Fused ring compounds and their complexes and uses

Abstract

The present disclosure relates to fused ring compounds, as well as conjugates and uses thereof. The compounds and conjugates of the present disclosure have excellent tumor cell inhibitory activity, stability, and efficacy in animals. [Summary] Figure 1

Description

[Technical Field]

[0001] This application claims priority from Chinese patent applications having application number 202211545125.3, entitled "Fused Ring Compounds, Complexes Thereof, and Uses Thereof," filed with the State Intellectual Property Office of China on November 22, 2022, and application number 202310683602.0, entitled "Fused Ring Compounds, Complexes Thereof, and Uses Thereof," filed with the State Intellectual Property Office of China on June 9, 2023. The entire texts of the above-mentioned prior applications are incorporated herein by reference.

[0002] The present disclosure relates to fused ring compounds and conjugates thereof and uses, particularly in the pharmaceutical field. [Background technology]

[0003] The concept of antibody-drug conjugates (ADCs), or ADC drugs, has been around for many years. In 1913, Nobel Prize winner Professor Paul Ehrlich first proposed the concept of a "magic bullet," which aimed to achieve highly selective killing of cancer cells by conjugating a cytotoxic drug to a specific monoclonal antibody. Currently available ADC drugs follow this theory by conjugating a cytotoxic drug to a monoclonal antibody, using the monoclonal antibody as a carrier to deliver small molecule cytotoxic drugs to target tumor cells with high efficiency.

[0004] ADC drugs are antibodies linked to small molecule cytotoxic drugs via a specific linker, and their main components include an antibody, a linker, and a small molecule cytotoxic drug. When an ADC drug is taken up into the blood, the antibody component recognizes the target and can bind to tumor cells that highly express cell surface antigens. When the ADC-antigen complex is taken up by tumor cells through endocytosis, the cytotoxic load (drug) is released from the complex by the degradation action of lysosomes, destroying DNA and tissue tumor cell division, thereby killing the tumor cells.

[0005] The first generation of ADC drugs, anti-mouse leukocyte immunoglobulin conjugated with methotrexate, was first used to treat leukemia in 1958. Mylotarg was the first ADC drug and was approved by the FDA in 2000 for the treatment of acute myeloid leukemia. However, it was discontinued due to the severe, fatal liver damage it caused and lack of significant survival benefits. The drawbacks of first-generation ADC drugs are that the antibody is a murine antibody, which has insufficient cytotoxicity and low site expression.

[0006] The starting point for second-generation ADC drug development was enmetratuzumab, the first approved ADC drug targeting breast cancer. The most successful ADC drug in the field of hematological malignancies is brentuximab, primarily targeted at classical Hodgkin's lymphoma and anaplastic large cell lymphoma. The advantages of second-generation ADC drugs include the development of diverse target antigens and humanized antibodies. Their disadvantages include low or high drug loading rates, a narrow therapeutic window, and poor efficacy.

[0007] A representative example of a third-generation ADC drug is enfortumab, the second ADC drug targeting solid tumors. This drug is indicated for patients who are refractory to PD-1 / PD-L1 antibody therapy, but it is characterized by low sensitivity to microtubule protein inhibitors.

[0008] Currently, there is a demand for the development of drug molecules and their conjugates with rational molecular structure design and improved pharmacological activity. Summary of the Invention

[0009] In order to solve the above technical problems, the present disclosure provides a complex represented by the following formula (C), a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof: [ka] where Tp indicates the target site, L is selected from a chemical bond or a linker; G represents a group represented by the following formula (G). [ka] where A is N or CR A Selected from. If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R B and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0010] A is CR A If R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R C and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, alkyloxy, cycloalkyloxy, alkyloxyalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0011] Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R DForms a 3- to 10-membered ring structure substituted with

[0012] z is selected from 0 or 1.

[0013] R 2 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0014] R 3 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0015] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a cyclic structure (e.g., a 5- to 10-membered cyclic structure) substituted with, wherein the 5- to 10-membered cyclic structure may be selected from, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0016] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a cyclic structure (e.g., a 4- to 10-membered cyclic structure) substituted with, wherein the 4- to 10-membered cyclic structure may be selected from, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0017] R 4is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0018] R 5 is selected from hydroxy groups.

[0019] R 6 is unsubstituted or has one, two or more R G and an amino group, each of which is selected from the following groups substituted with: a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, an alkyl group, an alkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, and an amino group.

[0020] B is absent, a triazole group, -NR 7 - or -N(NR 7 R 8 )- is selected from.

[0021] R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0022] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R10 ) m -(CR 11 R 12 ) n *、#N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*、#S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*、#O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*、#O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )*、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #、*N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#、*S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#、*O-(CR 9 R 10 ) m -(CR 11 R 12) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # indicates the binding site to L and * indicates the binding site to B.

[0023] Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I and selected from the following groups substituted with: alkyl groups, alkyloxy groups, cycloalkyl groups, cycloalkylalkyl groups, cycloalkyloxy groups, aryl groups, arylalkyl groups, aryloxy groups, heteroaryl groups, heteroarylalkyl groups, heteroaryloxy groups, heterocyclyl groups, heterocyclylalkyl groups, and heterocyclyloxy groups.

[0024] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a cyclic structure (e.g., a 3- to 10-membered cyclic structure) substituted with one, two, or more R IFor example, any of the ring structures may be unsubstituted or substituted with one, two or more R I The ring may be a 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group substituted with.

[0025] Each R 13 may be the same or different and may independently be unsubstituted or one, two or more R J and the aryl group is selected from the following groups substituted with: alkyl group, cycloalkyl group, cycloalkylalkyl group, aryl group, arylalkyl group, heteroaryl group, heteroarylalkyl group, heterocyclyl group, heterocyclylalkyl group.

[0026] Each m may be the same or different and is independently selected from integers of 0 to 10. Each n may be the same or different and is independently selected from integers of 0 to 10.

[0027] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R Kand substituted with: alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0028] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L and substituted with: alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0029] Each R L may be the same or different and are each independently selected from deuteration, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH- and heteroarylC(=O)NH-. The wavy line indicates the binding site for L.

[0030] The conditions are: 6 is unsubstituted or contains one, two or more R G when selected from an alkyl group, an alkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group or an amino group substituted with

[0031] A is N and R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E does not form a 5- to 10-membered ring structure substituted with R 7 If is hydrogen, T L is not a chemical bond,

[0032] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a 5- to 10-membered cyclic structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group, and R A is unsubstituted or contains one, two or more R C substituted with: cycloalkyl groups, cycloalkylalkyl groups, cycloalkyloxy groups. Or, B is -N(NR 7 R 8 )-.

[0033] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R Fand forming a 4- to 10-membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0034] According to an embodiment of the present invention, the groups in formula (G) may be independently selected from those defined below.

[0035] A is N or CR A Selected from.

[0036] If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R B and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0037] A is CR A If R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R C and is selected from the following groups substituted with: alkyl, cycloalkyl, cycloalkylalkyl, alkyloxy, cycloalkyloxy, alkyloxyalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0038] Or, R A and R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D It forms a 3- to 10-membered ring structure substituted with

[0039] z is selected from 0 or 1.

[0040] R 2 is a hydrogen atom, a halogen atom, unsubstituted or one, two or more R E and the substituted group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0041] R 3 is a hydrogen atom, a halogen atom, unsubstituted or one, two or more R E and the substituted group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0042] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E The 5- to 10-membered cyclic structure may be selected from, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a heteromonocyclic hydrocarbon group, and a heterobicyclic hydrocarbon group.

[0043] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a 4- to 10-membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0044] R 4 is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0045] R 5 is selected from hydroxy groups.

[0046] R 6 is unsubstituted or has one, two or more R G and a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, each substituted with .

[0047] B is absent, a triazole group, -NR 7 - or -N(NR 7 R 8 )- is selected from.

[0048] R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H and selected from the following groups substituted with: alkyl group, cycloalkyl group, cycloalkylalkyl group, aryl group, arylalkyl group, heteroaryl group, heteroarylalkyl group, heterocyclyl group, heterocyclylalkyl group, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0049] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 )n *、#N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*、#S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*、#O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*、#O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )*、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #、*N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#、*S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#、*O-(CR 9 R10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B.

[0050] Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I and is selected from the following groups substituted with: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group, aryl group, arylalkyl group, aryloxy group, heteroaryl group, heteroarylalkyl group, heteroaryloxy group, heterocyclyl group, heterocyclylalkyl group, and heterocyclyloxy group.

[0051] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a 3-10 membered ring structure substituted with one, two or more R I The ring may be a 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group substituted with.

[0052] Each R13 may be the same or different and independently of each other are unsubstituted or one, two or more R J and the aryl group is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups substituted with .

[0053] m and n may be the same or different and are independently selected from integers of 0 to 10.

[0054] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K and the aryl group is selected from the group consisting of alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, and heteroarylC(=O)NH-.

[0055] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R Land the aryl group is selected from the group consisting of alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, and heteroarylC(=O)NH-.

[0056] Each R L may be the same or different and are each independently selected from deuteration, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, and heteroarylC(=O)NH-.

[0057] According to embodiments of the present invention, the groups in formula (G) may be independently selected from the following definitions:

[0058] A is N or CR A is selected from.

[0059] If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R Band substituted with: alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0060] A is CR A If R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R c and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, alkyloxy, cycloalkyloxy, alkyloxyalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0061] Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D Forms a 3- to 10-membered ring structure substituted with

[0062] z is selected from 0 or 1.

[0063] R 2 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0064] R 3 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0065] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a 5- to 10-membered cyclic structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0066] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a 4- to 10-membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0067] R 4 is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, an amino group, and a cyano group.

[0068] R 5 is selected from hydroxy groups.

[0069] R 6 is unsubstituted or has one, two or more R G cycloalkyl, cycloalkylalkyl, cycloalkyloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, substituted with .

[0070] B is absent, -NR 7 -or-N(NR 7 R 8 )- is selected from.

[0071] R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0072] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*, #O-(CR 9 R 10 )m -(CR 11 R 12 ) n -P(=O)(OR 14 )*, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #, *N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B.

[0073] Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R Iand is selected from the following groups substituted with: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group, aryl group, arylalkyl group, aryloxy group, heteroaryl group, heteroarylalkyl group, heteroaryloxy group, heterocyclyl group, heterocyclylalkyl group, and heterocyclyloxy group.

[0074] Or, R 9 , R 10 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R I and forming a 3- to 10-membered ring structure substituted with, for example, one, two, or more R I and the following groups may be substituted with: a 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a heteromonocyclic hydrocarbon group, or a heterobicyclic hydrocarbon group.

[0075] Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J and the aryl group is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups substituted with .

[0076] m and n may be the same or different and are independently selected from integers of 0 to 10.

[0077] Each RB , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K and the aryl group is selected from the group consisting of alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, and heteroarylC(=O)NH-.

[0078] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L and the aryl group is selected from the group consisting of alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, and heteroarylC(=O)NH-.

[0079] Each R Lmay be the same or different and are each independently selected from deuteration, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, and heteroarylC(=O)NH-.

[0080] According to an embodiment of the present invention, in the formula (G) described in connection with the specification, hydrogen, carbon or other atoms in the structural formula may be optionally replaced with their isotopes, regardless of whether the group is defined as selected from the above definitions or directly plotted in the structural formula, and regardless of whether the group is defined as a substituent or a non-substituent. For example, a hydrogen atom on any group in the formula (G) may be: 1 H, 2 H or 3 Illustratively, in compounds of formula (G), any hydrogen atom in a substituent or ring atom (if present) in an unsubstituted or substituted alkyl group, alkylene group, alkynylene group, phenyl group, pyridinyl group, or lactone group can be independently selected from H. 1 H, 2 H or 3 H.

[0081] According to embodiments of the present invention, the groups in formula (G) may be independently selected from the following definitions:

[0082] A is N or CR A is selected from.

[0083] If A is N, then R 1 teeth, 1 H, 2H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, when A is N, R 1 teeth, 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0084] A is CR A If R A and R1 may be the same or different and may be independently 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R c is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyloxy group, C 1-10 Alkyloxy C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, A is CR A If R A and R 1 may be the same or different and may be independently 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyloxy group, C1-6 Alkyloxy C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0085] Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D and forming a 3-8 membered ring structure (eg, a 3, 4, 5, 6, 7, or 8 membered ring structure) substituted with

[0086] z is selected from 0 or 1.

[0087] R 2 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 2 teeth 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6Alkyl group, C 3-6 Cycloalkyloxy group.

[0088] R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10 Alkyl group, C 3-6 Cycloalkyloxy group.

[0089] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a 5-10 membered cyclic structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0090] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R Fand forming a 4-10 membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0091] R 4 is C 1-10 Alkyl, C 1-10 R is selected from the group consisting of an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group. 4 is C 1-6 Alkyl group, C 1-6 It is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0092] R 5 is selected from hydroxy groups.

[0093] R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0094] B is absent, a triazole group, -NR 7 -or-N(NR 7 R 8)- is selected from.

[0095] R 7 , R 8 may be the same or different and may be independently 1 H, 2 H, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10Aryl C(=O)NH-, 5- or 6-membered heteroaryl C(=O)NH-.

[0096] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​11 R 12 ) n -C(O)#, *S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # indicates the binding site to L and * indicates the binding site to B.

[0097] Each R 9 , R 10 , R 11 , R 12 may be the same or different and are independent of each other. 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, each R 9 , R 10 , R11 , R 12 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0098] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a 3-10 membered ring structure substituted with, for example, one, two or more R IThe ring may be a 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group substituted with.

[0099] Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group. Preferably, each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group.

[0100] m and n may be the same or different and are independently selected from integers of 0 to 10, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0101] Each R B , R C , R D , R E , R F , RG , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0102] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0103] Each R L may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 It is selected from arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-.

[0104] According to an embodiment of the present invention, the groups in formula (G) may be independently selected from the following definitions:

[0105] A is N or CR A Selected from.

[0106] If A is N, then R 1 teeth, 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, when A is N, R 1 teeth, 1 H, 2H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0107] A is CR A In the case of R A and R 1 may be the same or different and may be independently 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyloxy group, C 1-10 Alkyloxy C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 Aryl C(=O)NH-, 5-10 membered heteroaryl C(=O)NH-. Preferably, A is CR A In the case of R A and R 1 may be the same or different and may be independently 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyloxy group, C 1-6 Alkyloxy C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0108] Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D and forming a 3-8 membered ring structure (e.g., a 3, 4, 5, 6, 7, or 8 membered ring structure) substituted with

[0109] z is selected from 0 or 1.

[0110] R 2 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 2 teeth 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group.

[0111] R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10Alkyl group, C 3-6 Cycloalkyloxy group.

[0112] The conditions are: 1 and R 2 and the atom to which they are bonded or R 2 and R 3 and at least one pair of atoms to which they are attached are unsubstituted or one, two or more R E and forming a 4-10 membered cyclic structure substituted with, for example, a 4, 5, 6, 7, 8, 9, or 10 membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0113] R 4 is C 1-10 Alkyl group, C 1-10 is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group, and preferably R 4 is C 1-6 Alkyl group, C 1-6 It is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0114] R 5 is selected from hydroxy groups.

[0115] R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 6-10 Aryl group, C 6-10 Arylalkyl groups, C 6-10 Aryloxy group, 5- to 6-membered heteroaryl group, 5- to 6-membered heteroarylalkyl group, 5- to 6-membered heteroaryloxy group.

[0116] B is absent, a triazole group, -NR 7 -or-N(NR 7 R 8)- is selected from.

[0117] R 7 , R 8 may be the same or different and, independently of each other, 1 H, 2 H, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10Aryl C(=O)NH-, 5- or 6-membered heteroaryl C(=O)NH-.

[0118] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )*, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #, *N(R 13 )-(CR 9 R 10 ) m -(CR11 R 12 ) n -C(O)#, *S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # indicates the binding site to L and * indicates the binding site to B.

[0119] Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent: 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-10 Alkyl, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, each R 9 , R 10 , R11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0120] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a 3-10 membered ring structure substituted with, for example, one, two or more R I The ring may be a 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group substituted with.

[0121] Each R 13may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group. Preferably, each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group.

[0122] m and n may be the same or different and are each independently selected from integers of 0 to 10, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0123] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, an amino group, a nitro group, an unsubstituted group, or one, two or more RK is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0124] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0125] Each R L may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocycloalkyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-.

[0126] According to embodiments of the present invention, the groups in formula (G) may be independently selected from the following definitions:

[0127] A is selected from N.

[0128] R 1 teeth, 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, when A is N, R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0129] z is selected from 0 or 1.

[0130] R 2 teeth, 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 2 teeth 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group.

[0131] R 3 teeth, 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10 Alkyl group, C 3-6 Cycloalkyloxy group.

[0132] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a 5-10 membered ring structure substituted with, for example, 5, 6, 7, 8, 9 or 10 membered monocyclic hydrocarbons, bicyclic hydrocarbons, heteromonocyclic hydrocarbons, heterobicyclic hydrocarbons.

[0133] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a 4-10 membered ring structure substituted with, for example, 4, 5, 6, 7, 8, 9 or 10 membered monocyclic hydrocarbons, bicyclic hydrocarbons, heteromonocyclic hydrocarbons, heterobicyclic hydrocarbons.

[0134] R 4 is C 1-10 Alkyl group, C 1-10 R is selected from the group consisting of an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group. 4 is C 1-6 Alkyl group, C 1-6It is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0135] R 5 is selected from hydroxy groups.

[0136] R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0137] B is -NR 7 -or-N(NR 7 R 8 )- is selected from.

[0138] R 7 , R 8 may be the same or different and may be independently 1 H, 2 H, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0139] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9R 10 ) m -(CR 11 R 12 ) n -C(O)*、#S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*、#O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*、#O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )*、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #、*N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#、*S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#、*O-(CR 9 R 10 ) m -(CR 11 R12 ) n -P(=O)(OR 14 )#, where # indicates the binding site to L and * indicates the binding site to B.

[0140] Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent: 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I is selected from groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I is selected from groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0141] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming 3-10 membered ring structures substituted with, for example, one, two or more R I The hydrocarbon group may be a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with

[0142] Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group. Preferably, each R13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group.

[0143] m and n may be the same or different and are independently selected from integers of 0 to 10, for example 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[0144] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated, halogen atom, hydroxy group, cyano group, nitro group, unsubstituted or one, two or more R K is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated, halogen atom, hydroxy group, cyano group, nitro group, unsubstituted or one, two or more R K is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0145] Each R Kmay be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0146] Each R L may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclylalkyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-.

[0147] According to an embodiment of the present disclosure, R 1 , R 2 together with the quinolyl group to which they are attached form any of the following substructures, where said substructures may be unsubstituted or may contain one, two or more R Emay be substituted with [ka]

[0148] Alternatively, according to an embodiment of the present disclosure, R 2 , R 3 together with the quinolyl group to which they are attached form any of the following substructures, where said substructures may be unsubstituted or may contain one, two or more R F may be substituted with [ka] According to an embodiment of the present disclosure, B is absent, [ka] -NH- or -N(NR 7 R 8 )-, with the proviso that R 7 , R 8 have the definitions given above, independently of each other.

[0149] According to an embodiment of the present disclosure, G is selected from the group represented by the following formula (G-1): [ka] where A, B, T L , R 1 , R 2 , R 3 , R 6 has the definition given above.

[0150] According to an embodiment of the present disclosure, G is selected from groups represented by the following formula (G-2) or (G-3): [ka] [ka] where R A , B, TL , R 1 , R 2 , R 3 , R 6 has the definition given above.

[0151] According to an embodiment of the present disclosure, G is the following group or its wavy part -T L - is selected from groups linked to [ka]

[0152] where A, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , z have the definitions given above.

[0153] According to an embodiment of the present disclosure, G is the following group or its wavy part -T L - is selected from groups bonded to [ka] where A, R 1 , R 2 , R 3 , R 4 , R 7 has the definition given above.

[0154] According to embodiments described herein, G is the following group or its wavy part is -T L - is selected from groups bonded to [ka] where A, R 1 , R 4 , R 6 , R 7 , z has the definition given above.

[0155] According to an exemplary embodiment of the present disclosure, G is the following group or its wavy portion -T L - is selected from groups bonded to [Table 1] [Table 2]

[0156] In the above aspect of the invention, L is selected from a chemical bond or a linker of formula (L) defined below. [ka] where L 1 is the linking moiety to the targeting moiety Tp, and the reactive group L 1 ' to the targeting moiety Tp, and # indicates the binding site for the Tp moiety. For example, L 1 When ' is a maleamido group, L 1 has the following structure: [ka] L 2 is absent or L 1 and L 3 It is a spacer. L 3 is the peptide moiety. L 4 is absent or a peptide moiety and L 5 It is a spacer. L 5 L 4 and the biologically active molecule G, and the reactive group L 5 ' is produced by reaction with a biologically active molecule G or its intermediate, and * indicates the binding site to the biologically active molecule G.

[0157] Depending on the situation, Between the above moieties in L, preferably L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead of: [ka]

[0158] R 16 , R 16 ' may be the same or different, and at least one is a hydrophilic group, and the other is selected from the following substituents: hydrogen, halogen atom, cyano group, amino group, nitro group, unsubstituted or one, two or more R zg Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, aminocarbonyl group.

[0159] The hydrophilic group is a polyethylene glycol group, a C 1-10 Alkyl group or sugar ring-containing group or C 1-6 AlkylNHCO- (e.g., C 1-4 alkylNHCO-), preferably a polyethylene glycol group, more preferably -C(=O)-NH-(CH2CH2O) p -C 1-10 Alkyl group or -NH-(CH2CH2O) p -C 1-10 C substituted with alkyl groups or preferably 1 to 10 hydroxy groups 1-10 alkyl groups, more preferably [ka] Selected from.

[0160] Each p may be the same or different and is independently selected from integers of 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7 or 8.

[0161] Y is O, S, C 1-10alkylene groups, wherein one, two or three methylene groups of said alkylene groups may optionally be replaced by O or S.

[0162] R 14 , R 15 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an amino group, a nitro group, an unsubstituted or one, two or more R zh is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group.

[0163] Or, R 14 , R 15 together with the atoms to which they are attached, one, two or more R zh C replaced with 3-10 Forms a cycloalkyl group.

[0164] Each R zg , R zh may be the same or different and independently represent a halogen atom, a hydroxy group, an amino group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups.

[0165] In some embodiments of the present invention, L is free of hydrophilic or sterically hindering moieties as defined above.

[0166] In a further preferred embodiment of the present invention, L 1 is an optional group L capable of reacting with the targeting moiety Tp 1 ' is formed from L1 " may be a mercapto-reactive group, an amino-reactive group, a carboxyl-reactive group, a proline residue-reactive group, a tyrosine residue-reactive group, a disulfide cross-linking group, or the like. In the case of an antibody into which a non-natural amino acid has been introduced, the " may be selected from click chemistry reactive groups such as ketone, acid, alkyne, cyclopropene, or diene.

[0167] L 1 ' is preferably a mercapto reactive group.

[0168] L 1 L' is more preferably a maleimide group or a substituted maleimide group, and 1 -L 2 is preferably of the following structure:

[0169] It is a fragment obtained from N-(maleimidomethyl)-carboxylic acid-N-hydroxysuccinimide ester, and its structure is as follows: [ka] (q is an integer of 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7, or 8.)

[0170] or a fragment derived from meta-maleimidobenzyl-N-hydroxysuccinimide ester (MBS), the structure of which is as follows: [ka]

[0171] It is a fragment derived from 4-(N-maleimidomethyl)-cyclohexane-1-carboxylic acid succinimide ester (SMCC) and has the following structure: [ka] or L 1’ is preferably a mercapto reactive group of the structure: [ka] Hal is a halogen atom, OMs, OTs, OTf, a nitro group, and optionally one or more R z6 and R is selected from the group consisting of alkyl thioether groups, aryl thioether groups, heteroaryl thioether groups, alkyl sulfoxide groups, aryl sulfoxide groups, heteroaryl sulfoxide groups, alkyl sulfonyl groups, aryl sulfonyl groups, and heteroaryl sulfonyl groups, wherein R z6 are independently H (hydrogen), D (deuterium), halogen atoms, CN, nitro groups, and C 1-6 Alkyl groups, halogenated C 1-6 Alkyl group, C 1-6 It is selected from alkyloxy groups, 6- to 10-membered aryl groups, and 5- to 12-membered heteroaryl groups.

[0172] Het is optionally one or more R z7 wherein R is selected from 5-10 membered heteroaryl groups substituted with z7 are independently H (hydrogen), D (deuterium), halogen atoms, CN, nitro groups, and C 1-4 Alkyl and halogenated C 1-4 The alkyl group is selected from the group consisting of:

[0173] In a preferred embodiment, Hal is preferably a methylsulfonyl group and Het is preferably a pyrimidine.

[0174] In a preferred solution, Hal-Het- is as follows: [ka] Corresponding L 1 The structure of is as follows: [ka] And L 1 '-L 2 is preferably of the following structure: [ka] q is an integer selected from 0-10, with 1, 2, 3, 4, 5, 6, 7 or 8 being preferred.

[0175] R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-4 alkyl group, or R z4 Or R z5 Together, C 3-6 Forms a cycloalkyl group.

[0176] Further, the following are preferred: [ka]

[0177] In a further preferred embodiment of the present invention, L 2 is non-existent, C 1-10 Alkylene group, C 2-10 Alkenylene group, C 2-10 Alkynylene group, C 3-10 Cycloalkyl groups, C 6-12 selected from aryl or 6-12 membered heteroaryl groups or combinations of the above fragments, optionally spaced by carbonyl groups, O, S, N atoms, and optionally C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, halogen atoms, halogenated C 1-6 and any of said alkyl or halogenated alkyl groups together with the C atom to which it is attached is a C 3-6 Forming a cycloalkyl group, L 2 L via any functional group or covalent bond 1 or L 3 It combines with fragments of

[0178] Preferably, L 2 -C(R z4 Rz5 )-CO- to peptide fragment L 3 It binds to the N-terminus of

[0179] In a more preferred embodiment of the present invention, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group.

[0180] In a more preferred embodiment of the present invention, L 2 Ha-(CH2) q -, -(CH2) q -C(=O)-, -(C≡C)-(CH2) q -C(R z4 R z5 )-C(=O)-, where q is an integer from 0 to 10, with 1, 2, 3, 4, 5, 6, 7 or 8 being preferred.

[0181] In a further preferred embodiment of the present invention, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Let's get together and C 3-6 Forms a cycloalkyl group.

[0182] In yet another embodiment of the present invention, L 3is selected from a divalent peptide group comprising 2 to 8 optionally substituted natural or unnatural amino acid residues, any of which may be the same or different and are independently selected from alanine (Ala), cysteine ​​(Cys), aspartic acid (Asp), glutamic acid (Glu), phenylalanine (Phe), glycine (Gly), histidine (His), isoleucine (Ile), lysine (Lys), leucine (Leu), methionine (Met), and the like. The amino acid residues are selected from the group consisting of methylamino acid residues Met, asparagine (Asn), proline (Pro), glutamine (Gln), arginine (Arg), serine (Ser), threonine (Thr), valine (Val), tryptophan (Trp), tyrosine (Tyr), citraline (Cit), norvaline (Nva), norleucine (Nle), selenocysteine ​​(Sec), pyrrolysine (Pyl), homoserine, homocysteine, and demethylpyrrolysine.

[0183] More preferably, L 3is selected from a bivalent peptide group comprising a combination of 2, 3, 4, 5, or 6 optionally substituted natural or non-natural amino acid residues, any of which may be the same or different and are independently selected from alanine (Ala), cysteine ​​(Cys), aspartic acid (Asp), glutamic acid (Glu), phenylalanine (Phe), glycine (Gly), histidine (His), isoleucine (Ile), lysine (Lys), leucine (Leu), methionine (Met), asparagine (Asn), proline, Leucoline (Pro), glutamine (Gln), arginine (Arg), serine (Ser), threonine (Thr), valine (Val), tryptophan (Trp), tyrosine (Tyr), citraline (Cit), norvaline (Nva), norleucine (Nle), selenocysteine ​​(Sec), pyrrolysine (Pyl), homoserine, homocysteine, demethylpyrrolysine, e.g., -ValCit-, -CitVal-, -AlaAla-, -AlaCit-, -CitAla-, -AsnCit-, -CitAsn-, -CitCi t-, -ValGlu-, -GluVal-, -SerCit-, -CitSer-, -LysCit-, -CitLys-, -AspCit-, -CitAsp-, -AlaVal-, -ValAla-, -PheAla-, -AlaPhe-, -PheLys -, -LysPhe-, -ValLys-, -LysVal-, -AlaLys-, -LysAla-, -PheCit-, -CitPhe-, -LeuCit-, -CitLeu-, -IleCit-, -CitIle-, -PheArg-, -ArgPhe-, The amino acid residues are selected from the group consisting of -CitTrp-, -TrpCit-, -PhePheLys-, -LysPhePhe-, -DPhePheLys-, -DLysPhePhe-, -GlyPheLys-, -LysPheGly-, -GlyPheLeuGly-, -GlyLeuPheGly-, -AlaLeuAlaLeu-, -GlyGlyGly-, -GlyGlyGlyGly-, -GlyPheValGly-, -GlyValPheGly-, -GlyGlyPheGly-, and -AlaAlaAla-.

[0184] Most preferably, L3 is -GlyGlyPheGly-.

[0185] In yet another embodiment of the present invention, L 4 is preferably a group having self-cleavage properties, and a self-cleaving or self-immolative group causes release of the drug by an intramolecular reaction, such as 1,4-elimination, 1,6-elimination, or cyclic elimination, independent of the action of an enzyme.

[0186] L 5 is any reactive group L 5 ' with a biologically active molecule or its intermediate, 5 is preferably a carboxylic acid group or an active ester group, and reacts with OH, SH, or NH or NH2 in the biologically active molecule to form L 5 The structure is -C(O)O-, -C(O)S-, -C(O)N-, or -C(O)NH- (containing the O, S, and N atoms in the biologically active molecule).

[0187] L 4 -L 5 is preferably PABC spacer arm, its structure is as follows: [ka] The structure of the GABA spacer arm is as follows: [ka] α,α-dimethyl GABA spacer arm, the structure of which is shown below: [ka] or a β,β-dimethyl GABA spacer arm, the structure of which is shown below: [ka] Most preferably, L 4 -L 5Ga-NR z1 -C(R z2 R z3 )-T L -It is. where: R z1 is H or C1-4 alkyl; R z2 and R z3 may be the same or different and are independently selected from H or C1-4 alkyl; T L is as described above, and L 4 -L 5 or T in G L One of these is chemical bonding.

[0188] In the most preferred embodiment of the present invention, L 1 is generated by coupling a thiol-reactive group selected from a maleimido group, a substituted maleimido group, or Hal-Het- to Tp; L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead of the following hydrophilic moiety is contained: [ka]

[0189] In the most preferred embodiment of the present invention, L 1 is generated by coupling a thiol-reactive group selected from a maleimide group or a substituted maleimide group to Tp, L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead, a steric hindrance moiety such as: [ka]

[0190] In the most preferred embodiment of the present invention, L 1 is generated by coupling a thiol-reactive group selected from Hal-Het- to Tp, L 4 -L 5 Ha-NR z1 -C(R z2 R z3 )-T L - and where: R z1 is H or C 1-4 is an alkyl group, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, T L is as described above, and L 4 -L 5 and T in G L One of these is chemical bonding.

[0191] More preferably, In G, T as defined above L is a chemical bond, and L 4 -L 5 Ha-NR z1 -C(R z2 R z3 )-O-(CH2) m -C(R z4 R z5 )-CO-, where: R z1 is H or C 1-4 is an alkyl group, m is an integer between 0 and 4, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, R z4 and R z5may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 Alkyl group, or R z4 or R z5 Together they form C 3-6 Forms a cycloalkyl group. The present invention further provides a conjugate having the structure: [ka] where Tp is the targeting moiety defined above, D is a bioactive molecular fragment, preferably a molecular fragment having anti-tumor bioactivity.

[0192] wherein L is selected from linkers represented by formula (L), [ka] where L 1 is the linking moiety to the targeting moiety Tp, and the reactive group L 1 ' and the targeting moiety Tp, and # represents the binding site for the Tp moiety. L 2 is absent, or L 1 and L 3 is a spacer for L 3 is the peptide moiety, L 4 is absent, or the peptide moiety and L 5 is a spacer for L 5 L 4 and the bioactive molecule D, and the reactive group L 5 ' is produced by reaction with a bioactive molecule D or its intermediate, where * represents the binding site to D.

[0193] The conditions are as follows: Condition I is as follows: In L, the following hydrophilic moieties are inserted between each of the fragments defined above: [ka]

[0194] Or, as condition II, L 1 is generated by coupling a thiol-reactive group selected from a maleimide group or a substituted maleimide group to Tp, L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead, a steric hindrance moiety such as: [ka]

[0195] Alternatively, condition III is: L 1 is generated by coupling a thiol-reactive group selected from Hal-Het- to Tp, L 4 -L 5 Ha-NR z1 -C(R z2 R z3 )-T L - is. where: R z1 is H or C 1-4 is alkyl, R z2 and R z3 may be the same or different and independently represent H or C 1-4 selected from alkyl, T L is as described above.

[0196] In a further embodiment, L 1is generated by coupling a thiol-reactive group selected from a maleimide group or Hal-Het- to Tp, L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead of: [ka]

[0197] In a further embodiment, In the most preferred embodiment of the present invention, L 1 is generated by coupling a thiol-reactive group selected from Hal-Het- to Tp, L 4 -L 5 is -NR z1 -C(R z2 R z3 )-O-(CH2) m -C(R z4 R z5 )-CO-, where: R z1 is H or C 1-4 is an alkyl group, m is an integer from 0 to 4, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R z4 Or R z5 Let's get together and C 3-6 Forms a cycloalkyl group.

[0198] Or, as condition IV, L 1 -L 2 is produced by coupling a reactive group of the following structure to Tp: [ka] q is an integer from 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7 or 8; R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R z4 Or R z5 Let's get together and C 3-6 Forms a cycloalkyl group, provided that R z4 or R z5 At least one of them is not H.

[0199] More preferably, R z4 or R z5 Together, C 3-6 forming a cycloalkyl group, L 1 -L 2 is most preferably [ka] It is formed by coupling of Tp with

[0200] The present invention further provides intermediates in the synthesis of the conjugates. [ka] where L 1 ', L 2 , L 3 , L 4 , L 5 , G is as defined above.

[0201] The present invention further provides intermediates in the synthesis of the conjugates. [ka] where L 1 ', L 2 , L 3 , L 4 , L 5 , D is as defined above, and the conditions are as follows:

[0202] Condition I is as follows: L has the following hydrophilic portion inserted between each of the above-defined fragments: [ka]

[0203] Or, as condition II, L 1’ is selected from a thiol-reactive group that is a maleamido group or a substituted maleamido group; L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead, a steric hindrance moiety such as: [ka] Or, as condition III, L 1 ' is selected from the group consisting of thiol reactive groups Hal-Het-, L 4 -L 5 is -NR z1 -C(R z2 R z3 )-T L - and where: R z1 is H or C 1-4 is an alkyl group, R z2 and R z3 may be the same or different and independently represent H or C 1-4alkyl groups, T L is as defined above.

[0204] Or, as condition IV, L 1 '-L 2 has the following structure: [ka] q is an integer selected from 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7, or 8; R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group, provided that R z4 or R z5 At least one of them is not H.

[0205] More preferably, R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group. L 1 '-L 2 is most preferably the following structure: [ka] In a further embodiment, L 1 ' is selected from a maleimide group, a substituted maleimide group, or a thiol-reactive group such as Hal-Het-.

[0206] L 1 ' and L 2 Between or L 2 and L 3 Between or L 2Instead of: [ka]

[0207] In a further preferred embodiment, In the most preferred embodiment of the present invention, L 1 ' is selected from the group consisting of Hal-Het- thiol reactive groups, L 4 -L 5 is -NR z1 -C(R z2 R z3 )-O-(CH2) m -C(R z4 R z5 )-CO-. where: R z1 is H or C 1-4 is an alkyl group, m is an integer from 0 to 4, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group.

[0208] Those skilled in the art should understand that the biologically active molecule D can be a compound described in the Chinese, American, or European Pharmacopoeias, or a compound with biological activity or potential biological activity disclosed in other publications. For example, the drug can be selected from cytotoxic drugs, cell growth inhibitory drugs, or immunosuppressive drugs, such as antimicrotubule protein agents, microtubule protein inhibitors, DNA minor groove binders, DNA replication inhibitors, alkylating agents, antibiotics, antifolates, antimetabolites, chemotherapy sensitivity enhancers, topoisomerase inhibitors, nitinine alkaloids, etc. Examples of such cytotoxic drugs include oleic acid, camptothecin, docarbicine, etoposide, mitomycin and mitotaxin alkaloids, taxanes, benzodiazepines or benzodiazepine-containing drugs, and nitinine alkaloids.

[0209] Tp is a targeting moiety (eg, a small molecule ligand, a protein, a polypeptide, a non-protein reagent (eg, a sugar, RNA, or DNA)).

[0210] In some preferred embodiments, the target of Tp is epidermal growth factor, Trop-2, CD37, HER2, CD70, EGFRvIII, Mesothelin, Folate receptor 1, Mucin 1, CD138, CD20, CD19, CD30, SLTRK6, Nectin 4, Tissue factor, Mucin 16, Endothelin receptor, STEAP1, SLC39A6, Guanylylcyclase C, PSMA, CCD79b, CD22, Sodium phosphate cotransporter 2B, GPNMB, Trophoblast glycoprotein, AGS-16, EGFR, CD33, CD66e, CD74, CD56, PD-L1, TACSTD2, DR5, E16, 0772P, MPF, Napi3b, Sema 5b, PSCA. hlg, ETBR, MSG783, STEAP2, TrpM4, CRIPTO, CD21, CD79b, FcRH2, NCA, MDP, IL20Rα, Brevican, EphB2R, ASLG659, PSCA, GEDA, BAFF-R, CD79a, CXCR5, HLA-DOB, P2X5, CD72, LY64 , FcRH1, IRTA2, TENB2, integrin α5β6,α4β7, FGF2, FGFR2, Her3, CA6, DLL3, DLL4, P-cadherin, EpCAM, pCAD, CD223, LYPD3, LY6E, EFNA4, ROR1, SLITRK6, 5T4, ENPP3, Claudin18.2, BMPR1B, Tyro7, c-Met, ApoE, CD1 lc, CD40, CD45(PTPRC), CD49D(ITGA4), CD80, CSF1R, CTSD, GZMB, Ly86, MS4A7, PIK3AP1, PIK3CD, CCR5, IFNG, IL10RA1, I L-6, ACTA2, COL7A1, LOX, LRRC15, MCPT8, MMP10, NOG, SERPINEl, STAT1, TGFBR1, CTSS, PGF, VEGFA, C1QA, C1QB, ANGPTL4, The protein is selected from EGLN, EGLN3, BNIP3, AIF1, CCL5, CXCL10, CXCL11, IFI6, PLOD2, KISS1R, STC2, DDIT4, PFKFB3, PGK1, PDK1, AKR1C1, AKR1C2, CADM1, CDH11, COL6A3, CTGF, HMOX1, KRT33A, LUM, WNT5A, IGFBP3, MMP14, CDCP1, PDGFRA, TCF4, TGF, TGFB1, TGFB2, CDl 1b, ADGRE1, EMR2, TNFRSF21, UPK1B, TNFSF9, MMP16, MFI2, IGF-1R, RNF43, NaPi2b, and BCMA.

[0211] In some preferred embodiments, Tp is a small molecule ligand, such as a folic acid derivative, a glutamic acid urea derivative, a somatostatin derivative, an arylsulfonamide derivative (e.g., a carbonic anidase IX inhibitor), an ICG dye, a cyanine dye, or a derivative thereof.

[0212] According to embodiments of the present disclosure, the preferred ligand is selected from an antibody or an antigen-binding fragment thereof, said antibody being selected from a chimeric antibody, a humanized antibody, or a fully human antibody, preferably a monoclonal antibody.

[0213] According to exemplary embodiments of the present disclosure, the antibody or antigen-binding fragment thereof is selected from at least one of an anti-CD20 antibody, an anti-CD22 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD44 antibody, an anti-CD56 antibody, an anti-CD70 antibody, an anti-CD73 antibody, an anti-CD105 antibody, an anti-CEA antibody, an anti-A33 antibody, an anti-Cripto antibody, an anti-EphA2 antibody, an anti-G250 antibody, an anti-HER2 (ErbB2) antibody, an anti-EGFR antibody, an anti-B7-H3 antibody, an anti-c-Met antibody, an anti-HER3 (ErbB3) antibody, an anti-HER4 (ErbB4) antibody, an anti-MUCl antibody, an anti-LewisY antibody, an anti-VEGFR antibody, an anti-GPNMB antibody, an anti-integrin antibody, an anti-PSMA antibody, an anti-Tenascin-C antibody, an anti-SLC44A4 antibody, or an anti-Mesothelin antibody, or an antigen-binding fragment thereof. The antibody may be a bispecific or multispecific antibody.

[0214] By way of example, the antibody or antigen-binding fragment thereof is selected from at least one antibody or antigen-binding fragment thereof selected from Trastuzumab, Pertuzumab, Nimotuzumab, Enoblituzumab, Emibetuzumab, Inotuzumab, Pinatuzumab, Brentuximab, Gemtuzumab, Bivatuzumab, Lorvotuzumab, cBR96, and Glematumumab or Glembatumumab.

[0215] For example, Trastuzumab has a sequence selected from the following sequences: [ka] [ka]

[0216] Pertuzumab has a sequence selected from the following sequences: [ka] [ka]

[0217] Nimotuzumab has a sequence selected from the following sequences: [ka] [ka]

[0218] Below is the sequence of Patritumab. [ka] [ka]

[0219] According to an embodiment of the present disclosure, the conjugate, its linker, or linker-drug may be selected from any of the following: where u, v, and w are independently selected from integers of 0 to 10 (e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10), G has the definition given above, and LG has the definition given above for Tp. 20 , R 20’ may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R 20 , R 20’ C along with the carbon atoms to which they are attached 3-6 Forms a cycloalkyl group.

[0220] For example, the above C 1-4 The alkyl groups may be independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl groups, 3-6The cycloalkyl group may be selected from a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group.

[0221] For example, R 20 and R 20’ may both be H, or one may not be H, or neither may be H. [Table 3] [Table 4] [Table 5] [Table 6] [Table 7]

[0222] According to an embodiment of the present disclosure, the complex may have a structure as shown in the following formula: [ka] where A, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 11 , R 12 , L 1 , L 2 , Tp has the definition given above.

[0223] According to an embodiment of the present disclosure, the complex may have a structure as shown in the following formula: [ka] where A, R 1 , R 2 , R 3 , R4 , R 7 , R 11 , R 12 , L 1 , L 2 , Tp has the definition given above.

[0224] According to an embodiment of the present disclosure, the complex may have a structure as shown in the following formula: [ka] where R 11 , R 12 , L 1 , L 2 , Tp has the definition given above.

[0225] According to embodiments of the present disclosure, the conjugate may be selected from any of the following: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] where R 11 , R 12 , R 16 , R 16’ has the definition given above.

[0226] For example, R 11 , R 12 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R 11 , R 12 C along with the carbon atoms to which they are attached 3-6 Forms a cycloalkyl group.

[0227] For example, the above C 1-4 The alkyl groups may be independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl groups, 3-6 The cycloalkyl groups may be independently selected from cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups.

[0228] For example, R 11 and R 12 may both be H, or one may not be H, or both may not be H.

[0229] mAb stands for monoclonal antibody.

[0230] y represents the average number of small molecule drugs bound to each monoclonal antibody (DAR), and may be selected from integers or decimals, for example, from 1 to 50, from 1 to 20, or from 1 to 10.

[0231] According to an embodiment of the present disclosure, the complex may have a structure as shown in the following formula: [ka] where R 11 , R 12 , L 1 , L 2 , Tp has the definition given above.

[0232] According to embodiments of the present disclosure, the conjugate may be selected from any of the following: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] where R 11 , R 12 , R 16 , R 16’ are independently defined above.

[0233] mAb stands for monoclonal antibody.

[0234] y represents the average number of small molecule drugs bound to each monoclonal antibody (DAR), and may be selected from integers or decimals, for example, from 1 to 50, from 1 to 20, or from 1 to 10.

[0235] According to an embodiment of the present disclosure, the complex may have a structure as shown in the following formula: [ka] where R 11 , R 12 , L 1 , L 2 , Tp has the definition given above.

[0236] According to embodiments of the present disclosure, the complex may be selected from any of the following: [ka] [ka] [ka] [ka] [ka] [ka] where R 11 , R 12 , R 16 , R 16’ has the definition given above.

[0237] mAb stands for monoclonal antibody. y represents the average number of small molecule drugs bound to each monoclonal antibody (DAR), and may be selected from integers or decimals, for example, from 1 to 50, from 1 to 20, or from 1 to 10.

[0238] According to embodiments of the present disclosure, examples of the complex intermediate linker and drug conjugate may be selected from any of the following: [Table 8] [Table 9] [Table 10] [Table 11] [Table 12] [Table 13] [Table 14] [Table 15] [Table 16] Table 17 Table 18 Table 19 Table 20 Table 21 Table 22 Table 23 Table 24 Table 25 Table 26 Table 27 Table 28 Table 29 Table 30 Table 31 Table 32 Table 33 Table 34 Table 35 Table 36 Table 37 Table 38 Table 39 Table 40 Table 41 Table 42 Table 43 Table 44 Table 45 Table 46 Table 47 Table 48 Table 49 Table 50 Table 51 Table 52 Table 53 Table 54 Table 55 Table 56 Table 57 Table 58 Table 59 Table 60 Table 61 Table 62 Table 63 Table 64 Table 65 Table 66 Table 67 Table 68 [Table 69] [Table 70] [Table 71] [Table 72] [Table 73] [Table 74] [Table 75] [Table 76] [Table 77] [Table 78] [Table 79] [Table 80] [Table 81] [Table 82] [Table 83]

[0239] The present invention further provides a method for preparing the complex, its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide, or pharmacologically acceptable salt, which comprises the steps of: 1st step: L1 '-L 2 -L 3 -L 4 -L 5 providing a linker represented by '(L'); Preferably, in the linker, L 4 -L 5 '-NR z1 -C(R z2 R z3 )-T L - in the carboxylic acid form or the activated ester form of where: R z1 is H or C 1-4 is an alkyl group, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, More preferably, L 4 -L 5 '-NR z1 -C(R z2 R z3 )-O-(CH2) m -C(R z4 R z5 )-CO- in the form of a carboxylic acid or an activated ester, where: R z1 is H or C 1-4 is an alkyl group, m is an integer from 0 to 4, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5Together they form C 3-6 Forms a cycloalkyl group. Step 2: Coupling the linker with an intermediate compound of formula (G') to form L 1 '-L 2 -L 3 -L 4 -L 5 -G(C') coupling intermediate is obtained, wherein the intermediate structure of formula (G') is as follows: [ka] where A, B, T L , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , L 1 ', L 1 , L 2 , L 3 , L 4 , L 5 , L 5 ' are independently defined above, Preferably, the preparation method further comprises a third step of coupling the coupling intermediate of formula (C') with a targeting moiety Tp, In some cases, if necessary, functional groups of the reactants are protected with protecting groups known in the art to allow the reaction to proceed, and the protecting groups are removed after the reaction is complete.

[0240] According to an embodiment of the present invention, the protecting group may be selected from protecting groups known in the art (e.g., a hydroxy protecting group or an amino protecting group) to allow the reaction to proceed.

[0241] The present disclosure further provides compounds in which the above group G is bonded to a hydrogen atom, wherein the T of group G L is bonded to a hydrogen atom.

[0242] The present disclosure further provides a compound represented by the following formula (GH), a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, or a pharmacologically acceptable salt thereof: [ka] where T is HT L is selected from A is N or CR A is selected from If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R B and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0243] A is CR A If R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R C and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, alkyloxy, cycloalkyloxy, alkyloxyalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0244] Or, R A , R 1together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D It forms a 3- to 10-membered ring structure substituted with

[0245] z is selected from 0 or 1.

[0246] R 2 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0247] R 3 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0248] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a substituted ring structure, e.g., a 5-10 membered ring structure, wherein the 5-10 membered ring structure may be selected from, e.g., a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group.

[0249] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a substituted ring structure, e.g., a 4-10 membered ring structure, wherein the 4-10 membered ring structure may be selected from, e.g., a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group.

[0250] R4 is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0251] R 5 is selected from hydroxy groups.

[0252] R 6 is unsubstituted or has one, two or more R G and an amino group, each of which is selected from the following groups substituted with: a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, an alkyl group, an alkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, and an amino group.

[0253] B is absent, a triazole group, -NR 7 - or -N(NR 7 R 8 )- is selected from.

[0254] R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0255] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9R 10 ) m -(CR 11 R 12 ) n *、#N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*、#S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*、#O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*、#O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )*、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#、*O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #、*N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#、*S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#、*O-(CR 9 R 10 ) m -(CR 11 R12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # indicates the binding site to L and * indicates the binding site to B.

[0256] Each R 9 , R 10 , R 11 , R 12 may be the same or different and may be hydrogen, a halogen atom, a cyano group, unsubstituted or one, two or more R I and selected from the following groups substituted with: alkyl groups, alkyloxy groups, cycloalkyl groups, cycloalkylalkyl groups, cycloalkyloxy groups, aryl groups, arylalkyl groups, aryloxy groups, heteroaryl groups, heteroarylalkyl groups, heteroaryloxy groups, heterocyclyl groups, heterocyclylalkyl groups, and heterocyclyloxy groups.

[0257] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I forming a cyclic structure, for example a 3- to 10-membered cyclic structure, substituted with R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I forming a cyclic structure, for example a 3- to 10-membered cyclic structure, substituted with R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a cyclic structure, for example a 3- to 10-membered cyclic structure, substituted with one, two or more R IFor example, any of the ring structures may be unsubstituted or substituted with one, two or more R I The group may be a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with

[0258] Each R 13 may be the same or different and independently represent unsubstituted or one, two or more R J and the aryl group is selected from the following groups substituted with: alkyl group, cycloalkyl group, cycloalkylalkyl group, aryl group, arylalkyl group, heteroaryl group, heteroarylalkyl group, heterocyclyl group, heterocyclylalkyl group.

[0259] Each m may be the same or different and is independently selected from integers of 0 to 10.

[0260] Each n may be the same or different and is independently selected from integers of 0 to 10.

[0261] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R Kand substituted with: alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0262] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L and substituted with: alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0263] Each R L may be the same or different and independently represent deuteration, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclyl group, a heterocyclyloxy group, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, or heteroarylC(=O)NH-.

[0264] The conditions are: 6 is unsubstituted or one, two or more R G when selected from an alkyl group, an alkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group or an amino group substituted with A is N and R 1 , R 2 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R E does not form a 5- to 10-membered ring structure substituted with R 7 If is hydrogen, T L is not a chemical bond, Or, R 1 , R 2 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R E and R A is unsubstituted or one, two or more R C a cycloalkyl group, a cycloalkylalkyl group, or a cycloalkyloxy group substituted with Or, B is -N(NR 7 R 8 )- and Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a 4- to 10-membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0265] According to embodiments of the present invention, the groups in formula (GH) may be independently selected from the following definitions:

[0266] A is N or CR A is selected from.

[0267] If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R B and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0268] A is CR A If R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R C and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, alkyloxy, cycloalkyloxy, alkyloxyalkyl, heterocyclyl, heterocyclyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0269] Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D Forms a 3- to 10-membered ring structure substituted with

[0270] z is selected from 0 or 1. R 2is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0271] R 3 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0272] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a 5- to 10-membered cyclic structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0273] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a 4- to 10-membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0274] R 4 is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0275] R 5 is selected from hydroxy groups. R 6 is unsubstituted or has one, two or more R Gcycloalkyl, cycloalkylalkyl, cycloalkyloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, substituted with .

[0276] B is absent, a triazole group, -NR 7 - or -N(NR 7 R 8 )- is selected from.

[0277] R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0278] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #O-(CR9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )*, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #, *N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B.

[0279] Each R 9 , R 10 , R 11 , R 12may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I and selected from the following groups substituted with: alkyl groups, alkyloxy groups, cycloalkyl groups, cycloalkylalkyl groups, cycloalkyloxy groups, aryl groups, arylalkyl groups, aryloxy groups, heteroaryl groups, heteroarylalkyl groups, heteroaryloxy groups, heterocyclyl groups, heterocyclylalkyl groups, and heterocyclyloxy groups.

[0280] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a 3- to 10-membered ring structure substituted with one, two or more R I The ring structure may be a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with

[0281] Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J and the aryl group is selected from the following groups substituted with: alkyl group, cycloalkyl group, cycloalkylalkyl group, aryl group, arylalkyl group, heteroaryl group, heteroarylalkyl group, heterocyclyl group, heterocyclylalkyl group.

[0282] m and n may be the same or different and are independently selected from integers of 0 to 10.

[0283] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K and substituted with: alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0284] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L and substituted with: alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0285] Each R Lmay be the same or different and are each independently selected from deuteration, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, and heteroarylC(=O)NH-.

[0286] According to an embodiment of the present invention, the groups in formula (GH) may be independently selected from the following definitions:

[0287] A is N or CR A is selected from.

[0288] If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R B and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0289] A is CR A If R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R Cand substituted with: alkyl, cycloalkyl, cycloalkylalkyl, alkyloxy, cycloalkyloxy, alkyloxyalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0290] Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D Forms a 3- to 10-membered ring structure substituted with

[0291] z is selected from 0 or 1.

[0292] R 2 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group. R 3 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and the substituted alkyl group is selected from the following groups: alkyl group, alkyloxy group, cycloalkyl group, cycloalkylalkyl group, cycloalkyloxy group.

[0293] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a 5- to 10-membered cyclic structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0294] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a 4- to 10-membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0295] R 4 is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, an amino group, and a cyano group.

[0296] R 5 is selected from hydroxy groups.

[0297] R 6 is unsubstituted or has one, two or more R G cycloalkyl, cycloalkylalkyl, cycloalkyloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, substituted with .

[0298] B is absent, -NR 7 -or-N(NR 7 R 8 )- is selected from.

[0299] R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H and substituted with: alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0300] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*, #O-(CR<00​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B.

[0301] Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I and the aryl group is selected from the group consisting of alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, and heterocyclyloxy groups.

[0302] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more RI and forming a 3- to 10-membered ring structure substituted with one, two or more R I The hydrocarbon group may be a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with

[0303] Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J and the aryl group is selected from the following groups substituted with: alkyl group, cycloalkyl group, cycloalkylalkyl group, aryl group, arylalkyl group, heteroaryl group, heteroarylalkyl group, heterocyclyl group, heterocyclylalkyl group.

[0304] m and n may be the same or different and are each independently selected from integers of 0 to 10.

[0305] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated, halogen atom, hydroxy group, cyano group, nitro group, unsubstituted or one, two or more R K and substituted with: alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0306] Each R K may be the same or different and independently represent a deuterated, halogen atom, hydroxy group, cyano group, nitro group, unsubstituted or one, two or more R L and substituted with: alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-.

[0307] Each R L may be the same or different and independently represent deuteration, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, NH, HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, or heteroarylC(=O)NH-.

[0308] According to an embodiment of the present invention, in formula (GH) described throughout the specification, hydrogen, carbon or other atoms in the structural formula can be optionally substituted with isotopes. This substitution is possible regardless of whether the group is selected from the definitions above or is directly drawn in the structural formula, and regardless of whether the group is a substituted or unsubstituted group. For example, the hydrogen atom of any group in formula (GH) can be 1 H, 2 H or 3H. For example, any hydrogen atom of a substituent on an unsubstituted or substituted alkyl group, alkylene group, alkylidene group, phenyl group, pyridyl group or lactone group of a compound of formula (GH) or a ring-forming atom thereof (if present) may be selected independently from one another. 1 H, 2 H or 3 H.

[0309] According to embodiments of the present invention, the groups in formula (GH) may be independently selected from the following definitions:

[0310] A is N or CR A is selected from.

[0311] If A is N, then R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, when A is N, R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R Bis selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0312] A is CR A If R A and R 1 may be the same or different and, independently of each other, 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyloxy group, C 1-10 Alkyloxy C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, A is CR A If R A and R 1 may be the same or different and, independently of each other, 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyloxy group, C 1-6 Alkyloxy C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0313] Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D to form a 3-8 membered ring structure, for example a 3, 4, 5, 6, 7 or 8 membered ring structure, substituted with

[0314] z is selected from 0 or 1.

[0315] R 2 teeth1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 2 teeth 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group.

[0316] R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10 Alkyl group, C 3-6 Cycloalkyloxy group.

[0317] Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E The 5- to 10-membered ring structure may be selected from, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a heteromonocyclic hydrocarbon group, or a heterobicyclic hydrocarbon group.

[0318] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F The 4- to 10-membered ring structure may be selected from, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a heteromonocyclic hydrocarbon group, or a heterobicyclic hydrocarbon group.

[0319] R 4 is C 1-10 Alkyl group, C 1-10 It is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group. 4 is C 1-6 Alkyl group, C 1-6 It is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0320] R 5 is selected from hydroxy groups.

[0321] R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0322] B is absent, a triazole group, -NR 7 -or-N(NR 7 R 8 )- is selected from.

[0323] R 7 , R 8 may be the same or different and may be independently 1 H, 2 H, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R His selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0324] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*, #O-(CR 9 R 10 )m -(CR 11 R 12 ) n -P(=O)(OR 14 )*, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #, *N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # indicates the binding site to L and * indicates the binding site to B.

[0325] Each R 9 , R 10 , R 11 , R 12 may be the same or different and, independently of each other, 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0326] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a 3-10 membered ring structure substituted with, for example, one, two or more R I The group may be a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with

[0327] Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group. Preferably, each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group.

[0328] m and n may be the same or different and are independently selected from integers 0-10 (e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10).

[0329] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each RB , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0330] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0331] Each RL may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-.

[0332] According to embodiments of the present invention, the groups in formula (GH) may be independently selected from the following definitions:

[0333] A is N or CR A is selected from.

[0334] If A is N, then R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, when A is N, R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0335] A is CR A If R A and R 1 may be the same or different and may be independently 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C3-10 Cycloalkyl C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyloxy group, C 1-10 Alkyloxy C 1-10 Alkyl group, 3- to 10-membered heterocyclyl group, 3- to 10-membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5- to 10-membered heteroaryl group or 5- to 10-membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, A is CR A If R A and R 1 may be the same or different and may be independently 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyloxy group, C 1-6 Alkyloxy C 1-6 Alkyl group, 3- to 6-membered heterocyclyl group, 3- to 6-membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5- to 6-membered heteroaryl group or 5- to 6-membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0336] Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D and forming a 3- to 8-membered ring structure, for example a 3-, 4-, 5-, 6-, 7-, or 8-membered ring structure, substituted with

[0337] z is selected from 0 or 1.

[0338] R 2 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 2 teeth 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group.

[0339] R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10 Alkyl group, C 3-6 Cycloalkyloxy group.

[0340] The conditions are: 1 , R 2 and the atom to which it is attached, or R 2 , R 3 and the atom to which it is attached, at least one pair of groups is unsubstituted or is substituted with one, two or more R E The 4- to 10-membered ring structure may be selected from a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, and heterobicyclic hydrocarbon group.

[0341] R 4 is C 1-10 Alkyl group, C 1-10 It is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group. 4 is C 1-6 Alkyl group, C 1-6 It is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0342] R 5 is selected from hydroxy groups.

[0343] R 6is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 6-10 Aryl group, C 6-10 Arylalkyl groups, C 6-10 Aryloxy group, 5- to 6-membered heteroaryl group, 5- to 6-membered heteroarylalkyl group, 5- to 6-membered heteroaryloxy group.

[0344] B is absent, a triazole group, -NR 7 -or-N(NR 7 R 8 )- is selected from.

[0345] R 7 , R 8 may be the same or different and may be independently 1 H, 2 H, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-6 Alkyl group, C3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0346] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*, #O-(CR 9 R 10 ) m -(CR 11 R 12 )n -P(=O)(OR 14 )*, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #, *N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # indicates the attachment site to L and * indicates the attachment site to B.

[0347] Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent: 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0348] Or, R 9 , R 10 are unsubstituted or substituted with one, two or more R I or R 11 , R 12 are unsubstituted or substituted with one, two or more R Ior R 9 , R 11 are unsubstituted or substituted with one, two or more R I wherein any of the 3-10 membered ring structures can be, for example, unsubstituted or substituted with one, two or more R I The hydrocarbon group may be a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with

[0349] Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group. Preferably, each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group.

[0350] m and n may be the same or different and are each independently selected from integers of 0 to 10, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0351] Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, an amino group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R B , R C , R D , R E , R F , R G , R H , R I , R Jmay be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0352] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0353] Each R L may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-.

[0354] According to embodiments of the present invention, the groups in formula (GH) may be independently selected from the following definitions:

[0355] A is selected from N.

[0356] R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, when A is N, R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-.

[0357] z is selected from 0 or 1.

[0358] R 2 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 2 teeth 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group.

[0359] R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group. Preferably, R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10 Alkyl group, C 3-6 Cycloalkyloxy group.

[0360] Or, R 1 , R 2 are unsubstituted or substituted with one, two or more R E and forming a 5-10 membered ring structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

[0361] Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more RF and forming a 4- to 10-membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a monocyclic heterocyclyl hydrocarbon group, a heteromonocyclic hydrocarbon group, or a heterobicyclic hydrocarbon group.

[0362] R 4 is C 1-10 Alkyl group, C 1-10 is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group. 4 is C 1-6 Alkyl group, C 1-6 It is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group.

[0363] R 5 is selected from hydroxy groups.

[0364] R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, 3- to 10-membered heterocyclyl group, 3- to 10-membered heterocyclylC 1-10 alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, R 6 is unsubstituted or has one, two or more R G is selected from the following groups substituted with: C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, 3- to 6-membered heterocyclyl group, 3- to 6-membered heterocyclyl C 1-6 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0365] B is -NR 7 -or-N(NR7 R 8 )- is selected from.

[0366] R 7 , R 8 may be the same or different and are independent of each other. 1 H, 2 H, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3- to 10-membered heterocyclyl group, 3- to 10-membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 Aryl C(=O)NH-, 5- to 10-membered heteroaryl C(=O)NH-. Preferably, R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3- to 6-membered heterocyclyl group, 3- to 6-membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 Aryl C(=O)NH-, 5- to 6-membered heteroaryl C(=O)NH-.

[0367] T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )*, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n #, *N(R 13 )-(CR9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # indicates the binding site to L and * indicates the binding site to B.

[0368] Each R 9 , R 10 , R 11 , R 12 may be the same or different and are independent of each other. 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10alkyl group, 3- to 10-membered heterocyclyloxy group. Preferably, each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 Alkyl groups, 3- to 6-membered heterocyclyloxy groups.

[0369] Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I Any of the 3-10 membered ring structures may be unsubstituted or substituted with one, two or more R IThe hydrocarbon group may be a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with

[0370] Each R 13 may be the same or different and may be unsubstituted or may contain one, two or more R J is selected from the following groups substituted with: C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group. Preferably, each R 13 may be the same or different and may be unsubstituted or may contain one, two or more R J is selected from the following groups substituted with: C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group.

[0371] m and n may be the same or different and are independently selected from integers of 0 to 10, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0372] Each R B , R C , R D , R E , R F , R G , RH , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-. Preferably, each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 ArylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-.

[0373] Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5- to 10-membered heteroaryl group, 5- to 10-membered heteroaryl C 1-10 Alkyl group, 5- to 10-membered heteroaryloxy group, 3- to 10-membered heterocyclyl group, 3- to 10-membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10arylC(=O)NH-, 5- to 10-membered heteroarylC(=O)NH-. Preferably, each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L is selected from the following groups substituted with: C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5- to 6-membered heteroaryl group, 5- to 6-membered heteroaryl C 1-6 Alkyl group, 5- to 6-membered heteroaryloxy group, 3- to 6-membered heterocyclyl group, 3- to 6-membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 Aryl C(=O)NH-, 5- to 6-membered heteroaryl C(=O)NH-.

[0374] Each R L may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5- to 10-membered heteroaryl group, 5- to 10-membered heteroaryl C 1-10Alkyl group, 5- to 10-membered heteroaryloxy group, 3- to 10-membered heterocyclyl group, 3- to 10-membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH2, HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 It is selected from arylC(=O)NH- and 5- to 10-membered heteroarylC(=O)NH-.

[0375] According to an embodiment of the present disclosure, R 1 , R 2 together with the quinolyl group to which they are attached form one of the following substructures, which may be unsubstituted or may contain one, two or more R L It may be substituted with: [ka]

[0376] Alternatively, according to an embodiment of the present disclosure, R 2 , R 3 together with the quinolyl group to which they are attached form one of the following substructures, which may be unsubstituted or may contain one, two or more R F It may be substituted with: [ka]

[0377] According to an embodiment of the present disclosure, B is absent, [ka] or [ka] -NH- or -N(NR 7 R 8 )-, where R 7 , R8 are independently defined above.

[0378] According to an embodiment of the present disclosure, the compound represented by formula (GH) may be selected from the compounds represented by formula (GH-1) below. [ka] where R A , B, T, R 1 , R 2 , R 3 , R 6 are independently defined above.

[0379] According to an embodiment of the present disclosure, the compound represented by formula (GH) may be selected from the compounds represented by formula (GH-2) or (GH-3) below. [ka] where R A , B, T, R 1 , R 2 , R 3 , R 6 are independently defined above.

[0380] According to an embodiment of the present disclosure, the compound represented by formula (GH) may be selected from the following compounds: [Table 84] [Table 85] [Table 86] [Table 87]

[0381] The present disclosure further provides a method for preparing a compound of formula (GH), a stereoisomer, racemate, tautomer, isotope, isotopically labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof, comprising reacting a compound of formula (i) with a compound of formula (ii). [ka] where A, B, T, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , z independently have the definitions given above. LE represents a group that leaves or departs after the reaction.

[0382] The present invention further provides a process for preparing a compound of formula (ii), said process comprising reacting a compound of formula (iii) with a compound of formula (iv) to give a compound of formula (v). [ka] where A, B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , z independently have the definitions given above. R 21 is selected from H or a protecting group.

[0383] According to an embodiment of the present invention, R 21 When is selected from H, the compound of formula (v) is a compound of formula (ii).

[0384] According to an embodiment of the present invention, R 21 When is selected from a protecting group, after obtaining the compound of formula (v), the compound of formula (v) can be reacted under conditions to remove the protecting group to obtain the compound of formula (ii).

[0385] According to an embodiment of the present invention, said protecting groups are selected from amino protecting groups.

[0386] According to an embodiment of the present invention, the type of protecting group (eg, amino protecting group) and the conditions for removing said protecting group may be selected from types or conditions known to those skilled in the art.

[0387] The present disclosure further provides a compound having formula (iii): [ka] where R 5 , R 6 , z independently have the definitions given above.

[0388] The present disclosure further provides compounds having formula (v): [ka] where A, B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 21 , z independently have the definitions given above.

[0389] The present disclosure further provides a pharmaceutical composition comprising at least one selected from the compound represented by formula (GH), a stereoisomer, racemate, tautomer, isotope, isotope-labeled substance, nitrogen oxide, or pharmaceutically acceptable salt thereof, the complex represented by formula (C), a stereoisomer, racemate, tautomer, isotope, isotope-labeled substance, nitrogen oxide, or pharmaceutically acceptable salt thereof.

[0390] Preferably, when present, the compound of formula (GH), its stereoisomer, racemate, tautomer, isotope, isotopically labeled, nitroxide or pharmaceutically acceptable salt, the complex of formula (C), its stereoisomer, racemate, tautomer, isotope, isotopically labeled, nitroxide or pharmaceutically acceptable salt in the pharmaceutical composition is present in a therapeutically effective amount.

[0391] According to an embodiment of the present disclosure, the pharmaceutical composition comprises a therapeutically effective amount of at least one selected from the compound represented by formula (GH), a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled substance, a nitrogen oxide, or a pharmaceutically acceptable salt thereof, the complex represented by formula (C), a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled substance, a nitrogen oxide, or a pharmaceutically acceptable salt thereof.

[0392] The present disclosure further provides use of the compound represented by formula (GH), a stereoisomer, racemate, tautomer, isotope, isotopically labeled compound, nitrogen oxide or pharmaceutically acceptable salt thereof, or the complex represented by formula (C), a stereoisomer, racemate, tautomer, isotope, isotopically labeled compound, nitrogen oxide or pharmaceutically acceptable salt thereof, for the prevention and / or treatment of a disease or disorder and / or for the manufacture of a medicament.

[0393] According to an embodiment of the present disclosure, the medicament is used for the prevention and / or treatment of a disease or disorder.

[0394] The present disclosure further provides a method for preventing and / or treating a disease or disorder, comprising administering to a patient a therapeutically effective amount of at least one selected from the compound represented by formula (GH), its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitroxide, or pharmaceutically acceptable salt, or the complex represented by formula (C), its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitroxide, or pharmaceutically acceptable salt.

[0395] According to embodiments of the present disclosure, the disease or condition may be selected from cancer (e.g., solid tumor or hematological cancer).

[0396] Examples of solid tumors include malignant tumors of various organ systems, such as sarcoma, adenocarcinoma, blastoma, and cancers affecting the liver, lung, breast, lymphatic system, biliary intestine (e.g., colon), genitourinary tract (e.g., kidney, urothelial cells), prostate, and pharynx. Adenocarcinomas include malignant tumors such as most colon cancers, rectal cancer, renal cell carcinoma, liver cancer, small cell lung cancer, non-small cell lung cancer, small intestine cancer, and esophageal cancer. In one example, the cancer is melanoma, for example, advanced melanoma. Examples of other cancers that can be treated include bone cancer, pancreatic cancer, skin cancer, head and neck cancer, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, colorectal cancer, anal cancer, peritoneal cancer, stomach cancer, esophageal cancer, salivary gland cancer, testicular cancer, fallopian tube cancer, endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, penile cancer, glioma, neuroblastoma, Hodgkin's disease, non-Hodgkin's lymphoma, esophageal cancer, small intestine cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal gland cancer, soft tissue sarcoma, urethral cancer, chronic or acute leukemia (including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, and chronic lymphocytic leukemia), childhood solid tumors, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal pelvis cancer, and central nervous system (CNS) cancer. ) tumors, primary CNS lymphoma, tumor angiogenesis, spinal axis tumors, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, neuroendocrine tumors (including carcinoid, gastric uroma, and pancreatic islet cell carcinoma), mesothelioma, schwannoma (including acoustic neuroma), meningioma, epidermoid carcinoma, squamous cell carcinoma, T-cell lymphoma, environmentally induced cancers (including asbestos-induced cancer), and combinations of the above cancers.

[0397] Examples of hematological cancers include leukemia, lymphoma, and malignant lymphoproliferative disorders affecting the blood, bone marrow, and lymphatic system. Leukemia can be classified into acute and chronic leukemia. Acute leukemia can be further classified into acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Chronic leukemia includes chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Other related diseases include myelodysplastic syndromes (MDS, formerly called "preleukemias"), a diverse collection of hematological disorders consisting of ineffective production (or dysplasia) of bone marrow blood cells combined with the risk of transformation to AML. Lymphomas are a group of blood cell tumors that develop from lymphocytes. Exemplary lymphomas include non-Hodgkin's lymphoma and Hodgkin's lymphoma.

[0398] According to an embodiment of the present disclosure, the pharmaceutical composition may further include a pharmaceutically acceptable excipient, such as a carrier or excipient. The pharmaceutically acceptable excipient is preferably chemically unreactive with the active ingredient or inert. For example, the pharmaceutically acceptable excipient may include at least one selected from the group consisting of a filler, a disintegrant, an adhesive, a lubricant, a surfactant, a flavoring agent, a wetting agent, and a base, but is not limited thereto.

[0399] According to an embodiment of the present disclosure, the route of administration of the pharmaceutical composition includes, but is not limited to, gastrointestinal administration or non-gastrointestinal administration, where the gastrointestinal administration may be oral administration, and the non-gastrointestinal administration may be topical administration, transdermal administration, injection, etc.

[0400] In one embodiment, the administration route of the pharmaceutical composition can be a combination of topical and oral administration.

[0401] According to an embodiment of the present disclosure, the dosage form of the pharmaceutical composition may be selected from capsules, tablets, patches, films, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols, ointments, creams, suppositories, or injections.

[0402] Unless otherwise specified, definitions of terms provided in the specification and claims include exemplary definitions, exemplary definitions, preferred definitions, definitions set forth in tables, definitions of specific compounds in the examples, etc., which may be combined or linked together in any manner, and such combinations or links are intended to be within the scope of the present specification.

[0403] Unless otherwise specified, the numerical ranges described in the specification and claims correspond to at least the recitation of any specific integer value within the range. For example, the numerical range "1-10" corresponds to the recitation of each of the integer values ​​1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 within the numerical range "1-10." When "one, two, or more" is used to describe a substituent, "more" herein should be understood to refer to an integer greater than or equal to 3 (≧3), for example, 3, 4, 5, 6, 7, 8, 9, or 10. Furthermore, when a numerical range is defined as a "number," it should be understood that both ends of the range, each integer within the range, and each decimal point within the range are described. For example, "a number from 0 to 10" should be understood to describe not only the integers 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, but also at least each integer plus 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, and 0.9, respectively. Similarly, "an integer or decimal number from 1 to 50," "an integer or decimal number from 1 to 20," and "an integer or decimal number from 1 to 10" should be understood to describe both ends of the numerical range, as well as each integer and each decimal number within that range.

[0404] The term "isotope" includes the replacement of atoms in the compounds or complexes of the present disclosure with other isotopes having the same atomic number but different atomic masses or mass numbers. For example, "hydrogen" in the compounds or complexes of the present disclosure may be replaced with deuterium ( 1 H), deuterium ( 2 H) and tritium ( 3H). "Carbon" can be selected from 12 C. 13 C. 14 C. Thus, the compounds or complexes of the present disclosure should be understood to include at least various deuterated forms of the compounds or complexes. For example, each available hydrogen atom bonded to a carbon atom (e.g., C 1-10 One, two, or more of the hydrogen atoms of the alkyl group may be independently replaced by a deuterium atom. Those skilled in the art can synthesize deuterated forms of the compound or complex by referring to the relevant literature. When preparing deuterated forms of the compound or complex, commercially available deuterated starting materials can be used, or deuterated reagents can be used according to conventional techniques. Selectable deuterated reagents include, but are not limited to, deuterated borane, trideuterated borane in tetrahydrofuran, lithium aluminum deuteride, deuterated iodoethane, and deuterated iodomethane.

[0405] The term "isotopically labeled" refers to 111 In, 177 Lu, 212 Bi, 213 Bi, 211 At, 62 Cu, 67 Cu, 90 Y, 125 I, 131 I, 32 P, 33 P, 47 Sc, 111 Ag, 67 Ga, 142 Pr, 153 Sm, 161 Tb, 166 Dy, 166 Ho, 186 Re, 188 Re, 189 Re, 212 Pb, 223 Ra, 225 Ac, 59 Fe, 75 Se, 77 As, 89 Sr, 99 Mo,105 Rh, 109 Pd, 143 Pr, 149 Pm, 169 Er, 194 Ir, 198 Au, 199 Au, 227 Th and 211 Pb.

[0406] The term "halogen atom" refers to fluoro, chlorine, bromine, and iodine.

[0407] The term "alkyl group" preferably refers to a linear or branched saturated monovalent hydrocarbon group, preferably "C 1-10 It should be understood to mean "an alkyl group." 1-10 An "alkyl group" should be understood to mean a linear or branched saturated monovalent hydrocarbon group, preferably having 1 to 10 carbon atoms. For example, "C 1-6 The term "alkyl group" refers to straight-chain and branched-chain alkyl groups having 1, 2, 3, 4, 5, or 6 carbon atoms. Examples of the alkyl group include methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, s-butyl, t-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, and 1,2-dimethylbutyl, and isomers thereof.

[0408] The term "cycloalkyl group" refers to a saturated monovalent monocyclic or bicyclic (fused, bridged, or spiro) hydrocarbon group, preferably a "C 3-10 The term "C" should be understood to refer to a "cycloalkyl group."3-10 A "cycloalkyl group" should be understood to mean a monovalent saturated monocyclic, bicyclic (fused, bridged, or spiro) hydrocarbon group having 3-10 carbon atoms, such as 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms. 3-10 The cycloalkyl group can be a monocyclic hydrocarbon group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, or a cyclodecyl group, or a bicyclic hydrocarbon group such as a decahydronaphthalene ring.

[0409] The term "cyclic structure" should be understood to mean a group having a monocyclic, bicyclic (fused, bridged, or spiro) or more cyclic structure, such as a monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a tricyclic hydrocarbon group, a heteromonocyclic hydrocarbon group, a heterobicyclic hydrocarbon group, a heterotricyclic hydrocarbon group, etc. The cyclic structure may be saturated or unsaturated. The heteromonocyclic hydrocarbon group, the heterobicyclic hydrocarbon group, the heterotricyclic hydrocarbon group may contain 1 to 10, preferably 1 to 5 heteroatoms independently selected from N, O, and S, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 heteroatoms independently selected from N, O, and S. The bicyclic ring may be any of the following ring structures containing no heteroatoms or 1, 2, or 3 heteroatoms independently selected from N, O, and S: one or two of an aryl group, a heteroaryl group, a cycloalkyl group, a heterocyclyl group, either independently or fused together, a spiro[2.5] ring, a spiro[3.3] ring, a spiro[4.2] ring, a spiro[4.3] ring, a spiro[5.2] ring, a spiro[5.4] ring, a bicyclo[2.1.1], a bicyclo[2.2.1], a bicyclo[2.2.2], a bicyclo[3.2.1], a bicyclo[4.1.0], etc. Alternatively, the ring structure may have 1, 2, 3, 4, or 5 double bonds, such as carbon-carbon double bonds or carbon-nitrogen double bonds.

[0410] The term "3-10 membered ring structure" should be understood to mean a monocyclic or bicyclic (fused, bridged, or spiro) structure group having 3, 4, 5, 6, 7, 8, 9, or 10 ring members, such as a monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a heteromonocyclic hydrocarbon group, or a heterobicyclic hydrocarbon group. The ring structure may be saturated or unsaturated. The heteromonocyclic hydrocarbon group or heterobicyclic hydrocarbon group may contain 1-5, preferably 1-3 heteroatoms independently selected from N, O, and S, such as 1, 2, or 3 heteroatoms independently selected from N, O, and S. The bicyclic ring may be any of the following ring structures containing no heteroatoms or 1, 2, or 3 heteroatoms independently selected from N, O, and S: one or two of an aryl group, a heteroaryl group, a cycloalkyl group, a heterocyclyl group, independently or fused to one another, a spiro[2.5] ring, a spiro[3.3] ring, a spiro[4.2] ring, a spiro[4.3] ring, a spiro[5.2] ring, a spiro[5.4] ring, a bicyclo[2.1.1], a bicyclo[2.2.1], a bicyclo[2.2.2], a bicyclo[3.2.1], a bicyclo[4.1.0], etc. Alternatively, the ring structure may have 1, 2, 3, 4, or 5 double bonds, such as carbon-carbon double bonds or carbon-nitrogen double bonds.

[0411] The term "4-10 membered ring structure" should be understood to mean a monocyclic or bicyclic (fused, bridged, or spiro) structure group having 4, 5, 6, 7, 8, 9, or 10 ring members, such as a monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a heteromonocyclic hydrocarbon group, or a heterobicyclic hydrocarbon group. The ring structure may be saturated or unsaturated. The heteromonocyclic hydrocarbon group or heterobicyclic hydrocarbon group may contain 1 to 5, preferably 1 to 3 heteroatoms independently selected from N, O, and S, such as 1, 2, or 3 heteroatoms independently selected from N, O, and S. The bicyclic ring may be any of the following ring structures containing no heteroatoms or 1, 2, or 3 heteroatoms independently selected from N, O, and S: one or two of an aryl group, a heteroaryl group, a cycloalkyl group, a heterocyclyl group, independently or fused to one another, a spiro[2.5] ring, a spiro[3.3] ring, a spiro[4.2] ring, a spiro[4.3] ring, a spiro[5.2] ring, a spiro[5.4] ring, a bicyclo[2.1.1], a bicyclo[2.2.1], a bicyclo[2.2.2], a bicyclo[3.2.1], a bicyclo[4.1.0], etc. Alternatively, the ring structure may have 1, 2, 3, 4, or 5 double bonds, such as carbon-carbon double bonds or carbon-nitrogen double bonds.

[0412] The term "5-10 membered ring structure" should be understood to mean a monocyclic or bicyclic (fused, bridged, or spiro) structure group having 5, 6, 7, 8, 9, or 10 ring members, such as a monocyclic hydrocarbon group, a bicyclic hydrocarbon group, a heteromonocyclic hydrocarbon group, or a heterobicyclic hydrocarbon group. The ring structure may be saturated or unsaturated. The heteromonocyclic or heterobicyclic hydrocarbon group may contain 1-5, preferably 1-3 heteroatoms independently selected from N, O, and S, such as 1, 2, or 3 heteroatoms independently selected from N, O, and S. The bicyclic ring may be any of the following ring structures containing no heteroatoms or 1, 2, 3 heteroatoms independently selected from N, O, and S: one or two of aryl, heteroaryl, cycloalkyl, heterocyclyl groups, either independently or fused together; spiro[2.5] ring, spiro[3.3] ring, spiro[4.2] ring, spiro[4.3] ring, spiro[5.2] ring, spiro[5.4] ring, bicyclo[2.1.1], bicyclo[2.2.1], bicyclo[2.2.2], bicyclo[3.2.1], bicyclo[4.1.0], etc.

[0413] Alternatively, the "4-10 membered ring structure" and "5-10 membered ring structure" may have 1, 2, 3, 4 or 5 double bonds, for example, carbon-carbon double bonds or carbon-nitrogen double bonds.

[0414] After the group of the compound described in the present invention forms the ring structure, it forms a fused ring, a bridged ring, or a bicyclic ring with the ring structure of the compound, and when the ring structure of the compound has an unsaturated bond, it is preferable that the ring structure formed by the group retains the unsaturated bond in the ring structure of the compound.

[0415] The term "heterocyclyl group" refers to a saturated or unsaturated monovalent monocyclic, bicyclic (fused, bridged, or spirocyclic) hydrocarbon group containing 1 to 5 heteroatoms independently selected from N, O, and S, but lacking aromaticity. The "heterocyclyl group" is preferably a "3- to 20-membered heterocyclyl group." The term "3- to 20-membered heterocyclyl group" refers to a saturated monovalent monocyclic, bicyclic (fused, bridged, or spirocyclic) hydrocarbon group containing a non-aromatic ring group having 1 to 5 heteroatoms independently selected from N, O, and S, and a total of 3 to 20 ring atoms (e.g., 3, 4, 5, 6, 7, 8, 9, 10, etc. atoms), preferably a "3- to 10-membered heterocyclyl group." The term "3-10 membered heterocyclyl group" means a saturated or unsaturated monovalent monocyclic, bicyclic (fused, bridged, or spiro) hydrocarbon group that does not have aromatic character and contains 1-5, preferably 1-3 heteroatoms independently selected from N, O, and S, e.g., 1, 2, or 3 heteroatoms independently selected from N, O, and S. The heterocyclyl group can be attached to the remainder of the molecule via any of the carbon atoms or via the nitrogen atom, if present. In particular, the heterocyclyl group may include, but is not limited to, a four-membered ring such as an azetidinyl group, an oxetanyl group (e.g., azetidin-1-yl), a five-membered ring such as a tetrahydrofuranyl group, a dioxolyl group, a pyrrolidinyl group, an imidazolidinyl group, a pyrazolidinyl group, a pyrrolinyl group, a six-membered ring such as a tetrahydropyranyl group, a piperidinyl group, a morpholinyl group, a dithianyl group, a thiomorpholinyl group, a piperazinyl group, or a trithianyl group, or a seven-membered ring such as a diazepanyl group. Optionally, the heterocyclyl group may be benzo-fused. The heterocyclyl group may be, for example, but not limited to, a 5,5-membered ring such as a hexahydrocyclopenta[c]pyrrol-2(1H)-yl ring, or a 5,6-membered bicyclic ring such as a hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl ring.The nitrogen atom-containing ring may be partially unsaturated, i.e., it may contain one or more double bonds, such as, but not limited to, a 2,5-dihydro-1H-pyrrolyl group, a 4H-[1,3,4]thiadiazinyl group, a 4,5-dihydrooxazolyl group, or a 4H-[1,4]thiazinyl group, or it may be benzo-fused, such as, but not limited to, a dihydroisoquinolinyl group. According to the present disclosure, the heterocyclyl group is non-aromatic. When the 3-20-membered heterocyclyl group is bonded to another group to form a compound of the present disclosure, a carbon atom on the 3-20-membered heterocyclyl group may be bonded to the other group, or a heterocyclic atom on the 3-20-membered heterocyclyl group ring may be bonded to the other group. For example, when the 3-20-membered heterocyclyl group is selected from a piperazinyl group, the nitrogen atom on the piperazinyl group may be bonded to the other group. Alternatively, when the 3- to 20-membered heterocyclyl group is selected from a piperidinyl group, the nitrogen atom of the piperidinyl ring and the carbon atom para to it may be bonded to another group.

[0416] The term "aryl group" refers to a monovalent aromatic or partially aromatic monocyclic, bicyclic, or tricyclic hydrocarbon ring group, preferably "C 6-20 The term "C" should be understood to mean "aryl group." 6-20 An "aryl group" is preferably a monovalent aromatic or partially aromatic monocyclic, bicyclic or tricyclic hydrocarbon ring having 6-20 carbon atoms, preferably "C 6-14 The term "C" should be understood to mean "aryl group." 6-14 An "aryl group" is preferably a monovalent aromatic or partially aromatic monocyclic, bicyclic, or tricyclic hydrocarbon ring having 6, 7, 8, 9, 10, 11, 12, 13, or 14 carbon atoms ("C 6-14 aryl group"), in particular a ring having 6 carbon atoms ("C aryl group"), for example a phenyl group, or a biphenyl group, or a ring having 9 carbon atoms ("C aryl group"), such as an indanyl or indenyl group, or a ring having 10 carbon atoms ("C aryl group"), such as a tetralinyl, dihydronaphthyl or naphthyl group 10aryl group), or a ring with 13 carbon atoms, such as a fluorenyl group ("C 13 aryl group), or a ring with 14 carbon atoms, such as an anthracenyl group ("C 14 The C is an aryl group. 6-20 When aryl is substituted, it may be mono-substituted or poly-substituted, and there is no limitation on the position of the substitution, and it may be, for example, ortho-, para-, or meta-substituted.

[0417] The term "heteroaryl group" should be understood to mean a monovalent monocyclic, bicyclic or tricyclic aromatic ring system radical containing 1-5 heteroatoms independently selected from N, O and S, preferably a "5-20 membered heteroaryl group." The term "5-20 membered heteroaryl group" should be understood to include a monovalent monocyclic, bicyclic or tricyclic aromatic ring radical containing 1-5 heteroatoms independently selected from N, O and S and having 5-20 ring atoms, such as a "5-14 membered heteroaryl group." The term "5-14 membered heteroaryl group" is to be understood to include monovalent monocyclic, bicyclic or tricyclic aromatic ring groups having 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 ring atoms, in particular 5 or 6 or 9 or 10 carbon atoms, and containing 1 to 5, preferably 1 to 3 heteroatoms independently selected from N, O and S, and which may further be benzo-fused in each case. In particular, heteroaryl groups include thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, and the like, and benzo derivatives thereof, such as benzofuranyl, benzothiophenyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzotriazolyl, indazolyl, indolyl, and isoindolyl. or a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a triazinyl group, etc., and benzo derivatives thereof, such as a quinolyl group, a quinazolinyl group, an isoquinolyl group, etc., an azine group, an indolizine group, a purine group, etc., and benzo derivatives thereof, or a cinnolinyl group, a phthalazinyl group, a quinazolinyl group, a quinoxalinyl group, a naphthyridinyl group, a pteridinyl group, a carbazolyl group, an acridinyl group, a phenazinyl group, a phenothiazinyl group, a phenoxazinyl group, etc. When a 5- to 20-membered heteroaryl group is bonded to another group to form a compound of the present disclosure, a carbon atom on the 5- to 20-membered heteroaryl ring may be bonded to the other group, or a heteroatom on the 5- to 20-membered heteroaryl ring may be bonded to the other group.When the 5-20 membered heteroaryl is substituted, it may be mono-substituted or poly-substituted, and there is no limitation on the substitution position, for example, hydrogen bonded to a carbon atom of the heteroaryl ring may be substituted, or hydrogen bonded to a heteroatom of the heteroaryl ring may be substituted.

[0418] Unless otherwise specified, heterocyclyl group, heteroaryl group or heteroarylene group includes all possible isomers thereof, for example, positional isomers thereof.Thus, some illustrative and non-limiting examples may include forms substituted or bonded to other groups at one, two or more positions, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 positions (if present), for example, pyridin-2-yl, pyridinylene-2-yl, pyridin-3-yl, pyridinylene-3-yl, pyridin-4-yl and pyridinylene-4-yl, and thienyl or thienylene includes thiophen-2-yl, thienylene-2-yl, thiophen-3-yl and thienylene-3-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl and pyrazol-5-yl.

[0419] The term "oxo" refers to an oxo group substitution (=O) formed by oxidation of a carbon, nitrogen, or sulfur atom in a substituent. It should be understood that when a carbon atom is substituted with an oxo group, a carbonyl group -C(=O)- is formed.

[0420] Unless otherwise specified, the definition of a term in this specification also applies to groups that contain that term. For example, the definition of an alkyl group also applies to the alkyl group in an alkyloxy group or a cycloalkylalkyl group. The definition of a cycloalkyl group also applies to the cycloalkyl group in a cycloalkyloxy group or a cycloalkylalkyl group. 1-10 The definition of an alkyl group is C 1-10 Alkyloxy group or C 3-10 Cycloalkyl C 1-10 C in alkyl group 1-10 This also applies to alkyl groups. 3-10The definition of a cycloalkyl group is C 3-10 Cycloalkyloxy group or C 3-10 Cycloalkyl C 1-10 C in alkyl group 3-10 This also applies to cycloalkyl groups.

[0421] Those skilled in the art will understand that the compounds of the present disclosure can exist in the form of various pharmaceutically acceptable salts. When these compounds have a basic center, they can form acid addition salts; when these compounds have an acidic center, they can form base addition salts; and when these compounds contain both an acidic center (e.g., a carboxyl group) and a basic center (e.g., an amino group), they can also form internal salts.

[0422] The compounds of the present disclosure may exist in the form of solvates (e.g., hydrates), and the compounds of the present disclosure contain polar solvents, particularly, for example, water, methanol, or ethanol, as components of the crystal lattice of the compounds. The amount of polar solvent, particularly water, may be present in a stoichiometric or non-stoichiometric ratio.

[0423] The compounds or groups of the present disclosure may be chiral depending on their molecular structure, or may have chiral carbon atoms, and therefore may exist in various enantiomeric forms.Therefore, these compounds or groups may exist in racemic or optically active forms.For example, when the A group in the general formula (G), (G') or (GH) is CR Aand the groups to which the carbon atom is attached are different, the carbon atom is chiral and can have an R or S chiral configuration. The compounds of the present disclosure, or intermediates thereof, can be isolated into enantiomeric compounds by chemical or physical methods well known to those skilled in the art, or can be used in synthesis in such form. In the case of racemic amines, diastereomers can be obtained from the mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids, such as the R and S forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, appropriate N-protected amino acids (e.g., N-benzoylproline or N-benzenesulfonylproline), or various optically active camphorsulfonic acids. Chromatographic enantiomeric resolution can be advantageously carried out using optically active resolving agents (e.g., dinitrobenzoylphenylglycine, cellulose triacetate, or other carbohydrate derivatives immobilized on silica gel, or chiral derivatized isobutyrate polymers). Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures, such as hexane / isopropanol / acetonitrile.

[0424] The term "tautomer" refers to an isomer of a functional group resulting from the rapid shift of an atom between two positions within a molecule. Compounds of the present disclosure may exhibit tautomerism. Tautomeric compounds may exist in two or more interconvertible forms. Proton-shift tautomers result from the shift of a covalently bonded hydrogen atom between two atoms. Tautomers generally exist in equilibrium, and attempts to separate a single tautomer usually result in a mixture of tautomers. The physicochemical properties are consistent with a mixture of compounds. The position of the equilibrium depends on the chemical properties within the molecule. For example, in many aliphatic aldehydes and ketones, such as acetaldehyde, the ketone form predominates, and among phenols, the enol form predominates. The present disclosure includes all tautomeric forms of compounds.

[0425] Separation of the corresponding stable isomers can be accomplished by known methods, such as extraction, filtration, or column chromatography.

[0426] The term "patient" refers to any animal, including a mammal, preferably a mouse, rat, other rodent, rabbit, dog, cat, pig, cow, sheep, horse, or primate, and most preferably a human.

[0427] As used herein, the phrase "therapeutically effective amount" refers to an amount of an active compound or drug that elicits a biological or medical response found in a tissue, system, animal, individual, or human by a researcher, veterinarian, physician, or other clinician, including one or more of the following: (1) disease prevention: e.g., preventing a disease, disorder, or condition in an individual who is susceptible to the disease, disorder, or condition but who has not yet experienced or manifested the pathology or symptoms of the disease; (2) disease inhibition: e.g., inhibiting a disease, disorder, or condition (i.e., preventing further progression of the pathology and / or symptoms) in an individual who is experiencing or manifesting the pathology or symptoms of the disease, disorder, or condition; or (3) disease mitigation: e.g., alleviating a disease, disorder, or condition (i.e., reversing the pathology and / or symptoms) in an individual who is experiencing or manifesting the pathology or symptoms of the disease, disorder, or condition.

[0428] The term "ligand" refers to a macromolecular compound capable of recognizing and binding to an antigen or receptor associated with a target cell. Ligands serve to present drugs to a target cell population to which they bind, and include, but are not limited to, protein hormones, lectins, growth factors, antibodies, or other molecules capable of binding to cells. In an embodiment of the present disclosure, the ligand is represented by LG, which can form a linking bond with a linking unit via a heteroatom on the ligand, and is preferably an antibody or antigen-binding fragment thereof selected from a chimeric antibody, a humanized antibody, a fully human antibody, or a murine antibody, more preferably a monoclonal antibody.

[0429] The term "drug" refers to any compound having a desired biological activity and a reactive functional group, which reactive functional group is used to incorporate the drug into the conjugates of the present disclosure. The desired biological activity includes the diagnosis, treatment, mitigation, or prevention of disease in humans or other animals. The reactive functional group is represented by functional group L. 4 or L 5 In some embodiments, the drug comprises a functional group L 4 or L 5 The term "N" includes a nitrogen atom or a hydroxy group that can form a bond with the N- or N-alkyl group.

[0430] The term "antibody" refers to an immunoglobulin containing either a tetrapeptide chain structure in which two identical heavy chains and two identical light chains are linked by interchain disulfide bonds (also called "single antibody" or "single epitope antibody") or a tetrapeptide chain structure in which two different heavy chains and two different light chains are linked by interchain disulfide bonds (also called "diabody" or "diaepitope antibody"). The immunoglobulin heavy chain constant regions differ in their amino acid composition and sequence, resulting in different antigenicities. Therefore, immunoglobulins can be classified into five classes, or immunoglobulin isotypes: IgM, IgD, IgG, IgA, and IgE, with corresponding heavy chains consisting of μ, δ, γ, α, and ε chains. Ig within the same class can be further divided into different subclasses based on the amino acid composition of the hinge region and the number and location of heavy chain disulfide bonds. For example, IgG is classified into IgG1, IgG2, IgG3, and IgG4. Light chains are classified as either kappa or lambda chains depending on the constant region. Each of the five classes of Ig can have either kappa or lambda chains. The antibody of the present disclosure is preferably an antibody specific for a cell surface antigen on a target cell, and non-limiting examples include one or more of an anti-HER2 (ErbB2) antibody, an anti-EGFR antibody, an anti-B7-H3 antibody, an anti-c-Met antibody, an anti-HER3 (ErbB3) antibody, an anti-HER4 (ErbB4) antibody, an anti-CD20 antibody, an anti-CD22 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD44 antibody, an anti-CD56 antibody, an anti-CD70 antibody, an anti-CD73 antibody, an anti-CD105 antibody, an anti-CEA antibody, an anti-A33 antibody, an anti-Cripto antibody, an anti-EphA2 antibody, an anti-G250 antibody, an anti-MUCl antibody, an anti-LewisY antibody, an anti-VEGFR antibody, an anti-GPNMB antibody, an anti-integrin antibody, an anti-PSMA antibody, an anti-Tenascin-C antibody, an anti-SLC44A4 antibody, and an anti-Mesothelin antibody.Preferred are trastuzumab (trade name Herceptin), pertuzumab (trade name Perjeta, also known as 2C4), nituzumab (trade name Tagoximab), enoblituzumab, emibetuzumab, inotuzumab, pinatuzumab, brentuximab, gemtuzumab, bivatuzumab, lorvotuzumab, cBR96, and glematumumab or glembatumumab.

[0431] The sequence of approximately 110 amino acids near the N-terminus of antibody heavy and light chains is highly variable (Fv region), while the remaining amino acid sequence near the C-terminus is relatively stable (constant region). The variable region contains three hypervariable regions (HVRs) and four framework regions (FRs) with relatively stable sequences. The three hypervariable regions determine the specificity of the antibody and are also called complementarity-determining regions (CDRs). Each light chain variable region (LCVR) and heavy chain variable region (HCVR) consists of three CDR regions and four FR regions, which are arranged from the amino terminus to the carboxyl terminus as follows: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The three CDR regions of the light chain are referred to as LCDR1, LCDR2, and LCDR3, and the three CDR regions of the heavy chain are referred to as HCDR1, HCDR2, and HCDR3.

[0432] Antibodies of the present disclosure include murine antibodies, chimeric antibodies, humanized antibodies, and fully human antibodies, with humanized antibodies and fully human antibodies being particularly preferred.

[0433] The term "murine antibody" in this disclosure refers to the production of antibodies in mice according to the knowledge and skill in the art by injecting a specific antigen into a test subject and then isolating hybridomas expressing antibodies with the desired sequence or functional characteristics.

[0434] The term "chimeric antibody" refers to an antibody formed by fusing the variable region of a mouse antibody with the constant region of a human antibody. This reduces the immune response caused by mouse antibodies. Chimeric antibodies are produced by generating hybridomas that secrete mouse-specific monoclonal antibodies, cloning the variable region genes from the mouse hybridoma cells, optionally cloning the constant region genes of a human antibody, ligating the mouse variable region genes and human constant region genes into a chimeric gene, inserting it into an expression vector, and finally expressing the chimeric antibody molecule in a eukaryotic or prokaryotic system.

[0435] The term "humanized antibody," also known as a CDR-grafted antibody, refers to an antibody generated by grafting mouse CDR sequences onto a human antibody variable region framework, i.e., a different type of human germline antibody framework sequence. This overcomes the heterologous response induced by chimeric antibodies due to the presence of a large amount of mouse protein components. Such framework sequences can be obtained from consensus DNA databases or published references containing germline antibody gene sequences. For example, germline DNA sequences for human heavy and light chain variable region genes can be found in the "VBase" human germline sequence database (available online at www.mrccpe.com.ac.uk / vbase) and Kabat, EA et al. (1991), "Sequences of Proteins of Immunological Interest," 5th Edition. To avoid reduced immunogenicity and consequent loss of activity, minimal reverse mutations or back mutations can be made in the framework sequences of the variable regions of the human antibody to maintain activity. The humanized antibody of the present disclosure also includes humanized antibodies after affinity maturation of CDRs, which are further displayed by phage. References further describing humanization methods that can use mouse antibodies include, for example, Queen et al., Proc., Natl. Acad. Sci. USA, 88, 2869, 1991, and Winter and colleagues' methods [Jones et al., Nature, 321, 522 (1986); Riechmann et al., Nature, 332, 323-327 (1988); Verhoeyen et al., Science, 239, 1534 (1988)].

[0436] The terms "fully humanized antibody," "fully human antibody," or "fully humanized antibody" are also referred to as "fully humanized monoclonal antibody." Both the variable and constant regions of the antibody are humanized to eliminate immunogenicity and toxic side effects. The development of monoclonal antibodies has gone through four stages: mouse monoclonal antibodies, chimeric monoclonal antibodies, humanized monoclonal antibodies, and fully human monoclonal antibodies. The present disclosure relates to a fully humanized monoclonal antibody. Techniques related to the preparation of fully human antibodies mainly include the human hybridoma method, the EBV-transformed B lymphocyte method, the phage display method, transgenic mouse antibody preparation methods, and single B cell antibody preparation methods.

[0437] The term "antigen-binding fragment" refers to one or more fragments of an antibody that retain specific antigen-binding ability. It has been shown that fragments of a full-length antibody can be used to perform the antigen-binding function of the antibody. Examples of binding fragments included in "antigen-binding fragment" include: (i) a Fab fragment (a monovalent fragment consisting of the VL, VH, CL, and CH1 domains); (ii) a F(ab')2 fragment (including a bivalent fragment in which two Fab fragments are linked by a disulfide bridge in the hinge region); (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of a single-arm VH and VL domain of an antibody; (v) a single-domain or dAb fragment consisting of the VH domain (Ward et al., (1989) Nature 341:544-546); and (vi) an isolated complementarity-determining region (CDR); or (vii) a combination of two or more isolated CDRs, optionally linked by a synthetic linker. Furthermore, although the two domains of an Fv fragment, VL and VH, are encoded by separate genes, they can be recombinantly linked by a synthetic linker to generate a single protein chain in which the VL and VH regions pair to form a monovalent molecule (termed single-chain Fv (scFv); see, e.g., Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci USA 85:5879-5883). Such single-chain antibodies are also intended to be encompassed by the term "antigen-binding fragment" of an antibody. Such antibody fragments are obtained using conventional techniques known to those skilled in the art and are usefully screened in the same manner as intact antibodies. Antigen-binding portions can be produced by recombinant DNA techniques or by enzymatic or chemical cleavage of intact immunoglobulins. The antibodies can be of different isotypes, for example, IgG (eg, IgG1, IgG2, IgG3, or IgG4 subtypes), IgA1, IgA2, IgD, IgE, or IgM antibodies.

[0438] Fab is an antibody fragment with a molecular weight of approximately 50,000 that has antigen-binding activity and is obtained by treating an IgG antibody molecule with the protease papain (which cleaves the 224th amino acid residue of the H chain). Approximately half of the N-terminal end of the H chain is linked to the entire L chain via a disulfide bond.

[0439] F(ab')2 is an antibody fragment with a molecular weight of approximately 100,000, which is obtained by digesting the lower part of the two disulfide bonds in the hinge region of IgG with the enzyme pepsin, and which contains two Fab regions linked at the hinge position and retains antigen-binding activity.

[0440] Fab' is an antibody fragment with a molecular weight of approximately 50,000 that can be obtained by cleaving the disulfide bond in the hinge region of the F(ab')2 and that retains antigen-binding activity.

[0441] Furthermore, the Fab' can be produced by inserting DNA encoding the Fab' fragment of an antibody into a prokaryotic or eukaryotic expression vector, introducing the vector into a prokaryotic or eukaryotic organism, and expressing the Fab'.

[0442] The terms "single-chain antibody," "single-chain Fv," or "scFv" refer to a molecule comprising an antibody heavy chain variable domain (or region, VH) and an antibody light chain variable domain (or region, VL) connected by a linker. Such scFv molecules can have the general structure: NH2-VL-linker-VH-COOH or NH2-VH-linker-VL-COOH. Suitable prior art linkers consist of repeated GGGGS amino acid sequences or variants thereof, for example, using 1-4 repeat variants (Holliger et al. (1993), Proc. Natl. Acad. Sci. USA 90:6444-6448). Other linkers useful in the present disclosure are described by Alfthan et al. (1995), Protein Eng. 8:725-731, Choi et al. (2001), Eur. J. Immuno l. 31:94-106, Hu et al. (1996), Cancer Res. 56:3055-3061, Kipriyanov et al. (1999), J. Mol. Biol. 293:41-56, and Roovers et al. (2001), Cancer Immunol.

[0443] The term "CDR" refers to one of the six hypervariable regions in the variable domain of an antibody that primarily contributes to antigen binding. One of the most commonly used definitions of the six CDRs is provided by Kabat EA et al. (1991) Sequences of proteins of immunological interest. NIH Publication 91-3242). As used herein, the Kabat definition of CDR applies only to CDR1, CDR2, and CDR3 (CDR L1, CDR L2, CDR L3 or L1, L2, L3) of the light chain variable domain and CDR2 and CDR3 (CDR H2, CDR H3 or H2, H3) of the heavy chain variable domain.

[0444] The term "antibody framework" refers to the part of a variable domain VL or VH that serves as a scaffold for the antigen binding loops (CDRs) of the variable domain. Essentially, it is a variable domain without the CDRs.

[0445] The term "epitope" or "antigenic determinant" refers to a site on an antigen to which an immunoglobulin or antibody specifically binds. An epitope typically includes at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive or non-consecutive amino acids in a unique spatial conformation. See, e.g., Volume 66 of "Epitope Mapping Protocols in Methods in Molecular Biology," edited by GEMorris (1996).

[0446] The terms "selective binding," "specific binding," "selectively binds," and "specifically binds" refer to an antibody binding to an epitope on a given antigen. Typically, an antibody binds to an epitope on a given antigen. -7 Less than M, e.g., about 10 -8 M, 10 -9 M or 10 -10 It binds with an affinity (KD) less than M.

[0447] The term "nucleic acid molecule" refers to DNA molecules and RNA molecules. Nucleic acid molecules can be single-stranded or double-stranded, but are preferably double-stranded DNA. A nucleic acid is "operatively linked" when it is in a functional relationship with another nucleic acid sequence. For example, a promoter or enhancer is operatively linked to a coding sequence if it affects the transcription of the coding sequence.

[0448] The term "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid linked thereto. In one embodiment, the vector is a "plasmid," which refers to a circular double-stranded DNA loop into which another DNA segment can be ligated. In another embodiment, the vector is a viral vector into which another DNA segment can be ligated into the viral genome. The vectors disclosed herein can either replicate autonomously in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors), or can be integrated into the genome of the host cell after introduction into the host cell and replicate along with the host genome (e.g., non-episomal mammalian vectors).

[0449] Methods for producing and purifying antibodies and antigen-binding fragments are well known in the art, e.g., see Chapters 5-8 and 15 of Reisenko's Antibody Experimental Technology Guide. Antigen-binding fragments can likewise be prepared by conventional methods. The antibodies or antigen-binding fragments of the present invention can be obtained by adding one or more FR regions of human origin to CDR regions of non-human origin by genetic engineering methods. Human FR germline sequences can be obtained from the ImMunoGeneTics (IMGT) website at http: / / imgt.cines.fr or from Immunoglobulin Magazine, 2001, ISBN 012441351, by aligning them with the IMGT human antibody variable region germline gene database and MOE software.

[0450] The term "host cell" refers to a cell into which an expression vector has been introduced. Host cells can include bacterial, microbial, plant, or animal cells. Bacteria that are easily transformed include members of the Enterobacteriaceae family, such as strains of Escherichia coli or Salmonella, and Bacillaceae, such as Bacillus subtilis, Pneumococcus, Streptococcus, and Haemophilus influenzae. Suitable microorganisms include Saccharomyces cerevisiae and Pichia pastoris. Suitable animal host cell lines include CHO (Chinese hamster ovary cell line) and NS0 cells.

[0451] The engineered antibodies or antigen-binding fragments of the present disclosure can be prepared and purified using conventional methods. For example, cDNA sequences encoding the heavy and light chains can be cloned and recombined into a GS expression vector. The recombinant immunoglobulin expression vector can be stably transfected into CHO cells. A preferred prior art mammalian expression system results in glycosylation of the antibody, particularly at the highly conserved N-terminal site of the Fc region. Positive clones are expanded in serum-free medium in a bioreactor to produce the antibody. The antibody-secreted medium can be purified using conventional methods, for example, using an A or G Sepharose FF column containing a conditioned buffer. Nonspecifically bound components are washed away. The bound antibody is then eluted using a pH gradient, and the antibody fragments are detected and collected by SDS-PAGE. The antibody can be concentrated by filtration using conventional methods. Soluble mixtures and multimers can also be removed using conventional methods, such as molecular sieving or ion exchange. The resulting product is immediately frozen, for example at -70°C, or lyophilized.

[0452] The term "peptide" refers to a compound fragment between an amino acid and a protein, in which two or more amino acid molecules are linked together by a peptide bond, and is a structural and functional fragment of a protein, e.g., hormones, enzymes, etc. are peptides in nature.

[0453] The term "sugar" refers to a biopolymer consisting of three elements: C, H, and O, and can be classified as monosaccharides, disaccharides, polysaccharides, etc. Beneficial effects

[0454] The compounds and complexes of the present disclosure have excellent tumor cell-inhibitory activity, stability, and efficacy in animals, and can be used as drugs effective in inhibiting tumor cells and preventing and / or treating cancer. [Brief explanation of the drawings]

[0455] FIG. 1 shows the results of an assay of the bystander killing effect of the antibody-drug conjugate of the present disclosure on tumor cells in Test Example 4. FIG. 2 shows the assay results for the inhibition of tumor growth inoculated with NCI-N87 in nude mice in the experiment of Test 5A in Test Example 5. FIG. 3 shows a summary of the changes in body weight of the experimental mice in Test 5A of Test Example 5. FIG. 4 shows the assay results for the inhibition of tumor growth in nude mice transplanted with NCI-N87 in the experiment of Test 5B in Test Example 5. FIG. 5 shows a summary of the results of the weight changes of the experimental mice in the experiment of Test 5B in Test Example 5. FIG. 6 shows the assay results of the dissociation degree values ​​for the plasma stability of the antibody-drug conjugate of the present disclosure in Test Example 6. FIG. 7 shows the assay results for the inhibition of tumor growth inoculated with NCI-N87 in nude mice in the experiment of Test 5C in Test Example 5. FIG. 8 shows a summary of the results of changes in body weight of the experimental mice in Test 5C of Test Example 5. FIG. 9 shows an assay of the bystander effect of Pertuzumab antibody-drug conjugate in Test Example 7. FIG. 10 shows an assay of the bystander effect of the antibody-drug conjugate of Test Example 9 against EGFR target tumor cells. FIG. 11 shows the results of an assay for tumor growth inhibition in a JIMT-1 mouse subcutaneous transplant model in Test Example 10. FIG. 12 shows a summary of the results of changes in body weight of the experimental mice in Test Example 10. FIG. 13 shows the assay results of tumor growth inhibition in a subcutaneously transplanted NCI-H322 mouse model in Test Example 11. FIG. 14 shows a summary of the results of changes in body weight of the experimental mice in Test Example 11. FIG. 15 shows an assay of the bystander effect of ADC-113 on Her2 target tumor cells in Test Example 14. FIG. 16 shows an assay of the bystander effect of ADC-115 on Her2 target tumor cells in Test Example 15. FIG. 17 shows the results of an assay of different doses of ADC-113 on the inhibition of tumor growth in NCI-N87 xenografted nude mice in Test Example 16. FIG. 18 shows a summary of the results of body weight changes in experimental mice treated with different doses of ADC-113 in Test Example 16. FIG. 19 shows the results of an assay of ADC-115 for inhibiting the growth of tumors transplanted into nude mice with NCI-N87 in Test Example 17. FIG. 20 shows a summary of the results of changes in body weight of experimental mice caused by ADC-115 in Test Example 17. DETAILED DESCRIPTION OF THE INVENTION

[0456] The technical solutions of the present disclosure will be described in more detail below with specific examples. It should be understood that the following examples are only for illustrative purposes and interpretation of the present disclosure, and should not be construed as limiting the scope of protection of the present disclosure. The technology implemented based on the present disclosure is intended to be included in the scope of protection of the present disclosure.

[0457] Unless otherwise specified, all raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods. I. Antibody Examples

[0458] The following antibodies can be prepared according to standard antibody methods, and after vector construction, can be transfected into eukaryotic cells such as HEK293 cells (Life Technologies Cat. No. 11625019).

[0459] An exemplary antibody sequence is as follows:

[0460] Below is the sequence of Trastuzumab. [ka] [ka]

[0461] Below is the sequence of Pertuzumab. [ka] [ka]

[0462] Below is the sequence of Nimotuzumab. [ka] [ka]

[0463] Below is the sequence of Patritumab. [ka] [ka]

[0464] II. Compound Examples The structures of the compounds were determined by nuclear magnetic resonance (NMR) or mass spectrometry (MS). The chemical shifts δ were 10 -6 The NMR data were obtained using a Bruker nuclear magnetometer in deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD) solvents with tetramethylsilane (TMS) as the internal standard.

[0465] LCMS measurements were performed using an Agilent 1260 Infinity II (ESI) mass spectrometer, a Waters UPLC H Class plus (ESI) or a Shimadzu LCMS-2020 (ESI).

[0466] High performance liquid chromatography (HPLC) analysis was performed using an Agilent 1260 or Shimadzu LC-20AD.

[0467] For preparative high performance liquid chromatography (pre-HPLC), the liquid phase was prepared using a GILSON GX-281 or Agilent 1260 Infinity II.

[0468] For chiral preparation, supercritical fluid chromatography (SFC) was used, and the instrument used was Shimadzu LC-30Adsf or Shimadzu LC-20AD.

[0469] The silica gel sheets used for thin-layer chromatography were GF254 acrylic adhesive silica gel plates manufactured by Anhui Liangchen Silica Material Co., Ltd. The silica gel sheets used in thin-layer chromatography (TLC) were standardized to a thickness of 0.2 mm, and the silica gel sheets used for thin-layer chromatography separation and purification products were standardized to a thickness of 0.5 mm.

[0470] For column chromatography, 200-300 mesh silica gel manufactured by Anhui Liangchen Silica Material Co., Ltd. was generally used as the carrier.

[0471] Kinase mean inhibition rate and IC 50 The values ​​were measured using a SpectraMax i3X microplate reader (MD, USA).

[0472] TIFF2025537900000199.tif26170

[0473] In the following examples, unless otherwise specified, reactions were carried out under an argon or nitrogen atmosphere.

[0474] An argon or nitrogen atmosphere refers to a balloon of argon or nitrogen gas with a volume of approximately 1 L connected to the reaction bottle.

[0475] The hydrogen atmosphere refers to a hydrogen gas balloon with a volume of approximately 1 L connected to the reaction bottle.

[0476] The hydrogenation reaction was usually carried out by repeating evacuation and filling with hydrogen gas three times.

[0477] The oxygen atmosphere refers to a balloon of oxygen gas with a volume of approximately 1 L connected to the reaction bottle.

[0478] In the following examples, unless otherwise specified, the term "solution" refers to an aqueous solution, and the reaction temperature is room temperature, 20-30°C.

[0479] In the examples, the progress of the reaction was monitored by thin layer chromatography (TLC). The developing solvent used in the reaction, the eluent system of the column chromatography used to purify the compound, and the developing solvent system for the thin layer chromatography included A: dichloromethane / methanol system and B: petroleum ether / ethyl acetate system, and the volume ratio of the solvents may be adjusted depending on the polarity of the compound, or may be adjusted by adding a small amount of a basic or acidic reagent such as triethylamine or acetic acid.

[0480] Example 2-1: Preparation of Compound 1 and its isomers 1-A, 1-B, 1-C, and 1-D N-((1R,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 1-A N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 1-B N-((1S,9R)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 1-C N-((1R,9R)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 1-D [ka]

[0481] first step Ethyl 2-(6-cyano-5-oxo-2,3-dihydro-5H-spiro[indolizine-1,2'-[1,3]dioxolan]-7-yl)-3-cyclopropylpropionate 1b 1a (1.01 g, 3.31 mmol, prepared by the method disclosed in Example 30, page 28 of patent application WO2019238046) was dissolved in 15 mL of acetonitrile, and bromomethylcyclopropane (894.93 mg, 6.63 mmol) and potassium carbonate (916.16 mg, 6.63 mmol) were added. The mixture was stirred at 80 °C for 13 hours. 10 mL of water was added, and the diluted reaction mixture was extracted with ethyl acetate (15 mL × 2). The organic phase was washed with saturated aqueous sodium chloride solution (10 mL × 2), then dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by vacuum distillation. The resulting residue was purified by silica gel column chromatography using Development System A to obtain the title product 1b (1.12 g, yield: 92%) as a yellow solid. MS m / z (ESI): 359.1 [M+1].

[0482] Step 2 Ethyl 3-cyclopropyl-2-(6-formyl-5-oxo-2,3-dihydro-5H-spiro[indolizine-1,2'-[1,3]dioxolan]-7-yl)propionate 1c 1b (1.12 g, 3.05 mmol) was dissolved in a mixed solvent of 5 mL of water, 5 mL of acetonitrile, and 5 mL of formic acid, and the solution was protected with nitrogen gas. Raney nickel (261.72 mg) was added, and the atmosphere was purged with hydrogen gas three times. The reaction solution was stirred under hydrogen gas (15 Psi) at 60°C for 4 hours. The reaction mixture was filtered through diatomaceous earth, and the filter cake (50 mL × 3) was washed with dichloromethane. The filtrate was washed with aqueous hydrochloric acid (4 M, 20 mL) and then with aqueous sodium carbonate (12 M, 50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by reverse-phase liquid chromatography (separation conditions: column: 120 g Flash Cooln Welch Ultimate XB C1820-40 μM, mobile phase: A-water:B-acetonitrile, gradient elution, flow rate: 85 mL / min, equipment: ISCO) to obtain the title product 1c (680 mg, yield: 60%) as a yellow solid. MS m / z (ESI): 362.1 [M+1].

[0483] Step 3 4-(Cyclopropylmethyl)-1,4,7,8-tetrahydro-3H,10H-spiro[pyrano[3,4-f]indolizine-6,2'-[1,3]dioxolane]-3,10-dione 1d 1c (680 mg, 1.85 mmol) was dissolved in 10 mL of dichloromethane, protected with nitrogen gas, and cooled to 0 °C in an ice-water bath. Sodium borohydride (108.02 mg, 2.86 mmol) was added in batches, and the reaction mixture was stirred at 0 °C for 30 min. Acetic acid (133.15 mg, 2.22 mmol) was added dropwise at 25 °C to generate gas, and stirring was continued for 2 h. 30 mL of water was added dropwise at 15 °C to generate gas, and the mixture was stirred at 15 °C for 1.5 h. The reaction mixture was washed with water (50 mL) at 15 °C. p-Toluenesulfonic acid monohydrate (35.15 mg, 184.78 μmol) was added to the washed organic phase, and the mixture was stirred at 15 °C for 12 h. 50 mL of water was added, and the reaction mixture was extracted with dichloromethane (45 mL × 3). The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography using Development System B to obtain the title product 1d (200 mg, yield 32%) as a yellow oil. MS m / z (ESI): 318.1 [M+1].

[0484] Step Four 4-(Cyclopropylmethyl)-4-hydroxy-1,4,7,8-tetrahydro-3H,10H-spiro[pyrano[3,4-f]indolizine-6,2'-[1,3]dioxolane]-3,10-dione 1e 1d (202.13 mg, 598.74 μmol) was dissolved in 0.5 mL of methanol and cooled to 0°C in an ice-water bath. Potassium carbonate (82.75 mg, 598.74 μmol) was added in batches, and the mixture was stirred at 0°C for 5 hours under oxygen bubbling (15 psi). The reaction mixture was poured into 10 mL of saturated aqueous ammonium chloride solution, and the methanol was removed by distillation under reduced pressure. The reaction mixture was extracted with methylene chloride (20 mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by distillation under reduced pressure to give the crude title product 1e (140 mg) as a yellow oil, which was used directly in the next reaction without further purification. MS m / z (ESI): 334.1 [M+1].

[0485] Step 5 4-(Cyclopropylmethyl)-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione 1f 1e (64.52 mg, 180.00 μmol) was dissolved in a mixture of 0.5 mL of trifluoroacetic acid and 0.125 mL of water and stirred for 1 hour at 25° C. The reaction mixture was concentrated by distillation under reduced pressure, and the resulting residue was used without purification to obtain the crude title product 1f (40 mg) as a yellow solid, which was used directly in the next reaction without purification. MS m / z (ESI): 290.1 ​​[M+1].

[0486] Step 6 N-(9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7] indolizino[1,2-b]quinolin-1-yl)acetamide 1h 1f (40 mg, 128.59 μmol), 1g (38.62 mg, 154.31 μmol, prepared by the method disclosed in Example 5-1 on page 61 of patent application "CN111065621A"), and 4-methylbenzenesulfonyl pyridine (6.46 mg, 25.72 μmol) were dissolved in 0.5 mL of toluene, protected with nitrogen gas, and stirred at 130 °C for 2 h. The reaction mixture was filtered through diatomaceous earth, and the filtrate was added with 10 mL of water and extracted with dichloromethane (8 mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (TLC) using Development A to give the title product 1h (15 mg, 23% yield) as a brown solid. MS m / z (ESI): 504.2 [M+1].

[0487] Seventh Step 1-Amino-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione methanesulfonate 1i 1h (50 mg, 96.5 μmol) was dissolved in 1 mL of ethylene glycol dimethyl ether, and 0.5 mL of methanesulfonic acid and 0.5 mL of water were added, followed by stirring at 85° C. for 18 hours. The reaction mixture was poured into 10 mL of water, and the pH was adjusted to 7-8 with saturated sodium bicarbonate solution. The mixture was extracted with dichloromethane (10 mL × 5). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the crude title product 1i (40 mg) as a brown solid, which was used directly in the next reaction without further purification. MS m / z(ESI): 462.3[M+1].

[0488] Step 8 N-((1R,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b ]quinolin-1-yl)-2-hydroxyacetamide 1-A N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 1-B N-((1S,9R)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b ]quinolin-1-yl)-2-hydroxyacetamide 1-C N-((1R,9R)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 1-D The methanesulfonate salt of 1i (35 mg, 62.2 μmol) and glycolic acid (5.7 mg, 74.6 μmol) were dissolved in 1.5 mL of N,N-dimethylformamide. 1-Hydroxybenzotriazole (12.6 mg, 93.2 μmol), N,N-diisopropylethylamine (16.1 mg, 124 μmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (17.9 mg, 93.2 μmol) were added in that order and the mixture was stirred at 25°C for 1 h. 20 mL of water was added to the reaction mixture, and the diluted reaction mixture was extracted with dichloromethane (10 mL × 5). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by supercritical fluid chromatography to give the four single-configuration title products 1-A, 1-B, 1-C, and 1-D.

[0489] Single-configuration compound 1 (designated 1-B, 1.02 mg) SFC analysis: retention time 1.472 min, purity 98%. (Column: Chiralpak IC-350 × 4.6 mm ID, 3 μm; Mobile phase: A - carbon dioxide, B - methanol and acetonitrile (0.05% diethylamine); Isocratic elution: B: 60%; Flow rate: 3 mL / min; Instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 520.5[M+1].

[0490] 1H NMR(400MHz, CD3OD) δ 7.71-7.61(m, 2H), 5.73-5.66(m, 1H), 5.63-5.56(m, 1H), 5.40-5.32(m, 2H), 5.12-5.06(m, 1H), 4.28-4.22(m, 1H), 4.18-4.12(m, 1H), 3.32-3.32(m, 1H), 3.20-3.11(m, 1H), 2.42(s, 3H), 2.39-2.30(m, 1H), 2.29-2.19(m, 1H), 1.97-1.89(m, 1H), 1.88-1.80(m, 1H), 0.94-0.86(m, 1H), 0.51-0.38(m, 2H), 0.14-0.07(m, 1H), 0.04--0.01(m, 1H).

[0491] Compound 1's single stereoconfiguration compound 2 (1-Aとlabeled され, 1.02 mg) SFC analysis: holding time 2.075 min, purity 93%. (Camera: Chiralpak AS-350 × 4.6 mm ID, 3 μm, mobile phase: A-carbon diacid, B-methyl ether (0.05% zeolite), gravitational dissolution: B%: 5% - 40%, flow rate: 3 mL / min, instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 520.4[M+1].

[0492] 1 H NMR (400MHz, CD3OD) δ7.66-7.53(m,2H),5.70-5.63(m,1H),5.60-5.54(m,1H),5. 41-5.31(m,2H),5.22-5.14(m,1H),4.34-4.23(m,1H),4.22-4.11(m,1H),3.43-3. 36(m,1H),3.22-3.13(m,1H),2.43-2.37(m,3H),2.35-2.26(m,2H),1.95-1.80(m, 2H),0.93-0.86(m,1H),0.55-0.35(m,2H),0.17-0.08(m,1H),0.07--0.03(m,1H).

[0493] Compound 1’s single stereoconfiguration Compound 3 (1.21mg) SFC analysis: holding time 0.468 min, purity: 98%. (Color: Chiralcel OD-3 50×4.6mm ID, 3μm, mobile phase: A-carbon diacid, B-methylamine (0.05% zirconia), gravitational dissolution: B%: 5%-40%, flow rate: 3 mL / min, instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 520.1 [M+1].

[0494] 1 H NMR (400MHz, CD3OD) δ7.71-7.64(m,2H),5.73-5.67(m,1H),5.62-5.56(m,1H),5.43-5 .40(m,1H),5.38-5.35(m,1H),5.18-5.16(m,1H),4.28-4.21(m,1H),4.18-4.12(m,1H) ,3.50-3.45(m,1H),3.20-3.12(m,1H),2.49-2.40(m,3H),2.36-2.23(m,2H),1.96-1.8 2(m,2H),0.93-0.88(m,1H),0.52-0.39(m,2H),0.15-0.08(m,1H),0.06--0.02(m,1H).

[0495] Compound 1’s single stereoconfiguration compound 4 (0.27mg) SFC analysis: holding time 0.464 min, purity: 98%. (Color: Chiralcel OD-3 50×4.6mm ID, 3μm, mobile phase: A-carbon diacid, B-methylamine (0.05% zirconia), gravitational dissolution: B%: 5%-40%, flow rate: 3 mL / min, instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 520.1 [M+1].

[0496] 1H NMR(400MHz,CD3OD)δ7.71-7.62(m,2H),5.73-5.67(m,1H),5.62-5.56(m,1H),5 .41-5.35(m,2H),5.23-5.20(m,1H),4.33-4.23(m,1H),4.21-4.12(m,1H),3.38- 3.36(m,1H),3.22-3.13(m,1H),2.44(s,3H),2.37-2.28(m,2H),1.96-1.83(m,2 H),0.91-0.86(m,1H),0.50-0.38(m,2H),0.14-0.09(m,1H),0.06--0.01(m,1H).

[0497] Examples 2-2 to 2-6 The following compounds were prepared by selecting appropriate substrates with reference to the method of Example 2-1. [Table 88] [Table 89]

[0498] Example 2-2: Preparation of Compound 2 and its Isomers 2-A and 2-B (S)-N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxypropanamide 2-A (S)-N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxypropanamide 2-B [ka]

[0499] first step (S)-4-(Cyclopropylmethyl)-4-hydroxy-1,4,7,8-tetrahydro-3H,10H-spiro[3,4-f]indolizine-6,2'-[1,3]dioxolane]-3,10-dione 1e-1 (R)-4-(Cyclopropylmethyl)-4-hydroxy-1,4,7,8-tetrahydro-3H,10H-spiro[3,4-f]indolizine-6,2'-[1,3]dioxolane]-3,10-dione 1e-2 1e (1.30 g, 3.88 mmol) was separated by SFC (Separation conditions: Column: DAICEL CHIRALPAK AS 250 mm × 50 mm, 10 μm, Mobile phase: A - carbon dioxide: B - methanol (0.1% NH₃·H₂O), Isocratic elution: B: 20%, Flow rate: 120 mL / min, Instrument: Shimadzu LC-30ADsf) to give the title product 1e-1 (301 mg, Yield: 22.1%) as a yellow solid and the title product 1e-2 (285 mg, Yield: 19.4%) as a yellow solid.

[0500] Single configuration compound 1e-1 SFC analysis: retention time 1.392 min. (Column: Chiralpak AS-350 × 4.6 mm ID, 3 μm; Mobile phase: A - carbon dioxide, B - methanol (0.05% diethylamine); Gradient elution: B%: 5% - 40%; Flow rate: 3 mL / min; Instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 334.0 [M+1]. Single configuration compound 1e-2 SFC analysis: retention time 1.762 min. (Column: Chiralpak AS-3 50 × 4.6 mm ID, 3 μm, Mobile phase: A - carbon dioxide, B - methanol (0.05% diethylamine), Gradient elution: B%: 5% - 40%, Flow rate: 3 mL / min, Apparatus: Shimadzu LC-30ADsf). MS m / z (ESI): 333.9 [M+1].

[0501] Step 2 (S)-4-(Cyclopropylmethyl)-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione 1f-1 1e-1 (301 mg, 857 μmol) was dissolved in a mixed solution of 2 mL of trifluoroacetic acid and 0.5 mL of water, and the mixture was stirred for 4 hours at 25° C. The reaction solution was concentrated by distillation under reduced pressure, and the resulting residue was used without purification to obtain the crude title product 1f-1 (209 mg) as a yellow solid, which was used directly in the next reaction without purification. MS m / z (ESI): 290.1 ​​[M+1].

[0502] Step 3 N-((9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)acetamide 1h-1 1f-1 (50.0 mg, 159 μmol) was dissolved in 2 mL of toluene along with 1g (48.0 mg, 192 μmol) and 4-methylbenzenesulfonyl pyridine (8.0 mg, 31.8 μmol), and the solution was protected with nitrogen and stirred at 120 °C for 16 h. The reaction mixture was filtered through diatomaceous earth, 20 mL of water was added to the filtrate, and the mixture was extracted with dichloromethane (15 mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography using Development System A to give the title product 1h-1 (190 mg, 56% yield) as a yellow solid. MS m / z (ESI): 504.1 [M+1].

[0503] Step Four (9S)-1-Amino-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione 1i-1 1h-1 (60.0 mg, 111 μmol) was dissolved in 4.5 mL of ethylene glycol dimethyl ether, 1.5 mL of methanesulfonic acid and 1.5 mL of water were added, and the mixture was stirred at 85° C. for 16 h. The reaction mixture was added dropwise to 10 mL of water with stirring, extracted with methylene chloride (10 mL × 5), and the organic phase was washed with 25 mL of 0.05 M aqueous hydrochloric acid. The aqueous phase was filtered, and all the extracted aqueous phases were combined. The aqueous phase was adjusted to pH 7–8 with saturated potassium bicarbonate solution at 0° C. and extracted with a mixed solvent (dichloromethane / methanol: 20 / 3, 15 mL × 5). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the crude title product 1i-1 (22 mg) as a brown solid, which was used directly in the next reaction without purification. MS m / z (ESI): 462.1 [M+1].

[0504] Step 5 (S)-N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxypropanamide 2-A (S)-N-((1R,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxypropanamide 2-B The methanesulfonate salt of 1i-1 (22.0 mg, 47.7 μmol) and (2S)-2-hydroxypropionic acid (6.4 mg, 71.5 μmol) were dissolved in 1.5 mL of N,N-dimethylformamide, followed by the addition of 1-hydroxybenzotriazole (9.7 mg, 71.5 μmol), N,N-diisopropylethylamine (18.5 mg, 143 μmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (13.7 mg, 71.5 μmol), and the mixture was stirred at 25°C for 4 hours. Toluene (4 mL × 2) was added to the reaction mixture, which was then concentrated under reduced pressure at 25 °C. The resulting residue was diluted to 1.5 mL with N,N-dimethylformamide. The diluted solution was purified by pre-HPLC (column: Phenomenex luna C18150 × 25 mm × 10 μm, mobile phase: A - water (0.225% formic acid), B - acetonitrile, gradient elution: B%: 26-56%). The resulting mixture (10 mg) was purified by supercritical fluid chromatography to give the two single-configuration title products 2-A and 2-B.

[0505] Single-configuration compound 2-A (5.55 mg, yield: 20%, off-white solid) SFC analysis: retention time 1.381 min, purity 92%. (Column: Chiralcel OJ-3 50 × 4.6 mm ID, 3 μm, mobile phase: A - carbon dioxide, B - methanol (0.05% diethylamine), gradient elution: B%: 5% - 40%, flow rate: 3 mL / min, instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 534.1[M+1].

[0506] 1H NMR (400 MHz, CD3OD) δ 7.61 (s, 1H), 7.53-7.49 (m, 1H), 5.65-5.54 (m, 2H), 5.36-5.29 (m, 1H), 5.25-5.18 (m, 1H), 4.81-4.77 (m, 1H), 4.41-4.33 (m, 1H), 3.28-3.23 (m, 1H), 3.15-3.05 (m, 1H), 2.36-2.33 (m, 3H), 2.33-2.27 (m, 1H), 2.17-2.10 (m, 1H), 1.95-1.87 (m, 1H), 1.85-1.77 (m, 1H), 1.47-1.44 (m, 3H), 0.91-0.87 (m, 1H), 0.51-0.35 (m, 2H), 0.15-0.06 (m, 1H), 0.04--0.05 (m, 1H).

[0507] Compound 2’s single stereoconfiguration compound 2-B (4.06 mg, yield: 16%, yellow solid) SFC analysis: retention time 1.299 minutes, purity: 97%. (カラム:Chiralcel OJ-3 50×4.6mm ID, 3 μm, mobile phase: A-diacid carbon, B-メタノール (0.05% ジエチルアミン), グラジエント dissolution: B%: 5%-40%, flow rate: 3 mL / min, machine: Shimadzu LC-30ADsf). MS m / z(ESI): 534.1[M+1].

[0508] 1H NMR (400 MHz, CD3OD) δ 7.61 (s, 1H), 7.57-7.51 (m, 1H), 5.65-5.52 (m, 2H), 5.42-5.30 (m, 2H), 5.12-5.02 (m, 1H), 4.38-4.30 (m, 1H), 3.29-3.24 (m, 1H), 3.20-3.07 (m, 1H), 2.43-2.37 (m, 3H), 2.35-2.26 (m, 2H), 1.97-1.80 (m, 2H), 1.64-1.58 (m, 3H), 0.92-0.83 (m, 1H), 0.51-0.36 (m, 2H), 0.16-0.07 (m, 1H), 0.06--0.02 (m, 1H).

[0509] Example 2-3: Preparation of Compound 3 and its Isomers 3-A and 3-B (R)-N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxypropanamide 3-A (R)-N-((1R,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxypropanamide 3-B [ka]

[0510] first step (R)-N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxypropanamide 3-A (R)-N-((1R,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxypropanamide 3-B 1i-1 (40.0 mg, 80.8 μmol) and (2R)-2-hydroxypropionic acid (10.9 mg, 121 μmol) were dissolved in 1.5 mL of N,N-dimethylformamide, and then 1-hydroxybenzotriazole (16.4 mg, 121 μmol), N,N-diisopropylethylamine (31.3 mg, 242 μmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (23.2 mg, 121 μmol) were added in that order, followed by stirring at 25°C for 4 hours. Toluene (4 mL × 2) was added to the reaction mixture, which was then concentrated under reduced pressure at 25 °C. The resulting residue was diluted to 1.5 mL with N,N-dimethylformamide. The diluted solution was purified by pre-HPLC (column: Xtimate C18 150 × 40 mm × 10 μm; mobile phase: A - water (0.225% formic acid), B - acetonitrile, gradient elution: B%: 23%-53%). The resulting mixture was then purified by supercritical fluid chromatography to give the two single-configuration title compounds 3-A and 3-B.

[0511] Single-configuration compound 3-A (6.11 mg, yield: 14%, off-white solid) SFC analysis: holding time 1.413 min, purity: 97%. (Color: Chiralcel OJ-3 50×4.6mm ID, 3μm, mobile phase: A-carbon diacid, B-methylamine (0.05% zirconia), gravitational dissolution: B%: 5%-40%, flow rate: 3 mL / min, instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 534.3[M+1]. 1 H NMR(400MHz,CD3OD)δ7.61(s,1H),7.54-7.48(m,1H),5.70-5.62(m,1H),5.59-5.51(m,1H),5.38-5 .30(m,1H),5.29-5.21(m,1H),4.83-4.78(m,1H),4.33-4.25(m,1H),3.30-3.23(m,1H),3.20-3.09( m,1H),2.40-2.36(m,3H),2.35-2.31(m,1H),2.25-2.14(m,1H),1.95-1.88(m,1H),1.86-1.79(m,1 H),1.60-1.54(m,3H),0.95-0.82(m,1H),0.52-0.35(m,2H),0.15-0.07(m,1H),0.04--0.04(m,1H).

[0512] Monostereoscopic configuration of compound 3: Compound 3-B (2.78 mg, yield: 6%, grayish-white solid) SFC analysis: Holding time 2.013 min, purity: 97%. (Color: Chiralcel OD-3 50×4.6mm ID, 3μm, mobile phase: A-carbon diacid, B-methylamine (0.05% zeolite), gravitational dissolution: B%: 5%-40%, flow rate: 3 mL / min, instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 534.1 [M+1]. 1H NMR(400MHz,DMSO-d6)δ8.42-8.36(m,1H),7.81-7.75(m,1H),7.37(s,1H),6.57(s,1H) ,5.58-5.49(m,2H),5.41(s,2H),5.26-5.12(m,2H),4.17-4.09(m,1H),3.19-3.14(m,1H ),2.42-2.36(m,3H),2.23-2.10(m,2H),1.90-1.81(m,1H),1.79-1.71(m,1H),1.32-1.2 7(m,3H),0.85-0.77(m,1H),0.39-0.27(m,2H),0.10-0.02(m,1H),-0.03--0.11(m,1H).

[0513] Examples 2-4: Preparation of Compound 4 and its Isomers 4-A and 4-B (S)-2-Cyclopropyl-N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 4-A (S)-2-Cyclopropyl-N-((1R,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 4-B [ka]

[0514] first step The methanesulfonate salt of 1i-1 (37.0 mg, 78.5 μmol) and (2S)-2-cyclopropyl-2-hydroxyacetic acid (9.59 mg, 78.5 μmol) were dissolved in 1 mL of N,N-dimethylformamide, and then 1-hydroxybenzotriazole (15.9 mg, 118 μmol), N,N-diisopropylethylamine (30.4 mg, 236 μmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (22.6 mg, 118 μmol) were added sequentially, followed by stirring at 25°C for 12 hours. Ethyl acetate (10 mL) was added to the reaction mixture, which was washed with water (5 mL × 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by pre-HPLC (column: Phenomenexluna C18 150 × 25 mm × 10 μm, mobile phase: A - water (0.225% formic acid), B - acetonitrile, gradient elution: B: 31%-61%) to give the mixture as a yellow solid (15 mg, yield 31.2%). Further purification by preparative SFC (column: REGIS(s,s)WHELK-O 1250 × 30 mm, 5 μm, mobile phase: A - carbon dioxide (isopropyl alcohol), B - acetonitrile; isocratic elution: B: 65%) gave the two single-configuration title compounds 4-A and 4-B.

[0515] Single-configuration compound 4-A (7.0 mg, yield: 50.2%, yellow solid) SFC analysis: retention time 0.761 min, purity 98%. (Column: (S,S) WHELK-O1 50 × 4.6 mm ID, 3.5 μm, mobile phase: A - carbon dioxide, B - isopropyl alcohol and acetonitrile (0.05% diethylamine), isocratic elution: B: 65%, flow rate: 3 mL / min, instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 560.5 [M+1]. 1H NMR (400MHz, CD3OD) δ7.67(s,1H),7.64-7.60(m,1H),5.68-5.62(m,1H),5.61-5.55(m,1H),5.41-5.37( m,1H),5.36-5.33(m,1H),5.06-5.00(m,1H),3.87-3.84(m,1H),3.21-3.11(m,2H),2.43-2.40(m,3H),2. 37-2.31(m,1H),2.25-2.18(m,1H),1.96-1.89(m,1H),1.87-1.80(m,1H),1.32-1.28(m,1H),0.92-0.87 (m,1H),0.61-0.55(m,2H),0.53-0.45(m,3H),0.44-0.38(m,1H),0.14-0.08(m,1H),0.04--0.03(m,1H).

[0516] Compound 4's single stereoconfiguration compound 4-B (6.0 mg, yield: 41.9%, yellow solid) SFC analysis: retention time: 1.486 minutes, purity: 96%. (カラム:(S,S)WHELK-O1 50×4.6mmI.D., 3.5μm, mobile phase: A-diacid carbon, B-イソプロパノールとアセトニトリル (0.05% ジエチルアミン), アイソクラティック dissolution: B: 65%, flow rate: 3 mL / min, machine: Shimadzu LC-30ADsf). MS m / z(ESI): 560.3 [M+1]. 1 H NMR(400MHz,CD3OD)δ7.64(s,1H),7.61-7.57(m,1H),5.67-5.62(m,1H),5.59-5.52(m,1H),5.46-5 .39(m,1H),5.38-5.32(m,1H),5.21-5.14(m,1H),3.72-3.68(m,1H),3.22-3.11(m,2H),2.42-2.39( m,3H),2.34-2.28(m,2H),1.96-1.89(m,1H),1.87-1.81(m,1H),1.42-1.35(m,1H),0.91-0.85(m,1 H),0.69-0.58(m,3H),0.56-0.51(m,1H),0.48-0.40(m,2H),0.15-0.07(m,1H),0.06--0.02(m,1H).

[0517] Examples 2-5: Preparation of Compound 5 and its Isomers 5-A and 5-B (R)-2-Cyclopropyl-N-((1S,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 5-A (R)-2-Cyclopropyl-N-((1R,9S)-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetamide 5-B [ka]

[0518] first step The methanesulfonate salt of 1i-1 (25.0 mg, 42.3 μmol) and (2R)-2-cyclopropyl-2-hydroxyacetic acid (5.89 mg, 50.7 μmol) were dissolved in 1.5 mL of N,N-dimethylformamide, and then 1-hydroxybenzotriazole (8.57 mg, 63.4 μmol), N,N-diisopropylethylamine (16.4 mg, 127 μmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (12.2 mg, 63.4 μmol) were added in that order, and the mixture was stirred at 20°C for 4 hours. Toluene (4 mL × 2) was added to the reaction mixture, which was then concentrated under reduced pressure at 25 °C. The resulting residue was diluted to 1.5 mL with N,N-dimethylformamide, and the diluted solution was purified by pre-HPLC (column: Phenomenex luna C18 150 × 25 mm × 10 μm; mobile phase: A - water (0.225% formic acid), B - acetonitrile; gradient elution: B%: 28%-58%) to give two single-configuration title products 5-A and 5-B.

[0519] Single-configuration compound 5-A (4.95 mg, yield: 20%, off-white solid) SFC analysis: retention time 2.115 min, purity 97%. (Column: Chiralpak IC-3 50 × 4.6 mm ID, 3 μm, mobile phase: A - carbon dioxide, B - methanol and acetonitrile (0.05% diethylamine), isocratic elution: B: 50%, flow rate: 3 mL / min, instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 560.1 [M+1]. 1 H NMR(400MHz,CD3OD)δ7.70-7.64(m,2H),5.70-5.65(m,1H),5.60-5.54(m,1H),5.46-5.38(m,1H ),5.37-5.32(m,1H),5.23-5.17(m,1H),3.72-3.67(m,1H),3.36-3.34(m,1H),3.23-3.17(m,1H) ,2.48-2.42(m,3H),2.37-2.31(m,1H),2.31-2.25(m,1H),1.96-1.89(m,1H),1.88-1.80(m,1H), 1.34-1.31(m,1H),0.92-0.89(m,1H),0.68-0.42(m,6H),0.15-0.07(m,1H),0.05--0.02(m,1H).

[0520] Single-configuration compound 5-B (1.95 mg, yield: 8%, white solid) SFC analysis: retention time 1.179 min, purity 97%. (Column: Chiralpak IC-3 50 × 4.6 mm ID, 3 μm, Mobile phase: A - carbon dioxide, B - methanol and acetonitrile (0.05% diethylamine), Isocratic elution: B: 50%, Flow rate: 3 mL / min, Instrument: Shimadzu LC-30ADsf). MS m / z(ESI): 560.1 [M+1]. 1H NMR(400MHz,CD3OD)δ7.69(s,1H),7.69-7.62(m,1H),5.69-5.63(m,1H),5.61-5.55(m,1 H),5.49-5.42(m,1H),5.40-5.34(m,1H),5.24-5.16(m,1H),3.91-3.84(m,1H),3.38-3. 36(m,1H),3.24-3.16(m,1H),2.44(s,3H),2.40-2.23(m,2H),1.97-1.80(m,2H),1.29-1 .21(m,1H),0.95-0.85(m,1H),0.64-0.36(m,6H),0.17-0.07(m,1H),0.07--0.02(m,1H).

[0521] Examples 2-6: Preparation of Compound 6 [ka] [ka]

[0522] first step (1S,9S)-1-amino-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione 1i-1-1 (1R,9S)-1-amino-9-(cyclopropylmethyl)-5-fluoro-9-hydroxy-4-methyl1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione 1i-1-2 1i-1 (550 mg, 1.10 mmol) was separated by SFC (separation conditions: column: DAICEL CHIRALPAK IC 250 mm × 50 mm, 10 μm; mobile phase: An-hexane:B-ethanol, isocratic elution: B: 45%) to give the title product 1i-1-1 (260 mg, yield: 41%) as a yellow solid and the title product 1i-1-2 (290 mg, yield: 46%) as a yellow solid.

[0523] Single-configuration compound 1i-1-1 SFC analysis: retention time 3.039 min. (Column: Chiralpak IC-350 × 4.6 mm I.D., 3 μm; Mobile phase: A - n-hexane (0.05% isopropylamine), B - ethanol and acetonitrile (0.05% isopropylamine); Isocratic elution: B: 45%; Flow rate: 1 mL / min; Instrument: Shimadzu LC-20AD). MS m / z(ESI): 462.3 [M+1].

[0524] Single-configuration compound 1i-1-2 SFC analysis: retention time 4.951 min. (Column: Chiralpak IC-350 × 4.6 mm I.D., 3 μm; Mobile phase: An - hexane (0.05% isopropylamine), B - ethanol and acetonitrile (0.05% isopropylamine); Isocratic elution: B: 45%, Flow rate: 1 mL / min; Instrument: Shimadzu LC-20AD). MS m / z(ESI): 462.3 [M+1].

[0525] Step 2 1i-1-1 (13 mg, 25.35 μmol), 1-hydroxycyclopropanecarboxylic acid (4 mg, 38.03 μmol), and 2-(7-azobenzotriazazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (12 mg, 30.42 μmol) were dissolved in 1 mL of N,N-dimethylformamide, and N,N-diisopropylethylamine (10 mg, 76.06 μmol) was added. The mixture was stirred at 25 °C for 1 h. The reaction mixture was purified by pre-HPLC (InfinityLab Poroshell 120 SB-C182 column, 1.2 × 150 mm, 4 μm; mobile phase: A - water (0.1% formic acid), B - acetonitrile; gradient elution: B: 20% - 80%) to give the title product 6 (2.25 mg, 16% yield) as a white solid. MS m / z(ESI): 546.3 [M+1]. 1 H NMR(400MHz,DMSO-d6)δ8.66-8.58(m,1H),7.80-7.74(m,1H),7.41-7.34(m,1H),6.62-6.58(m,1H),6 .37-6.29(m,1H),5.61-5.53(m,1H),5.48-5.37(m,2H),5.33-5.24(m,1H),5.12-5.04(m,1H),3.28-3. 22(m,1H),3.17-3.06(m,1H),2.44-2.33(m,3H),2.28-2.15(m,2H),1.86-1.73(m,2H),1.27-1.15(m, 2H),1.00-0.89(m,2H),0.87-0.75(m,1H),0.40-0.25(m,2H),0.08-0.03(m,1H),-0.06--0.14(m,1H).

[0526] Examples 2-7 to 2-13 The following compounds were prepared by selecting appropriate substrates with reference to the method of Example 2-1. [Table 90]

[0527] Examples 2-14: Preparation of Compound 14 N'-acetyl-N-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetohydrazide 14 [ka] [ka]

[0528] first step 2-((1S,9S)-9-Ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)hydrazine-1-carboxylic acid tert-butyl ester 14b 14a (100 mg, 0.19 mmol) and 2-(tert-butyl) 3,3-diethyl 1,2-oxazolidine-2,3,3-tricarboxylate (54.9 mg, 0.19 mmol, prepared as described in Organic Letters, 2005, Vol. 7, #4, pp. 713-716) were dissolved in 10 mL of dichloromethane, triethylamine (38.4 mg, 0.38 mmol) was added, and the mixture was stirred at 25 °C for 12 h. 20 mL of water was added, and the diluted reaction mixture was separated. The organic phase was washed with saturated aqueous sodium chloride (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by vacuum distillation. The resulting residue was purified by preparative thin-layer chromatography using Development System A to give the title product 14b (55 mg, 53% yield) as a white solid. MS m / z (ESI): 551.2 [M+1].

[0529] Step 2 2- (2- (benzyloxy)acetyl) -2- ((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[ de ]pyrano[3',4':6,7]indolizino[1,2-b ]quinolin-1-yl)hydrazine-1-carboxylic acid tert-butyl ester 14c 14b (55 mg, 0.1 mmol) was dissolved in 10 mL of tetrahydrofuran, sodium bicarbonate (840 mg, 10 mmol) was added, and the mixture was protected with nitrogen gas at 25° C. A solution of 2-benzyloxyacetyl chloride in tetrahydrofuran (184 mg, 1.0 mmol, 5 mL) was added dropwise to the solution and stirred at 25° C. for 1 hour. The reaction mixture was poured into 10 mL of water and extracted with ethyl acetate (10 mL × 2). The organic phase was washed with saturated aqueous sodium chloride (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography using Development System A to give the title product 14c (58 mg, yield: 83%) as a white solid. MS m / z (ESI): 699.3 [M+1].

[0530] Step 3 2-(Benzyloxy)-N-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)acetylhydrazine 14d 14c (58 mg, 0.09 mmol) was dissolved in 10 mL of dichloromethane, and 1 mL of trifluoroacetic acid was added, followed by stirring for 5 hours at 25° C. The reaction mixture was concentrated by distillation under reduced pressure to give crude title product 14d (70 mg) as a light brown solid, which was used directly in the next reaction without purification. MS m / z (ESI): 599.2 [M+1].

[0531] Step Four N'-Acetyl-2-(benzyloxy)-N-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7] indolizino[1,2-b]quinolin-1-yl)acetylhydrazine 14e 14d (70 mg, 0.09 mmol) was dissolved in 10 mL of tetrahydrofuran, sodium bicarbonate (756 mg, 9 mmol) was added, and the mixture was protected with nitrogen gas. A solution of acetyl chloride in tetrahydrofuran (71 mg, 0.9 mmol, 3 mL) was added dropwise to the solution at 25° C. and stirred for 1 h at 25° C. The reaction mixture was poured into 10 mL of water and extracted with ethyl acetate (10 mL × 2). The organic phase was washed with saturated aqueous sodium chloride (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography using Development System A to give the title product 14e (45 mg, yield: 78%) as an off-white solid. MS m / z (ESI): 641.7 [M+1].

[0532] Step 5 N'-Acetyl-N-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-2-hydroxyacetylhydrazine 14 14e (45 mg, 0.07 mmol) was dissolved in 10 mL of tetrahydrofuran, protected with nitrogen gas, and cooled to −10 °C in an ice-salt bath. Palladium dichloride (50 mg, 0.282 mmol) was added, and the mixture was purged with hydrogen gas three times. The reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated by vacuum distillation. The resulting residue was purified by preparative HPLC (Separation conditions: Column: Sunfire Prep C18 OBD 10 μm, 19 × 250 mm, Mobile phase: A - acetonitrile / methanol = 1 / 1, B - water (0.2% formic acid), gradient elution, A%: 45% - 95%, Flow rate: 20 mL / min, Instrument: Gilson GX-281) to give the title product 14 (4.5 mg, Yield: 12%) as an off-white solid. MS m / z (ESI): 551.1 [M+1]. 1 H NMR (400 MHz, DMSO-d6) δ 10.22-9.65 (m, 1H), 7.79 (d, J = 10.8 Hz, 1H), 7.36-7.28 (m, 1H), 6.58-6.52 (m, 1H), 6.22-5.99 (m, 1H), 5.43 (s, 2H), 5.33 (s, 1H), 5.15-5.00 (m, 2H), 4.26-4.13 (m, 1H), 3.98-3.71 (m, 1H), 3.21-3.04 (m, 2H), 2.42-2.34 (m, 3H), 2.25-2.08 (m, 1H), 1.92-1.82 (m, 2H), 1.67-1.24 (m, 3H), 1.25-1.20 (m, 1H), 0.91-0.84 (m, 3H).

[0533] Examples 2-15 to 2-18, 2-20, 2-21, and 2-23 The following compounds were prepared using the methods of Examples 2-14 and appropriate substrates. [Table 91]

[0534] Example 2-19: Preparation of Compound 19 N'-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-N'-(2-hydroxyacetyl)cyclopropanemethanehydrazide 19 [ka] [ka]

[0535] first step N'-(2-(Benzyloxy)acetyl)-N'-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)cyclopropanemethane hydrazide 19a 14d (50 mg, 0.08 mmol) was dissolved in 10 mL of tetrahydrofuran, sodium bicarbonate (672 mg, 8 mmol) was added, and the mixture was protected with nitrogen gas. A solution of cyclopropaneoxy chloride (83 mg, 0.8 mmol) in tetrahydrofuran (5 mL) was added dropwise, and the reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (10 mL × 2). The organic phase was washed with saturated sodium chloride solution (10 mL × 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by pre-HPLC (Separation conditions: Column: Sunfire Prep C18 OBD 10 μm, 19 × 250 mm, Mobile phase: A - acetonitrile / methanol = 1 / 1, B - water (0.2% formic acid), gradient elution, A%: 45% to 95%, Flow rate: 20 mL / min, Instrument: GILSON GX-281) and lyophilized to give the title product 19a (19 mg, Yield: 34%) as an off-white solid. MS m / z(ESI): 667.2 [M+1].

[0536] Step 2 N'-((1S,9S)-9-Ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)-N'-(2-hydroxyacetyl)cyclopropanemethane hydrazide 19 19a (19 mg, 0.03 mmol) was dissolved in 5 mL of tetrahydrofuran, protected with nitrogen gas, and cooled to −10 °C in an ice-salt bath. Palladium dichloride (20 mg, 0.113 mmol) was added, and the mixture was purged with hydrogen gas three times. The reaction mixture was stirred at 0 °C for 15 h. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated by vacuum distillation. The resulting residue was purified by pre-HPLC (Separation conditions: Column: Sunfire Prep C18 OBD 10 μm, 19 × 250 mm, Mobile phase: A - acetonitrile / methanol = 1 / 1, B - water (0.2% formic acid), Gradient elution, A%: 45% - 95%, Flow rate: 20 mL / min, Instrument: Gilson GX-281) to give the title product 19 (4.2 mg, Yield: 26%) as a white solid. MS m / z(ESI): 577.2 [M+1].

[0537] Example 2-22: Preparation of Compound 22 (S)-N-(10-ethyl-6-fluoro-10-hydroxy-5-methyl-11,14-dioxo-3,4,10,11,14,16-hexahydro-13H-azacyclohepta[2,3,4-de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1(2H)-yl)-2-hydroxyacetamide 22 [ka] [ka]

[0538] first step N-(3-(3-((tert-butyldimethylsilyl)oxy)propyl)-2-(1,3-dioxolan-2-yl)-5-fluoro-4-methylphenyl)-1,1-diphenylmethyleneimine 22b Allyloxy-tert-butyl-dimethylsilane (6.89 g, 36.00 mmol, 90% purity, prepared by the method disclosed in Organic Letters, 2017, Vol. 19, #11, pp. 2869-2872) was dissolved in 70 mL of toluene, protected with nitrogen gas, and cooled to 10°C in an ice-water bath. 9-Borabicyclo[3.3.1]nonane (0.5 M, 86.41 mL, 43.20 mmol) was added, and the reaction mixture was stirred at 80°C for 20 minutes. Completion of the reaction was monitored by TLC. The reaction mixture was cooled to 10°C in an ice-water bath, and under nitrogen gas protection, an aqueous solution of sodium hydroxide (2.88 g, 72.01 mmol, 24 mL), tetrabutylammonium iodide (664.95 mg, 1.80 mmol), 22a (5.02 g, 10.80 mmol), and 1,1-bis(diphenylphosphino)ferrocenedichloride palladium (526.89 mg, 720.09 μmol) were added sequentially, and the mixture was stirred at 80°C for 15 h. The completion of the reaction was monitored by LC-MS. The reaction mixture was diluted with 100 mL of water, extracted with dichloromethane (100 mL × 3), and the organic phase was washed with water (100 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by reverse-phase high-performance liquid chromatography to give the title product 22b as a yellow gum (2.60 g, yield 12%, purity 88.75%). MS m / z (ESI): 534.5 [M+1].

[0539] Step 2 (S)-4-Ethyl-8-fluoro-4-hydroxy-10-(3-hydroxypropyl)-9-methyl-1,12-dihydro-14H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione 22d 22b (380 mg, 654.99 μmol) was dissolved in 5 mL of ethanol, and 22c (103.45 mg, 393.00 μmol, prepared by the method disclosed in patent application WO2019238046A1) and concentrated hydrochloric acid (12 M, 0.5 mL) were added. The mixture was stirred at 80 °C for 2 hours, and the reaction completion was monitored by LC-MS. The reaction solution was concentrated by vacuum distillation to remove ethanol, and 5 mL of water was added to dilute the reaction solution. The diluted reaction solution was extracted with dichloromethane (10 mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by vacuum distillation. The resulting residue was purified by silica gel column chromatography using development system A to obtain the title product 22d (80 mg, yield: 27%) as a yellow solid. MS m / z (ESI): 439.2 [M+1].

[0540] Step 3 (S)-4-Ethyl-8-fluoro-4-hydroxy-10-(3-hydroxypropyl)-9-methyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline 6-oxide 22e 22d (334 mg, 684 μmol) was dissolved in 30 mL of acetic acid, and hydrogen peroxide (12.8 g, 113 mmol, 30% content) was added. The mixture was stirred at 70 °C for 1.5 h. The reaction completion was monitored by LC-MS. The reaction mixture was cooled to 0 °C, and 15 mL of sodium thiosulfate solution was added to quench the reaction. The mixture was extracted with ethyl acetate (20 mL × 2). The organic phase was washed with saturated sodium chloride solution (15 mL × 2). The filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated by vacuum distillation. The resulting residue was purified by silica gel column chromatography using Development System A to obtain the title product 22e (110 mg, yield: 31%) as a yellow solid. MS m / z (ESI): 455.1 [M+1].

[0541] Step Four (S)-3-(11-chloro-4-ethyl-8-fluoro-4-hydroxy-9-methyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-10-yl) propyl formate 22f 22e (110 mg, 227 μmol) was dissolved in 5 mL of N,N-dimethylformamide, and oxalyl chloride (144 mg, 1.13 mmol) was added. The mixture was stirred at 0°C for 1 hour. To the reaction mixture was added 8 mL of water, and the mixture was extracted with ethyl acetate (10 mL × 3). The organic phase was washed with saturated sodium chloride solution (8 mL × 3). The filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude title product 22f (100 mg) as a yellow solid. The product was used directly in the next reaction without further purification. MS m / z (ESI): 501.1 [M+1].

[0542] Step 5 (S)-11-chloro-4-ethyl-8-fluoro-4-hydroxy-10-(3-hydroxypropyl)-9-methyl-1,12-dihydro-14H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione 22g 22f (100 mg, 199 μmol) was dissolved in 4 mL of methanol, and aqueous hydrochloric acid (2 M, 1.00 mL) was added. The mixture was stirred at 25° C. for 1 hour. The methanol was removed by concentration under reduced pressure. 3 mL of water was added to the resulting residue, which was then extracted with ethyl acetate (5 mL × 3). The organic phase was washed with saturated sodium chloride solution (8 mL × 3). The filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude title product 22g (90 mg) as a yellow solid. The product was used directly in the next reaction without further purification. MS m / z(ESI): 473.1[M+1].

[0543] Step 6 (S)-3-(11-chloro-4-ethyl-8-fluoro-4-hydroxy-9-methyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-10-yl)propionaldehyde 22h 22g (90.0 mg, 190 μmol) was dissolved in 4 mL of dichloromethane, Dess-Martin reagent (242 mg, 570 μmol) was added, and the mixture was stirred at 25°C for 2 hours. 5 mL of water was added to the reaction mixture, which was then extracted with dichloromethane (3 mL x 2). The filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude title product 22h (90 mg) as a yellow solid. The product was used directly in the next reaction without further purification. MS m / z(ESI): 471.1[M+1].

[0544] Seventh Step tert-Butyl (S)-(10-ethyl-6-fluoro-10-hydroxy-5-methyl-11,14-dioxo-3,4,10,11,14,16-hexahydro-13H-azacycloheptane[2,3,4-de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1(2H)-yl)carbamate 22i 22h (90.0 mg, 191 μmol) and t-butyl carbazate (27.8 mg, 210 μmol) were dissolved in 1 mL of methanol, and sodium cyanoborohydride (60.1 mg, 955 μmol) was added. The mixture was stirred at 25 °C for 4 h. The methanol was removed by concentration under reduced pressure. 2 mL of water was added to the residue, which was then extracted with dichloromethane (3 mL × 2). The filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. 15 mg of the residue was purified by pre-HPLC (separation conditions: column: Phenomenex Luna C18, 150 × 25 mm × 10 μm; mobile phase: A - water (0.2% formic acid), B - acetonitrile, gradient elution, B%: 33% to 63%) to give the title product 22i (1.01 mg, yield: 13%) as an off-white solid. MS m / z(ESI): 551.4[M+1].

[0545] Step 8 (S)-1-Amino-10-ethyl-6-fluoro-10-hydroxy-5-methyl-2,3,4,10,13,16-hexahydro-14H-azacycloheptane[2,3,4-de]pyran[3',4':6,7]indolizino[1,2-b]quinoline-11,14(1H)-dione 22j 22i (20.0 mg, 22.3 μmol) was dissolved in 1 mL of dichloromethane, and trifluoroacetic acid (2.05 g, 17.9 mmol) was added. The mixture was stirred at 25°C for 1 h. Methanol was removed by concentration under reduced pressure. 2 mL of water was added to the residue, which was then extracted with dichloromethane (3 mL × 2). The filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. 6 mg of the residue was purified by pre-HPLC (separation conditions: column: Welch Xtimate C18, 150 × 25 mm × 5 μm; mobile phase: A - water (0.2% formic acid), B - acetonitrile, gradient elution, B%: 8% to 38%) to give the title product 22j (1.06 mg, yield: 64%) as a yellow gum. MS m / z(ESI): 451.4[M+1].

[0546] Step 9 (S)-2-(Benzyloxy)-N-(10-ethyl-6-fluoro-10-hydroxy-5-methyl-11,14-dioxo-3,4,10,11,14,16-hexahydro-13H-azacycloheptane[2,3,4-de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1(2H)-yl)acetamide 22k 22j (20 mg, 25.44 μmol) was dissolved in 0.5 mL of tetrahydrofuran and 0.5 mL of saturated sodium bicarbonate solution, protected with nitrogen gas, and 2-benzyloxyacetyl chloride (23.48 mg, 127.18 μmol) was added. The mixture was protected with nitrogen gas and stirred at 25°C for 10 hours. 1 mL of water was added to the reaction mixture, which was then extracted with ethyl acetate (2 mL × 3). The organic phase was washed with saturated sodium chloride solution (2 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography using Development System A to give the title product 22k (4 mg, 22% yield) as a yellow solid. MS m / z(ESI): 599.1[M+1].

[0547] Step 10 (S)-N-(10-ethyl-6-fluoro-10-hydroxy-5-methyl-11,14-dioxo-3,4,10,11,14,16-hexahydro-13H-azacyclohepta[2,3,4-de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1(2H)-yl)-2-hydroxyacetamide 22 22k (3.5 mg, 4.85 μmol) was dissolved in 1 mL of tetrahydrofuran, palladium(II) chloride (860.53 μg, 4.85 μmol) was added, and the atmosphere was purged with hydrogen gas three times. The reaction mixture was stirred under hydrogen gas (15 Psi) at 0 °C for 0.5 h. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by pre-HPLC (separation conditions: column: Phenomenex Luna C18, 150 × 25 mm × 10 μm, mobile phase: A - water (0.2% formic acid), B - acetonitrile, gradient elution, B%: 13% - 43%) to give the title product 22 (0.3 mg, yield: 9%) as a yellow solid. MS m / z(ESI):509.3[M+1].

[0548] Examples 2-24: Preparation of Compound 24 (S)-N-((8-ethyl-4-fluoro-8-hydroxy-9,12-dioxo-2,3,8,9,12,14-hexahydro-1H,11H-cyclopenta[f]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-15-yl)methyl)-2-hydroxyacetamide 24 [ka] [ka]

[0549] first step 4-Bromo-7-fluoro-5-nitro-2,3-dihydro-1H-indene 24b 24a (17 g, 79.05 mmol, prepared as described in Example 9, page 31, of Patent Application WO2021093820A1) was dissolved in 200 mL of trifluoroacetic acid, protected with nitrogen gas, and cooled to 0 °C in an ice-water bath. Nitric acid (20.45 g, 292.08 mmol, 90% content) was slowly added dropwise to the reaction mixture, which was stirred at 0 °C for 10 min. The ice-water bath was removed, and the mixture was stirred at 25 °C for 30 min. 100 mL of water was added, and the diluted reaction mixture was extracted with ethyl acetate (500 mL × 3). The organic phase was washed with water (500 mL × 3), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by vacuum distillation. The resulting residue was purified by silica gel column chromatography using elution system B to give the title product 24B (8.96 g, 44% yield) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ7.45 (d, J=8.0Hz, 1H), 3.05-3.16 (m, 4H), 2.18-2.27 (m, 2H).

[0550] Step 2 4-Bromo-7-fluoro-2,3-dihydro-1H-inden-5-amine 24c 24b (8.96 g, 34.61 mmol) was dissolved in a mixture of 100 mL of ethanol and 20 mL of water, and iron powder (5.80 g, 103.82 mmol) and ammonium chloride (5.55 g, 103.82 mmol) were added sequentially. The reaction mixture was protected with nitrogen and stirred at 80 °C for 1 h. The reaction mixture was filtered, and the filtrate was concentrated by distillation under reduced pressure to give crude title product 24c (7.2 g) as a white solid. The product was used directly in the next reaction without further purification. MS m / z(ESI):229.9[M+1].

[0551] Step 3 tert-Butyl (4-bromo-7-fluoro-2,3-dihydro-1H-inden-5-yl) (tert-butoxycarbonyl)carbamate 24d 24c (7.2 g, 31.29 mmol) was dissolved in 50 mL of tetrahydrofuran, and di-tert-butyl dicarbonate (27.32 g, 125.18 mmol), 4-dimethylaminopyridine (38.23 mg, 312.94 μmol), and triethylamine (12.67 g, 125.18 mmol) were added. The reaction mixture was stirred at 25 °C for 16 h. The reaction mixture was concentrated by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography using Developer System B to give the title product 24d (9.2 g, 68% yield) as a white solid. MS m / z(ESI):317.9[M+1-56-56].

[0552] Step Four tert-Butyl (tert-butoxycarbonyl) (7-fluoro-4-vinyl-2,3-dihydro-1H-inden-5-yl)carbamate 24e 24d (1.5 g, 4.38 mmol) and vinylboronic acid pinacol ester (810.20 mg, 5.26 mmol) were dissolved in a mixture of 6 mL of 1,4-dioxane and 2 mL of water, and the mixture was protected with nitrogen. Potassium phosphate tripotassium (2.79 g, 13.15 mmol) and (2-dicyclohexylphosphino-2',4',6'-tri-isopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (371.07 mg, 438.38 μmol) were added sequentially. The mixture was protected with nitrogen and stirred at 95°C for 10 h. 20 mL of water was added, and the diluted reaction solution was extracted with ethyl acetate (10 mL × 3). The organic phase was washed with saturated sodium chloride solution (5 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography using Development System B to give the title product 24e (350 mg, yield 26%) as a colorless oil. MS m / z(ESI):222.1[M+1-100-56].

[0553] Step 5 t-Butyl (t-butoxycarbonyl) (7-fluoro-4-formyl-2,3-dihydro-1H-inden-5-yl)carbamate 24f 24e (755 mg, 2.00 mmol) was dissolved in a mixture of 1.5 mL of dioxane and 1.5 mL of water, and sodium periodate (1.29 g, 6.01 mmol) and potassium osmate dihydrate (73.8 mg, 200 μmol) were added and stirred for 5 hours at 25° C. The reaction mixture was filtered, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography using development system B to give the title product 24f (538 mg, 71% yield) as a yellow solid. MS m / z(ESI):180.2[M+1-100-100].

[0554] Step 6 (S)-8-Ethyl-4-fluoro-8-hydroxy-1,2,3,8,11,14-hexahydro-9H,12H-cyclopenta[f]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-9,12-dione 24h 24f (538 mg, 1.42 mmol) and 24g (i.e., compound 22C above) (375 mg, 1.42 mmol, prepared by the method disclosed in Example 30, page 28 of patent application WO2019238046A1) were dissolved in 10 mL of ethanol, and concentrated hydrochloric acid (12 M, 1.58 mL) was added and stirred at 80 °C for 2 hours. The reaction mixture was concentrated by vacuum distillation to remove ethanol, and 10 mL of water was added. The cake was filtered to obtain the crude title product 24h (500 mg) as a yellow solid. The product was used directly in the next reaction without further purification. MS m / z(ESI): 407.2 [M+1].

[0555] Seventh Step (S)-8-Ethyl-4-fluoro-8-hydroxy-9,12-dioxo-2,3,8,9,12,14-hexahydro-1H,11H-cyclopenta[f]pyrano[3',4':6,7]indolizino[1,2-b]quinoline 6-oxide 24i 24h (500 mg, 1.21 mmol) was dissolved in 70 mL of acetic acid and protected with nitrogen gas. Hydrogen peroxide solution (16.9 g, 149 mmol, 30% content) was added and the mixture was stirred at 75 °C for 3 h. LCMS showed that the starting material 24h remained, so hydrogen peroxide solution (16.5 g, 145 mmol, 30% content) was added again and the mixture was stirred at 75 °C for 4 h. The reaction mixture was poured into 100 mL of water and filtered to obtain a cake, which gave the crude title product 24i (400 mg) as a yellow solid. The product was used directly in the next reaction without further purification. MS m / z(ESI): 423.2 [M+1].

[0556] Step 8 (S)-15-Chloro-8-ethyl-4-fluoro-8-hydroxy-1,2,3,8,11,14-hexahydro-9H,12H-cyclopenta[f]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-9,12-dione 24j 24i (100 mg, 142 μmol) was dissolved in 2 mL of N,N-dimethylformamide, protected with nitrogen gas, and cooled to 0 °C in an ice-water bath. Oxalyl chloride (45.0 mg, 355 μmol) was added and stirred at 25 °C for 1 h. The reaction mixture was poured into 10 mL of water and filtered to give a cake, affording the crude title product 24j (70 mg) as a brown solid. The product was used directly in the next reaction without further purification. MS m / z(ESI): 441.2 [M+1].

[0557] Step 9 t-Butyl (S)-((8-ethyl-4-fluoro-8-hydroxy-9,12-dioxo-2,3,8,9,12,14-hexahydro-1H,11H-cyclopenta[f]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-15-yl)methyl)carbamate 24k 24j (20.0 mg, 26.3 μmol) and potassium ((tert-butoxycarbonylamino)methyl)trifluoroborate (14.0 mg, 59.2 μmol) were dissolved in a mixture of 1 mL of dioxane and 0.2 mL of water, protected with nitrogen gas, and 1,1-bis(diphenylphosphine)ferrocenium palladium dichloride (2.89 mg, 3.95 μmol) and potassium carbonate (25.1 mg, 118 μmol) were added. The mixture was stirred at 95°C under nitrogen gas for 1 hour. The reaction mixture was poured into aqueous hydrochloric acid (1 M, 2 mL), and the filtrate was concentrated by distillation under reduced pressure to give the crude title product 24k (20 mg) as a brown oil. The product was used directly in the next reaction without further purification. MS m / z(ESI):436.2[M+1-100].

[0558] Step 10 (S)-15-(Aminomethyl)-8-ethyl-4-fluoro-8-hydroxy-1,2,3,8,11,14-hexahydro-9H,12H-cyclopenta[f]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-9,12-dione 24l 24k (1.00 mg, 1.87 μmol) was dissolved in 0.6 mL of dichloromethane, and a solution of hydrochloric acid in dioxane (4 M, 0.2 mL) was added. The mixture was stirred at 25°C for 1 hour. 1 mL of water was added, and the diluted reaction mixture was extracted with ethyl acetate (1 mL x 3). The aqueous phase was filtered, and the filtrate was concentrated by distillation under reduced pressure to give the crude title product 24l (0.5 mg) as a yellow solid. The product was used directly in the next reaction without further purification. MS m / z(ESI): 436.1 [M+1].

[0559] The eleventh step (S)-N-((8-ethyl-4-fluoro-8-hydroxy-9,12-dioxo-2,3,8,9,12,14-hexahydro-1H,11H-cyclopenta[f]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-15-yl)methyl)-2-hydroxyacetamide 24 24l (13.3 mg, 22.9 μmol) and 2-hydroxyacetic acid (2.10 mg, 27.5 μmol) were dissolved in 1 mL of dichloromethane, and N,N-diisopropylethylamine (8.90 mg, 68.9 μmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.60 mg, 34.4 μmol), and 1-hydroxybenzotriazole (4.65 mg, 34.4 μmol) were added, followed by stirring at 25°C for 30 minutes. The reaction mixture was concentrated by distillation under reduced pressure, 2 mL of water was added, and the mixture was extracted with ethyl acetate (1 mL × 3). The organic phase was washed with saturated sodium chloride solution (1 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by distillation under reduced pressure. The resulting residue was purified by preparative HPLC (separation conditions: column: Welch ultimate C18150 × 25 mm × 7 μm, mobile phase: A-water (containing 0.225% formic acid), B-acetonitrile, gradient elution, flow rate: 25 mL / min, equipment: GILSON GX-281) to obtain the title product...

Claims

1. A complex represented by the following formula (C), its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide or pharmaceutically acceptable salt. 【Chemistry 1】 where Tp is a targeting moiety; L is selected from a chemical bond or a linker; G represents a group represented by the following formula (G): 【Chemistry 2】 In the formula, A is N or CR A is selected from If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R B an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, a heterocyclyl group, a heterocyclylalkyl group, an aryl group, an arylalkyl group, a heteroaryl group or a heteroarylalkyl group substituted with NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; A is CR A In the case of R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R C an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkyloxy group, a cycloalkyloxy group, an alkyloxyalkyl group, a heterocyclyl group, a heterocyclylalkyl group, an aryl group, an arylalkyl group, a heteroaryl group or a heteroarylalkyl group substituted with NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D forming a 3-10 membered ring structure substituted with z is selected from 0 or 1; R 2 is a hydrogen atom, a halogen atom, unsubstituted or one, two or more R E and selected from alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, and cycloalkyloxy groups substituted with R 3 is a hydrogen atom, a halogen atom, unsubstituted or one, two or more R E and selected from alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, and cycloalkyloxy groups substituted with Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E forming a cyclic structure, for example a 5-10 membered cyclic structure, substituted with, wherein the 5-10 membered cyclic structure may be selected from a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group; Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F forming a cyclic structure, for example a 4-10 membered cyclic structure, substituted with, wherein the 4-10 membered cyclic structure may be selected from a 4, 5, 6, 7, 8, 9, or 10 membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group; R 4 is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group, R 5 is selected from hydroxy groups, R 6 is unsubstituted or has one, two or more R G a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, an alkyl group, an alkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, or an amino group, each of which is substituted with B is absent, a triazole group, -NR 7 -or-N(NR 7 R 8 )-selected from R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-, T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ 10 ) m -(CR 11 R 12 ) n -C(=O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # indicates the binding site to L and * indicates the binding site to B, Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, or a heterocyclyloxy group, each of which is substituted with Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I forming a cyclic structure, for example a 3-10 membered cyclic structure, substituted with R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I forming a cyclic structure, for example a 3-10 membered cyclic structure, substituted with R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a cyclic structure, e.g., a 3-10 membered cyclic structure, substituted with one, two or more R I For example, any of the ring structures may be unsubstituted or substituted with one, two or more R I a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J and selected from alkyl groups, cycloalkyl groups, cycloalkylalkyl groups, aryl groups, arylalkyl groups, heteroaryl groups, heteroarylalkyl groups, heterocyclyl groups, and heterocyclylalkyl groups, substituted with each m may be the same or different and is independently selected from an integer from 0 to 10; each n may be the same or different and is independently selected from an integer from 0 to 10; Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, or an NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, or an NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Each R L may be the same or different and each independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; The wavy line indicates the binding site to L. The conditions are: 6 is unsubstituted or one, two or more R G When the group is selected from an alkyl group, an alkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, or an amino group substituted with A is N and R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E does not form a 5- to 10-membered ring structure substituted with R 7 If is hydrogen, T L is not a chemical bond, Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E and forming a 5-10 membered cyclic structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group, and R A is unsubstituted or has one, two or more R C a cycloalkyl group, a cycloalkylalkyl group, or a cycloalkyloxy group substituted with Or, B is -N(NR 7 R 8 )- and Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F and forming a 4- to 10-membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group.

2. The groups in formula (G) are independently selected from the following definitions: A is N or CR A Selected from If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R B an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, a heterocyclyl group, a heterocyclylalkyl group, an aryl group, an arylalkyl group, a heteroaryl group or a heteroarylalkyl group substituted with NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; A is CR A If R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R C an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkyloxy group, a cycloalkyloxy group, an alkyloxyalkyl group, a heterocyclyl group, a heterocyclylalkyl group, an aryl group, an arylalkyl group, a heteroaryl group or a heteroarylalkyl group substituted with NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Or, R A , R 1 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R D forming a 3- to 10-membered ring structure substituted with z is chosen from 0 or 1, R 2 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and selected from alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, and cycloalkyloxy groups substituted with R 3 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and selected from alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, and cycloalkyloxy groups substituted with Or, R 1 , R 2 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R E forming a 5-10 membered ring structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group; Or, R 2 , R 3 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R F forming a 4-10 membered ring structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group; R 4 is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group, R 5 is selected from hydroxy groups, R 6 is unsubstituted or has one, two or more R G a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, a heterocyclyl group, a heterocyclylalkyl group, or a heterocyclyloxy group, each substituted with B is absent, a triazole group, -NR 7 -or-N(NR 7 R 8 )-selected from R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-, T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 )<00​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B; Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I and selected from alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, and heterocyclyloxy groups substituted with Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a 3-10 membered ring structure substituted with one, two or more R I a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J and selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups substituted with m and n may be the same or different and are independently selected from integers from 0 to 10; Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, or an NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, or an NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Each R L may be the same or different and each independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, NH 2 HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-, a stereoisomer, racemate, tautomer, isotope, isotopically labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof.

3. The groups in formula (G) are independently selected from the following definitions: A is N or CR A is selected from If A is N, then R 1 is hydrogen, a hydroxy group, unsubstituted or one, two or more R B an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, a heterocyclyl group, a heterocyclylalkyl group, an aryl group, an arylalkyl group, a heteroaryl group or a heteroarylalkyl group substituted with NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; A is CR A If R A and R 1 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxy group, a mercapto group, a cyano group, a nitro group, an unsubstituted or one, two or more R C an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkyloxy group, a cycloalkyloxy group, an alkyloxyalkyl group, a heterocyclyl group, a heterocyclylalkyl group, an aryl group, an arylalkyl group, a heteroaryl group or a heteroarylalkyl group substituted with NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D forming a 3- to 10-membered ring structure substituted with z is selected from 0 or 1; R 2 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and selected from alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, and cycloalkyloxy groups substituted with R 3 is a hydrogen, halogen atom, unsubstituted or one, two or more R E and selected from alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, and cycloalkyloxy groups substituted with Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E forming a 5-10 membered ring structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group; Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F forming a 4-10 membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group; R 4 is selected from an alkyl group, an alkyloxy group, a halogen atom, a hydroxy group, an amino group, and a cyano group, R 5 is selected from a hydroxy group, R 6 is unsubstituted or has one, two or more R G a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, a heterocyclyl group, a heterocyclylalkyl group, or a heterocyclyloxy group, substituted with B is absent, -NR 7 - or -N(NR 7 R 8 )-selected from R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, HC(=O)-, alkylC(=O)-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-, T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 )<000035​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B; Each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I and selected from alkyl, alkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocyclyl, heterocyclylalkyl, and heterocyclyloxy groups substituted with Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a 3-10 membered ring structure substituted with, for example, one, two or more R I a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J and selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups substituted with m and n may be the same or different and are independently selected from integers from 0 to 10; Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated, halogen atom, hydroxy group, cyano group, nitro group, unsubstituted or one, two or more R K an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, or an NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Each R K may be the same or different and independently represent a deuterated, halogen atom, hydroxy group, cyano group, nitro group, unsubstituted or one, two or more R L an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, or an NH 2 , HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-; Each R L may be the same or different, and each independently represents a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an alkyl group, an alkyloxy group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkyloxy group, an aryl group, an arylalkyl group, an aryloxy group, a heteroaryl group, a heteroarylalkyl group, a heteroaryloxy group, a heterocyclyl group, a heterocyclylalkyl group, a heterocyclyloxy group, NH 2 HC(=O)NH-, alkylC(=O)NH-, cycloalkylC(=O)NH-, heterocyclylC(=O)NH-, arylC(=O)NH-, heteroarylC(=O)NH-, a stereoisomer, racemate, tautomer, isotope, isotopically labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof.

4. The groups in formula (G) are independently selected from the following definitions: A is N or CR A is selected from If A is N, then R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably when A is N, R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 selected from cycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-; A is CR A If R A and R 1 may be the same or different and may be independently 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyloxy group, C 1-10 Alkyloxy C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably A is CR A If R A and R 1 may be the same or different and may be independently 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyloxy group, C 1-6 Alkyloxy C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 selected from cycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-; Or, R A , R 1 together with the atoms to which they are attached, may be unsubstituted or may contain one, two or more R D forming a 3-8 membered ring structure substituted with, for example, a 3, 4, 5, 6, 7 or 8 membered ring structure, z is selected from 0 or 1; R 2 teeth, 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups, preferably R 2 teeth, 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 cycloalkyloxy groups; R 3 teeth, 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups, preferably R 3 teeth, 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10 Alkyl group, C 3-6 cycloalkyloxy groups; Or, R 1 , R 2 may be unsubstituted or may contain one, two or more R E forming a 5-10 membered cyclic structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group; Or, R 2 , R 3 may be unsubstituted or may contain one, two or more R F forming a 4-10 membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group; R 4 is C 1-10 Alkyl group, C 1-10 R is selected from the group consisting of an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group. 4 is C 1-6 Alkyl group, C 1-6 selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group; R 5 is selected from a hydroxy group, R 6 is unsubstituted or has one, two or more R G Replaced by C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group, and 3- to 10-membered heterocyclyloxy group, preferably R 6 is unsubstituted or has one, two or more R G Replaced by C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 alkyl group, 3- to 6-membered heterocyclyloxy group; B is absent, a triazole group, -NR 7 -or-N(NR 7 R 8 )-selected from R 7 , R 8 may be the same or different and may be independently 1 H, 2 H, unsubstituted or one, two or more R H Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )*, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)#, *O-(CR<> 9 R 10 ) m -(CR<000>R 12 )<00><000682>#, *N(R 13 )-(CR<00>)<00>R 10 ) m -(CR<> 11 R 12 ) n -C(O)#, *S-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B; Each R 9 , R 10 , R 11 , R 12 may be the same or different and, independently of each other, 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 alkyl group, and 3- to 10-membered heterocyclyloxy group, preferably each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R I Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 alkyl group, 3- to 6-membered heterocyclyloxy group; Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming a 3-10 membered ring structure substituted with, for example, one, two or more R I a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl groups, preferably each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 alkyl groups, m and n may be the same or different and are independently selected from integers from 0 to 10, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; Each R L may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 The complex of claim 1, wherein the aryl C(=O)NH- is selected from the group consisting of aryl C(=O)NH-, 5- to 10-membered heteroaryl C(=O)NH-, and a stereoisomer, racemate, tautomer, isotope, isotopically labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof.

5. The groups in formula (G) are independently selected from the following definitions: A is N or CR A is selected from If A is N, then R 1 teeth, 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably when A is N, R 1 teeth, 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 selected from cycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-; A is CR A If R A and R 1 may be the same or different and independently represent: 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyloxy group, C 1-10 Alkyloxy C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably A is CR A If R A and R 1 may be the same or different and independently represent: 1 H, 2 H, halogen atoms, hydroxy groups, mercapto groups, deuterated hydroxy groups, deuterated mercapto groups, cyano groups, nitro groups, unsubstituted or one, two or more R C Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyloxy group, C 1-6 Alkyloxy C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 selected from cycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-; Or, R A , R 1 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R D forming a 3-8 membered ring structure, for example a 3, 4, 5, 6, 7 or 8 membered ring structure, substituted with z is selected from 0 or 1; R 2 teeth, 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups, preferably R 2 teeth, 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 cycloalkyloxy groups; R 3 teeth, 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups, preferably R 3 teeth, 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10 Alkyl group, C 3-6 cycloalkyloxy groups; The conditions are: 1 , R 2 and the atom or R to which they are bonded 2 , R 3 and at least one pair of groups of the atoms to which they are attached together are unsubstituted or one, two or more R E forming a 4-10 membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group; R 4 is C 1-10 Alkyl group, C 1-10 is selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group, and preferably R 4 is C 1-6 Alkyl group, C 1-6 selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group; R 5 is selected from a hydroxy group, R 6 is unsubstituted or has one, two or more R G Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 6-10 Aryl group, C 6-10 Arylalkyl groups, C 6-10 an aryloxy group, a 5- to 6-membered heteroaryl group, a 5- to 6-membered heteroarylalkyl group, or a 5- to 6-membered heteroaryloxy group; B is absent, a triazole group, -NR 7 -or-N(NR 7 R 8 )-selected from R 7 , R 8 may be the same or different and independently represent: 1 H, 2 H, unsubstituted or one, two or more R H Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(=O)*, #O-(CR 9 R 10 ) m -(CR 11 R 12 ) n *, #N(R 13 )-(CR 9 R 10 ) m -(CR 11 R 12 [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B; Each R 9 , R 10 , R 11 , R 12 may be the same or different and may be independently 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 alkyl group, and 3- to 10-membered heterocyclyloxy group, preferably each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 alkyl group, 3- to 6-membered heterocyclyloxy group; Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming 3-10 membered ring structures substituted with, for example, one, two or more R I a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl groups, preferably each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 alkyl groups, m and n may be the same or different and are independently selected from integers of 0 to 10, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, an amino group, a nitro group, an unsubstituted group, or one, two or more R K Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; Each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably each R K may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R L Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; Each R L may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 The complex according to claim 1, characterized in that it is selected from the group consisting of arylC(=O)NH-, 5- to 10-membered heteroarylC(=O)NH-, and its stereoisomers, racemates, tautomers, isotopes, isotope-labeled compounds, nitrogen oxides, and pharmaceutically acceptable salts.

6. The groups in formula (G) are independently selected from the following definitions: A is selected from N, R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group or 5-10 membered heteroaryl C 1-10 Alkyl group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably when A is N, R 1 teeth 1 H, 2 H, hydroxy, deuterated hydroxy, unsubstituted or one, two or more R B Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, phenyl group, phenyl C 1-6 Alkyl group, 5-6 membered heteroaryl group or 5-6 membered heteroaryl C 1-6 Alkyl group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 selected from cycloalkylC(=O)NH-, 3- to 6-membered heterocyclylC(=O)NH-, phenylC(=O)NH-, 5- to 6-membered heteroarylC(=O)NH-; z is chosen from 0 or 1, R 2 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups, preferably R 2 teeth 1 H, 2 H, hydrogen, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 cycloalkyloxy groups; R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups, preferably R 3 teeth 1 H, 2 H, halogen atoms, unsubstituted or one, two or more R E Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-10 Alkyl group, C 3-6 cycloalkyloxy groups; Or, R 1 , R 2 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R E forming a 5-10 membered cyclic structure substituted with, for example, a 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group; Or, R 2 , R 3 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R F forming a 4-10 membered cyclic structure substituted with, for example, a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, heterobicyclic hydrocarbon group; R 4 is C 1-10 Alkyl group, C 1-10 R is selected from the group consisting of an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group. 4 is C 1-6 Alkyl group, C 1-6 selected from an alkyloxy group, a halogen atom, a hydroxy group, a mercapto group, an amino group, and a cyano group; R 5 is selected from a hydroxy group, R 6 is unsubstituted or has one, two or more R G Replaced by C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl group, and 3- to 10-membered heterocyclyloxy group, preferably R 6 is unsubstituted or has one, two or more R G Replaced by C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 alkyl group, 3- to 6-membered heterocyclyloxy group; B is -NR 7 -or-N(NR 7 R 8 )-selected from R 7 , R 8 may be the same or different and are independent of each other. 1 H, 2 H, unsubstituted or one, two or more R H Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 Alkyl group, HC(=O)-, C 1-10 AlkylC(=O)-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably R 7 , R 8 may be the same or different and independently represent hydrogen, unsubstituted or one, two or more R H Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 Alkyl group, HC(=O)-, C 1-6 AlkylC(=O)-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; T L is a chemical bond, #O-(CR 9 R 10 ) m -(CR 11 R[[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​) m -(CR 11 R 12 ) n -C(O)#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -C(NR 13 )#, *O-(CR 9 R 10 ) m -(CR 11 R 12 ) n -P(=O)(OR 14 )#, where # represents the binding site to L and * represents the binding site to B; Each R 9 , R 10 , R 11 , R 12 may be the same or different and are independent of each other. 1 H, 2 H, halogen atoms, cyano groups, unsubstituted or one, two or more R I Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 alkyl group, and 3- to 10-membered heterocyclyloxy group, preferably, each R 9 , R 10 , R 11 , R 12 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an unsubstituted or one, two or more R I Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-10 selected from alkyl groups and 3- to 6-membered heterocyclyloxy groups; Or, R 9 , R 10 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 11 , R 12 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I or R 9 , R 11 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R I and forming 3-10 membered ring structures substituted with, for example, one, two or more R I may be a 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic hydrocarbon group, bicyclic hydrocarbon group, heteromonocyclic hydrocarbon group, or heterobicyclic hydrocarbon group substituted with Each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J Replaced by C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclyl C 1-10 alkyl groups, preferably each R 13 may be the same or different and independently of each other are unsubstituted or one, two or more R J Replaced by C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclyl C 1-6 alkyl groups, m and n may be the same or different and are independently selected from integers from 0 to 10, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; Each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably each R B , R C , R D , R E , R F , R G , R H , R I , R J may be the same or different and independently represent a deuterated group, a halogen atom, a hydroxy group, a cyano group, a nitro group, an unsubstituted group, or one, two or more R K Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; Each R K may be the same or different and independently represent a deuterated, halogen atom, hydroxy group, cyano group, nitro group, unsubstituted or one, two or more R L Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-10 membered heteroarylC(=O)NH-, preferably each R K may be the same or different and independently represent a deuterated, halogen atom, hydroxy group, cyano group, nitro group, unsubstituted or one, two or more R L Replaced by C 1-6 Alkyl group, C 1-6 Alkyloxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-6 Alkyl group, C 3-6 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-6 Alkyl group, C 6-10 Aryloxy group, 5-6 membered heteroaryl group, 5-6 membered heteroaryl C 1-6 Alkyl group, 5-6 membered heteroaryloxy group, 3-6 membered heterocyclyl group, 3-6 membered heterocyclylC 1-6 Alkyl group, 3-6 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-6 AlkylC(=O)NH-, C 3-6 CycloalkylC(=O)NH-, 3-6 membered heterocyclylC(=O)NH-, C 6-10 arylC(=O)NH-, 5-6 membered heteroarylC(=O)NH-; Each R L may be the same or different and independently represent a deuterium atom, a halogen atom, a hydroxy group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 Cycloalkyloxy group, C 6-10 Aryl group, C 6-10 Aryl C 1-10 Alkyl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryl C 1-10 Alkyl group, 5-10 membered heteroaryloxy group, 3-10 membered heterocyclyl group, 3-10 membered heterocyclylC 1-10 Alkyl group, 3-10 membered heterocyclyloxy group, NH 2 , HC(=O)NH-, C 1-10 AlkylC(=O)NH-, C 3-10 CycloalkylC(=O)NH-, 3-10 membered heterocyclylC(=O)NH-, C 6-10 The complex of claim 1, wherein the aryl C(=O)NH- is selected from the group consisting of aryl C(=O)NH-, 5- to 10-membered heteroaryl C(=O)NH-, and a stereoisomer, racemate, tautomer, isotope, isotopically labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof.

7. R 1 , R 2 together with the quinolyl group to which they are attached form one of the following substructures, where said substructures may be unsubstituted or may be substituted with one, two or more R E may be substituted with 【Transformation 3】 Or, R 2 , R 3 together with the quinolyl group to which they are attached form one of the following substructures, where said substructures may be unsubstituted or may be substituted with one, two or more R F may be substituted with 【Chemistry 4】 Or preferably, B is absent, 【Transformation 5】 -NH- or -N(NR 7 R 8 )-, where R 7 , R 8 are independently defined as defined in any one of claims 1 to 6, a stereoisomer, a racemate, a tautomer, an isotope, an isotopically labeled compound, a nitrogen oxide or a pharmaceutically acceptable salt thereof.

8. The complex according to any one of claims 1 to 7, characterized in that G is selected from groups represented by the following formula (G-1), or a stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof: 【Transformation 6】 (In the formula, A, B, T L , R 1 , R 2 , R 3 , R 6 and independently have the definitions set forth in any one of claims 1 to 7.

9. The complex according to any one of claims 1 to 7, wherein G is selected from the group represented by formula (G-2) or (G-3), or a stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof. 【Transformation 7】 【Transformation 8】 (In the formula, R A , B, T L , R 1 , R 2 , R 3 , R 6 has the definition set forth in any one of claims 1 to 7.

10. G is the following group or -T in the wavy part of the following group: L The complex according to any one of claims 1 to 7, characterized in that the complex is selected from the group consisting of a group bonded to -, a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, and a pharmaceutically acceptable salt thereof. 【Chemistry 9】 (In the formula, A, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , z has the definition as defined in any one of claims 1 to 7.

11. G is the following group or -T in the wavy part of the following group: L The complex according to any one of claims 1 to 7, characterized in that the complex is selected from the group consisting of a group bonded to -, a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, and a pharmaceutically acceptable salt thereof. 【Chemistry 10】 (In the formula, A, R 1 , R 2 , R 3 , R 4 , R 7 has the definition set forth in any one of claims 1 to 7.

12. G is the following group or -T in the wavy part of the following group: L The complex according to any one of claims 1 to 7, characterized in that the complex is selected from the group consisting of a group bonded to -, a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, and a pharmaceutically acceptable salt thereof. 【Chemistry 11】 (In the formula, A, R 1 , R 4 , R 6 , R 7 , z has the definition as defined in any one of claims 1 to 7.

13. G is the following group or -T in the wavy part of the following group: L The complex according to any one of claims 1 to 7, characterized in that the complex is selected from the group consisting of a group bonded to -, a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, and a pharmaceutically acceptable salt thereof. Table 1 Table 2

14. The conjugate according to any one of claims 1 to 7, wherein L is selected from a chemical bond or a linker represented by the following formula (L): 【Chemistry 12】 (In the formula, L 1 is the linking moiety to the targeting moiety Tp, and the reactive group L 1 ' and the targeting moiety Tp, and # indicates the binding site to the targeting moiety Tp, For example, L 1 When L' is a maleimide group, 1 The structure of is as follows: 【Chemistry 13】 L 2 is absent, or L 1 and L 3 is a spacer for L 3 is the peptide moiety, L 4 is absent, or the peptide moiety and L 5 is a spacer for L 5 is L 4 and the biologically active substance G, and the reactive group L 5 ' is formed by the reaction of ' with a biologically active substance G or its intermediate, * indicates the binding site to the biologically active substance G, Depending on the situation, Between the above moieties in L, preferably L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead of 【Chemistry 14】 【Chemistry 15】 R 16 , R 16 ' may be the same or different, at least one of them being a hydrophilic group, the other one being a hydrogen atom, a halogen atom, a cyano group, an amino group, a nitro group, an unsubstituted or one, two or more R zg Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 selected from a cycloalkyloxy group and an aminocarbonyl group; The hydrophilic group is a polyethylene glycol group, a C substituted with 1 to 10 hydroxy groups 1-10 Alkyl group or sugar ring-containing group, or C 1-6 AlkylNHCO- (e.g., C 1-4 alkylNHCO-), preferably a polyethylene glycol group, more preferably -C(=O)-NH-(CH 2 CH 2 O) p -C 1-10 Alkyl group or -NH-(CH 2 CH 2 O) p -C 1-10 C alkyl group or preferably substituted with 1 to 10 hydroxy groups 1-10 alkyl group, more preferably 【Chemistry 16】 and each p may be the same or different and is independently an integer from 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7 or 8; Y is O, S, or C 1-10 alkylene groups, wherein 1, 2, or 3 methylene groups of the alkylene group may be replaced by O or S; R 14 , R 15 may be the same or different and independently represent a hydrogen atom, a halogen atom, a cyano group, an amino group, a nitro group, an unsubstituted or one, two or more R zh Replaced by C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups, Or, R 14 , R 15 together with the atoms to which they are attached may be unsubstituted or may contain one, two or more R zh C replaced with 3-10 forming a cycloalkyl group, Each R zg , R zh may be the same or different and independently represent a halogen atom, a hydroxy group, an amino group, a cyano group, a nitro group, C 1-10 Alkyl group, C 1-10 Alkyloxy group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl C 1-10 Alkyl group, C 3-10 cycloalkyloxy groups, The hydrophilic moiety or steric hindrance moiety defined above may or may not be present.

15. L 1 optionally a group L reactive with the targeting moiety Tp 1 ' is formed by L 1 is preferably a mercapto reactive group, an amino reactive group, a carboxyl reactive group, a proline residue reactive group, a tyrosine residue reactive group, a disulfide cross-linking group, or the like, and for antibodies into which a non-natural amino acid has been introduced, may be selected from click chemistry reactive groups such as ketone, azide, alkyne, cyclopropene, or diene; L 1 ' is preferably a mercapto reactive group, L 1 ' is preferably a maleimide group or a substituted maleimide group, and L 1 -L 2 is preferably the following structure: The fragments obtained from (N-maleimidomethyl)-carboxylic acid-N-hydroxysuccinimide ester and their structures are as follows: 【Chemistry 17】 (q is an integer from 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7, or 8.) Or the fragment obtained from meta-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) and its structure are as follows: [Chemistry 18] The fragments obtained from 4-(N-maleimidomethyl)-cyclohexane-1-carboxylic acid succinimide ester (SMCC) and their structures are as follows: 【Chemistry 19】 or L 1 ' is preferably a mercapto reactive group having the structure shown below, Hal-Het- Hal is a halogen atom, OMs, OTs, OTf, a nitro group, and one or more R z6 and R is selected from alkyl thioether groups, aryl thioether groups, heteroaryl thioether groups, alkyl sulfoxide groups, aryl sulfoxide groups, heteroaryl sulfoxide groups, alkyl sulfonyl groups, aryl sulfonyl groups, and heteroaryl sulfonyl groups, optionally substituted with R z6 are independently H (hydrogen), D (deuterium), halogen atoms, CN, nitro groups, C 1-6 Alkyl groups, halogenated C 1-6 Alkyl, C 1-6 selected from alkyloxy groups, 6- to 10-membered aryl groups, and 5- to 12-membered heteroaryl groups; Het is one or more R z7 5-10 membered heteroaryl optionally substituted with z7 are independently H (hydrogen), D (deuterium), halogen atoms, CN, nitro groups, C 1-4 Alkyl and halogenated C 1-4 alkyl groups, In a preferred embodiment, Hal is preferably methylsulfonyl and Het is preferably pyrimidine; In a preferred embodiment, Hal-Het- is as follows: 【Chemistry 20】 Corresponding L 1 The structure is as follows: 【Chemistry 21】 And L 1 '-L 2 is preferably the structure shown below: 【Chemistry 22】 q is an integer selected from 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7 or 8; R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R z4 Or R z5 Together they form C 3-6 forming a cycloalkyl group, More preferably 【Chemistry 23】 15. The complex according to claim 14, wherein the complex is a stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof.

16. L 2 is non-existent, C 1-10 Alkylene group, C 2-10 Alkenylene group, C 2-10 Alkynylene group, C 3-10 Cycloalkyl groups, C 6-12 aryl or 6- to 12-membered heteroaryl groups or combinations of the above fragments, optionally interrupted by carbonyl groups, O, S, N atoms, C 1-6 Alkyl group, C 3-6 Cycloalkyl groups, halogen atoms, halogenated C 1-6 and any of said alkyl or halogenated alkyl groups together with the C atom to which they are attached are C 3-6 Forming a cycloalkyl group, L 2 is bonded to L by any functional group or covalent bond. 1 or L 3 Combine with the fragment, Preferably, L 2 -C(R z4 R z5 )-CO- to the N-terminus of the peptide fragment, Preferably, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl C 1-4 alkyl groups or R z4 Or R z5 Together they form C 3-6 forming a cycloalkyl group, Preferably, L 2 is further -(CH 2 ) q -, -(CH 2 ) q -C(=O)-, -(C≡C)-(CH 2 ) q -C(R z4 R z5 )-C(=O)-, where q is selected from integers of 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7 or 8; Preferably, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R z4 Or R z5 Together they form C 3-6 15. The complex of claim 14, characterized in that it forms a cycloalkyl group, a stereoisomer, a racemate, a tautomer, an isotope, an isotopically labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof.

17. L 3 is selected from a divalent peptide group containing 2 to 8 optionally substituted natural or unnatural amino acid residues, any of which may be the same or different and are independently selected from alanine (Ala), cysteine ​​(Cys), aspartic acid (Asp), glutamic acid (Glu), phenylalanine (Phe), glycine (Gly), histidine (His), isoleucine (Ile), lysine (Lys), leucine (Leu), ), methionine (Met), asparagine (Asn), proline (Pro), glutamine (Gln), arginine (Arg), serine (Ser), threonine (Thr), valine (Val), tryptophan (Trp), tyrosine (Tyr), citrulline (Cit), norvaline (Nva), norleucine (Nle), selenocysteine ​​(Sec), pyrrolysine (Pyl), homoserine, homocysteine, demethylpyrrolysine; More preferably, L 3 is a bivalent peptide group comprising a combination of two, three, four, five, or six optionally substituted natural or non-natural amino acid residues, any of which may be the same or different and are independently selected from the group consisting of alanine (Ala), cysteine ​​(Cys), aspartic acid (Asp), glutamic acid (Glu), phenylalanine (Phe), glycine (Gly), histidine (His), isoleucine (Ile), lysine (Lys), leucine (Leu), methionine (Met), asparagine (Asn), proline, and methylpyrrolysine, such as -ValCit-; -CitVal-; -AlaAla-; -AlaCit-; -CitAla-; -AsnCit-; -CitAsn-. ;-CitCit-;-ValGlu-;-GluVal-;-SerCit-;-CitSer-;-LysCit-;-CitLys-;-AspCit-;-CitAsp-;-AlaVal-;-ValAla-;-PheAla-;-AlaPhe- ;-PheLys-;-LysPhe-;-ValLys-;-LysVal-;-AlaLys-;-LysAla-;-PheCit-;-CitPhe-;-LeuCit-;-CitLeu-;-IleCit-;-CitIle-;-PheArg-; -ArgPhe-;-CitTrp-;-TrpCit-;-PhePheLys-;-LysPhePhe-;-DPhePheLys-;-DLysPhePhe-;-GlyPheLys-;-LysPheGly-;-GlyPheLeuGly-;-G selected from lyLeuPheGly-;-AlaLeuAlaLeu-, -GlyGlyGly-;-GlyGlyGlyGly-;-GlyPheValGly-;-GlyValPheGly-;-GlyGlyPheGly-;-AlaAlaAla-; Most preferably, L 3 15. The complex of claim 14, wherein -GlyGlyPheGly-, its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide or pharmaceutically acceptable salt.

18. L 4 is preferably a group having self-cleavage properties, and a self-cleaving group or a self-immolative group is a group that causes release of a drug by an intramolecular reaction, such as 1,4-elimination, 1,6-elimination or cyclization elimination, independent of the action of an enzyme; L 5 is any reactive group L 5 ' is produced by reacting with a biologically active molecule or its intermediate, 5 is preferably a carboxylic acid group or an active ester group, and is preferably OH, SH, or NH or NH of the biologically active molecule. 2 reacts with and forms L 5 is of the structure -C(O)O-, -C(O)S-, -C(O)N- or -C(O)NH- (including the O, S and N atoms of the biologically active molecule); L 4 -L 5 is preferably PABC spacer arm, the structure of which is shown below: 【Chemistry 24】 GABA spacer arm, the structure of which is shown below: 【Chemistry 25】 an α,α-dimethyl GABA spacer arm, the structure of which is: 【Chemistry 26】 or a β,β-dimethyl GABA spacer arm, the structure of which is: 【Chemistry 27】 Most preferably, L 4 -L 5 is -NR z1 -C(R z2 R z3 )-T L - and where: R z1 is H or C 1-4 is alkyl, R z2 and R z3 may be the same or different and are independently H or C 1-4 selected from alkyl, T L is as defined in claims 1 to 7, and L 4 -L 5 or T in G L 15. The complex of claim 14, wherein one of the groups is a chemical bond, a stereoisomer, a racemate, a tautomer, an isotope, an isotopically labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof.

19. L 1 is generated by coupling a thiol-reactive group selected from a maleimide group, a substituted maleimide group, or Hal-Het- to Tp; 【Chemistry 28】 L 1 and L 2 Between or L 2 and L 3 Between or L 2 The complex according to any one of claims 14 to 18, characterized in that the complex, its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide, or pharmaceutically acceptable salt contains the hydrophilic moiety instead of

20. L 1 is generated by coupling a thiol-reactive group selected from a maleimide group or a substituted maleimide group to Tp, 【Chemistry 29】 L 1 and L 2 Between or L 2 and L 3 Between or L 2 The complex according to any one of claims 14 to 18, characterized in that the complex, its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide, or pharmaceutically acceptable salt contains the sterically hindered moiety instead of

21. L 1 is generated by coupling to Tp a thiol reactive group selected from Hal-Het-, L 4 -L 5 is -NR z1 -C(R z2 R z3 )-T L - and where: R z1 is H or C 1-4 is an alkyl group, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, T L is as defined in claims 1 to 13, and L 4 -L 5 or T in G L One of them is chemical bonding, More preferably, T in G L is a chemical bond, L 4 -L 5 is -NR z1 -C(R z2 R z3 )-O-(CH 2 ) m -C(R z4 R z5 )-CO-, where: R z1 is H or C 1-4 is an alkyl group, m is an integer from 0 to 4, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 The complex according to any one of claims 14 to 18, which forms a cycloalkyl group, a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof.

22. L 1 -L 2 is the L of the following structure 1 '-L 2 is generated by coupling to Tp, 【Transformation 30】 q is an integer selected from 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7 or 8; R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group, provided that R z4 or R z5 At least one of them is not H, More preferably, R z4 or R z5 Together they form C 3-6 forming a cycloalkyl group, Most preferably, L 1 -L 2 teeth, 【Chemistry 31】 19. The complex of any one of claims 14 to 18, characterized in that it is produced by coupling of the following to Tp, or a stereoisomer, racemate, tautomer, isotope, isotopically labeled product, nitrogen oxide or pharmaceutically acceptable salt thereof.

23. 23. The conjugate of any one of claims 1 to 22, wherein Tp is a targeting moiety selected from a small molecule ligand, a protein, a polypeptide, a non-protein reagent (e.g., a sugar, RNA, or DNA), a stereoisomer, a racemate, a tautomer, an isotope, an isotopically labeled product, a nitrogen oxide, or a pharmaceutically acceptable salt thereof. Trop-2, CD37, HER2, CD70, EGFRvIII, Mesothelin F, and Mucin receptor 1 1、CD138、CD20、CD19、CD30、SLTRK6、Nectin 4、Tissue factor、Mucin16、Endothelin receptor、STEAP1、SLC39A6、Guanylyl cyclase C、PSMA CCDM972 CDb Sodium phosphate cotransporter 2B、GPNMB、Trophoblast glycoprotein, AGS-16, EGFR, CD33, CD66e, CD74, CD56, PD-L1, TACSTD2, DR5, E16, 0772P, MPF, Napi3b, Sema PSCA 5b hlg, ETBR, MSG783, STEAP2, TrpM4, CRIPTO, CD21, CD79b, FcRH2, NCA, MDP, IL20Rα, Bre vican, EphB2R, ASLG659, PSCA, GEDA, BAFF-R, CD79a, CXCR5, HLA-DOB, P2X5, CD72, LY64 FcRH1, IRTA2, TENB2, α5β6, α4β7, FGF2, FGFR2, Her3, CA6, DLL3, DLL4, P-cadh erin、EpCAM、pCAD、CD223、LYPD3、LY6E、EFNA4、ROR1、SLITRK6、5T4、ENPP3、Claudin18.2, BMPR1B, Tyro7, c-Met, ApoE, CD1 lc, CD40, CD45(PTPRC), CD49D(ITGA4), CD80, CSF1R, CTSD, GZMB, Ly86, MS4A7, PIK3AP1, PIK3CD, CCR5, IFNG, IL10RA1, I L-6, ACTA2, COL7A1, LOX, LRRC15, MCPT8, MMP10, NOG, SERPINEl, STAT1, TGFBR1, CTSS, PGF, VEGFA, C1QA, C1QB, ANGPTL4. EGLN, EGLN3, BNIP3, AIF1, CCL5, CXCL10, CXCL11, IFI6, PLOD2, KISS1R, STC2, DDIT4, PFKFB3, PGK1, PDK1, AKR1C1, AKR1C 2. CADM1, CDH11, COL6A3, CTGF, HMOX1, KRT33A, LUM, WNT5A, IGFBP3, MMP14, CDCP1, PDGFRA, TCF4, TGF, TGFB1, TGFB2, CDl lb, ADGRE1, EMR2, TNFRSF21, UPK1B, TNFSF9, MMP16, MFI2, IGF-1R, RNF43, NaPi2b, and BCMA are highly conserved. Preferably, Tp is a small molecule ligand, such as a folinic acid derivative, a glutamic acid urea derivative, a somatostatin derivative, an arylsulfonamide derivative (e.g., a carbonic anhydrase IX inhibitor), an ICG dye, a cyanine dye, or a derivative thereof; Preferably, Tp is selected from an antibody or an antigen-binding fragment thereof, said antibody being selected from a chimeric antibody, a humanized antibody or a fully human antibody, preferably a monoclonal antibody; Preferably, the antibody or antigen-binding fragment thereof is selected from at least one antibody or antigen-binding fragment thereof selected from the group consisting of an anti-CD20 antibody, an anti-CD22 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD44 antibody, an anti-CD56 antibody, an anti-CD70 antibody, an anti-CD73 antibody, an anti-CD105 antibody, an anti-CEA antibody, an anti-A33 antibody, an anti-Cripto antibody, an anti-EphA2 antibody, an anti-G250 antibody, an anti-HER2 (ErbB2) antibody, an anti-EGFR antibody, an anti-B7-H3 antibody, an anti-c-Met antibody, an anti-HER3 (ErbB3) antibody, an anti-HER4 (ErbB4) antibody, an anti-MUCl antibody, an anti-LewisY antibody, an anti-VEGFR antibody, an anti-GPNMB antibody, an anti-integrin antibody, an anti-PSMA antibody, an anti-Tenascin-C antibody, an anti-SLC44A4 antibody, and an anti-Mesothelin antibody, and the antibody may be a bispecific antibody or a multispecific antibody; More preferably, the antibody or antigen-binding fragment thereof is selected from at least one antibody or antigen-binding fragment thereof selected from Trastuzumab, Pertuzumab, Nimotuzumab, Enoblituzumab, Emibetuzumab, Inotuzumab, Pinatuzumab, Brentuximab, Gemtuzumab, Bivatuzumab, Lorvotuzumab, cBR96, and Glematumumab or Glembatumumab; For example, Trastuzumab has a sequence selected from the following sequences: 【Chemistry 32】 【Transformation 33】 Pertuzumab has a sequence selected from the following sequences: 【Transformation 34】 【Chemistry 35】 Nimotuzumab has a sequence selected from the following sequences: 【Transformation 36】 【Chemistry 37】 Below is the sequence of Patritumab, 【Transformation 38】 【Chemistry 39】

24. wherein the conjugate, its linker, or linker-drug is selected from any of the following: Table 3 Table 4 Table 5 Table 6 Table 7 wherein u, v, and w are independently selected from integers 0 to 10 (e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10), G has the definition of any one of claims 1 to 23, LG has the definition of Tp as defined in any one of claims 1 to 23, and R 20 , R 20’ may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R 20 , R 20’ along with the carbon atoms to which they are attached, C 3-6 forming a cycloalkyl group, For example, the above C 1-4 The alkyl groups may be independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl groups, and 3-6 the cycloalkyl groups may be independently selected from cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; For example, R 20 and R 20’ 24. The complex of any one of claims 1 to 23, wherein both of the groups are H, or one is not H, or neither of the groups are H, or a stereoisomer, racemate, tautomer, isotope, isotopically labeled compound, nitrogen oxide, or pharmaceutically acceptable salt thereof.

25. 24. The conjugate according to any one of claims 1 to 23, wherein the conjugate has a structure represented by the following formula: 【Chemistry 40】 (In the formula, A, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 11 , R 12 , L 1 , L 2 , Tp has the definition set forth in any one of claims 1 to 23.

26. 24. The complex according to any one of claims 1 to 23, wherein the complex has a structure represented by the following formula: 【Chemistry 41】 (In the formula, A, R 1 , R 2 , R 3 , R 4 , R 7 , R 11 , R 12 , L 1 , L 2 , Tp has the definition set forth in any one of claims 1 to 13.

27. 24. The complex according to any one of claims 1 to 23, wherein the complex has a structure represented by the following formula: 【Chemistry 42】 (In the formula, R 11 , R 12 , L 1 , L 2 , Tp has the definition set forth in any one of claims 1 to 13.

28. 24. The conjugate according to any one of claims 1 to 23, wherein the conjugate is selected from the following: a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof. 【Chemistry 43】 【Chemistry 44】 【Chemistry 45】 【Chemistry 46】 【Chemistry 47】 【Chemistry 48】 【Chemistry 49】 [Transformation 50] 【Chemistry 51】 【Chemistry 52】 【Chemistry 53】 【Chemistry 54】 【Transformation 55】 【Transformation 56】 (In the formula, R 11 , R 12 may be identical or different and independently have the definitions according to any one of claims 1 to 23, e.g., R 11 , R 12 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R 11 , R 12 C along with the carbon atoms to which they are attached 3-6 forming a cycloalkyl group, For example, the above C 1-4 The alkyl may be independently selected from a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, or a tert-butyl group, 3-6 The cycloalkyl groups may be independently selected from cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups; For example, R 11 and R 12 Both of them are H, or one is not H, or both are not H, R 16 , R 16’ have independently of one another the definitions set forth in claim 14, mAb stands for monoclonal antibody; y represents the average number of small molecule drugs bound to each monoclonal antibody (DAR), and may be selected from integers or decimals, for example, from 1 to 50, from 1 to 20, or from 1 to 10.

29. 24. The conjugate according to any one of claims 1 to 23, wherein the conjugate has a structure represented by the following formula: 【Chemistry 57】 (In the formula, R 11 , R 12 , L 1 , L 2 , Tp has the definition set forth in any one of claims 1 to 23.

30. 24. The conjugate according to any one of claims 1 to 23, wherein the conjugate is selected from the following: a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof. 【Chemistry 58】 【Chemistry 59】 【Transformation 60】 【Chemistry 61】 【Transformation 62】 【Transformation 63】 【Chemistry 64】 【Transformation 65】 【Chemical Formula 66】 【Transformation 67】 【Transformation 68】 【Transformation 69】 【Transformation 70】 【Chemistry 71】 (In the formula, R 11 , R 12 may independently have the definitions according to any one of claims 1 to 23, for example R 11 , R 12 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R 11 , R 12 C along with the carbon atoms to which they are attached 3-6 forming a cycloalkyl group, For example, the above C 1-4 The alkyl groups may be independently selected from a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, or a tert-butyl group, 3-6 The cycloalkyl groups may be independently selected from cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups; For example, R 11 and R 12 Both of them are H, or one is not H, or both are not H, R 16 , R 16’ have independently of one another the definitions set forth in claim 14, mAb stands for monoclonal antibody; y represents the average number of small molecule drugs bound to each monoclonal antibody (DAR), and may be selected from integers or decimals, for example, from 1 to 50, from 1 to 20, or from 1 to 10.

31. 24. The conjugate according to any one of claims 1 to 23, wherein the conjugate has a structure represented by the following formula: 【Chemistry 72】 (In the formula, R 11 , R 12 may independently have the definitions according to any one of claims 1 to 23, for example R 11 , R 12 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl groups or R 11 , R 12 C along with the carbon atoms to which they are attached 3-6 forming a cycloalkyl group, For example, the above C 1-4 The alkyl groups may be independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl groups, and 3-6 The cycloalkyl groups may be independently selected from cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups; For example, R 11 and R 12 Both of them are H, or one is not H, or both are not H, L 1 , L 2 , Tp independently have the definitions set forth in any one of claims 1 to 23.

32. 24. The conjugate according to any one of claims 1 to 23, wherein the conjugate is selected from the following: a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof. 【Transformation 73】 【Chemistry 74】 【Chemistry 75】 【Transformation 76】 【Chemical 77】 【Transformation 78】 (In the formula, R 11 , R 12 have, independently of one another, the definitions according to any one of claims 1 to 23, e.g. R 11 , R 12 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R 11 , R 12 C along with the carbon atoms to which they are attached 3-6 forming a cycloalkyl group, For example, the above C 1-4 The alkyl groups may be independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl groups, and 3-6 the cycloalkyl groups may be independently selected from cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups; For example, R 11 and R 12 Both of them are H, or one is not H, or both are not H, R 16 , R 16’ have, independently of one another, the definitions set forth in claim 14, mAb stands for monoclonal antibody; y represents the average number of small molecule drugs conjugated to each monoclonal antibody (DAR), and may be selected from integers or decimals, for example, from 1 to 50, from 1 to 20, or from 1 to 10.

33. The conjugate of any one of claims 1 to 32, wherein the conjugate is selected from the following: a stereoisomer, a racemate, a tautomer, an isotope, an isotopically labeled product, a nitrogen oxide, or a pharmaceutically acceptable salt thereof. Table 8 Table 9 Table 10 Table 11 Table 12 Table 13 Table 14 Table 15 Table 16 Table 17 Table 18 Table 19 Table 20 Table 21 Table 22 Table 23 Table 24 Table 25 Table 26 Table 27 Table 28 Table 29 Table 30 Table 31 Table 32 Table 33 Table 34 Table 35 Table 36 Table 37 Table 38 Table 39 Table 40 Table 41 Table 42 Table 43 Table 44 Table 45 Table 46 Table 47 Table 48 Table 49 Table 50 Table 51 Table 52 Table 53 Table 54 (y represents the average number of small molecule drugs conjugated to each monoclonal antibody (DAR), and may be selected from integers or decimals, for example, from 1 to 50, from 1 to 20, or from 1 to 10.)

34. A method for preparing the conjugate of any one of claims 1 to 33, its stereoisomer, racemate, tautomer, isotope, isotopically labeled product, nitrogen oxide or pharmaceutically acceptable salt, comprising: L 1 '-L 2 -L 3 -L 4 -L 5 a first step of providing a linker designated '(L'); (Preferably, in the linker, L 4 -L 5 '-NR z1 -C(R z2 R z3 )-T L - in the carboxylic acid form or the activated ester form of where: R z1 is H or C 1-4 is an alkyl group, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, More preferably, L 4 -L 5 '-NR z1 -C(R z2 R z3 )-O-(CH 2 ) m -C(R z4 R z5 )-CO- in the form of a carboxylic acid or an activated ester, where: R z1 is H or C 1-4 is an alkyl group, m is an integer from 0 to 4, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group.) The linker is coupled with an intermediate compound of formula (G') to form L 1 '-L 2 -L 3 -L 4 -L 5 a second step of obtaining a coupling intermediate of -G(C'); wherein the intermediate structure of formula (G') is as follows: 【Chemistry 79】 (In the formula, A, B, T L , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , L 1 ', L 1 , L 2 , L 3 , L 4 , L 5 , L 5 ' independently have the definition set out in any one of claims 1 to 33. Preferably, it further comprises a third step of coupling the coupling intermediate of formula (C') with a targeting moiety Tp, In some cases, if necessary, the functional groups of the reaction substrates are protected with protecting groups known in the art to ensure smooth reaction, and the protecting groups are removed after the reaction is completed.

35. A compound represented by the following formula (GH), a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide or a pharmaceutically acceptable salt thereof. 【Chemistry 80】 (Wherein, T is HT L is selected from T L , A, B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , z independently of one another have the definition according to any one of claims 1 to 32.

36. The compound of claim 35, wherein the compound represented by formula (GH) may be selected from the compounds represented by the following formula (GH-1): a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof. 【Chemistry 81】 (In the formula, R A , B, T, R 1 , R 2 , R 3 , R 6 independently have the definition set forth in claim 35.

37. The compound of claim 35, wherein the compound represented by formula (GH) may be selected from compounds represented by the following formula (GH-2) or (GH-3), a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof. 【Chemistry 82】 【Chemistry 83】 (In the formula, R A , B, T, R 1 , R 2 , R 3 , R 6 independently have the definition set forth in any one of claims 1 to 32.

38. 36. The compound of claim 35, wherein the compound is selected from the following compounds: a stereoisomer, a racemate, a tautomer, an isotope, an isotopically labeled compound, a nitrogen oxide, or a pharmaceutically acceptable salt thereof. Table 55 Table 56 Table 57 Table 58

39. 39. A method for preparing the compound of any one of claims 35 to 38, or a stereoisomer, racemate, tautomer, isotope, isotopically labeled product, nitrogen oxide, or pharmaceutically acceptable salt thereof, comprising the step of reacting a compound of formula (i) with a compound of formula (ii). 【Chemical 84】 (In the formula, A, B, T, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , z independently have the definition according to any one of claims 35 to 38; LE represents a group that leaves or departs after the reaction.

40. 36. A method for preparing a compound of formula (ii) according to claim 35, comprising reacting a compound of formula (iii) with a compound of formula (iv) to obtain a compound of formula (v). 【Chemical 85】 (In the formula, A, B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , z independently have the definition according to any one of claims 35 to 38; R 21 is selected from H or a protecting group, preferably an amino protecting group.

41. A compound represented by formula (iii): 【Chemical 86】 (In the formula, R 5 , R 6 , z independently have the definition set forth in any one of claims 35 to 38.

42. A compound represented by formula (v): 【Chemistry 87】 (In the formula, A, B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 21 , z independently have the definition set forth in any one of claims 35 to 38.

43. A complex with the structure shown below. 【Chemical 88】 where Tp is a targeting moiety; D is a biologically active molecular fragment, preferably a biologically active molecular fragment having anti-tumor biological activity; wherein L is selected from a linker represented by formula (L): 【Chemistry 89】 where L 1 is the linking moiety to the targeting moiety Tp, and the reactive group L 1 ' is formed by reaction of the targeting moiety Tp with the # representing the binding site for the Tp moiety, L 2 is absent, or L 1 and L 3 is a spacer for L 3 is a peptide moiety, L 4 is absent, or the peptide moiety and L 5 is a spacer for L 5 L 4 and the biologically active molecule D, and the reactive group L 5 ' is formed by reaction with a biologically active molecule, and * represents the binding site for the biologically active molecule D, Preferably, L 1 ', L 1 , L 2 , L 3 , L 4 , L 5 , L 5 ' is as defined in any one of claims 14 to 22, The conditions are as follows: Condition I is as follows: L has the following hydrophilic moieties inserted between each of the above-defined fragments: [Chemical 90] Or, as condition II, L 1 is formed by coupling a thiol-reactive group selected from a maleimide group or a substituted maleimide group to Tp; L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead of 【Chemistry 91】 Or, as condition III, L 1 is formed by coupling a thiol reactive group selected from Hal-Het- to Tp; L 4 -L 5 is -NR z1 -C(R z2 R z3 )-T L - and where: R z1 is H or C 1-4 is an alkyl group, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, T L is defined in any one of claims 1 to 13, In a further preferred embodiment, L 1 is formed by coupling a thiol-reactive group selected from a maleimide group or Hal-Het- to Tp, L 1 and L 2 Between or L 2 and L 3 Between or L 2 Instead of 【Chemistry 92】 In a further preferred embodiment, L 1 is formed by coupling a thiol reactive group selected from Hal-Het- to Tp; L 4 -L 5 is -NR z1 -C(R z2 R z3 )-O-(CH 2 ) m -C(R z4 R z5 )-CO-, where: R z1 is H or C 1-4 is alkyl, m is an integer between 0 and 4, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 Alkyl group, or R z4 or R z5 Together they form C 3-6 forming a cycloalkyl group, Or, as condition IV, L 1 -L 2 is the L of the following structure 1 '-L 2 is formed by coupling of to Tp, 【Chemistry 93】 q is an integer of 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7, or 8; R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group, where R z4 or R z5 At least one of is not H, More preferably, R z4 or R z5 Let's get together and C 3-6 forming a cycloalkyl group, Most preferably, L 1 -L 2 teeth 【Chemical 94】 is formed by coupling of to Tp.)

44. the biologically active molecule D is a compound having biological activity or potential biological activity described in the Chinese, American, or European Pharmacopoeia or disclosed in other publications; The drug may be selected from cytotoxic drugs, cell growth inhibitory drugs or immunosuppressive drugs, and preferably may be selected from antitubulin agents, tubulin inhibitors, DNA minor groove binders, DNA replication inhibitors, alkylating agents, antibiotics, antifolinic acid agents, antimetabolites, chemotherapy sensitizers, topoisomerase inhibitors, vincristine, etc.; 44. The conjugate of claim 43, further preferably selected from oleitatine, camptothecin, duocarmycin, etoposide, maytansine and maytansinoid alkaloids, taxanes, benzodiazepines or benzodiazepine-containing drugs, and vincristine.

45. A pharmaceutical composition comprising at least one of the following: A complex represented by formula (C) according to any one of claims 1 to 33, a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide or a pharmaceutically acceptable salt thereof, and / or A compound of formula (GH) according to any one of claims 35 to 38, a stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide or pharmaceutically acceptable salt thereof, and / or A complex represented by formula (D) according to any one of claims 43 to 44, a stereoisomer, a racemate, a tautomer, an isotope, an isotope-labeled compound, a nitrogen oxide or a pharmaceutically acceptable salt thereof; Preferably, the compound represented by formula (GH), its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide or pharmaceutically acceptable salt, the complex represented by formula (C) or (D), its stereoisomer, racemate, tautomer, isotope, isotope-labeled compound, nitrogen oxide or pharmaceutically acceptable salt in the pharmaceutical composition are present in a therapeutically effective amount.

46. Use of a compound represented by formula (GH) according to any one of claims 35 to 38, a stereoisomer, racemate, tautomer, isotope, isotope-labeled substance, nitrogen oxide or pharmaceutically acceptable salt thereof, or a complex represented by formula (C) according to any one of claims 1 to 33 or a complex represented by formula (D) according to any one of claims 43 to 44, a stereoisomer, racemate, tautomer, isotope, isotope-labeled substance, nitrogen oxide or pharmaceutically acceptable salt thereof for the prevention and / or treatment of a disease or disorder and / or the manufacture of a drug, Preferably, the disease or disorder may be selected from tumors, such as solid tumors or hematological cancers.

47. The drug is used for the prevention and / or treatment of a disease or disorder, Preferably, the disease or condition may be selected from a tumor, such as a solid tumor or a blood cancer; The solid tumor is selected from malignant tumors of various organ systems, such as sarcomas, adenocarcinomas, blastomas, and carcinomas, including those affecting the liver, lung, breast, lymphatic system, large intestine (e.g., colon), genitourinary tract (e.g., kidney, urothelial cells), prostate, and pharynx, where adenocarcinomas include most colon, rectal, renal cell, liver, small cell lung, non-small cell lung, small intestine, and esophageal cancers; 47. The use according to claim 46, wherein the hematological cancer is selected from leukemia, lymphoma, and malignant lymphoproliferative disorders affecting the blood, bone marrow, and lymphatic system.

48. A conjugate of a linker and a drug, characterized by having the following structure: 【Chemical 95】 (wherein G is defined as in any one of claims 1 to 13, L 1 ', L 2 , L 3 , L 4 , L 5 is defined in any one of claims 14 to 22.)

49. The conjugate of a linker and a drug according to claim 4, characterized in that the conjugate is selected from any of the following: Table 59 Table 60 Table 61 Table 62 Table 63 Table 64 Table 65 Table 66 Table 67 Table 68 Table 69 Table 70 Table 71 Table 72 Table 73 Table 74 Table 75 Table 76 Table 77 Table 78 Table 79 Table 80 Table 81 Table 82 Table 83 Table 84 Table 85 Table 86

50. A conjugate of a linker and a drug, characterized by having the following structure: 【Chemistry 96】 (In the formula, L 1 ', L 2 , L 3 , L 4 , L 5 is defined in claims 14 to 22, D is defined in claims 43 to 44, The conditions are as follows: Condition I is as follows: Between the above-defined fragments, preferably L 1 ' and L 2 Between or L 2 and L 3 Between or L 2 In place of 【Chemistry 97】 Or, as condition II, L 1 ' is a thiol-reactive group selected from a maleimide group or a substituted maleimide group; L 1 ' and L 2 Between or L 2 and L 3 Between or L 2 Instead of the steric hindrance moiety: 【Chem.98】 Or, as condition III, L 1 ' is a thiol reactive group selected from Hal-Het-, L 4 -L 5 Ha-NR z1 -C(R z2 R z3 )-T L - and where: R z1 is H or C 1-4 is an alkyl group, R z2 and R z3 may be the same or different and independently represent H or C 1-4 alkyl groups, T L has the definition given above, Or, as condition IV, L 1 '-L 2 has the following structure: 【Chem.99】 q is an integer selected from 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7 or 8; R z4 and R z5 may be the same or different, and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group, provided that R z4 or R z5 At least one of them is not H, More preferably, R z4 or R z5 Together they form C 3-6 forming a cycloalkyl group, Most preferably, L 1 '-L 2 teeth 【Chemistry 100】 It is.)

51. L 1 ' is a thiol-reactive group selected from a maleimide group, a substituted maleimide group, or Hal-Het-; L 1 and L 2 Between or L 2 and L 3 Between or L 2 51. A conjugate of a linker and a drug according to claim 50, characterized in that the following hydrophilic moiety is contained instead of: 【Chemistry 101】

52. L 1 ' is a thiol-reactive group selected from a maleimide group or a substituted maleimide group; L 1 ' and L 2 Between or L 2 and L 3 Between or L 2 51. The conjugate of linker and drug described in claim 50, characterized in that the following steric hindrance moiety is contained instead of: 【Chemical Engineering 102】

53. L 1 ' is a thiol-reactive group selected from Hal-Het-, L 4 -L 5 is -NR z1 -C(R z2 R z3 )-O-(CH 2 ) m -C(R z4 R z5 )-CO-, where: R z1 is H or C 1-4 is an alkyl group, m is an integer from 0 to 4, R z2 and R z3 may be the same or different and are independently H or C 1-4 alkyl groups, R z4 and R z5 may be the same or different and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 A conjugate of a linker and a drug according to claim 50, characterized in that it forms a cycloalkyl group.

54. L 1 '-L 2 51. The linker-drug conjugate according to claim 50, wherein: 【Chemistry 103】 wherein q is an integer selected from 0 to 10, preferably 1, 2, 3, 4, 5, 6, 7, or 8; R z4 and R z5 may be the same or different and independently represent H, C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkyl-C 1-4 alkyl group, or R z4 Or R z5 Together they form C 3-6 Forms a cycloalkyl group, provided that R z4 or R z5 At least one of them is not H, More preferably, R z4 or R z5 Together they form C 3-6 forming a cycloalkyl group, Most preferably, L 1 '-L 2 teeth, 【Chemical 104】 It is.)

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