to 10-membered saturated or partially unsaturated carbocyclic, wherein -Cyr- is unsubstituted or independently substituent R. cx replace; Each R wa R wb R za R zb R wx R zx ,R cx Each can be independently represented as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, or -OR. r -SR r -N(R) ra (R) rb -C(O)R r -CO2R r -C(O)C(O)R r -C(O)CH2C(O)R r -S(O)R r -S(O)2R r -C(O)N(R) ra (R) rb -SO2N(R) ra (R) rb -OC(O)R r -N(R)SO2R r or by R r Optional substitution of C 1-6 Aliphatic groups; Each R r R ra R rb Each of these can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; The -L b - indicates a peptide residue consisting of 2 to 7 amino acids; The -L c -Selected from the following groups: , , , , , ,and ; Where R L1 R L2 Each of the following is independently selected: hydrogen, protium, deuterium, tritium, halogens, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, and C 1-6 Aliphatic groups; Where R 1 Selected from the following groups: -O-, -(R) 2 )N-,-P(=O)(R 2 )-, and -S-; X is -L 1 -CH2-C(O)-; L 1 -(C(R) 3a (R) 3b )) m -, where L 1 The zero or at least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b - or -C(=N2)- substitution; Each R 2 R 3a R 3b R 4b Each can be independently classified as hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OR, -SR, -N(R) a (R) b ), -C(O)R, -CO2R, -C(O)C(O)R, -C(O)CH2C(O)R, -S(O)R, -S(O)2R, -C(O)N(R a (R) b -SO2N(R) a (R) b -OC(O)R, -N(R)SO2R, or C substituted by R (optionally) 1-6 Aliphatic groups; Where each R, R a R b Each can be independently hydrogen, protium, deuterium, tritium, halogen, -NO2, -CN, -OH, -SH, -NH2, -C(O)H, -CO2H, -C(O)C(O)H, -C(O)CH2C(O)H, -S(O)H, -S(O)2H, -C(O)NH2, -SO2NH2, -OC(O)H, -N(H)SO2H, or C 1-6 Aliphatic groups; m is selected from an integer that is at least 0, and n is selected from an integer that is at least 1; When R 1 When L is -O- or -HN-, 1 At least one methylene unit is independently converted by -C(O)-, -C(=S)-, or -C(=NR)-. 4b )- or -C(=N2)- substitution, or each R 3a R 3b They are not both hydrogen.

10. The compound according to any one of claims 7-9, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein X is -L 1 -CH2-C(O)-, L 1 -(C(R) 3a (R) 3b )) m -, m is not 0, each R 3a R 3b They are not both hydrogen.

11. The compound according to any one of claims 7-9, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein m is 1, L 1 -C(R) 3a (R) 3b )-.

12. The compound according to any one of claims 7-9, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L 1 The 0 methylene units are replaced by -C(O)-, -C(=S)-, -C(=NR)-. 4b )- or -C(=N2)- substitution.

13. The compound according to any one of claims 7-9, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 3a C 1-6 Aliphatic groups.

14. The compound according to any one of claims 7-9, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 3b It is hydrogen or C 1-6 Aliphatic groups.

15. The compound according to any one of claims 7-9, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 1 It is either -O- or -HN-.

16. The compound according to any one of claims 7-9, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R 2 It can be hydrogen or methyl.

17. The compound according to any one of claims 7-9, or a tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R, R a R b It is hydrogen.

18. The compound according to claim 2 or 5, or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically usable salt thereof, wherein Ab is an antibody or an antigen-binding fragment thereof.

19. The compound of claim 18 or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein the ligand Ab targets the group consisting of: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70, and EGFR.

20. The compound according to claim 2 or 5, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein -L a -L b -L c -Selected from the following groups: 。 21. The compound according to claim 3 or 6, or its tautomer, meso compound, racemic mixture, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein L ax -L b -L c -Selected from the following groups: 。 22. A pharmaceutical composition comprising the compound of any one of claims 1-6 or a tautomer, meso compound, racemic compound, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

23. A method for preparing the compound of claim 2 or 5 or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically usable salts thereof, comprising contacting the ligand Ab with the compound of claim 3 or 6.

24. Use of the compound comprising any one of claims 1-21 or its tautomers, meso compounds, racemates, enantiomers, diastereomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, and / or the pharmaceutical composition of claim 22 in the preparation of a medicament for treating and / or preventing tumors.

25. The use as claimed in claim 24, wherein the tumor is selected from tumors associated with expression of the following groups: HER2, HER3, B7H3, TROP2, Claudin 18.2, CD30, CD33, CD70 and EGFR.

26. The use as described in claim 24 or 25, wherein the tumor is selected from the group consisting of: lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer, and esophageal cancer.

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